bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12070: Extracellular Vesicles, Derived Early After Myocardial Infarction, Inhibits Staurosporin Induced Cardiac Cell Death
Authors: Khandagale Avinash , Lindahl Bertil , Siegbahn Agneta G , Christersson Christina
Published: April 2022

Introduction:
Adverse ventricular remodeling may occur after myocardial infarction (MI) and is associated with an increased risk of heart failure and death. Extracellular vesicles (EVs) derived exogenously from pluripotent stem cells exert cardioprotective effects after injury and being tested for therapeutic efficacy for MI. However role of endogenous EVs from MI patients in this regard is not yet addressed.

Hypothesis:
We aim to characterize EVs derived from MI patients and explore their cardioprotective potential on human primary cardiomyocytes (HCM) upon chemically induced cell death.

Methods:
The EVs from plasma of MI patients with preserved or reduced left ventricular ejection fraction (LVEF) and healthy controls (HC) were purified and characterized by flow cytometry and transmission electron microscopy (TEM). HCM and human cardiac microvascular endothelial cells (hCMVECs) were used to study functional effects of EVs upon staurosporin (STS), etoposide and rapamycin induced cell death.

Results:
Higher concentrations of platelet-, leukocyte-, endothelial- and erythrocyte-derived EVs were found in MI patients compared to HC. TEM analysis demonstrated the presence of heterogenous vesicles of different sizes (50-1000-nm) across all tested samples. Human cardiac cells- hCMVECs and HCM when pre-incubated with both preserved and reduced LVEF MI EVs showed significant attenuation to STS-induced caspase 3 activity compared to HC EVs or mock treatment. Lactate dehydrogenase (LDH) release, as a marker for membrane integrity, upon etoposide stimulation was not affected in hCMVECs and partly increased in HCM, whereas pre-incubation with HC EVs or MI EVs did not affect eotoposide treatment outcome by these cells. While rapamycin induced cleavage of LC3-I to LC3-II in hCMVECs, the presence of EVs from either HC or MI patients did not influence autophagic response. Whereas, baseline LC3-II expression in HCM was observed to be too high to be perturbed by the presence of rapamycin.

Conclusions:
Diverse nature of MI EVs in terms of cells of origin can be further elaborated to consolidate their biomarker potential. Cardioprotective ability of endogenously presented heterogenous mixture of MI EVs opens new avenues to consider in preclinical EV/MI research.
Abstract 12079: Demographic and State-Level Trends in Mortality Due to Ischemic Heart Disease in the United States From 1999 to 2019
Authors: Essa Mohammed , Ghajar Alireza , DeLago Augustin , Hammond-Haley Matthew , Shalhoub Joseph , Marshall Dominic , Salciccioli Justin , Sugeng Lissa , Krumholz Harlan M , Philips Binu , Faridi Kamil
Published: April 2022

Introduction:
Mortality from ischemic heart disease (IHD) in the United States (U.S.) has decreased recently, yet variation in IHD-related mortality trends for different demographic across U.S. states is not well described.

Hypothesis:
IHD mortality differs based on geography, gender, ethnicity, and race.

Methods:
We performed analysis using CDC WONDER database to evaluate IHD mortality trends in the U.S. between 1999 and 2019. Age-adjusted mortality rates (AAMR) per 100,000 people were evaluated and stratified by sex, race, and state. Joinpoint regression was used to assess annual rates of change in IHD-related mortality.

Results:
From 1999 to 2019, AAMR due to IHD decreased from 194.6/100,000 to 88.0/100,000 nationally. Black men had the highest AAMR, and Hispanic white women had the lowest AAMR throughout this period. AAMR for white men decreased nationally by 51.4% from 251.2 to 122.1; 59.1% for white women from 150.5 to 61.5; 51.8% for black men from 278.7 to 134.2; 59.9% for black women from 188 to 75.4; 54.3% for Hispanic men from 200.1 to 91.4; and 63.1% for Hispanic women from 133.1 to 49.0 (Figure). Relative decreases in AAMR across states ranged from 27.0%-70.9% for white men, 30.9%-68.9% for white women, 7.3%-80.9% for black men, 27.2%-74.7% for black women, 30.5%-79.8% for Hispanic men, and 35.8%-76.8% for Hispanic women. Based on the regression model, the annual average percent decline in IHD-related AAMR for all groups has decreased since 2011 (Figure).

Conclusions:
AAMR due to IHD in the U.S. has decreased from 1999 to 2019 for all demographic groups, though the rate of decline has lessened since 2011. There is significant geographic variation in reductions of IHD-related AAMR across U.S. states. These findings indicate that race, ethnicity, and geography are strongly associated with trends in mortality due to IHD. Given the ongoing disparities in mortality, further investigation into geographic differences in prevention and treatment of IHD is needed.
Abstract 12089: Dual Actions of β
2
AR-Agonism Confer Protection Against Heart Failure and Renal Dysfunction via Inotropic and Lusitropic Effects and Normalized Cholesterol Homeostasis in a Mouse Model of Alport Syndrome
Authors: CHAHDI AHMED , Yousefi Keyvan , Condor Capcha Jose Manuel , Irion Camila , Lambert Guerline , Shehadeh Serene A , Dunkley Julian , Lee Yee-Shuan , Khan Aisha , Ramic Melina , Andrade Nadja , Zeier Zane , Dykxhoorn Derek , Katsoufis Chryso , freundlich michael , Hare Joshua M , Nabity Mary , Rivera Carolina , Lymperopoulos Anastasios , Webster Keith A , Zelcer Noam , Shehadeh Lina A
Published: April 2022

Introduction:
Col4a3-/- Alport mice present a model of heart failure with preserved ejection fraction (HFpEF) secondary to chronic kidney disease(CKD) wherein etiological relationships have been established between hypertension, pulmonary edema, inflammation, cardiac hypertrophy and fibrosis, diastolic dysfunction and underlying abnormalities of elevated low-density lipoprotein receptor (LDLR) expression, excess LDL-cholesterol(LDL-C) accumulation, and mitochondrial dysfunction in renal tubules.

Hypothesis:
We tested the hypothesis that selective β2-Adrenoceptor (β2AR) modulation with salbutamol, a short-acting β2AR agonist, could alleviate symptoms of CKD and simultaneously augment cardiac function.

Methods:
Alport mice were injected i.p.with salbutamol or DMSO vehicle as a single bolus of 200μg/dose in short-term studies or daily with 100 μg/dose for 2 wks long-term. Cardiac and renal functions, cAMP levels, in vivo renal tubular LDL-C uptake and renal histology were evaluated post-injection. N=3-8 for all experiments.

Results:
Short-term, salbutamol improved renal function in parallel with decreased LDLR levels and reduced uptake of LDL-C into renal tubules. Long-term, cardiac diastolic function assessed by isovolumetric relaxation time, filling pressures, and myocardial performance index, and systolic function reflected by ejection fraction, stroke volume and cardiac output improved significantly in parallel with increased cardiac cAMP (p<.05). Mechanistically, in the kidney, salbutamol activated IDOL and hence lysosomal ubiquitination and degradation of LDLR via a novel β2AR-mediated, cAMP-independent pathway involving the Rac1/Cdc42 β1PixGEF. β1Pix reversibly sequesters IDOL into a complex with LDLR, thereby blocking the degradation pathway. β2AR stimulation dissipates the complex reactivating IDOL-mediated LDLR degradation thereby re-establishing LDL-C homeostasis and renal function. Using flow cytometry in 293T cells, ectopic expression of bPix stabilized membrane LDLR, sensitive to IDOL- but not PCSK-mediated degradation.

Conclusions:
β2AR agonism represents a potential treatment strategy to alleviate progression of CKD and HF associated with HFpEF phenogroup 3.
Abstract 12093: Tafamidis Use and New Onset Atrial Fibrillation in Patients With Cardiac Amyloidosis
Authors: Sweat Austin O , Girvin Zachary P , Boursiquot Brian C , Redel-traub Gabriel , Jou Stephanie , Kochav Stephanie , Maurer Mathew , Dizon Jose , Biviano Angelo B , Garan Hasan , Yarmohammadi Hirad
Published: April 2022

Introduction:
Atrial fibrillation (AF) is the most common sustained arrhythmia seen in patients with cardiac amyloidosis (CA). Tafamidis, a transthyretin stabilizer, has been associated with reductions in all-cause mortality and other promising outcomes in patients with CA. However, its effect on incidence of AF still remains unknown.

Hypothesis:
Tafamidis therapy in patients with CA is associated with lower incidence of AF.

Methods:
A group of 200 patients with transthyretin CA following at our institution between 2003 and 2019 were retrospectively reviewed. Baseline characteristics, onset of AF (determined by ECG, device interrogation, or ambulatory monitoring) and tafamidis use data were collected. Patients with diagnosis of AF at baseline were excluded. Patients were matched based on age, sex, BMI, DM, HTN, ischemic heart disease, and stage of amyloid disease. Time to event analysis was performed to assess the incidence of new-onset AF in patients who had received tafamidis versus those who had not.

Results:
In total, 36 patients met inclusion criteria. Of these 36 patients diagnosed with incident AF, 10 received tafamidis therapy prior to AF diagnosis and 26 did not. Median time to Tafamidis initiation after diagnosis of cardiac amyloidosis was 243 [64, 776] days [IQR]. Average follow-up time was 21.8 ± 24.4 months. There were no significant differences between baseline characteristics, however there were more African Americans (27% vs. 0%) and Val122Ile mutations (23% vs. 10%) in the control group. Overall, tafamidis initiation was associated with lower incidence of new-onset AF compared to those who had not received the therapy (p=0.026). Persistent AF was the most common type of AF, no matter being on tafamidis or not.

Conclusions:
Tafamidis therapy in patients with CA might be associated with lower incidence of AF. The mechanism however is not clear and further studies are needed to re-examine this finding and elucidate the potential mechanism.
Abstract 12101: Clinical Implications of Integrating Polygenic Risk Into Established Cardiovascular Disease Risk Scores
Authors: Riveros-Mckay Fernando , Selzam Saskia , Seth Priyanka , Moore Rachel , Tarran William A , O'Sullivan Jack W , Ashley Euan A , McVean Gilean , Plagnol Vincent , Donnelly Peter , Weale Michael E
Published: April 2022

Risk-guided intervention in the US, informed by the pooled cohort equations (PCE) risk calculator, is the accepted practice for prevention of atherosclerotic cardiovascular disease (ASCVD). We recently showed that a polygenic risk score (PRS, summarising common genetic risk) can be integrated with PCE into an integrated risk tool (IRT) and we validated its utility across multiple contexts including sex, age, genetic ancestry and self-identified ethnicity (Weale et al 2021). The addition of PRS is always beneficial, but its contribution varies by context. When meta-analysed across multiple cohorts, the PRS is more predictive in men (odds ratio per standard deviation, ORsd=1.57) than women (ORsd=1.46). Across ethnicities, the group with the lowest effect size is African American (ORsd=1.14 in men, ORsd=1.11 in women), a result that predominantly reflects a lack of available training samples.

The availability of a CVD IRT has practical clinical implications. Because the IRT substantially spreads the risk scores in a given patient stratum, the inclusion of genetic factors can result in some individuals crossing actionable risk thresholds in both directions. Using UK Biobank, a large UK population cohort aged 45-64 with extensive medical and genetic information, we show that the rates of up/down classification are 7.8%/4.2% in younger men (40-54yo), 1.9%/11.6% in older men (55-69yo), 1.0%/0.2% in younger women, and 6.5%/6.6% in older women. This implies a tendency to under-treat in younger and over-treat in older individuals under current guidelines. Model discrimination (Harrell’s C, a measure of area-under-the-curve for survival data) is also greatest in the younger (C=0.751/0.732 in men/women) vs older (C=0.666/0.697 in men/women) age group. Given the increased up-classification and discrimination in the younger group, the addition of genetics provides an opportunity for earlier intervention in those most at risk.
Abstract 12111: Metformin Maintains Mitochondrial Integrity and Preserve Heart From Ischemia Reperfusion Injury Through Sestrin2-AMPK Signaling
Authors: Bates Lauryn , Fedorova Julia , Le Van , Yang Yi , Murphy Jiayuan , Davitt Kayla , Logan Cole , Ren Di , Li Ji
Published: April 2022

Introduction:
Metformin activates AMP-activated protein kinase (AMPK) to improve cardiac function during ischemia and reperfusion (I/R). We reported that Sestrin2 (Sesn2) is associated with AMPK and maintains oxidative phosphorylation (OXPHOS) under I/R stress. The role of age-related Sesn2-AMPK signaling in the beneficial actions of metformin on ischemic insults remains unknown.

Hypothesis:
Metformin maintains mitochondrial integrity and limits cardiac damage caused by ischemic insults through the Sesn2-AMPK signaling pathway.

Methods:
Young (3-6 months) and aged (22-24 months) C57BL/6J wild type mice, and 3 months of Sesn2

f/f

and cardiomyocyte-specific Sesn2 knockout (cSesn2
-/-
) C57BL/6J mice were subjected to 45 minutes of ischemia followed by 2 mM metformin injection 5 minutes before 24-hour of reperfusion. Cardiac function and myocardial infarction were determined with echocardiography and 2,3,5-triphenyl tetrazolium chloride staining. Immunoblotting determines the mechanism of metformin in modulating Sesn2 to preserve mitochondrial OXPHOS components. The Seahorse XF Analyzer examined the mitochondrial respiratory functions.

Results:
Metformin administration can significantly improve cardiac function and reduce myocardial infarction size during I/R conditions in both young and aged wild-type C57BL/6J mice. Intriguingly, the beneficial effects of metformin administration on cardiac function and myocardial infarction were significantly blunted in the cSesn2
-/-
versus Sesn2

f/f

C57BL/6J mice. The immunoblotting showed metformin treatment augmented mitochondrial OXPHOS Complex II levels in young/aged wild type, and Sesn2

f/f

but not cSesn2
-/-
heart during I/R stress. Moreover, the mitochondrial respiration data displayed that metformin treatment improved the respiration rate of mitochondrial states 2 and 3μ in the isolated cardiomyocytes from Sens2

f/f

but not from cSesn2
-/-
mouse hearts under I/R stress conditions.

Conclusions:
Metformin can stabilize age-related Sesn2 levels in cardiomyocytes and improve cardiac function under I/R stress through maintaining mitochondrial integrity. Metformin is a potential therapeutic drug for ischemic heart disease in the elderly.
Abstract 12116: Sex Differences in Arrhythmia Prevalence in a Large Patient Cohort Examined With Mobile Cardiac Telemetry
Authors: Johnson Linda S , Dziubinski Marek J , Napiorkowski Natan , Witkowska Olga , Grotek Agnieszka , Slusarczyk Magdalena E , Russo Andrea M
Published: April 2022

Introduction:
The frequency of clinically relevant arrhythmia on long-term ambulatory ECG recordings is not sufficiently well described. We aimed to address this in a large patient cohort monitored with mobile cardiac telemetry.

Methods:
All patients 18-100 years who were monitored in the USA in 2017 (n=27.203, 58% female) with the PocketECG device (MediLynx), which registers and transmits a full-disclosure ECG for ≤30 days with beat-to-beat analysis, were included. Frequent premature ventricular complexes (PVCs) and frequent premature atrial complexes (PACs) were defined as ≥200 PVCs or ≥500 PACs in any recording day. Supraventricular tachycardia (SVT) episodes were defined as both any SVT >3 beats, and SVT ≥30 seconds. AV-blocks II and III were not differentiated.

Results:
In the 18-40-year age group the overall prevalence of any arrhythmia was low (Figure 1 a-f). Frequent PACs, atrial fibrillation, AV-blocks and ventricular arrhythmias were more common in men than women (all p<0.0001), and SVTs, both >3 beats and >30 seconds, were more common in women (p<0.001 and p<0.004, respectively). The overall prevalence of any VT event was 22.9% in women and 40.8% in men (p<0.0001) and the mean age at onset of VT was lower in women (71.9 vs 72.6 years, 95%CI for difference (-1.3; -0.3).

Conclusions:
Most arrhythmias are more prevalent among men of all ages, but SVTs are more prevalent among women. VT events are common in a patient population, and the age at onset of ventricular tachycardia is lower among women.
Abstract 12118: Patterns of Anticoagulation Use in Atrial Fibrillation and Active Cancer: Observations From Medicare
Authors: Chen Sean , Hellkamp Anne , Alhanti Brooke , Melloni Chiara , Piccini Jonathan P , Khouri Michel G , Granger Christopher , Pokorney Sean
Published: April 2022

Introduction:
Use of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and cancer is challenging due to increased thrombotic and bleeding risks, and data on prescription patterns are lacking.

Hypothesis:
Underutilization of OAC among patients with AF and cancer is associated with cancer specific factors.

Methods:
This study examined OAC use and factors associated with discontinuation of OAC among Medicare patients with AF and a new diagnosis of cancer from 2011-2016. We described OAC use patterns prior to and after a diagnosis of cancer. Logistic regression was used to evaluate clinical variables associated with discontinuation of OAC at time of cancer diagnosis and cox proportional hazards model was used to evaluate variables associated with discontinuation after diagnosis.

Results:
Among 44,769 patients with established AF and newly diagnosed cancer, 30.2% (n=13,508) were taking OAC at the time of cancer diagnosis. A total of 15,228 patients (34%) had an OAC prescription fill after index cancer diagnosis. Warfarin was the most commonly used OAC, but direct oral anticoagulant use increased over the study period. A total of 29.5% of patients had their OAC discontinued at the time of cancer diagnosis. Patients with gastric (OR 2.75, CI 2.12-3.57), pancreatic (OR 2.71, CI 2.15-3.41), and colorectal (OR 1.97, CI 1.70-2.28) cancer were most likely to have their OAC discontinued at diagnosis (Figure). Bleeding (HR1.37, CI 1.28-1.48) and chemotherapy (HR 1.38, CI 1.06-1.80) were associated with subsequent discontinuation in those who remained on OAC after diagnosis.

Conclusions:
Nearly 2 in 3 patients with established AF were not treated with OAC after cancer diagnosis despite an elevated stroke risk. Significant heterogeneity in OAC use exists depending on cancer type, baseline comorbidities, and chemotherapy use. Studies are needed to characterize the thrombotic and bleeding risks in this population to establish management guidelines.
Abstract 12217: Accurate Prediction of Systolic Peak-to-Peak Gradient in Children With Pulmonary Valve Stenosis
Authors: Rodriguez Franco Salvador A , Zablah Jenny E , Frank Benjamin S , Morgan Gareth J
Published: April 2022

Objective:
To evaluate the correlation between transthoracic echocardiography (TTE) derived gradients and invasive RV-PA peak-to-peak systolic gradient (iPG) and the predictability of these values in children with pulmonary valve stenosis (PVS).

Introduction:
Historically, correlations have been found between the Doppler-derived peak echo gradient (ePG), using the modified Bernoulli equation and invasive hemodynamic indices. This has led to the ePG being a widely used estimate of the degree of stenosis and an indicator of timing to consider intervention in children with PVS. However, large disparities observed between these invasive and non-invasive measurements have called into question the reliability of ePG to screen patients for consideration of pulmonary valvoplasty.

Methods:
We performed a retrospective chart review of 119 children who underwent pulmonary valvoplasty between January 2010 and January 2020 and selected 51 patients who had "simple" PVS in whom a TTE was performed within 6 months prior to the procedure. We evaluated the correlation between TTE parameters [Maximum velocity (Vmax), Mean Gradient (MG), ePG], and iPG. We then used the mathematical functions resulting from the correlation models to predict iPG.

Results:
All the assessed models were statistically significant and presented a strong correlation. When the differences between echocardiographic parameters and iPG were evaluated, ePG demonstrated the least accuracy in predicting iPG, erroneously estimating the real value by >10mm Hg in 66% of cases. The MG presented a more accurate estimation of iPG, showing a narrower range of variance, with an error of >10mm Hg in less than 30% of cases. We then modeled several mathematical functions of Vmax, MG, and ePG to predict iPG, and found that a derived function of Vmax (
f
iPG) distributed by BSA (fiPG =12.7[Vmax]-17.3[BSA]) produced the most accurate results.

Conclusions:
There is a strong correlation between pre-procedural TTE parameters and iPG, but when ePG is used to estimate iPG, up to two-thirds of cases could be inappropriately characterized. We found that MG was a better predictor and that a mathematical function derived from Vmax and BSA (
f
iPG) was the most accurate predictor of iPG.
Abstract 12220: Deep Learning Segmentation and Quantification of Epicardial Adipose Tissue in CT Calcium Score Images
Authors: Hoori Ammar , Hu Tao , Lee Juhwan , Al-Kindi Sadeer , Rajagopalan Sanjay , Wilson David
Published: April 2022

Introduction:
Studies have linked the epicardial adipose tissue (EAT) volume with the risk of adverse cardiovascular (CV) events, suggesting a role for clinical decision making. Manual quantification of EAT is time-consuming, requires specialized training, and is prone to human error, thus limiting its routine use in clinical practice.

Hypothesis:
Deep-learning approach can facilitate EAT quantification on archival coronary artery calcium scoring (CAC) scans.

Methods:
We developed a deep learning semantic segmentation method using the DeepLab-v3 plus network and applied it to gated, non-contrast cardiac CT calcium score scans. Analysts manually identified the enclosing pericardial sac using interactive visualization software. Our algorithm was trained to segment the image region enclosed by the pericardial sac. To keep the sac-increasing curvature, we segmented the heart into two halves. The lower half was analyzed from bottom-to-middle, while the slices in the upper half were analyzed from top-to-middle. Each 2D slice was associated with two consecutive slices, giving a three-slice image slab. A window/level of 350/40 Hounsfield unit (HU) was applied to axial slices providing a uniform HU-attention-window. A median filter with kernel size 3mm was applied to reduce noise. After deep learning semantic segmentation of the enclosing region, we determined EAT using the standard CT fat window [-190, -30] HU.

Results:
Using 89 CT scans (50 training/39 testing), our algorithm showed excellent results compared to ground-truth manual labeling. The total average Dice score was (88.52%±3.35) with a high correlation against manually derived EAT (R=98.52%, p-value<0.001). The average Dice score per slice was 91.80% (with R=96.62%, p-value<0.001). The average percent EAT volume error was only 5.74%±5.04.

Conclusions:
Our developed end-to-end deep learning segmentation approach, using HU-attention-window and slab-of-slices gives accurate EAT volume segmentation. Our results provide an important avenue for automated analysis of EAT and its relationship with CV events in large data sets.
Abstract 12228: Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes
Authors: Bliden Kevin , Tantry Udaya , Usman Abira , Cho Alastair , Walia Naval , Jerijan Christophe , Singh Arvind , Makadia Sunal , Gurbel Paul A
Published: April 2022

Introduction:
Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear.

Hypothesis:
We hypothesize that inhibitory effect of metformin on markers of inflammation, oxidative stress, and hypercoagulability is associate with better clinical outcomes.

Methods:
Patients with DM on metformin (n=34) and metformin naïve (n=41), and patients without DM (n=73) were enrolled within 48 hours of hospital admission and were diagnosed with COVID-19 by reverse transcription-polymerase chain reaction assay. Laboratory assessments were conducted within 48 hours of hospital admission. The chi-squared test was used to determine whether there was a significant difference in frequencies between disease groups; p< 0.05 was considered a significant difference between groups.

Results:
DM patients on metformin compared to naïve patients had a lower white blood cell count (p=0.02), d-dimer (p=0.04), urinary 11-dehydro thromboxane B
2
(p=0.01) and urinary liver-type fatty acid binding protein (p=0.03) levels and had lower sequential organ failure assessment score (p=0.0002), intubation rate (p=0.03), and a trend for fewer hospitalized days (p=0.13), lower in-hospital mortality (p= 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p=0.10). Patients on metformin had similar clinical outcomes compared to patients without DM.

Conclusion:
In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis; and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings.
Abstract 12243: Overview of In-Patient Burden of Lower Extremity Peripheral Artery Disease in Hispanics
Authors: Luna Paulina , Harris Kristie , Castro-Dominguez Yulanka , Carolina Severiche-Mena , Smolderen Kim G , Mena-hurtado Carlos
Published: April 2022

Background:
Hispanics have high rates of cardiovascular risk factors and prior data suggests that they undergo more amputations than non-Hispanic Whites (NHW) for peripheral artery disease (PAD). Little is known of treatment patterns and outcomes for this group in contemporary data. Thus, this study examined revascularizations, amputations, and mortality in Hispanics and NHW hospitalized with PAD.

Methods:
Data from the 2011-2017 National Inpatient Sample were used. Cross-sectional analysis of revascularizations and amputations were done by ethnicity using standardized differences (
d≥
0.20 considered significant). Temporal trends in revascularizations and amputations by year were evaluated with the Cochran-Mantel-Haenszel test and stratified by ethnicity. Data were combined across years and multivariable logistic regression was used to evaluate the association of ethnicity with revascularization, amputation, and mortality, adjusting for risk factors.

Results:
From 2011-2017, 141,551 Hispanics were admitted with PAD (12-16% of annual admissions). Hispanics had higher rates of amputations (32% vs. 21%,
d
=0.31) and lower rates of revascularizations (43% vs. 60%,
d
=0.38) than NHW in the overall sample and over time (Fig. 1, all P
trend
<0.0001). Hispanic ethnicity was associated with lower odds of revascularization and mortality but higher odds of amputation (Fig. 2).

Conclusion:
A growing number of Hispanics are hospitalized for PAD. Despite an overall decline, amputations were more prevalent in Hispanics, suggesting that earlier systemic strategies for PAD awareness, diagnosis, and prevention are needed in Hispanic populations to eradicate this disparity.
Abstract 12260: Reoperation Was an Effective Therapy in Patients with Obstructive Hypertrophic Cardiomyopathy After Septal Reduction Therapy
Authors: Zhang Yang , Zhu Changsheng , Song Changpeng , Yin Kunlun , Zhang Jian , Huang Manyun , Zheng Xinxin , Lu Jie , Fang Xiaonan , Zhou Zhou , Shuiyun WANG , Huang Xiaohong
Published: April 2022

Introduction:
This study aims to analyze the clinical characteristics of patients with obstructive hypertrophic cardiomyopathy (OHCM) undergoing repeated septal reduction therapy (SRT), and preliminarily describe the genotype in the recruited patients.

Methods:
Patients with OHCM who received repeated SRT were recruited from 2014 to 2019 in Fuwai Hospital. Patients were divided into septal myectomy (SM) group or alcohol septal ablation (ASA) group according to the primary procedure of SRT. Sixteen of these patients underwent genetic testing. Pathogenic mutations were those mutations identified as pathogenic, likely pathogenic, or variants of uncertain significance according to the ACMG criteria.

Results:
A total of 31 patients (21 males) was included. The average age was 48.7±12.2 years. There were 7 patients in the SM group and 24 patients in the ASA group. Preoperative electrocardiogram showed that 7 patients in the ASA group presented with complete right bundle branch block (CRBBB). After the operation, 4 patients were implanted with permanent pacemakers due to complete atrioventricular block, of which 3 patients were in the ASA group with CRBBB. Pathogenic mutations were identified in 50.0% (8/16) of the study patients. Pathogenic mutations were mostly located in the MYH7 gene (5/9,55.6%), MYBPC3 gene (3/9,33.3%), and TNNT2 gene (1/9,11.1%). There was no difference between patients carrying pathogenic mutations or not, in terms of interventricular septal thickness and left ventricular outflow tract gradient. During the perioperative period, except for one death caused by electrical storm, the remaining patients had no serious complications. The results of follow-up echocardiography showed that except for 2 patients who had left ventricular outflow tract obstruction again, the thickness of interventricular septum and left ventricular outflow tract gradient was significantly lower compared with preoperative echocardiography.

Conclusions:
In conclusion, the surgery of SM is an effective treatment in OHCM patients with a history of previous SRT procedures. Patients with the first procedure of ASA are at high risk of developing atrioventricular block after a repeated SM.
Abstract 12298: A Sequential Deep Learning Approach for Automated Detection and Attribution of Coronary Artery Calcification in Non-Contrast CT
Authors: Hoori Ammar , Song Yingnan , Lee Juhwan , Al-Kindi Sadeer , Rajagopalan Sanjay , Wilson David
Published: April 2022

Introduction:
Coronary artery calcium (CAC) is strongly predictive of adverse cardiovascular events, and is widely utilized for risk stratification. There is considerable interest in automated machine learning techniques for analysis of coronary calcification, that may provide incremental prognostic value and personalization in CV care.

Hypothesis:
Deep-learning (DL) approaches provide accurate and time-efficient automated detection of individual calcifications and classification of their corresponding territory.

Methods:
Two automated deep learning (DL) techniques are proposed. We use a standard detection criterion (3 connected voxels >130-HU). The first DL classifies “true” CAC from an extra-coronary calcification (NON-CAC). NON-CACs include bone, aortic calcifications, noise, and lung calcifications. Candidate calcifications are centered in 2D CT patches. Each patch contains three channels of the lesion with 3 scales (х0.5, original, х2), respectively. The second DL classifies CACs as belonging to coronary territories (LAD, LCX, and RCA) using CAC patches associated with their corresponding coronary territories.

Results:
We used a dataset of 66 patients that generates (1903/4745: CAC/NON-CAC) patches for the first DL, while the CAC patches are subdivided into (695/321/887: LAD/LCX/RCA) patches for the second DL. We trained, validated, and tested our first DL in 80%, 10%, and 10% of patches and the second DL with a 70%,10%, and 20% split respectively. ResNet50 DL outperformed other DL algorithms for both determinations of CAC and classification of territory. Our method provides a highly accurate solution for automated CAC detection with accuracy and precision of 98.8% and 97.9%, respectively. CAC arterial classification (artery-based) showed an accuracy of 99.5%, 99.7%, and 100% for LAD, LCX, and RCA, respectively. with a precision of 98.6%, 100%, 100%, respectively.

Conclusions:
In this preliminary study, an automated DL framework correctly identified coronary calcifications and their corresponding territories. Further studies are warranted to scale our approach to automate CAC analysis for precision medicine approaches.
Abstract 12319: 16alpha-Hydroxyestrone Downregulates SOX17 During the Development of Pulmonary Arterial Hypertension
Authors: Sangam Shreya , Schwantes-An Tae-Hwi , Zagorski John , Shi Yinan , Morrisroe Seth , Cook Todd , Fisher Amanda , Frump Andrea , Coleman Anna , Tang Haiyang , Crawford Howard , Lutz Katie , Pauciulo Michael W , Chaudhary Ketul R , Stewart Duncan J , Lahm Tim , Nichols William C , Desai Ankit A
Published: April 2022

Introduction:
Sexual dimorphism in pulmonary arterial hypertension (PAH) is attributed, in part, to estrogen signaling. 16α-hydroxyestrone (16αOHE) is considered a major contributor to PAH pathogenesis. Recent genetic studies have also suggested that deficiency of SOX17, an endothelial cell (EC)-specific transcription factor, contributes to PAH risk. While functional studies of SOX17 are absent, we hypothesized that 16αOHE contributes to PAH, in part, via, SOX17 downregulation.

Methods/Results:
Sox17 expression was reduced in 3 animal PAH models and in human pulmonary artery ECs (HPAECs) isolated from patients with PAH (vs controls). Inducible Tie2-specific
Sox17
knockout (
Sox17
EC-/-
) mice exhibited increased right ventricular systolic pressure (RVSP), RV hypertrophy (RVH), and PA wall thickness (PAWT) after chronic hypoxia (CH) (Fig 1A). Inducible Tie2-
Sox17
transgenic overexpressing (
Sox17
Tg
) mice attenuated CH-induced PH (Fig 1B). While not evident across murine sex, Sox17 expression was increased in baseline lungs from male compared to female rats. Supporting
in silico
evidence of estrogen response elements (ERE) on the
SOX17
promoter, HPAECs exposed to 16αOHE reduced SOX17 expression and promoter luciferase activity via ERα, which was partly negated by serial ERE mutagenesis (Fig 1C
)
. Lungs from ERα loss-of-function mutant rats (vs control) confirmed
in vivo
reductions of Sox17 expression.
Sox17
Tg
mice attenuated 16αOHE-mediated PH after CH (Fig 1D). To translate these data, we identified a functional coding SNP in the
ESR1
gene (encoding ERα), rs746432, previously shown to reduce transcriptional activity of ERα. The SNP was associated with reduced pulmonary vascular resistance in patients with PAH (n=702, Fig 1E) in adjusted analyses.

Conclusion:
Validating genetic studies, SOX17 deficiency augments preclinical PAH. 16αOHE mediates PH development via downregulation of SOX17, linking
SOX17
genetics with the observed sexual dimorphism.
Abstract 12511: Differential Regulation of Circulating Damage-Associated Molecular Patterns in Patients With Coronary Artery Ectasia
Authors: Tsoporis James N , Triantafyllis Andreas , Gupta Sahil , Izhar Shehla , Sakadakis Eleftherios , Rigopoulos Angelos G , Parker Thomas G , Rizos Ioannis
Published: April 2022

Introduction:
Coronary artery ectasia (CAE) defined as localized or diffuse non-obstructive coronary lesions is a rare but well-recognized pathological entity of the coronary arteries and characterized as a variant of coronary atherosclerosis. CAE commonly coexists with coronary artery disease (CAD). Although inflammation appears to be involved, the pathophysiology behind CAE remains unclear. Danger-associated molecular patterns (DAMPs) are altered metabolism products of necrotic or stressed cells, which are deemed as alarm signals by the innate immune system. Inflammatory agents are DAMP generators and DAMPs create a pro-inflammatory state.

Hypothesis:
We aimed to investigate the different patterns of serum DAMPs in patients with CAE, obstructive CAD and normal coronary arteries and the prognostic role of these in the pathogenesis of CAE.

Methods:
In this prospective cross-sectional study, 28 patients with CAE and nonobstructive CAD were enrolled in the study, 19 patients with obstructive CAD but without CAE, and 18 control subjects with normal coronary arteries that have been matched with the CAE patients for age and sex were also enrolled in our study population. Venous blood samples of the participants were collected for serum DAMP evaluation.

Results:
Patients with CAE and non-obstructive CAD had increased (30-35%) serum levels of the DAMPs, the receptor for advanced glycation end products (RAGE) ligand S100B and the toll-like receptor 4 ligand heat shock protein (HSP)70 compared to control subjects and patients with CAD. Additionally, CAE and non-obstructive CAD patients had decreased (30-40%) serum levels of potential DAMPs, the antioxidant DJ-1 and soluble (s)RAGE, a decoy molecule that bind excess RAGE ligands, compared to control subjects and CAD patients. Positive correlations were observed between S100B and HSP70 (p=00564), and DJ-1 and sRAGE (p=0.00461). All evaluated serum DAMPs were not different in CAD patients compared to control subjects.

Conclusion:
The differential regulation of the DAMPs S100B, HSP70, DJ-1 and sRAGE in CAE versus CAD makes them attractive novel biomarkers as therapeutic targets and therapeutics.
Abstract 12800: Echocardiographic Findings in Hospitalized Patients With COVID-19
Authors: Jehangir Qasim , Lee Yi , Poisson Laila , Latack Katie , Sule Anupam , Song Shiyi , Apala Dinesh Reddy , Halabi Abdul R , Patel Kirit , Krishnamoorthy Geetha , Wang Dee Dee
Published: April 2022

Introduction:
Data on echocardiographic findings in COVID-19 patients is limited. Atrial arrhythmias (AA) are common in COVID-19 but their impact on echocardiographic phenotypes is not well studied. We aimed to assess transthoracic echocardiographic (TTE) findings in adult hospitalized patients with COVID-19 undergoing TTE, and compare patients with new-onset or history of AA to patients with normal sinus rhythm (NSR).

Methods:
We studied TTE findings in adult patients who were admitted to one tertiary care and five community hospitals in Michigan with PCR-proven SARS-CoV-2 infection from 3/1/2021 to 12/1/2020, and stratified them into three groups: Group 1 (NSR), group 2 (new-onset AA including atrial fibrillation and atrial flutter), and group 3 (history of AA).

Results:
Among 6927 (5522 in group 1, 626 in group 2, 779 in group 3) hospitalized patients (mean age 65.4 ± 17.1 years, 50.7 % females) 115 patients underwent TTE (Table). Group 2 and 3 patients were significantly older, more commonly males, Whites, smokers, and more frequently had diabetes mellitus, hypertension, heart failure, history of coronary artery disease, and cerebrovascular accident compared to group 1 (p≤0.05 for all). The most common TTE abnormalities were valvular abnormalities (40.9%), RV dilation (29.6% of patients), elevated PASP (16.5%), reduced LV ejection fraction (13.9%), pericardial effusion (9.6%), and LV dilation (6.1%) with no significant difference in the prevalence of these echocardiographic abnormalities between the 3 groups.

Conclusions:
TTE abnormalities are common in hospitalized COVID-19 patients with valvular abnormalities, RV dilation, and PASP elevation being the most common. Current or prior history of atrial arrhythmias did not increase the prevalence of echocardiographic abnormalities. Clinicians should have a low threshold to obtain echocardiogram in hospitalized COVID-19 patients if clinically indicated even in the absence of AA.
Abstract 12875: The Impact of Social Determinants of Health and Race Disparities in Heart Transplant Long-Term Survival
Authors: Alnajar Ahmed , Blackstone Eugene H , Reis Isildinha M , Dar Tawseef A , Callahan Connor , Rana Abbas , Palacio Ana M , Rao J Sunil
Published: April 2022

Introduction:
: Patients of color have a higher early mortality risk after heart transplantation than White recipients, even after taking differences in comorbidities into account. We aimed to assess long-term heart transplantation success based on patient's social determinants of health.

Hypothesis:
Socio-demographic indices that identify patients of socioeconomic (SES) disadvantage can predict poorer heart graft survival.

Methods:
We studied 34,584 adult heart transplant recipients from 2004 to 2020 using OPTN database. Established and modern SES indices—including the Agency for Healthcare Research and Quality index (AHRQ), the Area Deprivation Index (ADI), Social Vulnerability Index (SVI), Social Deprivation Index (SDI), and Crime Risk index—were evaluated. We performed survival analysis using Kaplan-Meier, univariable and multivariable Cox regression. Penalized LASSO algorithm was used during model development for variable selection among large number of patient characteristics (e.g., recipient and donor biological factors and comorbidities) related to heart transplantation.

Results:
On average, the worst level of disadvantage across different SES indices resulted in a 20% increased risk of graft failure (Table 1A). After accounting for the recipient and donor biological factors and comorbidities, the recipients' indices remained statistically significant. Non-white patients (HR:1.10, p<0.001), no private insurance (HR:1.19,p<0.001), and education less than college (HR:1.09,p=0.006) were also statistically significant . Donor SES indices had numerically higher hazard ratios, without statistical significance (Table 1B).

Conclusions:
Recipients access to health care and nonadherence may stem from low health literacy, limited social support, and financial burden. Further efforts should be taken to counsel patients with socioeconomic disadvantages to improve heart transplant outcomes.
Abstract 12885: A Challenging Case of Endocarditis— Multi-Disciplinary Approach is an Achievable Chimera
Authors: Blumer Vanessa , Martinez Omar , Pomeroy Jordan E , Anderson D Ryan , Andonian Brian , Parsons Joshua , Glass Carolyn , SKETCH Michael H , Bloomfield Gerald S , Ward Cary C
Published: April 2022

A 60-year-old man with history of coronary artery bypass grafting and mitral valve repair presented with confusion, gait instability and lethargy. Cardiology was consulted after a transthoracic echocardiogram demonstrated a mobile mass on the mitral valve (MV). A subsequent transesophageal echocardiogram showed a large vegetation encompassing and adherent to the anterior annulus and leaflet. Serial blood cultures were negative. The initial differential considered causes of blood culture negative endocarditis (BCNE) with embolic phenomena to the central nervous system. This diagnosis was challenged after the patient developed progressive neurologic symptoms out of proportion to findings on brain imaging. A multidisciplinary team was established to revisit the available data and facilitate a coordinated care approach. The patient was found to fulfill 5 out of 8 criteria for hemophagocytic lymphohistiocytosis (HLH). Furthermore, an H-Score of 268 supported this diagnosis with a >99% probability. Therapy was started with Dexamethasone 5mg/m
2
BID and Anakinra 100mg Q6h, resulting in a rapid improvement in mental status. Secondary HLH in adults is most commonly due to malignancy and infection. Although initial workup was negative, several days into the hospital stay
Mycobacterium chimaera
was detected on next-generation sequencing of microbial cell-free DNA (Karius test).
M. chimaera
is a non-tuberculous mycobacterium belonging to the Mycobacterium avium complex and has been associated with a global outbreak following cardiothoracic surgery related to exposure to 3T heater-cooler units (HCU). Endocarditis due to
M. chimaera
acquired during prior cardiac surgery, complicated by HLH, was considered the most likely unifying diagnosis. This case illustrates: (1) the differential diagnosis of BCNE and the benefit of microbial cell-free DNA testing in its diagnosis, (2) HLH as an unrecognized entity in adults and infectious endocarditis as a possible trigger, (3) the need for improved awareness of
M. chimaera
infection in patients who have been exposed to HCU presenting with compatible symptoms, and (4) the critical role of communication and a multidisciplinary approach to provide high-quality care in challenging cases such as this one.
Abstract 12932: An Epigenetic Upregulation of Dynamin 2, a Regulator of Mitochondrial Fission, Promotes Human and Experimental Pulmonary Arterial Hypertension
Authors: Das Gupta Asish , Chen Kuang-Huieh , Tian Lian , Wu Danchen , Mewburn Jeffrey , Lima Patricia , Archer Stephen L
Published: April 2022

Introduction:
Increase in mitotic fission in pulmonary arterial smooth muscle cells (PASMC) contributes to the obstructive vasculopathy in pulmonary arterial hypertension (PAH). PAH’s fissogenic phenotype is due, in part, to excessive mitochondrial fission caused by activation of dynamin related protein-1 (Drp1). Recent observation suggests that to complete mitochondrial fission, Drp1 requires assistance from the GTPase dynamin 2 (DNM2). In this study we explore the role of DNM2 in the pathogenesis of PAH.

Hypothesis:
In PAH, increased expression of DNM2 increases mitochondrial fission and proliferation of PASMC.

Methods:
Immunoblot was used to quantify the expression of DNM2 in control (n=4) and PAH PASMC (n=5). Immunofluorescence was used to quantify the expression of DNM2 in the pulmonary arteries of monocrotaline (MCT) vs control rats. Flow cytometry was used to assess the effects of manipulating the expression of DNM2 on cell proliferation, cell cycle progression and rates of unstimulated apoptosis. Mitochondrial network structure was assessed using confocal imaging of cells infected with Adv-TOM20 mNeon green.

Results:
The expression of DNM2 was increased in human PAH PASMC vs control PASMC. Increase in the expression of DNM2 expression was also observed in the pulmonary arteries of MCT-PAH rats. Silencing DNM2 inhibited mitochondrial fission in PAH PASMC. Furthermore, silencing DNM2 inhibited proliferation in PAH PASMC by blocking the cell cycle at G1/G0. Conversely, augmenting DNM2 in normal PASMC induced mitochondrial fission and accelerated cell proliferation, recapitulating the PAH phenotype. In silico analysis identified miR-124-3p as a putative negative regulator of DNM2. Augmenting miR-124-3p decreased DNM2 expression, inhibited proliferation and induced apoptosis in PAH PASMC.

Conclusion:
DNM2 promotes mitochondrial fission and regulates cell proliferation in human PAH PASMC. Decreased miR-124-3p expression may contribute to upregulation of DNM2 in PAH. This work highlights the importance of DNM2 as partner with Drp1 in regulation of mitochondrial fission and shows that like Drp1, DNM2 is increased in human PAH. DNM2 may constitute new therapeutic target for PAH.