bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12240: Sarcomere Mutation Was Not Related To The Prognosis Of Obstructive Hypertrophic Cardiomyopathy Patients With Atrial Fibrillation
Authors: Zhang Jian , Zhu Changsheng , Nie Changrong , Yin Kunlun , Song Changpeng , Zhang Yang , Huang Manyun , Zheng Xinxin , Lu Jie , Zhou Zhou , Shuiyun WANG , Huang Xiaohong
Published: April 2022

Introduction:
Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited heart disease. The presence of a sarcomere mutation is a powerful predictor of adverse outcomes. Two-thirds of the patients are obstructive HCM (OHCM). Atrial fibrillation (AF), a common complication, is associated with poor long-term prognosis in OHCM patients. However, the effect of sarcomere mutation on the clinical phenotype or prognosis in OHCM patients with AF is unknown.

Methods and Results:
We retrospectively collected 41 OHCM patients with AF who underwent septal myectomy in Fuwai hospital which were separated into 2 groups, sarcomere mutation (+) group and sarcomere mutation (-) group (n=25 and 16). Statistical analysis was performed by Mann-Whitney
U
test, Chi-square test, Kaplan-Meier survival analysis, and log-rank test with SPSS 23.0 and GraphPad 8.0. Patients in sarcomere mutation (+) group were younger (42.0±14.5 vs. 57.6±11.7 years, p=0.001). There was no significant difference between sarcomere mutation (+) and sarcomere mutation (-) group on other baseline variables and prognosis (log-rank p=0.077).

Conclusions:
In conclusion, we did not find that the presence of a sarcomere mutation worsen the prognosis in OHCM patients with AF. Multi-center prospective studies with large samples are needed to further confirm our results.
Abstract 12242: Nanoporous Microgel Encapsulation of Extracellular Vesicles Enhances Lung Delivery for the Treatment of Pulmonary Vascular Diseases
Authors: Cober Nicholas D , Deng Yupu , Rowe Katelynn , Benavente-Babace Ainara , Courtman David W , Godin Michel , Stewart Duncan J
Published: April 2022

Introduction:
Pulmonary arterial hypertension (PAH) is a devastating lung disease with no curative treatments available. Cell-based therapies are a promising regenerative approach, including the direct application of stem cell derived extracellular vesicles (EVs). Mesenchymal stromal cells (MSCs) have shown promise as a treatment for many cardiovascular diseases; their therapeutic effects are predominately mediated by paracrine mechanisms, in particular the release of EVs. Yet, systemically administered EVs are rapidly cleared to the liver and spleen, with minimal lung accumulation.

Hypothesis:
We hypothesized that encapsulation of EVs within nanoporous microgels would provide a novel therapeutic product to improve EV lung delivery and retention and therefore enhance their therapeutic benefits.

Methods & Results:
MSC-derived EVs were purified using tangential flow filtration resulting in a median size of 108±53nm by nanoparticle tracking analysis, and positive for CD63 by Western blot. EV-loaded microgels were prepared using a microfluidic device producing agarose-gelatin (1%-1%) microgels of 47.2±0.4um diameter. In vitro uptake assays were performed with DiR or pkh26 labelled EVs and quantified by microscopy. Encapsulated EVs demonstrated a delayed-release profile in vitro with reduced HUVEC uptake over 24h (9.7±1.1% encap. vs. 46±5.3% free). In vivo biodistribution studies were performed in the monocrotaline model of PAH using central intravenous delivery. EV-loaded microgels were efficiently retained within the lungs after 24h (81±12% encap vs. 7.5±0.4% free), while free EVs accumulated in the liver (74±2.3% free vs 10±2.5% encap). Furthermore, lung digestion and flow cytometry analysis revealed that encapsulated EVs were readily taken up by CD45+ immune cells and CD31+ endothelial cells to a greater extent than free EVs, indicating enhanced interaction with the local lung microenvironment.

Conclusion:
Microencapsulation of EVs results in significantly enhanced local retention within the lung, leading to increased local cellular uptake compared to systemically administered EVs.
Abstract 12250: Trends in Retractions of Peer Reviewed Literature: Comparison Between Cardiology and Other Medical Specialties
Authors: Wadhwa Raoul R , Rasendran Chandruganesh , Popovic Zoran B , Nissen Steven E , Desai Milind Y
Published: April 2022

Introduction:
Peer-reviewed manuscript retractions are increasingly being recognized, wasting valuable scientific resources and magnifying false conclusions. The temporal trend and downstream impact of retracted cardiology articles on research and knowledge dissemination remain largely unexplored. We sought to compare retraction trends between cardiology and clinical medicine overall.

Methods:
We conducted a systematic review of retracted publications using the Retraction Watch database. Articles were selected based on manual classification. The Welch two-sample t-test and Mann-Kendall trend test were used for statistical inference.

Results:
Out of 22,740 articles, 6,594 (29%) and 445 (2%) were related to medicine overall and cardiology, respectively. The ratio of retractions to published articles has increased over recent years for medicine overall and cardiology (Figure upper panel, p < 0.01 for trends). Relative to 1990 levels, retractions in medicine have increased at over double the rate in comparison to cardiology (p < 0.01 for rate difference). There has been a downward trend in the time between publication and retraction for articles in cardiology and medicine (Figure lower panel, p < 0.01 for trends). There was no significant difference in time to retraction between the two fields.

Conclusions:
We report a sharp increase in the retracted articles in the medical literature over time. Although retractions in cardiology are increasing, they are doing so at a slower rate than other specialties. Sharing research guidelines from cardiology to other medical specialties could improve their retraction statistics, thus decreasing patient harm and waste of valuable scientific resources. Retractions are being identified earlier, potentially due to improved policing of the published literature. However, more stringent quality checks should occur during the peer review processes to prevent eventually retracted articles from being published.
Abstract 12262: The Role of Machine Learning-Based Decision Support Tools for Diagnosing and Assessing Congenital Heart Disease
Authors: Helman Stephanie , Herrup Elizabeth , Christopher Adam , Al-Zaiti Salah S
Published: April 2022

Introduction:
Machine learning (ML) is frequently applied in healthcare to optimize diagnostic classification through discovery of hidden patterns in data, not obvious to the human brain. ML research in CHD entails one of the most promising clinical applications, where timely and accurate diagnosis is essential. The objective of this scoping review was to summarize the accuracy and role of ML techniques used in pediatric cardiology research, specifically focusing on approaches that optimize diagnosis and assessment of underlying CHD.

Methods:
All original, peer-reviewed studies published in PubMed between January 2015 and February 2021 describing “(machine learning) AND ((congenital heart disease) OR (cardiovascular disease in children))” for predicting diagnostic outcomes in children with critical and non-critical CHD were included. An independent reviewer extracted and summarized primary data elements using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines.

Results:
This search yielded 217 journal articles of which 48 full-text articles (22%) met inclusion criteria. The most common application included optimizing the diagnosis and assessment of critical and non-critical CHD (38%). Deep learning (48%) and support vector machine (19%) were the most common ML algorithms used, with more interpretable algorithms being less common including decision trees (5%). Studies focusing on optimizing diagnostic classification reported a pooled overall diagnostic accuracy ranging from of 0.864 to 0.955, but only two of these models were externally validated. Clinical applications primarily focused on the classification of auscultatory heart sounds, transthoracic echocardiograms, and cardiac magnetic resonance images.

Conclusions:
These findings indicate that ML is a very promising tool for diagnosing and assessing critical and non-critical CHD, yet extensive research is still needed to build interpretable, robust, and generalizable models for clinical use, especially considering the extreme heterogeneity of complex CHD.
Abstract 12274: Intensive Cardiac Rehabilitation: Impact on Mortality
Authors: Lai Andrew F , Husaini Mustafa , RACETTE Susan B , Deych Elena , Park Lauren , Rashdi Serene , McKenzie Kristin , Mckenzie Erin , Stranczek Natalie A , Das Nikhil , Talpade Nidhi , Joynt Maddox Karen , de las Fuentes Lisa , Rich Michael W , Peterson Linda R
Published: April 2022

Introduction:
Intensive cardiac rehabilitation (ICR) combines exercise sessions as in traditional cardiac rehabilitation (CR) with additional educational sessions focused on a heart-healthy diet and a healthy mindset. The effects of ICR, particularly outpatient Pritikin ICR, on mortality and cardiovascular outcomes have not been evaluated. Thus, the aim of our study is 1) to prospectively evaluate survival in a large cohort of patients enrolled in an outpatient Pritikin ICR program; and 2) to compare survival within a 5% Medicare sample between beneficiaries who participated in ICR versus those who did not participate in cardiac rehabilitation.

Hypothesis:
We hypothesize that 1) outpatient Pritikin ICR is associated with excellent survival (i.e. over 90% at 1 year) and 2) Medicare beneficiaries participating in ICR have better survival than those not participating in any cardiac rehabilitation.

Methods:
1) This is a prospective longitudinal study of participants engaging in ICR at the first-ever outpatient Pritikin ICR center. For the single-center data, mortality was obtained via review of electronic medical records and direct patient follow-up for 1 year. 2) Within a 5% national Medicare sample, mortality was evaluated in all subjects utilizing a Cox proportional hazard model adjusted for age, gender, Medicaid status, number of comorbidities, and qualifying event type. The Kaplan-Meier curve is based on a subgroup matched for these same variables.

Results:
1) There were 433 patients who participated in Pritikin ICR at our institution. The survival rate was 98% at 1 year. 2) In the Medicare sample, enrollees in ICR had a lower mortality than those not attending cardiac rehabilitation (HR = 0.49, 95% CI 0.28, 0.86) after adjustments; median follow-up time was 27.0 months.

Conclusions:
Outpatient Pritikin ICR is associated with an outstanding survival rate at 1 year. ICR in general is associated with better survival rates, even after multivariable adjustment.
Abstract 12280: Exercise Chronotropic Response And Left Atrial Performance In Patients With Heart Failure
Authors: Sugimoto Tadafumi , Generati Greta , Losito Maurizio , Bandera Francesco , alfonzetti eleonora , Guazzi Marco
Published: April 2022

Introduction:
The hemodynamic impact of left atrial (LA) intrinsic properties in heart failure (HF) in relation to heart rate (HR) response to exercise has not received attention.

Hypothesis:
We aimed at investigating the link between LA stiffness and function vs HR reserve (rest to peak exercise) in patients with HF.

Methods:
A total of 191 patients with HF: 157 β blockers user (LVEF 38 ± 12%, HR reserve 42 ± 18 beats/min) and 34 Non-β blockers user (LVEF 45 ± 19%, HR reserve 36 ± 19 beats/min) underwent cardiopulmonary exercise testing combined with exercise Echo with assessment of LA strain. LA stiffness (median 0.84, IQR 0.44 to 1.89) was assessed using mitral E/E’ /LA strain ratio at rest.

Results:
HR reserve was positively associated with LA-strain both at rest (20 ± 11%, R = 0.29) and during exercise (20 ± 11%, R = 0.19), LA-strain rate [absolute value] both at rest (1.7 ± 1.0 /s, R = 0.27) and during exercise (1.6 ± 1.2 /s, R = 0.26) and peak VO
2
(14 ± 4 mL/kg/min, R = 0.62), and negatively associated with LA volume index (44 ± 23 ml/m
2
, R = -0.29), log-transformed LA stiffness (R = -0.35), mitral regurgitation (from 0 to 4+) both at rest (R = -0.28:) and peak exercise (R = -0.25) and VE/VCO
2
slope (32 ± 8, R = -0.32)(figure) (P<0.05, respectively). There was no significant association between HR reserve and LVEF both at rest and peak exercise, stroke volume index (SVI) both at rest and peak exercise. In multivariable analysis HR reserve had a significant association with age and log-transformed LA stiffness (standardized β-coefficients: -0.17 and -0.22, P <0.05, respectively) after adjusting for age, gender, hypertension, diabetes mellitus, β blockers use, ivabradine use, LA volume index, log-transformed LA stiffness, peak LVEF, peak SVI and peak mitral regurgitation ≥2.

Conclusions:
In HF patients, age and LA stiffness play a key role in HR response to exercise irrespective of β blockers prescription. These data may offer additional insights in the concepts of exercise limitation in HF.
Abstract 12302: Na
V
1.6 Dysregulation by Mutant Calmodulin Enhances Late Sodium Current in Human iPSC Cardiomyocytes and Promotes Arrhythmias in D96V Calmodulin-Expressing Transgenic Mice
Authors: Tarasov Mikhail , olgar yusuf , Struckman Heather , Miller Alec , Davis Jonathan , Gyorke Sandor , Veeraraghavan Rengasayee , Radwanski Przemyslaw
Published: April 2022

Calmodulin (CaM) mutants are associated with severe arrhythmias (calmodulinopathy). While dysregulation of Ca
2+
handling proteins (RyR2, Ca
V
1.2) are known mediators of calmodulinopathy, the role of Na
+
channels (Na
V
s) remains unclear. Interestingly, effects on Ca
V
1.2 do not fully explain action potential (AP) prolongation by the long QT syndrome CaM mutant D96V. We investigated Na
V
dysregulation by D96V-CaM and its arrhythmogenic impact.

In wild-type (WT) murine cardiomyocytes (CM) dialysis of D96V-CaM (6.5 μM) via a patch pipette prolonged AP, induced early and delayed afterdepolarizations (EADs and DADs) and increased Ca
2+
waves compared to WT-CaM. The effects of D96V-CaM were abrogated by a Na
V
1.6 blocker, 4,9-anhydrotetrodotoxin (4,9ahTTX, 300 nM;
Fig. 1A
). Dialysis of D96V-CaM dysregulated inactivation of 4,9ahTTX-sensitive Na
+
current (I
Na
) promoting late I
Na
in WT murine CM (
Fig. 1B
) and in
Chinese Hamster Ovary
(CHO) cells expressing Na
V
1.6 but not Na
V
1.5. D96V-CaM, but not WT-CaM, also promoted late I
Na
in human induced pluripotent stem cell (iPSC)
-
derived ventricular myocytes, underscoring translational relevance (
Fig. 1C
). To examine the arrhythmia potential of Na
V
1.6 dysregulation by D96V-CaM, we generated mice with cardiac-specific expression of D96V-CaM (cD96V; tgD96V-CaM x β-MHC-Cre). cD96V mice exhibited increased late I
Na
and Ca
2+
waves resembling those in D96V-CaM-dialyzed WT CMs.
In vivo
cD96V mice evidenced prolonged QTc intervals and ventricular tachycardia (VT) during bradycardia (carbachol 0.5 mg/kg intraperitoneal). Cardiac-specific Na
V
1.6 knockout protected cD96V mice from impaired I
Na
inactivation and arrhythmogenic Ca
2+
waves on cellular level as well as long QT and VT
in vivo
(
Fig. 1D, E
).

In summary, D96V-CaM promotes arrhythmias by dysregulating Na
V
1.6 and thereby, facilitating aberrant Ca
2+
release. Importantly, Na
V
1.6 may be a therapeutic target for management of CaM-related arrhythmias.
Abstract 12303: Management of Severe and Moderate Hypercholesterolemia in Young Adults
Authors: Newton Shauna L , Hoffmann Alexander P , Haidermota Sara , Natarajan Pradeep , Honigberg Michael C
Published: April 2022

Introduction:
Cardiovascular guidelines advise statin therapy for adults aged 20-75 years with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL with a goal of lowering LDL-C by ≥50%. Further, early-life accumulation of cholesterol exposure increases future cardiovascular risk independent of total cumulative cholesterol exposure, highlighting the importance of LDL-C management in young adults. However, real-world management of hypercholesterolemia in young adults is not well described.

Methods:
Using the Mass General Brigham clinical data registry, we isolated 2 cohorts of patients with hypercholesterolemia who had cholesterol testing on ≥2 occasions and were 20-39 years old at the time of a qualifying LDL-C value between 2005-2018: those with LDL-C ≥190 mg/dL (Cohort 1) and LDL-C 160-<190 mg/dL (Cohort 2). Follow-up LDL-C values were extracted through 2019. Primary endpoints were 50% reduction in LDL-C for Cohort 1 and 30% reduction for Cohort 2.

Results:
Cohort 1 (severe hypercholesterolemia) included 5,475 patients (37.9% female, mean [SD] age 32.6 [5.1] years at qualifying LDL-C), and Cohort 2 (moderate hypercholesterolemia) included 12,608 patients (39.6% female, mean [SD] age 32.6 [5.1] years). In Cohort 1, 1,638 individuals (29.9%) achieved ≥50% LDL-C reduction overall (31.7% of men vs. 27.1% of women, P<0.001;
Figure
) over median (IQR) 7.8 (4.5-11.3) years of follow-up. The youngest individuals were less likely to achieve 50% LDL-C reduction (e.g., 20-24 years old: 24.8% vs. 35-39 years old: 32.7%; P
trend
<0.001). In Cohort 2, 4,515 individuals (35.8%) achieved ≥30% LDL-C reduction over median (IQR) 7.5 (4.2-11.1) years of follow-up.

Conclusions:
In a large, integrated healthcare system, <30% of young adults with severe hypercholesterolemia achieved guideline-directed LDL-C-lowering over 8 years of follow-up. These findings highlight the need for strategies to promote guideline-recommended cholesterol management in young adults.
Abstract 12503: A Randomized Controlled Trial of Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease
Authors: Beaton Andrea Z , Okello Emmy , Rwebembera Joselyn , Grobler Anneke , Engelman Daniel , Carapetis Jonathan , Canales Lesley , DEWYER ALYSSA , Lwabi Peter , Mirabel Mariana , Mocumbi Ana O , Murali Meghna , nakitto miriam , Ndagire Emma , Nunes Maria , Omara Isaac , Sarnacki Rachel , Scheel Amy , Wilson Nigel , Zimmerman Meghan , Zuhlke Liesl , Karthikeyan Ganesan , Sable Craig A , Steer Andrew
Published: April 2022

Introduction:
Rheumatic heart disease affects 40.5 million people globally and causes 306,000 annual deaths. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. However, it is unknown if secondary antibiotic prophylaxis is effective at preventing progression of latent rheumatic heart disease.

Methods:
We conducted a randomized controlled trial of secondary antibiotic prophylaxis among Ugandan children (5-17 years) with latent rheumatic heart disease. We randomized children to receive either 4-weekly injections of benzathine benzylpenicillin G or no prophylaxis. All children underwent echocardiography at baseline and 2 years after randomization. Changes from baseline were adjudicated by a panel blinded to treatment allocation. The primary outcome was rheumatic heart disease progression. The trial was registered at ClinicalTrials.org (NCT03346525) on November 17, 2017.

Results:
818 were included in the modified intention to treat analysis and 799 participants (97.7%) reached study completion. Three participants in the prophylaxis group (0.8%) demonstrated echocardiographic progression, compared to 33 (8.3%) in the control group (risk difference -7.5%, 95%CI, -10.2 to -4.7, p<0.001). The number of children with latent rheumatic heart disease needed to receive prophylaxis to prevent one child from developing progression was 13 (95%CI, 10 to 21). There were 2 serious adverse events in the prophylaxis group, including one episode of a mild anaphylactic reaction (0.01% of all treatment doses).

Conclusions:
Secondary antibiotic prophylaxis reduces the risk of latent rheumatic heart disease progression at 2 years. These data provide new information for our understanding of the role of screening for latent rheumatic heart disease. Further research is needed before the implementation of population-level screening can be recommended.
Abstract 12506: Exploring the Absence of an Intervention: A Randomized, Placebo-Controlled, Triple Blind Study on Notoginseng Supplementation in A Population With Normal to Mild Hypertension and Hypercholesterolemia
Authors: Evans Malkanthi , Lewis Erin D , Crowley David C , Zeng Andy , Struve Jing , Guthrie Najla
Published: April 2022

Introduction:
The concept of a lack of intervention in a pre-disease population with hypercholesterolemia has not been previously reported. This study examined the concept of the effects of the absence of an intervention in the placebo group vs. supplementation of a special formulation of
Panax Notoginseng
(FNG) in relation to cardiovascular disease (CVD) risk markers and validated CVD-risk factor scores.

Methods:
Participants in this randomized, placebo-controlled, triple-blind study were supplemented with FNG or placebo for 12 weeks. Lipid profile, blood pressure (BP), and endothelial vasodilation parameters were assessed at baseline and weeks 4, 8 and 12 and safety assessed at screening and end of study. The participants in both groups followed the Therapeutic Lifestyle Change (TLC) diet during a 4-week run-in and throughout the study. The TLC diet for 4 weeks ensured all participants starting the study had similar baseline measurements and placebo effects were adequately addressed.

Results:
Participants in the placebo group had a non-significant 1.37% reduction in HDL-C at 8 and 12 weeks, as well, as an increase in systolic BP from baseline at week 12. Participants in the placebo had no change in estimated Framingham Heart Study 10-year risk for CVD, while the FNG group had a 0.1% reduction from baseline at week 12. A total of 67.5% of participants supplemented with FNG had improvements in at least two CVD risk factors (LDL-C, HDL-C and systolic BP) compared to 40.0% of those on placebo (p=0.007). In a post-hoc subgroup analysis of participants with baseline LDL-C >3.5 mmol/L, 41.7% of participants in the FNG group had reductions in their systolic BP and LDL-C and improvements in HDL-C levels at week 12, compared to placebo where there were no improvements.

Conclusions:
The lack of an intervention in a population at risk of CVD, represented by the placebo group, resulted in a negative impact on cardiovascular risk factors and warrants further investigation on the importance of pre-emptive supplementation of notoginseng in populations with mild hypertension and hypercholesterolemia. This study supports a previously defined concept in nutritional interventions which described changing from proof of efficacy to that of probable harm in pre-disease populations.
Abstract 12510: Monitoring of Chemotherapy-Induced Vascular Toxicity in Pediatric, Adolescent, and Young Adult Lymphomas Using PET/CT Imaging
Authors: Deep Kyra , Hardisky Dariya , Tram Nguyen K , Chou Ting-heng , Ettefagh Laila , Bobbey Adam J , Audino Anthony N , Stacy Mitchel R
Published: April 2022

Introduction:
Lymphoma treatment with chemotherapy, alone or in combination with radiation therapy, can have off-target effects that lead to vascular toxicity, which has recently gained attention in the field of cardio-oncology. Positron emission tomography (PET)/computed tomography (CT) imaging with fluorine-18 (
18
F)-fluorodeoxyglucose (FDG) is standard of care for monitoring lymphoma treatment responses and is a widely accepted tool for assessing vascular inflammation. We hypothesized that
18
F-FDG PET/CT imaging could detect and quantify chemotherapy-induced increases in vascular inflammation following the first cycle of lymphoma treatment in pediatric, adolescent, and young adult (AYA) patients.

Methods:
Whole-body
18
F-FDG PET/CT images were retrospectively acquired at initial staging of disease and first treatment follow-up for pediatric and AYA lymphoma patients (n=33). Regions of interest were manually drawn using each axial slice of fused PET/CT images for the femoral and popliteal arteries/veins to quantify serial changes in vascular uptake of
18
F-FDG. The changes in the average maximum standard uptake value (SUV
max
) for the femoral-popliteal vessels were calculated.

Results and Conclusions:
The patient population consisted of Non-Hodgkin (55%) and Hodgkin (45%) lymphoma patients with a mean age of 13 years (SD=4.7).
18
F-FDG PET/CT imaging detected (
Fig. 1A
) and quantified a significant increase in the mean SUV
max
from baseline (0.94±0.03) to first treatment follow-up (1.06±0.02) for the femoral and popliteal arteries/veins (
Fig. 1B
). Standard of care
18
F-FDG PET/CT imaging can non-invasively quantify chemotherapy-induced vascular inflammation in young cancer patients in response to the first cycle of treatment, thus representing an approach for evaluating vascular toxicity and creating novel opportunities for personalized medicine focused on reducing cardiovascular side effects of chemotherapy.
Abstract 12518: Susceptibility of Mature Human Myocardial Cell Types to SARS-CoV-2
Authors: Sotolongo Alex , Klein Jon , Pena-Hernandez Mario , Johnson Justin , Geirsson Arnar , Pober Jordan S , Iwasaki Akiko , Gruber Peter J
Published: April 2022

Background:
SARS-CoV-2 is a highly transmissible and virulent respiratory pathogen responsible for the global coronavirus disease 2019 (COVID-19) pandemic. A significant number of patients infected with SARS-CoV-2 show signs of myocardial injury ranging from asymptomatic troponemia to acute congestive heart failure and cardiogenic shock. The precise mechanisms underlying myocardial injury in this cohort are unclear, and it is difficult to distinguish weather new onset cardiac dysfunction is representative of active myocardial infection or a consequence of systemic illness. To address this gap in knowledge we constructed a model to assess replicative potential of SARS-CoV-2 in primary cell lines derived from adult and pediatric myocardium including cardiomyocytes, fibroblasts, and endothelial cells and corroborated our
in vitro
findings with a pathologic analysis of myocardial tissue obtained from patients infected with SARS-CoV-2.

Methods:
Samples of atrial myocardium obtained from patients undergoing cardiac surgery were enzymatically digested and purified into cardiomyocyte, fibroblast, and endothelial cell populations. Susceptibility to infection with SARS-CoV-2 was then assessed in primary human myocardial cell types and compared against induced cardiomyocytes derived from human pluripotential stem cells. Infectivity was quantitatively assessed using qPCR against genomic and subgenomic viral RNA and normalized to GAPDH. Postmortem heart and lung FFPE tissue from de-identified patients who died from SARS CoV-2 infection were obtained and analyze by immunofluorescence for viral spike and nucleocapsid protein or stained with hematoxylin and eosin for histological evaluation.

Results:
Primary cardiomyocytes obtained from adult (n=7) and pediatric (n=7) atrial myocardium could not support active replication SARS-CoV-2 virus and there was no evidence of viral replication in pathologic myocardial specimens obtained from COVID infected patients (n=7). Collectively our data indicate that primary cardiac cell types are unable to support the level of viral replication observed in iPSCM (p=0.0007) suggesting that induced pluripotential stem cells may not adequately model the response of mature myocardium to SARS-CoV-2.
Abstract 12556: The Matrikine Proline-Glycine-Proline is a Novel Biomarker of Coronary Artery Disease Amongst Patients With Chronic Obstructive Pulmonary Disease
Authors: Osula Jean Paul O , Lin Vivian , Song Chunyan , Xu Xin , Xing Dongqi , Wells James M , Payne Gregory A
Published: April 2022

Introduction:
Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of coronary artery disease (CAD). Proline-glycine-proline (PGP) is an extracellular matrix-derived chemokine (
matrikine
) that is increased in COPD and known to promote neutrophil chemotaxis, endothelial dysfunction, and vascular inflammation through activation of the CXC Chemokine Receptor 2 (CXCR2). Despite these observations, no study has examined PGP as a marker of CAD within COPD patients.

Hypothesis:
We hypothesized that circulating PGP is associated with comorbid CAD amongst COPD patients.

Methods:
Current and former smokers with COPD enrolled in the UAB
P
rospective
R
epository for coupling
EVE
nts to
N
ovel pa
T
hways in COPD (PREVENT COPD) cohort underwent phlebotomy and spirometry. Cardiovascular diagnoses were adjudicated by two physician reviewers with access to medical records. CAD was defined as a composite of prior myocardial infarction, coronary revascularization, or by physician diagnosis of CAD. Plasma PGP was measured using a solid-phase extraction method coupled with tandem mass spectrometry. Other known CXCR2 ligands (e.g. GRO alpha, IL-8) were measured by multiplex protein assay. SPSSv27 was used for logistic regression models to measure associations between plasma biomarkers and the presence of CAD.

Results:
The 104 participants were 60±9 years old, 50% male, and 50% Black race. CAD was prevalent in 21 (21%) of the cohort. Plasma PGP was detectable for all participants (0.05 - 15.1 ng/mL). Participants with CAD had higher PGP concentrations compared to participants without CAD (1.26 vs. 0.52 ng/mL, p=0.042). Similarly, PGP was increased among participants with prior coronary revascularization (p<0.01). Associations between plasma PGP and CAD remained significant after adjustment for FEV1 % predicted and smoking status (OR 1.62, 95%CI 1.02-2.56). Concentrations of other CXCR2 ligands were low and not associated with CAD.

Conclusions:
Our results highlight PGP as a potentially novel biomarker of CAD among individuals with COPD. Future studies are needed to assess whether plasma PGP is predictive of CAD outcomes in COPD, as well as determine the significance of endothelial CXCR2 activation on the development of atherosclerosis.
Abstract 12804: Knowledge of Cardiovascular Disease Risk in Young Women of Reproductive Age: A Cross-Sectional Survey-Based Study
Authors: Nelson Lauren , Baldridge Abigail S , Hibler Elizabeth , Bello Natalie , Epps Kelly C , Cameron Kenzie , Gooding Holly , Catov Janet , Rich-edwards Janet , Yee Lynn , Toledo Paloma , Banayan Jennifer , Khan Sadiya
Published: April 2022

Introduction:
Knowledge of cardiovascular disease (CVD) as the leading cause of death (LCOD) among women in the United States is declining. Young women who experience an adverse pregnancy outcome (APO) are at increased risk for CVD, but knowledge of CVD risk has not been well characterized in this population in the perinatal period. Our objective was to examine knowledge of CVD risk in postpartum women and to determine whether risk perception differs based on experience of APO.

Methods:
A cross-sectional study was conducted among postpartum individuals who had a live birth at a single high-volume quaternary care center between 1/1/20 and 7/1/20. Knowledge of CVD risk was assessed through a self-administered online survey adapted from the American Heart Association Survey of Women’s CVD Awareness. Survey data were collected between 3/1/21 and 4/18/21. We examined differences in knowledge of CVD risk factors based upon self-reported APO status.

Results:
Of the 5,612 eligible individuals contacted, 13% completed the survey. Among respondents, the majority identified as White (70%) with a mean age of 34
+
4.2 years, and 25% reported an APO. Similar proportions of women with (62%) and without (62%) an APO identified CVD as the LCOD in women. There was no significant difference in knowledge of traditional or pregnancy-specific CVD risk factors by APO status (
TABLE
). Women who experienced an APO were more likely to report intention to contact a healthcare professional regarding personal CVD risk compared with women who did not.

Conclusions:
Gaps remain in knowledge of CVD risk factors among young women, in whom primary prevention of CVD may be most beneficial over the lifespan. Heterogeneity in knowledge deficits related to APO subtypes as CVD risk factors present a unique opportunity for targeted education at a time when healthcare engagement is high. Given the modest response rate to this survey, awareness may be even lower in the general population.
Abstract 12808: Nobel Murine Model of Atherosclerosis Progression Induced by a Modified-Paigen Diet
Authors: Alvarez Mary , Virgen-Ortiz Adolfo , RODRIGUEZ-HERNANDEZ ALEJANDRINA , Ceballos-Gutierrez Adriana , Figueroa Alejandro , Andrade Felipa , ENRIQUE ALEJANDRO SANCHEZ PASTOR
Published: April 2022

To better understand the mechanisms involved in the atherosclerosis progression, different models have been used. Currently there is no ideal model, each one has its advantages and disadvantages, especially when you want to study the disease progress. In this context we tested the hypothesis: the atherogenic “Paigen type” diet with modifications (APTDM), generates a stable model for the study of each phase of atherogenic process. Atherosclerosis was induced in 80 Wistar rats using APTDM consisting of 2 phases: 1) Hypervitamin, administered orally at a dose of 1.5 ml / kg / day for 12 days and 2) Hyperlipidic, administered for 48 days
ad libitum
. Experiments were carried out in 4 groups (n=16) with different doses (G1 = 75%, G2 = 50%, G3 = 33% and G4 = 25%) to obtain a dose-response curve, a healthy group (n=8; C) and a positive control (100% of the diet for 15 days; n=8; C+). Analysis was performed at day 15 for C+ and at day 30 (D30) and day 60 (D60) for the other groups. Aorta artery descending portion was extracted and histological analysis was performed to evaluate the atherosclerosis degree. Rats from C+ had severe grades (V-VII) at D15. All rats from G1 were sacrificed due to a poisoning for vitamin D2 excess. G2 rats were sacrificed at the end of D30 showing atherosclerotic lesions classified severe grades (V-VII). G3 showed mild degrees (I-III) at D30 and showed severe degrees (IV-VII) at D60. G4 showed mild degrees (I-III) at D30 and D60. Glucose, lipid profile, systolic (SBP) and diastolic (DBP) blood pressure was determined for G3. SBP decreased on D30 and D60 (123 ± 1 vs 109 ± 2 (p <0.01) and 124 ± 1 vs 99 ± 2 mmHg (p <0.01) respectively). Similar results in DBP were observed (83 ± 2 vs 69 ± 1 mmHg (p <0.01) at D60). Glucose increased on D30 and D60 (C = 98 ± 5 vs 159 ± 17 (p = 0.02) and 134 ± 4 mg/dL (p <0.01) respectively). Similar behavior for cholesterol (C = 56 ± 1 vs 114 ± 5 (p <0.01) and 128 ± 8 mg/dL (p <0.01) respectively), LDL (C = 39 ± 3 vs 103 ± 3 (p <0.01) and 123 ± 13 mg/dL (p <0.01) respectively) and triglycerides (C = 39 ± 2 vs 40 ± 1 (p = 0.01) and 74 ± 11 mg/dL (p = 0.01) respectively) was observed. HDL only increased on D60 (C = 22 ± 1 mg/dL vs 34 ± 3 (p <0.01)). In conclusion, APTDM to 33% (G3), generates a stable model for the study of the progress of each of the atherosclerosis phases in rats.
Abstract 12810: Data-Driven Clusters of Cardiac Structure and Function and Association With Premature Cardiovascular Disease: The Coronary Artery Disease in Young Adults (CARDIA) Study
Authors: Wang Michael C , Pool Lindsay R , Allen Norrina B , Reyfman Paul A , Luo Yuan , Lima Joao A , Lloyd-jones Don M , Khan Sadiya S
Published: April 2022

Introduction:
Abnormal indices of cardiac structure and function likely cluster together. However, the clinical relevance of data-driven patterns of cardiac remodeling across a broad range of echocardiographic measures, particularly in mid-life, is not known.

Hypothesis:
Latent class analysis (LCA) will identify distinct clusters of cardiac structure and function based on echocardiographic indices in middle-aged adults that differ in risk of CVD.

Methods:
We included all CARDIA participants without CVD who underwent an echocardiogram. Continuous parameters were indexed to participant height (if appropriate), imputed with the SVDImpute algorithm (if missing), and filtered to remove pairwise correlations >0.6. We applied LCA using a total of 31 echocardiographic indices (standardized to mean 0 and standard deviation 1) to identify distinct groups based on model convergence, the Bayesian Information Criterion, and class membership >5%. We examined the association between groups and risk of premature CVD (coronary artery disease, stroke, or heart failure) with Cox regression adjusted for traditional risk factors.

Results:
Of 3,361 participants, mean (SD) age was 50.1 (3.6) years, 57% were female, and 46% were non-Hispanic Black. LCA identified 3 groups: (1) optimal cardiac mechanics; (2) impaired systolic function; and (3) impaired diastolic function (
FIGURE
). Over a median 8.9 years of follow-up, risk of CVD was higher in the impaired diastolic function group (unadjusted hazard ratio [HR] 4.08 [95% CI: 2.48, 6.71] and adjusted HR 1.95 [1.12, 3.40]) compared with the optimal group. The impaired systolic function group had a higher unadjusted risk of CVD (1.86 [1.10, 3.15], which attenuated after adjustment (1.36 [0.79, 2.36]).

Conclusions:
Unbiased, model-based clustering of cardiac structure and function in middle-aged adults identified distinct patterns of cardiac remodeling that were associated with risk of future CVD.
Abstract 12811: Dual Antiplatelet Therapy Duration and Long-Term Risks of Adverse Outcomes After Percutaneous Coronary Intervention With Second-Generation Drug-Eluting Stents
Authors: Kinlay Scott , Young Melissa M , Sherrod Rebecca J , Gagnon David
Published: April 2022

Introduction:
Randomized trials show that short dual antiplatelet (DAPT) regimens have similar adverse events to longer regimens in patients treated by percutaneous coronary intervention (PCI) using second-generation drug-eluting stents (DES2). However, these studies are underpowered for death.

Hypothesis:
After PCI with DES2, patients discontinuing DAPT before six months had higher risks of adverse ischemic outcomes than patients continuing DAPT for longer durations.

Methods:
We assessed adverse outcomes in patients having PCI between 2008-2016 in the Veterans Affairs Clinical Assessment Report and Tracking (CART) database. DAPT use was determined from the VA Pharmacy database. Outcomes after PCI were all-cause death (from the VA death index), and myocardial infarction, recurrent coronary revascularization, and major bleeding from ICD 9, ICD 10 and CPT codes in VA and Medicare/Medicaid records. Hazard ratios (HR) and 95% confidence intervals (95%CI) from Cox proportional hazards models weighted with a stabilized inverse probability of treatment weight were used to assess the risk of outcomes from stopping DAPT in 4 time intervals after PCI (1-5, 6-9, 10-12, and 13-18 months).

Results:
After exclusions, there were 40,871 PCIs with DES2 during the study period. Outcomes were followed for an average of 4.6 years. Compared to continuing DAPT, the risks for death were significantly higher for stopping DAPT 1-5 months after PCI (HR=2.04, 95%CI=1.82, 2.29) and stopping DAPT 6-9 months after PCI (HR=2.2, 95%CI=1.98, 2.44). There was no significant increase in death from stopping DAPT more than 10 months after PCI. Stopping DAPT 10 or more months after the index PCI associated with lower rates of myocardial infarction (HR=0.74, 95%CI=0.68, 0.81) and major bleeding (HR=0.81, 95%CI 0.73, 0.91), and lower repeat revascularization at all time periods. There was no interaction of effects with acute coronary syndrome at index PCI.

Conclusion:
Among Veterans having PCI with DES2, stopping DAPT less than 10 months after PCI was associated with a higher risk of death but no increased risk in myocardial infarction or major bleeding. Short DAPT regimens after PCI may increase the risk of death. Clinical trials of short DAPT duration should powered to assess this endpoint.
Abstract 12812: Creatine Chemical Exchange Transfer MRI Demonstrates Abnormal Calf Muscle Energetics in Peripheral Arterial Disease
Authors: Betz Yaqub , Patel Toral , Sporkin Helen , Mathew Roshin C , Schumann Chris , Meyer Craig , Kramer Christopher M
Published: April 2022

Introduction:
Creatine chemical exchange saturation transfer (CrCEST) is a novel MRI technique utilizing radiofrequency pulses to monitor creatine concentrations at high spatial resolution. The study utilized CrCEST kinetics to compare post-exercise creatine decay in peripheral arterial disease (PAD) patients to normal subjects and to validate against phosphocreatine (PCr) recovery by
31
phosphorus (P) MR spectroscopy (MRS).

Methods:
23 subjects with PAD (claudication and ankle-brachial index<0.9) and 28 healthy subjects were enrolled. All underwent 3T MRI (Siemens Prisma) using a knee coil around the calf. Pre- and post-exercise images were obtained around plantar flexion ergometry (Ergospect) until exhaustion. Regions of interests were drawn around major muscle groups. Creatine decay times were obtained by fitting an exponential curve to the CrCEST values.
31
P spectra were obtained 20 minutes later at peak exercise using a surface-coil localized, free induction decay acquisition with 25 signal averages at a repetition time of 550s with calculation of PCr recovery time constant.

Results:
23 PAD subjects (mean ABI 0.66 ± 0.11, age 64 ± 8, 17% females) had prolonged median overall calf muscle creatine decay time of 286 seconds (s) (Interquartile Range (IQR) 134 to 370) versus 152 s (IQR 114 to 193) in controls (age 63 ± 9, 70% females), p = 0.009. The gastrocnemius muscle demonstrated a creatine decay time of 316 s in PAD (IQR 189 to 510) versus 181 s in controls (IQR 102 to 236), p = 0.003 and the posterior tibialis muscle, 186 s (IQR 119 to 653) versus 125 s (IQR 72 to 221), p = 0.013. 8 PAD patients and 6 controls underwent CrCEST and
31
P MRS which were compared over the entire calf. Bland-Altman analysis (Figure 1B) yielded a mean difference of 71s (SD 109).

Conclusions:
Imaging with CrCEST demonstrates prolonged creatine kinetics in PAD patients compared to normal subjects with high spatial resolution and good agreement with
31
P MRS, although PCr recovery appears faster.
Abstract 12813: Left Main Disease—Not as Straightforward as It Seems
Authors: Dong Tiffany , Sabbak Nabil , Lo Presti Saberio , Grimm Richard A , Menon Venugopal
Published: April 2022

A 51 year-old female with a past medical history of hypertension presents with chest pain that began 12 hours earlier. EKG showed biphasic T waves in the anterior leads and ST depressions in the lateral leads with a dynamic trend in troponins. LHC showed severe LM stenosis extending into the proximal LAD and LCx. An IABP was placed due to persistent angina despite being on a nitroglycerin drip. Given the minimal involvement the other coronary arteries, a coronary CT angiogram was pursued to evaluate for other non-atherosclerotic etiologies. The CT showed a periaortic soft tissue mass that encased the left main and the right pulmonary artery. The differential for conditions causing compression of the coronaries includes aortic or pulmonary artery aneurysms, abscesses, thymoma, lymphoma, teratoma and bronchogenic cysts. A PET scan showed metabolic activity of a supraclavicular lymph node, the mediastinal mass and a pericardial effusion. Her lymph node biopsy and mediastinal mass biopsy were consistent with a thymic carcinoma. Although thymomas are the most common anterior mediastinal tumor in adults, thymic carcinoma are rarer, more aggressive and thus spread outside the thymus. For thymic carcinomas, the ideal treatment is complete surgical resection while non-surgical candidates should undergo chemotherapy and radiation. Due to the proximity of the carcinoma the aorta and pulmonary artery, our patient was deemed not a surgical candidate and underwent radiation. This unique case highlights that non-athlerosclerotic etiologies should be entertained in cases of isolated left main disease and the importance of utilizing multimodality imaging to identify such causes.
Abstract 12819: Feasibility of Transradial Primary Percutaneous Coronary Intervention for STEMI Complicated by Cardiac Arrest
Authors: Kassis Nicholas , Kumar Anirudh , Zhou Leon , Huded Chetan , Reed Grant W , Krishnaswamy Amar , Martin Joseph , Puri Rishi , Ziada Khaled , Khatri Jaikirshan , Lincoff A M , Ellis Stephen G , Kapadia Samir R , Khot Umesh N
Published: April 2022

Introduction:
The American Heart Association recommends a “radial-first” strategy in patients with ST-elevation myocardial infarction (STEMI). It is uncertain whether the benefits of transradial (TR) access extends to high-risk patients who present with STEMI and cardiac arrest (CA).

Methods:
Consecutive patients with STEMI complicated by CA who underwent percutaneous coronary intervention (PCI) within 24 hours at the Cleveland Clinic between 2011-2018 were included. TR-PCI was implemented as the standard approach during the study period (2014). Temporal changes in the use and technical success rates of TR-PCI were assessed, and procedural outcomes were compared with those who underwent transfemoral (TF)-PCI as the initial attempted approach. To evaluate for predictors of major bleeding, variables were assessed in univariable logistic regression and those with p<0.10 were included in multivariable analysis.

Results:
Among 216 patients, TR-PCI use increased from 2.9% in 2011 to 87.1% in 2018 (p<0.001). TR-PCI was successful in 80/91 (87.9%) patients. Door-to-balloon-time (90 [68, 116] vs. 105 [76, 141] minutes, p=0.03) and contrast volume (150 vs. 153 mL, p=0.03) were significantly lower in TR-PCI relative to TF-PCI with no differences in fluoroscopy dose, mechanical circulatory support use (30.8% vs. 41.6%, p=0.14), or in-hospital mortality (13.2% vs. 19.2%, p=0.32). After adjusting for peripheral arterial disease, diabetes, fluoroscopy dose, mechanical circulatory support, and total femoral access, TR-PCI was an independent predictor for less major bleeding {OR=0.34 (95% CI [0.11-0.93], p=0.045)}.

Conclusions:
Among patients with STEMI and CA, TR-PCI is feasible and can be successfully adopted via implementation of a “radial-first” strategy. With a high technical success rate, no adverse effect on door-to-balloon-time, and reduced major bleeding, TR-PCI should be the initial access strategy in high-risk patients with STEMI and CA.