bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13570: Quantitative 3D Echocardiographic Predictors for Risk Stratification and Improved Management of Congenital Mitral Valve Disease
Authors: Lang Nora , Staffa Steven , Zurakowski David , Baird Christopher W , Emani Sitaram , Shea Melinda H , Del Nido Pedro J , Marx Gerald R
Published: April 2022

Background:
Congenital mitral valve disease (CMVD) presents major challenges regarding medical and surgical management. Three dimensional echocardiography (3DE) allows precise delineation of area tracing from cross-sectional planes for more precise measurements and outcome analysis. However, there are no available data to inform clinicians on how 3DE can help guide management. We hypothesized that quantitative 3DE measurements can provide improved risk stratification and guide management of CMVD.

Methods and Results:
Demographic, procedural and outcome data were obtained for all 183 children who underwent MV reconstruction for CMVD from 2002 to 2017. 92 patients had mitral stenosis (MS), 68 mitral regurgitation (MR), and 23 mixed disease (MD). 13 patients (7%) died. MD patients had higher rates of mortality, reoperation, and valve replacement. Quantitative 3DE measurements of the effective orifice area (EOA) and vena contracta regurgitant area (VCRA) were determined preoperatively and before discharge. Changes from baseline in EOA and VCRA were significant independent predictors of reoperation with excellent area under the curve (AUC) values (EOA: AUC = 0.888; VCRA: AUC = 0.962; both P<0.001). As shown in Figure 1, decision analysis revealed that an increase in EOA<30% for patients with MS is associated with 76% risk of reoperation (HR=11.4; 95% CI: 3.4-37.8; P<0.001), whereas a decrease in VCRA <40% for MR patients is associated with 93% risk of reoperation (HR=18.1; 95% CI: 2.3-142; P=0.006). Comparison of the AUC indicated that the change in EOA is a significantly stronger predictor of reoperation than change in mean gradients (MG; P=0.018; DeLong’s test).

Conclusions:
Reconstructive surgery for CMVD can be performed with good outcomes. 3DE EOA and VCRA aids in postoperative clinical and surgical management. Further, 3DE is more predictive of patient outcomes than 2DE measurements of MG. Thus, we now incorporate 3DE EOA and VCRA into clinical decision making.
Abstract 13579: Serum Neural Biomarkers and Neuroimaging Markers in Neonates With Congenital Heart Disease Undergoing Cardiac Surgery
Authors: Lin Jiuann-huey I , Lorenzi-Quigley Lauren , Baust Tracy , Panigraphy Ashok , Lee Vincent , Sanchez-De-Toledo Joan
Published: April 2022

Introduction:
Congenital heart disease (CHD) patients requiring neonatal cardiopulmonary bypass (CPB) surgery often experience abnormal neurodevelopment. Open heart surgery and anesthesia induce changes in the developing brain concomitant with an increase in the level of neuromarkers. The aim of this study is to assess the relationship between neuromarkers, brain dysplasia and neurodevelopmental outcomes for CHD patients undergoing neonatal CPB.

Hypothesis:
Neuromarkers and neuroimaging brain dysplasia can predict the neurodevelopmental outcomes for CHD patients undergoing neonatal CPB.

Methods:
42 neonates with CHD requiring CPB were included in this prospective, observational study. Using the Neurology 4-Plex A Assay, serum levels of glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), neurofilament light (NF-L), and Tau protein were measured pre-operatively and at 0 hours, 24 hours, and 48 hours post-operatively. Brain MRIs were obtained in 24 neonates. Neurodevelopment testing was completed at 6 months to 36 months of age using the Bayley-III Scales of infant. Findings of brain MRI were scored using an internally developed scoring system which evaluates the brains structures individually on degrees of dysplasia, hypoplasia, and abnormalities, as well as providing a comprehensive assessment of overall brain development combining the individual structural abnormalities into a composite total brain dysplasia score (TBDS).

Results:
Bayley-III scales were negatively correlated with NF-L and Tau. For UCH-L1, a positive correlation was seen at immediate postop. Hemorrhage is associated with low language score (P=0.009) and elevated UCH-L1 levels at 24 hours and 48 hours. Infraction (P=0.0375) and lower maturation (P=0.03) are associated with low fine motor scores. Lower maturation is related to more domains below average (P=0.01). Infarction is associated with high postoperative Tau level (P=0.04).TBDS is associated with high levels of GFAP, NFL-1, and decreased language development.

Conclusion:
A negative correlation of Tau and NF-L to Bayley-III scales was consistent with their known roles as markers of neural injury. High NF-L and GFAP are associated with brain dysplasia.
Abstract 13589: The Mechano-Signaling Roles of the Adaptor Protein Nck1 in Atherogenic Endothelial Activation
Authors: Alfaidi Mabruka , Reddick Milla , Shen Xinggui , Orr A. Wayne
Published: April 2022

Rational:
Alterations in hemodynamic shear stress (SS) at atherosclerosis-prone sites promotes endothelial activation, characterized by nuclear factor-κB (NF-κB)-driven expression of cell adhesion molecules that mediate leukocyte homing. In addition, proinflammatory cytokines (e.g. IL-1β) promote NF-κB-dependent endothelial activation. While the recent CANTOS trial using an IL-1β antagonist highlights the potential for treating atherogenic inflammation beyond lipid lowering therapies alone, our understanding of how endothelial activation contributes to this effect remains limited.

Methodology & Results:
We identified the signaling adaptor Nck1 as a critical regulator of atherogenic endothelial activation. Endothelial cells deficient in Nck1 lack SS-induced NF-κB activation and proinflammatory gene expression. Additionally, we demonstrated an interaction between Nck1 and IL-1β signaling in response to SS, showing that SS activates the IL-1β receptor (IL1R1) signaling partner IRAK-1 in a Nck1-dependent manner both
in vitro
and
in vivo
. IRAK-1 depletion inhibited the proinflammatory response to SS. Mechanistically, point mutation analysis suggest a critical role for the Nck1 SH2 domain (phosphotyrosine binding domain) in mediating these effects. Consistent with our cell culture studies, Global Nck1 knockout mice show reduced atherosclerosis characterized by diminished macrophage and smooth muscle incorporation and bone marrow chimeras suggest non-hematopoietic Nck1 mediates this response.

Conclusions:
A recent GWAS analysis linked Nck1 to coronary artery disease, underscoring its importance to human disease. Therefore, our data suggest that Nck1 mediates the formation of IL-1-related signaling complexes to induce atherogenic endothelial activation, and selective inhibition of Nck1 or its critical domains will allow efficient inhibition of atherosclerosis in humans.
Abstract 13601: Cardiovascular Outcomes of Transradial versus Transfemoral Percutaneous Coronary Intervention in End Stage Renal Disease. A Meta Regression Analysis
Authors: sattar yasar , Alhajri Noora , Faisaluddin Mohammed , Song David , Shah Rajendra , Latachana Sharaad , Zghouzi Mohamed , Ullah Waqas , Elgendy Islam Y , Alraies M C
Published: April 2022

Introduction:
Limited data is available on comparison of outcomes among transradial (TR) and transfemoral (TF) access of percutaneous coronary intervention (PCI) in End Stage Renal Disease (ESRD).

Hypothesis:
Which access route is better for better cardiovascular outcomes or lower procedural complications among ESRD patients.

Methods:
Online databases including MEDLINE and Cochrane Central were queried to compare cardiovascular outcomes among TR and TF in ESRD patients. The primary outcome of this meta-analysis was to compare the bleeding complications and in-hospital mortality difference between TR PI and TF PCI in patients with ESRD. The secondary outcomes included differences in Mortality, Cardiovascular accident (CVA), Myocardial infarction (MI), Bleeding, Transfusion, Cardiogenic shock, and Heart failure. Unadjusted odds ratios (OR) were calculated using a random effect model with a 95% confidence interval (CI) and P <0.05 as a statistical significance.

Results:
A total of 5 studies including 7383 patients ( TR-PCI = 1208 ; TF-PCI = 6275) were included in this analysis. The overall mean age was 70 years; while the mean for TR-PCI and TF-PCI was 71 years and 69.1 years respectively. TR-PCI was associated with lower odds of bleeding (OR 0.48 95% CI 0.33, 0.69, p<0.05, I2 0.00%) (Figure 1A), transfusion requirement (OR 0.52 95% CI 0.40, 0.68, p<0.05, I2 0.00%), and mortality (OR 0.41 95% CI 0.26, 0.66, p<0.05, I2 0.00%) (Figure 1B). We did not find any statistically significant difference in CVA (OR 1.06 95% CI 0.37, 3.00 p>0.05, I2 0.00%), MI (OR 0.97 95% CI 0.57, 1.63, p>0.05, I2 0.00%), CS (OR 0.53 95% CI 0.06, 4.42, p>0.05, I2 48.48%) between TR and TF PCI in ESRD population. We didn’t find any effect modifier in our study on regression analysis.

Conclusions:
TR access is associated with better cardiovascular outcomes as compared to TF access PCI in ESRD patients with any coronary artery disease.
Abstract 13605: Kidney Function, Body Mass Index and Bleeding Complications in Patients Undergoing Percutaneous Coronary Intervention: Obesity Paradox Redux?
Authors: Bimal Tia , Bhuiyan Md , Gandotra Puneet , Fishbein Joanna , Selim Samy , Ong Lawrence , Gruberg Luis
Published: April 2022

Background:
Low body mass index (BMI) patients (pts) undergoing percutaneous coronary intervention (PCI) are at the highest risk for in-hospital complications and cardiac death when compared to overweight or obese pts (“obesity paradox”). Likewise, chronic kidney disease (CKD) (eGFR <60 mL/min/1.73m
2
) pts are at a higher risk of adverse events following PCI.

Aim:
To assess the impact of BMI on bleeding complications in pts with and without CKD undergoing PCI.

Methods:
Between 12/2010 and 03/2018 a total of 4,400 CKD pts (eGFR <60 mL/min) and 13,197 pts without CKD underwent PCI. Pts were divided into three groups: BMI <24.9 (normal), BMI 25 to 29.9 (overweight), and BMI >30 (obese). Bleeding complications were classified by the Bleeding Academic Research Consortium (BARC). BARC Type 4 (CABG-related) and Type 5 (fatal) bleeding events were excluded. Multiple logistic regression was utilized with p<0.05 significance level.

Results:
Pts were 72% male, mean age 67 and 43% were diabetic. Both BMI category and CKD status were significantly associated with BARC score ≥3 in a multiple logistic regression model (p=0.004, and p<0.0001, respectively). There was no evidence of an interaction between CKD status and BMI and the effect on BARC score (p= 0.08). Among those with CKD, BMI category failed to associate with BARC≥3 status (p=0.1), but among those without CKD, BMI category was significantly associated with BARC ≥3 status (p= 0.003), as shown in Figure. Multivariate logistic regression analysis will be presented.

Conclusion:
In pts undergoing PCI: 1) BMI and CKD status are associated with severe bleeding (BARC≥3) complications; 2) normal BMI, non-CKD patients had a significantly higher rate of severe bleeding complications when compared to overweight or obese patients; and 3) obese CKD patients had a lower rate of severe bleeding complications compared to normal BMI or overweight patients but did not achieve statistical significance.
Abstract 13610: Obesity in Pediatric Hypertrophic Cardiomyopathy is Associated With Increased Inpatient Morbidity
Authors: Jones Edward G , Lupo Philip J , Spinner Joseph A , Tunuguntla Hari P , Price Jack F , Kim Jeffrey J
Published: April 2022

Introduction:
While obesity is associated with adverse outcomes among adults with hypertrophic cardiomyopathy (HCM), there has been little work to describe its impact on outcomes among children with HCM.

Hypothesis:
Obesity is associated with increased in-hospital morbidity in pediatric patients with HCM.

Methods:
In this cohort study, data from 52 children’s hospitals contained in the Pediatric Health Information System database from 2009 to 2019 were analyzed. Patients aged 2-18 years old with a primary diagnosis of HCM were included and assessed for obesity based on ICD-9/ICD-10 codes. Patients with a concomitant diagnosis of a congenital heart disease were excluded.

Results:
Out of a total of 2,667 children with HCM, the prevalence of obesity was 9.6%. Obese patients were more likely to be male, Black, Hispanic, older at age of initial hospitalization, and have a family history of sudden cardiac death (Table 1). After adjusting for age, sex, race, and ethnicity in multivariable analysis, obesity was independently associated with arrhythmia (OR 1.390 [1.029-1.879], P=0.032), heart failure (OR 1.809 [1.247-2.624, P=0.002), number of admissions (IRR 1.349 [1.158-1.573], P<0.001), and cumulative length of stay (IRR 1.276 [1.093-1.491], P=0.002). Obesity was not associated with mortality.

Conclusions:
In pediatric patients hospitalized with a diagnosis of HCM, obesity was more common in underrepresented minorities and associated with increased morbidity after accounting for other risk factors. Reducing the burden of obesity in this population with effective counseling and lifestyle interventions may play a role in preventing obesity-related adverse outcomes.
Abstract 13613: Incidence of Heart Failure Among Black versus White Patients With Human Immunodeficiency Virus Infection in the United States, 2011-2017
Authors: Kalogeropoulos Andreas P , Cao Kerry , Kane Jesse , Papamanoli Aikaterini , Jacob Robin , Bloom Michelle E , Skopicki Hal
Published: April 2022

Introduction:
Black patients suffer higher rates of human immunodeficiency virus (HIV) and heart failure (HF) than any other race. In patients with HIV, rates of HF have declined, but disparities in incident HF may persist. To explore these disparities, we evaluated incidence of HF in Black and White patients with HIV.

Methods:
Using data from the TriNetX electronic health records network, we identified 93,322 adults (age 18+) patients from 47 centers in the United States with an HIV infection diagnosis (ICD-10 code B20) between 2011 and 2017 (to allow for ≥3-year follow up), without any previous record of HF diagnosis (ICD-10 code I50). We compared the incidence of HF (new ICD-10 code I50), HFrEF (codes I50.2 or I50.4), and HFpEF (codes I50.1 or I50.3) over a 3-year follow up in propensity-matched subsets of White and Black patients. We matched for demographics and clinically relevant background history, including antiviral medications. We used Kaplan-Meier (K-M) estimates and Cox models to compare incidence.

Results:
The baseline characteristics of the matched cohorts (27,388 Black and 27,388 White) were well balanced (with standardized mean differences ≤0.02 for all clinical characteristics),
Table 1
. Within 3 years, there were 302 new cases of HF in Black and 220 in White patients. The corresponding 3-year K-M incidence of HF was 1.4% vs 1.0% (HR 1.34; 95%CI 1.12-1.59; P=0.001). The rates of presumable HFrEF (120 cases in Black vs 74 in White) were 0.55% vs 0.36% (HR 1.58; 95%CI 1.18-2.11; P=0.002) and those of presumable HFpEF (83 vs 65 cases) were 0.38% vs 0.31% (HR 1.24; 95%CI 0.90-1.72; P=0.19), respectively. Mortality at 3 years did not differ between Black (n=863; 3.8%) vs White (n=850; 3.8%) patients (HR 0.99; 95%CI 0.90-1.09; P=0.85).

Conclusions:
In matched cohorts of HIV patients, the 3-year incidence of HF was higher in Black vs White patients. These findings demonstrate racial disparities in HIV and HF, highlighting an intersection of diseases that warrants further study.
Abstract 13619: Obese Patients With New Onset Atrial Fibrillation/Flutter Have Higher Rates of Hospitalization, Cardioversion, and Ablation
Authors: Norton Jonathan , Foy Andrew , Naccarelli Gerald
Published: April 2022

Atrial fibrillation (AF) is the most common arrhythmia and can lead to frequent healthcare encounters. Obesity is a rapidly growing epidemic, and greater than one third of all adults in the USA are obese. Additionally, obese patients have over twice the prevalence of AF compared to the non-obese. Despite the frequency of these conditions, there is limited research assessing the relationship between obesity and healthcare resource utilization (HRU) in AF patients.

We hypothesized that obese patients with new onset atrial fibrillation/flutter (AFL) would have higher AF/AFL related hospitalizations and procedures compared to non-obese patients.

We utilized MarketScan® claims data to select patients with new onset atrial fibrillation or atrial flutter in 2017 and 2018 and classified them according to diagnosis codes as obese or non-obese. We then stratified by the diagnosis of obesity.

There were 95,314 patients with new onset atrial fibrillation/flutter, which included 72,218 (76%) who were non-obese and 23,096 (24%) who were obese. There were significantly more males than females (64.4% vs. 35.6%). The average age was similar at 54.4 (+/- 0.04) in the non-obese and 54.6 (+/- 0.06) in the obese cohort. The rate of hospitalizations (35.9% vs. 24.8%, p<0.001), cardioversions (16% vs. 10%, p<0.001), and ablation procedures (10% vs. 7%, p<0.0001) were significantly higher in the obese versus non-obese cohort.

Obese patients with new onset AF/AFL had significantly higher HRU than non-obese patients. This increased health resource utilization increases the cost of care in such patients and future studies should concentrate on understanding the reasons for this difference.
Abstract 13640: Endothelial Dysfunction in Chronic Stress-Related Cardiovascular Disease May Be Driven by Epinephrine Exacerbating TNFα Effects in a JAK/Stat3-Dependent Manner
Authors: Baumer Yvonne , Tirado Brian , Gray Veronica , Mitchell Valerie , Collins Billy , Powell-wiley Tiffany
Published: April 2022

Background:
Chronic psychosocial and environmental stress (PSES) impairs endothelial function and accelerates cardiovascular disease (CVD); however, underlying signaling pathways are less understood. Studies have independently shown that chronic PSES increases catecholamine levels (e.g. epinephrine) and induces a low-grade chronic inflammation by cytokines (e.g. tumor necrosis factor α - TNFα). The potential impact of a combination of increased levels of epinephrine and TNFα on the endothelium has not been fully investigated. We sought to elucidate if epinephrine and TNFα synergistically impair endothelial function and which signaling pathways might underlie this phenomenon.

Methods:
Human aortic endothelial cells (HAoEC) were treated with 10μM epinephrine (E), 10ng/ml TNFα (T), or their combination (E+T). Endothelial monolayer integrity was measured in a transwell filter setup and visualized by immunofluorescence. Signaling pathway analysis was performed by western blotting and PCR. Various pathway inhibitors were deployed to identify key pathways for the observed effects.

Results:
The addition of epinephrine exacerbated the observed TNFα-induced loss of the adherens junction protein VE-cadherin accompanied with accelerated intercellular gap formation and loss of endothelial barrier integrity. Signaling pathway analysis revealed that E+T induced delayed and prolonged Stat3 activation lasting up to 24h of treatment, which could not be observed in the individual E or T treatments. Inhibition of the Stat3 pathway using Tofacetinib, an inhibitor of JAK/Stat signaling, prevented the E+T-induced activation of Stat3, loss in VE-cadherin, E+T-induced gap formation and loss in barrier integrity, indicating the crucial importance of JAK/Stat signaling in the E+T-induced effects on the endothelium.

Conclusion:
These data indicate long-term PSES-induced CVD might in part be mediated by a combined effect of epinephrine and TNFα that can induce endothelial dysfunction dependent on a JAK/Stat3 pathway. Understanding pathways involved in PSES-related CVD is crucial to elucidate the biology of adversity in CVD health disparities, or mechanisms by which populations most impacted by PSES are disproportionately susceptible to CVD.
Abstract 13641: High Precordial Leads Increase the Detection of Brugada-Like Electrocardiographic Changes in Arrhythmogenic Right Ventricular Cardiomyopathy Patients and Healthy Controls
Authors: Yee Lauren A , Pearman Charles M , Laksman Zachary W , Davies Brianna , Krahn Andrew D
Published: April 2022

Introduction:
Diagnosis of Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) relies on the 2010 Task Force Criteria (TFC), known to have high specificity and low sensitivity. Diagnosis is complicated by variable phenotypic expression, potentially fatal first presentation of disease, and modest yield of genetic testing. Phenotypic overlap has been described between ARVC and Brugada Syndrome (BrS), while high precordial lead positioning increases the sensitivity for BrS diagnosis.

Purpose:
To explore the scope and nature of ECG changes in high precordial leads in ARVC.

Methods:
Patients seen in the Inherited Arrhythmia Clinic in Vancouver, Canada between 2013-2020 had high precordial lead ECGs recorded and were enrolled in the Canadian ARVC/HiRO Registry (www.heartsinrhythm.ca). ECGs of cases and matched healthy controls were interpreted blinded to phenotype/genotype. We defined 10 ECG variables, including features of the TFC and novel markers. We compared standard vs. high leads within-patient, and cases vs. controls in standard and high lead positions.

Results:
There were 58 ARVC patients (age 41±14, 48% male, TFC 3.6±1.7) and 58 controls (age 47±15, 43% male) included. Brugada-like ECG changes were seen in 5 patients (4.3%), exclusively in high leads (p<0.001 compared to standard leads). No type 1 pattern was detected. Type 2 pattern was seen in 1 ARVC patient (0.9%) in high lead V2. Type 3 pattern was seen in 2 ARVC patients (1.7%) and 2 controls (1.7%) in the high leads position, with no difference between cases and controls (p=NS). Epsilon waves were observed in 2 ARVC patients (1.7%). The SAECG was positive for late potentials in one patient, and the other negative. Both patients had an epsilon wave in a standard lead, and in one patient epsilon waves were seen in a further 2 high leads. No sex-differences were evident.

Conclusions:
High precordial leads increase detection of Brugada-like ECG changes to a similar extent in ARVC patients and controls. Our study supports the finding that Type 3 pattern is a benign finding in healthy individuals. High precordial leads do not substantially increase the sensitivity for detection of epsilon waves. Further investigation is warranted into novel diagnostic methods that improve sensitivity for ARVC diagnosis.
Abstract 13810: Diabetes versus Cardiovascular Mortality in the Context of Food Insecurity Among United States Adults
Authors: Banerjee Srikanta K , Dunn Patrick
Published: April 2022

Food insecurity has become an important global concern with close associations with cardiovascular disease. However, how food insecurity affects individuals with long-term diabetes is currently unknown. In this study, we assessed the hypothesis that positive diabetes history modifies the effect of food insecurity on cardiovascular disease (CVD) mortality.

We analyzed data on adults (≥ 20 years) from the 1999-2010 National Health and Nutrition Examination Survey, with mortality data obtained through 2015. The causes of death for adults (N=4037) were defined using the International Classification of Disease coding (ICD-10). Complex Samples Cox regression was used to assess if diabetes status modified the relationship between food insecurity and CVD-mortality.

During a 11.1-year follow-up, among adults with diabetes, 184 individuals died (15%). The hazard ratio (HR) for CVD-mortality among adults with food insecurity compared with adults without food insecurity, with adjustment for age and gender only, was 1.66; 95% confidence interval [CI: 1.26, 2.20]. The adjusted HR was elevated, 2.13 (CI 1.30-3.48, p < 0.05), among adults with diabetes and food insecurity but close to 1.0 (1.57 CI 0.97-2.54, p = 0.07) among adults with only food insecurity after the results were controlled for medical risk factors (chronic kidney disease (CKD) and obesity) and demographic risk factors (age, gender, ethnicity, education).

In conclusion, individuals who are food-insecure and have diabetes have a higher probability of death from cardiovascular disease in long-term follow-up than those individuals without diabetes. Risk scoring and CVD prevention strategies should include screening and surveillance for food insecurity status. Comprehensive and interdisciplinary approaches to reducing cardiovascular disease-related disparities and health risks should be implemented through equity research.
Abstract 13814: Prediction of Transthyretin Cardiac Amyloidosis in Heart Failure With Preserved Ejection Fraction: Artificial Intelligence Electrocardiogram versus Traditional Risk Scores
Authors: Davies Daniel , Murphree Dennis , Scott Christopher , Lopez-jimenez Francisco , Baez Suarez Abraham , Attia Zachi , Kapa Suraj , Borgeson Daniel D , FRIEDMAN Paul A , Angela Dispenzieri , Grogan Martha , Redfield Margaret M , Abouezzeddine Omar F
Published: April 2022

Introduction:
Transthyretin cardiac amyloidosis (TTR-CA) can cause heart failure with preserved EF (HFpEF). We previously reported a clinical/echo-based score (TCAS) and defined a cut-off that predicted risk of TTR-CA in HFpEF. Herein, we assess the comparative performance of an artificial-intelligence ECG-based screening tool (AI-ECG).

Hypothesis:
AI-ECG successfully identifies TTR-CA in HFpEF cohorts across a range of TTR-CA prevalence

Methods:
Referral HFpEF cohort was constructed from a referral population of HFpEF patients (EF ≥ 40%) undergoing
99m
Tc-pyrophosphate scintigraphy (PYP) at Mayo Clinic (2013-2020, n=484, 38% with TTR-CA). Community HFpEF cohort was prospectively screened with PYP (n=275; age ≥ 60, LV wall thickness (WT) ≥ 12 mm, 4% with TTR-CA). TCAS was built using a multivariable logistic regression model and converted to a simple point score comprised of age (60-69, 70-79, ≥ 80: +2, +3, +4 points respectively), male sex (+2), relative WT > 0.57 (+2), posterior WT ≥ 12 mm (+1), EF < 60% (+1), and hypertension diagnosis (-1). TCAS was validated in the community cohort. A deep neural network trained to predict cardiac amyloidosis from a single 12-lead ECG, was applied to both referral and community cohorts. Patients were excluded if ECG was not available ≤ 12 months before PYP or if used in development of the AI-ECG. Standard ROC methods were applied. Youden’s index was used to define optimal cut-off.

Results:
Predictive characteristics of AI-ECG were strong and compared favorably with TCAS across a range of true TTR-CA prevalence (Table).

Conclusions:
Using a single ECG, AI-ECG effectively predicts TTR-CA with an excellent negative predictive value to rule out TTR-CA and a positive predictive value sufficient to warrant specific TTR-CA testing. This was particularly evident in the community. AI-ECG holds promise for simple, cost-effective global screening of at-risk populations, especially those with limited access to advanced cardiac imaging.
Abstract 13818: Polyoxazoline Modification of Bovine Pericardial Bioprosthetic Heart Valve Leaflets Mitigates Protein-Glycation Associated Structural Degeneration
Authors: Zakharchenko Andrey , Keeney Samuel , Alferiev Ivan S , Chorny Michael , Xue Yingfei , Takano Hajime , Stachelek Stanley J , Ferrari Giovanni , LEVY Robert
Published: April 2022

Introduction:
Bioprosthetic heart valves (BHV) fabricated from glutaraldehyde treated bovine pericardium (BP) are widely used to treat heart valve disease. BHV dysfunction from structural valve degeneration (SVD) develops over time, often necessitating device replacement. SVD is associated with both calcification and the accumulation of advanced glycation end products (AGE) and serum proteins within BHV leaflets. Here, we introduce a new strategy for mitigating AGE-associated SVD by modifying BP with a poly(2-methyl-2-oxazoline) (POZ).

Hypothesis:
Attached POZ will prevent BP deterioration by mitigating serum protein and pro-inflammatory AGE uptake.

Methods:
Covalently modified BP-POZ was studied for its effects on serum albumin and AGE entry
in vitro
via a mass-uptake assay and immunostaining. Resistance of BP-POZ to oxidation was assessed in comparison to poly(ethylene glycol) (PEG). Macrophage studies assessed the inflammatory properties of BP-POZ. A juvenile rat subdermal model was used to study serum protein and AGE uptake and calcification within BP-POZ, with or without ethanol pretreatment. A heart valve pulse duplicator was used to assess the protective effects of BP-POZ on BHV hydrodynamics following accelerated glycation.

Results:
POZ mitigated the accumulation of serum albumin and AGE
in vitro
. After exposure to AGE and macrophages, POZ preserved BP collagen structure while TNFα levels remained at baseline. Under oxidation conditions, POZ retained its protective function, unlike PEG. In the rat model, POZ reduced BP AGE (p<0.001) and albumin (p<0.001) uptake. Ethanol pretreatment of BP-POZ was effective at reducing both AGE and calcification. POZ mitigated the hydrodynamic dysfunction of BHV exposed to accelerated glycation conditions (p<0.001).

Conclusions:
SVD due to AGE and serum proteins can be effectively mitigated through POZ modification, that does not interfere with ethanol pretreatment mitigation of BP calcification.
Abstract 13819: Circulating PON Lactonase Activity Predicts Major Adverse Cardiac Events in Subjects With Atherosclerotic Renal Artery Disease
Authors: Kennedy David J , Connolly Jacob , Sun Zhen , Brewster Pamela S , Reid Tyler , Dube Prabhatchandra , Cooper Christopher J , Dworkin Lance D , Malhotra Deepak , Haller Steven , Kennedy David J
Published: April 2022

Introduction:
Decreased plasma lactonase activity, catalyzed by high-density lipoprotein (HDL)-associated paraoxonase (PON), is associated with increased oxidant stress and cardiovascular risk in settings such as coronary artery disease as well as some etiologies of chronic kidney disease (CKD). However, whether circulating PON lactonase activity predicts outcomes in atherosclerotic renal artery stenosis (ARAS) is unknown. We sought to determine the prognostic value of circulating PON lactonase activity in subjects with ARAS, particularly in relation to established risk factors.

Methods/Results:
PON lactonase activity was measured in plasma of subjects with ARAS and either systolic hypertension while taking ≥2 antihypertensive drugs or CKD (n=718) enrolled in the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study as well as a cohort of apparently healthy, normotensive non-ARAS subjects (n=33). Participants with ARAS were prospectively followed for incident major adverse cardiac events (MACE, composite of cardiovascular death, nonfatal myocardial infarction, and stroke) over a median follow-up period of 43 months (interquartile range, 31 to 55). PON lactonase activity in ARAS subjects was significantly lower compared with that in non-ARAS control subjects [mean±SD, 2466±839 vs 3514±745 pmol/min/mL, P<0.001]. Next, participants were dichotomized based on the baseline plasma levels of PON lactonase activity, into high (> median) or low (≤ median) groups and were used to predict incident MACE at 3 years. Participants with lower PON lactonase activity had increased MACE at 3 years [67/359 (17%) vs 44/359 (12%), p<0.05]. Lower circulating PON lactonase activity (hazard ratio 1.26, 95% CI 1.0 to 1.53, p=0.016) was a predictor of MACE. After adjusting for traditional risk factors and medication use, lower PON lactonase activity (hazard ratio 1.22, 95% CI 1.01 to 1.50, p=0.04) still conferred an increased risk of MACE.

Conclusions:
In patients with ARAS, decreased circulating PON lactonase activity, a measure of diminished antioxidant properties of HDL, predicts higher risk of incident long-term adverse cardiovascular events in multivariate models adjusting for established clinical and biochemical risk factors.
Abstract 13827: The Effect of Tanshinone IIA on Megakaryopoiesis in Immune Vasculitis
Authors: Yang Mo , Su Weiqing , Yang Liuming , Zhou Min , Chen Hui
Published: April 2022

Introduction and Objective:
Tanshinone IIA is an active component of Danshen (Radix Salviae Miltiorrhiza Bge), which has been used to treat hypercoagulation-related diseases for centuries. However, its role in megakaryopoiesis remains unclear. Therefore, the present study aimed to examine the effect of Tanshinone IIA on megakaryocytes and platelets in immune vasculitis, and to identify the underlying mechanism(s).

Methods:
Albino rabbits, aged 3-4 weeks, were used in the present study. Immune vasculitis was established by intravenous injection of BSA (2.5 ml/kg). Tanshinone IIA (5 mg/kg/d) was given through intravenous injection as well. Blood sample was collected from the ear vein and bone marrow was harvested from the femur. Megakaryocytes and CFU-MK were counted with Wright’s and acetylcholine esterase staining, respectively. The coagulation activity and IL-1β level were determined by ELISA. Megakaryocytic cell line CHRF was used to examine the effect of Tanshinone IIA (1-30 μg/mL) on apoptosis; the assay was performed with Annexin V/PI, Caspase 3 and JC-1 using flow cytometry.

Results:
In rabbits with immune vasculitis, the platelet count, platelet aggregation and prothrombin fragment were significantly increased when compared to their counterparts. Megakaryocytes and CFU-MK were also significantly increased in immune vasculitis. In addition, the level of IL-1β was significantly higher in rabbits with immune vasculitis, which was positively correlated with platelet count and platelet aggregation. Tanshinone IIA (5 mg/kg/d, 7d) significantly reduced the number of megakaryocytes, CFU-MK and platelets, and decreased the coagulation activity. It also significantly lowered the IL-1β level. In megakaryocytic cell line CHRF, Tanshinone IIA (1-30 μg/mL) induced dose-dependent apoptosis.

Conclusion:
The present study shows that not only platelets, but also megakaryocytes are involved in the pathogenesis of immune vasculitis. IL-1β contributes to the thrombocytosis by inducing megakaryopoiesis. Tanshinone IIA exerts anti-platelet, anti-inflammation and anti-megakaryocyte effects in immune vasculitis; the underlying mechanism may be related to its inhibitory effect on IL-1β and the proapoptotic effect on megakaryocytes.
Abstract 13830: Prediction of Cardiac Rejection Trajectories via Machine Learning Derived Features From Digital Endomyocardial Biopsy Images
Authors: Arabyarmohammadi Sara , Yuan Cai , Peyster Eliot G , Lal Priti , Feldman Michael , Margulies Kenneth B , Madabhushi Anant
Published: April 2022

Introduction:
Cellular rejection occurs in 20-40% of transplant recipients with an increased risk of graft failure. Previously, we developed a model for predicting ISHLT rejection grades via the automated extraction of morphologic features in Endomyocardial biopsy (EMB) images. Considering the frequent discordance between conventional rejection grade and clinical rejection severity, in this work, we sought to identify morphologic features that predict the clinical trajectory of rejection events.

Methods:
Our study comprised 299 EMBs with grade and trajectory labels. Trajectory labels are based on the development of overt clinical signs of allograft injury as “clinically evident” or “clinically silent”. Morphologic features describing number, spatial arrangement of lymphocytes, and shape, orientation of interstitial fibers were computationally extracted. To identify the top features associated with clinically evident disease, the T-test method was applied across 500 iterations of 3-fold cross validation. In each iteration, a quadratic discriminant analysis model was trained with top 10 features on 2 folds of dataset using trajectory labels (M
trj
) and was validated on one hold out test set. This model was trained using grade labels (M
grd
) to predict “high” (2R + 3R) or “low” (0R + 1R). To assess feature importance, in each model, the frequency of every feature appearing in the classifier was measured through iterations.

Results:
The mean area under the receiver operating curve of M
trj
and M
grd
was 0.80±0.04 and 0.84±0.02 correspondingly. The top features for predicting grades differ substantially from those for predicting clinical trajectory (Figure 1).

Conclusions:
The additional features required to predict clinical trajectory vs. rejection grade may explain the discordance between conventional histology and rejection syndrome observed in clinical practice, and highlights the translational potential of computer-assisted histologic analysis of EMBs.
Abstract 13833: Cardiac Sympathetic Denervation in Patients With Ventricular Tachycardia or Electrical Storm: A 6 Months Follow-Up
Authors: Mahmoud Ahmad , Taha Yasmeen , Hanayneh Seri , Assaf Yazan , Betageri Omkar , Elzeneini Mohammed , Pepine Carl , Mckillop Matthew , Goel Ramil
Published: April 2022

Introduction:
Cardiac sympathetic denervation (CSD) is considered in the management of patients with refractory ventricular arrhythmias or storm. It has been shown to decrease the burden of ventricular arrhythmias and the ICD shocks acutely in previous studies, however, follow-up data is still limited.

Hypothesis:
The purpose of this study is to evaluate ventricular tachycardia (VT) recurrence within a 6-month period after CSD.

Methods:
We analyzed all patients who underwent CSD at the University of Florida hospital between 2011 to 2017. The primary outcome was the recurrence of sustained VT at 6 months. The burden of ICD shocks, the need for VT ablation/redo ablation, and cardiovascular-related mortality in the first 6 months were also reported.

Results:
A total of 29 patients with CSD were included (9 patients had left CSD and 20 patients had bilateral CSD, mean age 60.1±11.5, 86 % male, and EF 27.3±15.4% by 2D-echocardiography), 13 (44.8%) of them presented with VT storm and 15 (51.7%) had prior VT ablation. One patient had cardiovascular-related mortality by 1 month and 7 patients by 6 months. The rate of VT recurrence was 31% by 1 month and increased to 35% by 6 months. By the end of the follow-up period, 17 (58.6%) patients remained free of recurrent ICD shocks and VT ablation was needed in 12 (41.4%) patients, 6 of them were redo-ablations. We further divided patients based on the underlying heart disease including ischemic heart disease (HD) and non-ischemic HD and there was no difference in the rate of VT recurrence at 6 months (p=0.18). There was also no difference in the primary outcome between left only CSD and bilateral CSD (P=0.98).

Conclusions:
Our data show that CSD showed benefit in VT recurrence rate at 6 months post-procedure. Reduction and freedom of ICD shocks were noted in patients with refractory VT or electrical storm. These benefits were independent of the underlying heart disease etiology. More studies with a longer follow-up period are warranted to confirm these results and follow long-term outcomes.
Abstract 13835: MG53 Preserves Mitochondrial Integrity of Cardiomyocytes in Pre-Clinical Models of Ischemia Reperfusion-Induced Oxidative Stress
Authors: Zhu Hua , Gumpper Kristyn , Ma Hanley , Zhou Xinyu , Bian Zehua , Krishnamurthy Karthikeyan , Park Ki Ho , Sermersheim Matthew , Zhou Jingsong , Tan Tao , Li Lei , Liu Jianxun , LIN PEI-HUI , Ma Jianjie
Published: April 2022

Introduction:
Ischemic injury to the heart induces mitochondrial dysfunction due to an increase in oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle and is essential for repairing damaged plasma membranes by interacting with the membrane lipid phosphatidylserine. We have previously shown that mg53-/- mice are more susceptible to ischemia-reperfusion injury, and treatment with exogenous recombinant human MG53 (rhMG53) reduces infarct damage, restores cardiac function and preserves mitochondrial membrane potential.

Hypothesis:
We hypothesize MG53 preserves mitochondrial integrity after an ischemic event by binding to the mitochondrial-specific lipid, cardiolipin (CL), for mitochondrial membrane repair, preventing the formation of superoxides and mitophagy.

Methods:
Fluorescent imaging and western blotting experiments were conducted after ischemic injury
in vivo
and
in vitro
to measure the formation of superoxides and activation of mitophagy. A lipid binding assay was used to determine MG53’s ability to bind to CL. Transfection of murine cardiomyocyte cells with the mitochondria-targeted mt-mKeima was used to measure engulfment of the mitochondria by the lysosome.

Results:
We found that recombinant human MG53 (rhMG53) delivered prior ischemia/reperfusion translocated to the mitochondria both in vivo and in vitro. Additionally, superoxide generation was reduced by rhMG53 treatment using ex vivo and in vitro models. A lipid binding assay revealed rhMG53 binds to CL. Treating with rhMG53 inhibited mitophagy after ischemia/reperfusion, as demonstrated by the reduction of mitochondria in the lysosome after rhMG53 treatment and a reduction in mitochondria-bound parkin, a key mediator of mitophagy.

Conclusions:
In this study we provide evidence that rhMG53 treatment may preserve cardiac function by preserving mitochondria in cardiomyocytes. These findings suggest MG53’s interactions with mitochondria could be an attractive avenue for the development of MG53 as a targeted protein therapy for cardioprotection.
Abstract 13841: Sex Disparities in ST-Elevation Myocardial Infarction Stratified by Age: Insights From Regional ST-Elevation Myocardial Infarction Systems of Care
Authors: Yildiz Mehmet , Mattingly Georgia M , Lantz Rebekah H , Okeson Brynn K , Shah Ananya A , Garberich Ross , Garcia Santiago A , Sharkey Scott W , Rohm Heather S , Henry Timothy D , Quesada Odayme
Published: April 2022

Introduction:
Sex disparities in STEMI care are well recognized, with worse outcomes reported for women; however, it remains unknown whether these disparities are seen across all age groups.

Methods:
Using prospective data from 2 large regional STEMI systems; Minneapolis Heart Institute, Minneapolis, MN, and The Christ Hospital, Cincinnati, OH, from 2010 to 2020, we analyzed 4,815 consecutive STEMI patients stratified by sex and age groups as follows; young (18 to 44 years), middle-aged (45 to 64 years), and older (≥65 years).

Results:
Among 4,815 patients with STEMI, 30.7% were women. Among
young
patients, women had more diabetes. There were no differences in reperfusion times, but young women received medical management more often and were more likely to receive aspirin or antiplatelet at discharge. There were no differences in outcomes at 1-year follow-up between young women or men. Among
middle-aged
patients, women had more diabetes, hypertension, and stroke. There were no differences in PCI rates, but middle-aged women presented directly to the PCI center had longer door-to-balloon time (DBT). Middle-aged women were less likely to receive antiplatelet or statin at discharge and had higher in-hospital death rates than men. Among
older
patients, women had more hypertension but less history of smoking or coronary artery disease. There were no differences in PCI rates, but older women transferred to the PCI center had longer DBT. Middle-aged women were less likely to receive antiplatelet or statin at discharge. There were no differences in outcomes at 1-year follow-up between older women or men
(Table).

Conclusions:
In 2 large regional STEMI databases, sex disparities varied among different age groups, with less PCI use in young women and less guideline-directed medical therapy at discharge in middle-aged or older women, supporting the need for ongoing standardized protocols to eliminate sex disparities.
Abstract 13846: Prognostic Value of Echocardiographic Markers of Diastolic Dysfunction for Heart Failure in Overweight and Obese Patients in CAMELLIA-TIMI 61
Authors: Gong Jingyi , Scirica Benjamin M , Weissman Neil J , Tang Minao , Inzucchi Silvio E , McGuire Darren K , Keech Anthony C , Wiviott Stephen D , Sabatine Marc S , Bohula Erin
Published: April 2022

Background:
Recent guidelines have outlined echo markers of diastolic dysfunction (DD); evidence is limited for their prognostic value for hospitalization for heart failure (HHF) in overweight and obese pts.

Methods:
CAMELLIA-TIMI 61 was a randomized placebo-controlled trial of the weight loss agent lorcaserin in 12,000 pts with BMI ≥27 with or at risk for CV disease (median follow-up, 3.3 yrs). Echo with core lab interpretation was performed on a subset of pts. Established DD parameters were measured, including the ratio of the peak early transmitral diastolic flow velocity over the early diastolic mitral annulus velocity (average E/e’), left atrium volume index (LAVi), and tricuspid regurgitation jet velocity (TRV). These were analyzed continuously, using the standard cutpoints of >14, >34 mL/m
2
, and >2.8 m/s, respectively, and separately to determine the optimal cutpoints. The primary outcome for this analysis was HHF.

Results:
In 3,972 pts with baseline ejection fraction ≥50%, all 3 variables on a continuous scale predicted increased risk of HHF; using standard cutpoints, only E/e’>14 remained independently associated with HHF after adjustment for the other 2 echo parameters and clinical variables (
Panel A
). In an analysis of optimal cutpoints in these overweight and obese pts, >13 was optimal for E/e’, >2.5 m/s for TRV, and >58 mL/m
2
for LAVi. In a model with all 3 echo parameters, all remained significant predictors of HHF. After incorporation of clinical variables, E/e’ (HR 2.15, 95%CI 1.24-3.72) and LAVi (HR 2.41, 1.33-4.36) remained independent predictors of HHF (
Panel A
). Rates of HHF were 0.6, 3.3, and 10.1% (p-trend<0.0001) in pts with none, one, or both measures of DD (
Panel B
).

Conclusions:
Several echocardiographic markers of diastolic dysfunction used in current guidelines predict increased risk of HHF events in the understudied obese and overweight population. A higher LAVi (> 58 ml/m
2
) cutpoint should be considered in these pts to prognosticate risk of HHF.