bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13402: Racial Differences in Incidence of Acute Kidney Injury in Patients With ST-Elevation Myocardial Infarction
Authors: Nair Raunak M , Kumar Anirudh , Huded Chetan , Johnson Michael , Kravitz Kathleen A , Reed Grant W , Krishnaswamy Amar , Menon Venu , Lincoff A M , Kapadia Samir R , Khot Umesh N
Published: June 2023

Background:
Racial differences in outcomes of STEMI patients continue to persist. Our study aimed to assess the difference in the incidence of acute kidney injury (AKI) post percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI), stratified by race into African Americans (AA) vs Caucasians.

Methods:
All STEMI patients who underwent PCI at the Cleveland Clinic main campus between January 1, 2011, to July 15, 2019, were included in our study. Patients were categorized into two groups depending on a diagnosis of the presence or absence of AKI post PCI. AKI was defined as >0.3mg/dl rise in post PCI creatinine from pre-procedure value. Relative risk of developing AKI depending on race was calculated with the help of a two by two table.

Results:
Overall, 1847 patients were admitted to our hospital with a STEMI and underwent PCI during the study period. Of these, 267 (15%) developed AKI post PCI. 19% of AA patients developed AKI compared to 13% of Caucasian. Comparison of baseline characteristics amongst patients who developed AKI revealed that AA patients with AKI were younger than their Caucasian counterparts (median age 63 vs 68, p=0.006), but were more likely to having smoking history (52% vs 35%, p=0.014). Upon analyzing the association between race and AKI, AA patients were 48% more likely to develop AKI post PCI compared to Caucasian patients (RR of 1.48, 95% CI 1.17-1.86, p=0.0015). This difference was observed in spite of no significant differences in radial access, contrast dose, or mechanical circulatory support use between the two races.

Conclusion:
African Americans STEMI patients are almost 50% more likely than Caucasians to develop AKI post PCI. Developing race-specific process measures and further optimization of procedural characteristics may be necessary to improve the outcomes of AA STEMI patients.
Abstract 13403: Substance Use is Associated With an Increased Risk for Hospital Readmission and Mortality in Patients With Heart Failure
Authors: Yeung Samantha L , Wang Mengxi , Lou Mimi , Ng Tien M
Published: June 2023

Introduction:
Both heart failure (HF) and substance use disorders are associated with substantial morbidity and mortality. Many illicit substances exert adverse cardiovascular effects and socioeconomic impact.

Hypothesis:
Substance use will be independently associated with worse clinical outcomes in patients with HF.

Methods:
Retrospective, cohort study of adult patients with a primary diagnosis of HF enrolled in the Optum Clinformatics Data Mart (2010 – 2020). Demographics and clinical outcomes were obtained via ICD-9/10 codes. Patients were stratified by history of substance use [anytime; prior or current use; type of substance (i.e., cannabis, opiates, stimulants – cocaine and methamphetamine, and hallucinogens – phencyclidine and sedative/hypnotic/anxiolytics)] and compared to patients with no history of substance use. A multivariable logistic regression analysis was conducted in a propensity-score 1:1 matched cohort. Outcomes were 30 and 180-day, and 1-year hospital readmission and mortality.

Results:
There were 184,508 patients included; 11,611 (6.3%) with documented substance use at any time. Prior to matching, patients with substance use were younger, more often male, and with fewer comorbidities compared to those with no history of substance use. Substance use was associated with greater 30 and 180-day, and 1-year hospital readmissions and mortality (table). The associated risk of substance use was confirmed in the propensity matched analysis. The risk was retained when substance use was restricted to use prior to or at time of index hospitalization and use after index hospitalization. Stimulant use was associated with a 2-fold increase in risk of hospital readmission.

Conclusions:
Despite younger age and fewer comorbidities, substance use in patients with HF was associated with an increased risk of all-cause and HF-related hospital readmissions and mortality.
Abstract 13406: Atrial Fibrillation and Atrial Flutter as Predictors of Cardiovascular Outcomes in Patients Hospitalized With Covid-19 Infection
Authors: Rivera Rodriguez Beatriz , Aponte Becerra Laura , Yan Crystal , MCDERMOTT LAURA , Romano Peralta Ramon , Olarte Neal , Andrade-Bucknor Sharon
Published: June 2023

Introduction:
Patients with atrial structural changes have a higher risk of developing atrial arrhythmias, such as atrial fibrillation (AF) and flutter (AFL), particularly during pro-inflammatory states such as a COVID-19 infection. Amongst these patients, AF/AFL have been found to be markers of disease severity. Our aim was to evaluate AF/AFL as predictors of cardiovascular outcomes, and their synergistic relationship with atrial dilatation, in patients with COVID-19.

Methods:
We conducted a two-center retrospective study in patients hospitalized with COVID-19 from 2020 to 2021. Atrial enlargement was defined by 2D-guided linear measurement by echocardiography. The primary outcome of interest was to determine the association of MACE, defined as myocardial infarction, non-fatal stroke, cardiac arrest, and/or death, in patients who developed AF/AFL. The secondary outcome was to explore the synergistic risk of atrial enlargement and AF/AFL on MACE. Statistical analyses were performed using SAS 9.4.

Results:
From 488 patients, 68 (14%) developed AF/AFL. These patients were older (74±11 vs. 64±15 years), had higher rates of hypertension (79% vs. 64%), coronary artery disease (29% vs. 12%), and heart failure (28% vs 10%). There was a significant unadjusted effect of right atrial enlargement (OR 2.12, CI 1.15-3.91) and AF/AFL (OR 1.90, CI 1.14-3.19) on MACE, whereas the effect was not sustained for left atrial enlargement. Multivariable adjusted models showed that AF/AFL and right atrial enlargement had no longer a significant effect on MACE, and only age remained an independent significant predictor (OR 1.27, CI 1.09-1.47). Moreover, there was no joint effect of AF/AFL and right atrial enlargement on MACE when their interaction was accounted for.

Conclusion:
AF and AFL were not associated with a higher risk of MACE, nor was atrial enlargement shown to modify the relationship between AF/AFL and MACE in patients who were hospitalized with COVID-19. Age remains to be a predictor of poor outcomes. Studies with a larger sample size would be needed to determine if there’s a significant relationship.
Abstract 13414: Promoting Health Equity Using a Hybrid Virtual Cardiac Rehabilitation Program
Authors: Johnson Trent B , Isakadze Nino , Mathews Lena , Gao Yumin , MacFarlane Zane , Spaulding Erin , Martin Seth S , Marvel Francoise A
Published: June 2023

Background:
Cardiac rehabilitation (CR) is an effective program for the secondary prevention of cardiovascular disease. Novel CR delivery methods are needed to increase access in an equitable and cost-effective manner. Herein, we present lessons learned in developing and implementing our hybrid CR program.

Methods:
We established a 5-step approach to increase engagement in CR using a hybrid in-center and virtual model:
1-Assemble a Team and Technology Platform
Develop a team with diverse perspectives and integrate technology to facilitate patient participation.
2-Establish an Equitable Onboarding Process
Combine patient navigators with video tutorials to support equitable access for patients at different levels of digital literacy.
3-Gather Feedback
Conduct design sessions to elicit feedback.
4-Implement Feedback
Use quality improvement (QI) protocols to iteratively improve onboarding and refine logistics.
5-Evaluate Clinical Efficacy
Conduct studies to investigate the program's efficacy in improving outcomes.

Results:
In step 3, we used human centered design (HCD) to solicit feedback from patients, caregivers, and clinician stakeholders to influence the creation of our program. Our patient sample was 27% African American, 9% Asian, 18% Hispanic or Latino, 55% female, with a median (IQR) age of 63 (56-66) years. Feedback led to the creation of a video on CR benefits, the introduction of motivational coaches, and the creation of an EPIC order set. In step 4, using QI, we were successful in promoting equitable access as demonstrated by the fact that the patients had a mean age of 59.2 (SD: 10.4) years, 40% were female, 39% were of minority race/ethnicity, 58% were insured by Medicare/Medicaid.

Conclusions:
Our novel hybrid CR program shows promise for improving CR. Future directions (Step 5) include evaluation of the program in an mTECH REHAB Trial as part of AHA’s Strategic Focused Research Network.
Abstract 13417: Deletion of the Asialyloglycoprotein Receptor-1 Causes Athero-Protective Effects
in vitro
and
in vivo
Authors: Pullen Benjamin J , Vidanapathirana Achini K , Sandeman Lauren , Everest-Dass Arun , Kolarich Daniel , Tan Joanne T , Psaltis Peter , Nicholls Stephen , Packer Nicolle H , Bursill Christina A
Published: June 2023

Introduction:
The asialoglycoprotein receptor-1 (ASGR-1) is known to be a hepatic receptor that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR-1 was reported to associate with a 34% reduction in coronary artery disease (CAD) risk, suggesting a role for ASGR-1 in CAD.

Hypothesis:
ASGR-1 is an important player in atherosclerosis and deletion of ASGR-1 will reduce atherosclerotic plaque via athero-protective mechanisms in macrophages.

Methods and Results:
Using immunofluorescence, we detected ASGR-1 in aortic sinus plaques from apolipoprotein (Apo)e-/- mice fed a high cholesterol diet (HCD)-fed apolipoprotein (Apo)e-/- mice. Bone marrow-derived macrophages (BMDMs) from Asgr1-/- mice elicited greater cholesterol efflux (39%, P<0.05) and decreased oxLDL uptake (15%, P<0.05), compared to wildtype BMDMs. Plasma from Asgr-1
-/-
mice had lower total cholesterol (25%, P<0.05) and LDL cholesterol (36%, P<0.05) concentrations than wildtype control mice. Apoe
-/-
x Asgr-1
-/+
mice fed HCD for 8 weeks developed less plaque in the aortic sinus (32.75%, P<0.001) than Apoe
-/-
controls, and had fewer circulating neutrophils (38%, P<0.05). In the tandem stenosis model of unstable plaque, Apoe
-/-
x Asgr-1
-/-
mice also developed smaller plaques in their carotid arteries (49%, P<0.05), than Apoe
-/-
controls. Furthermore, ASGR-1 was measured in peripheral blood mononuclear cells (PBMCs) isolated from patient samples (n=10-12/group). ASGR-1 protein levels were higher in PBMCs from patients with coronary plaque (61%, P<0.05), than those without plaque, as determined from coronary angiograms.

Conclusions:
ASGR-1 plays an important role in atherosclerosis. Deletion of ASGR-1 causes athero-protective effects in macrophages
in vitro
and reduced plaque burden
in vivo
. Elevated ASGR-1 levels in PBMCs from clinical blood samples was also associated with the presence of coronary plaque. These studies have significant implications for the potential of ASGR-1 as a therapeutic target for the prevention of atherosclerosis.
Abstract 13441: Transcriptomic Analysis of Endothelial Colony Forming Cells From the BioHEART-CT Study to Unravel New Biomarkers for Coronary Artery Disease
Authors: Ng Hooi H , Besnier Marie , Schnitzler Kirsten , Tran Andy , Yang Jean Y , Figtree Gemma A
Published: June 2023

Coronary artery disease (CAD) remains the leading cause of death worldwide. There are unmet needs for the diagnosis and treatment for patients with CAD, especially those without modifiable risk factors who are suspected to be at low risk for CAD. Endothelial function has predictive value for future cardiovascular events. We previously showed that endothelial colony forming cells (ECFCs) derived from the BioHEART-CT (The BioHEART Study: Assessing Patients with Suspected Cardiovascular Disease for New Biomarkers and Risk Factors) cohort can be used as a viable tool to evaluate endothelial function in patients as these cells retain the memory of their host. Here, we aimed to characterize the transcriptomic profiles of ECFCs in non-CAD and CAD patients. Based upon our previous findings on the positive correlation between mitochondrial superoxide level and the severity of CAD, we hypothesize that the transcriptomic and functional analyses of the mitochondrial pathways are dysregulated in the ECFCs in CAD patients. RNA-sequencing was performed in ECFCs cultured from the peripheral blood of 44 patients from the BioHEART-CT cohort who had computed tomography coronary angiograms scored for coronary artery calcium (CAC) and Gensini to measure CAD severity. The cohort included 45.5% women and 54.5% men with an average age of 61.6 years. Non-CAD group was determined by a Gensini score of zero, whereas CAD group was determined by a Gensini score of greater than 5. These CAD patients had median CAC score of 266.8, with significant presence of calcified and soft plaques in their coronary arteries. Transcriptomic analysis of ECFCs showed that a total of 37 genes were upregulated and 77 genes were downregulated in the CAD patients. To investigate the functional relevance of the pathways altered in the CAD cohort, dysregulation of genes was analyzed using gene set enrichment analysis. We found that the metabolic processes, those associated with mitochondrial biogenesis, were significantly altered in the ECFCs. Our approach of using RNA-sequencing to determine the gene characteristics of CAD patients and their functional relevance to disease has the potential to unravel previously un-identified genes or biomarkers that are distinct to CAD patients.
Abstract 13449: Patient-Triggered Symptomatic Events Poorly Predict Presence of Atrial Arrhythmia on Ambulatory Electrocardiogram Monitors in Heart Failure Patients
Authors: Herner Maranda , Abedin Zameer , Torre Michael , Zhang yue , Orton Cody , Lyons Ann , Butcher Ryan , Steinberg Benjamin A
Published: June 2023

Introduction:
Emerging evidence supports more aggressive rhythm control of atrial fibrillation (AF) among heart failure (HF) patients. Yet, the impact of AF on symptom status in HF and the relationship to rate control have not been well studied in the setting of prolonged, ambulatory monitoring.

Hypothesis: Patient-triggered symptomatic events (PTSEs) can predict the simultaneous presence of atrial tachycardia/AF (ATAF) on cardiac event monitors(CEM) among HF patients with documented atrial arrhythmia.

Methods:
All UHealth HF patients with at least 1 ATAF event over ≥7 days on CEMs were retrospectively reviewed. Tetrachoric correlation analysis between PTSEs and ATAF events and t-tests of mean heart rates(HR) were performed.

Results:
A total of 3,162 events were analyzed among 185 HF patients. The mean age was 68 years and 43% were female; 61% had CAD; the mean ejection fraction was 54% (SD 16%); and 74% were on beta-blockers. There were 2347 ATAF events, 1031 PTSEs, and 216 symptomatic ATAF events. Of PTSEs, 21.0% were ATAF, and of ATAF events, 9.2% were symptomatic. Overall mean HR of PTSEs was 94bpm (SD 29), lower than asymptomatic events, 103bpm (SD 29, p<0.001). Mean HR of symptomatic ATAF events was 117bpm (SD 35), compared with asymptomatic ATAF (110bpm, SD 31, p=0.008). See Figure 1. PTSEs were less likely to predict simultaneous ATAF compared to sinus rhythm, with a moderate inverse tetrachoric correlation of -0.69 (bootstrapped 95% CI -0.65, -0.72).

Conclusion:
Among patients with AF & HF, symptoms are a poor marker of atrial arrhythmia. PTSEs on ambulatory monitoring are not correlated with ATAF events in a clinically meaningful association and are not adequately explained by the heart rate differences. Classic symptom-based treatment of AF and HF should give way to more comprehensive quality-of-life and substrate guides for therapy.
Abstract 13457: Ability of CHARGE-AF and CHA
2
DS
2
-VASc Scores to Predict Prevalent Atrial Fibrillation in a High-Risk Population
Authors: Chami Hassan , Li Linzi , Quyyumi Arshed A , Alonso Alvaro
Published: June 2023

Introduction:
The CHARGE-AF score estimates 5-year risk of developing atrial fibrillation (AF) using information on age, race, weight, height, systolic and diastolic blood pressure, diabetes, smoking, use of antihypertensive medication, and prevalence of heart failure and myocardial infarction. Similarly, the CHA
2
DS
2
-VASc score for estimation of stroke risk in AF has been proposed as a useful tool for incident AF prediction. It is unclear whether these scores can predict AF in a high-risk population. We evaluated whether the CHARGE-AF and CHA
2
DS
2
-VASc scores predict the prevalence of AF in the Emory Cardiovascular Biobank cohort (EmCAB) that recruited patients undergoing cardiac catheterization with suspected or confirmed coronary artery disease.

Methods:
In 6951 EmCAB participants, logistic regression was used to determine the association between baseline characteristics, CHARGE-AF and CHA
2
DS
2
-VASc scores and the presence of prevalent AF. To assess the discrimination of the CHARGE-AF and CHA
2
DS
2
-VASc models, we estimated the C-statistic. Internal calibration was determined with the Hosmer-Lemeshow test.

Results:
Mean age of patients was 62 (SD=13), 64% male, 76% White. Median 5-year risk of AF using the CHARGE-AF score was significantly higher in those with compared to those without prevalent AF (11% vs. 4%, p=<0.001). However, the median CHA
2
DS
2
-VASc scores were similar in both groups (3.0). The C-statistic for predicting prevalent AF was better with the CHARGE-AF compared to the CHA
2
DS
2
-VASc score (0.662 vs. 0.606). The strongest risk predictor of prevalent AF was heart failure (OR 2.52, 95%CI 2.13-2.98).

Conclusion:
In a high risk cohort of patients with CAD, the CHARGE-AF score had a moderate discrimination ability to predict AF and showed better performance than the CHA
2
DS
2
-VASc score. Whether the CHARGE-AF score is useful in predicting incident AF in high risk patients needs to be further investigated.
Abstract 13469: A Risk Score Model to Identify Patients With High Likelihood of Left Main or 3-vessel Coronary Artery Disease
Authors: Braghieri Lorenzo , Hariri Essa , Fares Maan , Barzilai Benico , Jaber Wael A , Rothberg Michael
Published: June 2023

Introduction:
Revascularization improves outcomes only for stable coronary artery disease (CAD) patients with high-risk coronary anatomy (HRCA). While exercise stress test (EST) is the screening modality for CAD, identifying HRCA noninvasively is challenging. We aimed to derive a prediction model, incorporating clinical and EST characteristics, to screen for HRCA.

Methods:
We included adult patients who underwent EST followed by elective invasive coronary angiography (ICA) at our center between 2017 and 2019. HRCA was defined as left main (LM) or 3-vessel disease on ICA. Significant CAD was defined as ≥50% stenosis in the LM and/or ≥70% stenosis in the 3 main vessels. We excluded patients with acute coronary syndrome or ejection fraction <50%. Variables with p<0.1 at univariable analysis were selected as candidates to enter a multivariable stepwise backward regression model to derive a HRCA risk model.

Results:
304 consecutive patients met inclusion criteria (64[13]years, 81.6% M). 15.5% were found to have HRCA on ICA. Median time from EST to ICA was 11[31]days. The following hit the threshold for inclusion into the multivariable model: hypertension, maximal predicted heart rate (MPHR), diabetes, rate pressure product, metabolic equivalents, exercise time, chronotropic response index ≥0.8, heart rate recovery, Duke Treadmill Score (DTS). After backward selection, hypertension (OR 17.08, p=0.008), MPHR (0.98, p=0.048), and very abnormal DTS (8.26, p=0.001) were the only significant predictors of HRCA (
Fig.1A
). The fully adjusted model showed good discrimination for HRCA (AUC 0.74, p<0.001,
Fig.1B
).

Conclusions:
In an era of declining emphasis on EST in favor of imaging stress test, we identified a risk model based on clinical and EST-derived parameters, that can accurately predict likelihood of HRCA, enabling personalized risk-stratification. Further studies are needed to externally validate our model.
Abstract 13470: Circulating microRNA-122-5p is Associated With a Lack of Improvement in Left-Ventricular Function After Transcatheter Aortic Valve Replacement and Regulates Viability of Cardiomyocytes via Extracellular Vesicles
Authors: Hosen M. Rabiul , Boon Reinier , Moore Joseph , Uchida Shizuka , Latz Eicke , Jansen Felix , Nickenig Georg
Published: June 2023

Transcatheter aortic valve replacement is a well-established treatment option for high- and intermediate-risk patients with severe symptomatic AVS. However, a specific role for circulating microRNAs in the improvement of cardiac function for patients after TAVR has not yet been investigated.

Methods:
Circulating EV-associated miRNAs were investigated by using an unbiased Taqman-based human miR array. Several EV-miRNAs were significantly deregulated in AVS patients on day seven after TAVR in comparison to the pre-procedural levels in patients without LVEF-improvement. The higher levels of miR-122-5p were negatively correlated with LVEF improvement at both day seven (r=-0.264 and p=0.015) and at six months (r=-0.328 and p=0.0018).

Results:
By utilization of patient-derived samples and a murine AVS model, we observed that the expression of miR-122-5p correlates negatively with cardiac function, which is associated with LVEF. Graded wire-injury-induced AVS mice demonstrated a higher level of miR-122-5p, which was related to cardiomyocyte dysfunction. Murine
ex vivo
experiments revealed that miR-122-5p is highly enriched in ECs in comparison to cardiomyocytes. Co-culture, copy-number analysis, and immunofluorescence demonstrated that miR-122-5p can be shuttled via large EVs from ECs into cardiomyocytes. Gain- and loss-of-function suggested that EV-shuttling of miR-122-5p increases the level of miR-122-5p in recipient cardiomyocytes. Mechanistically, mass spectrometry, miR-pull down, EMSA, and RNA-IP experiments confirmed that miR-122-5p interacts with the RBP, hnRNPU, in a sequence-specific manner to encapsulate miR-122-5p into large EVs. Upon shuttling, miR-122-5p reduces the expression of the anti-apoptotic gene
BCL2
, by binding to its 3' untranslated region to inhibit its translation.

Conclusion:
Increased levels of circulating pro-apoptotic EV-incorporated miR-122-5p are associated with reduced LVEF after TAVR.
Abstract 13481: Incidence of Post-Cardiac Injury Syndrome in Transcatheter and Surgical Aortic Valve Replacement
Authors: Sharew Betemariam , Shu Jeffrey , Jaber Wael A , Johnston Douglas , Kapadia Samir R , Riggs Jennifer , Puri Rishi , Reed Grant W , Krishnaswamy Amar , Klein Allan L , Cremer Paul C
Published: June 2023

Introduction:
Cardiac procedures and surgeries can cause injury to the pericardium and result in pericarditis, termed post-cardiotomy syndrome or post-cardiac injury syndrome (PCIS). The incidence of PCIS after transcatheter aortic valve replacement (TAVR) is unknown, and the aim of the current study is to compare the incidence of PCIS in surgical versus transcatheter aortic valve replacement (SAVR, TAVR).

Methods:
In a single-center retrospective cohort study of randomly selected patients who had TAVR or SAVR in 2019, the primary outcome was PCIS, defined according to ESC guidelines. Pericarditis recurrence was also defined according to ESC guidelines. Due to baseline differences in SAVR and TAVR patients, propensity score matching was performed using calipers of width equal to 0.2 of the standard deviation of the logit of the propensity score.

Results:
Patients undergoing TAVR (n=103) were older, had higher STS-PROM scores, and generally more co-morbidities compared to patients undergoing SAVR (n=100), with the exception of atrial fibrillation (Table). Overall, 17 patients (17%) with SAVR had PCIS compared to 1 patient (1%) with TAVR (p<0.001). Ten patients (4.9%) were treated with pericarditis specific medications, of whom 7 (3.4%) received colchicine. Two patients (1.0%) developed recurrent pericarditis. In the sub-group (n=44) of propensity matched patients (Figure), 6 SAVR patients (27.3%) and no TAVR patients had PCIS.

Conclusions:
After TAVR, PCIS appears rare, which suggests that occult pericardial injury is uncommon. PCIS may also be less common after TAVR compared to SAVR, though larger studies are needed.
Abstract 13501: Gaps in Care With Pediatric Hypertension Diagnosis: Role of Social Determinants of Health
Authors: Zaidi Abbas H , Miller Jonathan , Maiden Kristin , Gao Zhongcui , Cuffee Yendelela L
Published: June 2023

Background:
Primary hypertension (HTN) in pediatrics is a significant public health concern with increasing prevalence. The risk for adult HTN and end-organ damage begins in childhood. Therefore, evidence-based guidelines were developed by the American Academy of Pediatrics (AAP) in 2017 with detailed recommendations on screening and diagnosis. Ongoing follow-up is essential for diagnosis (at least 3 follow-up visits are needed to diagnose HTN if BP is high). However, gaps in care(GIC) exist in detecting and diagnosing HTN in clinical practice with barriers to accurate HTN detection at the patient, provider, and health system levels. Patient factors such as social determinants of health (SDoH), including the Childhood Opportunity Index (COI), leading to GIC with recommended follow-up needed for HTN diagnosis at primary care visits are poorly understood.

Methods:
A total of 69,960 patients aged 6-22 years seen at Nemours Children’s Health in DE and PA between August 2017- March 2019 formed the cohort. SDoH, including language, race, ethnicity, and COI, were explored. Data were analyzed using descriptive statistics and logistic regression.

Results:
Only 596 patients(0.9%) had HTN or were recognized as having a high BP. 73%(432) patients had over a 1-year GIC. GIC was associated with insurance type(P=0.05) and having 2 or fewer caregivers(P=0.004). GIC was not associated with race, ethnicity, language, interpreter use, or COI.

Conclusions:
Despite evidence-based guidelines, HTN detection remains poor. Patient factors, including insurance and the number of caregivers, likely lead to GIC with follow-up for HTN in pediatric patients. However, GIC for routine HTN follow-up are not broadly associated with SDoH. Other barriers likely exist at the provider and health system level leading to GIC and poor HTN detection.
Abstract 13513: Favorable Neighborhood Walkability is Associated With Lower Burden of CV Risk Factors Among Patients Within an Integrated Health System: Houston Methodist CVD Learning Health System Registry
Authors: Makram Omar M , Nwana Nwabunie , Nicolas Charlie , Pan Alan P , Gullapelli Rakesh , BOSE BUDHADITYA , Hagan Kobina , Parekh Tarang , Yahya Tamer , Javed Zulqarnain , Patel Kershaw , Al-Kindi Sadeer , Sharma Garima , Jones Stephen , Cainzos Miguel , Maddock Jay E , Nasir Khurram
Published: June 2023

Background:
Optimizing modifiable cardiovascular risk factors is critical to achieving AHA’s 2020 Strategic Impact Goals. Neighborhood and urban factors with a supportive walkable environment can enhance physical activity and hence impact CVH across a wide range of populations. We assessed whether a more walkable environment is associated with CV risk factor burden irrespective of CVD burden among a large diverse population within an integrated health system.

Methods:
Cross-sectional study using data from 1.01 million patients aged 18+ years in the Houston Methodist Cardiovascular Disease Learning Health System Registry (2016-2021). Individuals lacking NW (177,674) & BMI <18.5 kg/m
2
(27,065) were excluded. Neighborhood walkability (NW) was defined using 2019 Walk Score. Patients were assigned to 1 of 4 NW categories (
Figure
). Study participants were classified as poor (>3 CV risk factors), average (1-2 CV risk factors) or optimal (0 CV risk factors).

Results:
We included 901,860 patients (mean age 51.88, female 59%, NHB 15%, and 16% Hispanics), most of these (86%) resided in the 2 least walkable neighborhoods. Age-adjusted prevalence of CV risk factors was significantly lower among participants in most favorable walkable neighborhoods irrespective of CVD status (
Figure
). In adjusted analysis, favorable NW (somewhat/very walkable) vs unfavorable NW (car dependent) was associated with 2-fold odds for optimal vs poor CVD risk (OR 2.07 95%CI: 2.01-2.12) among those without CVD. Similar results were found in those with CVD (OR 1.58 95% CI:1.41-1.77).

Conclusions:
Our findings demonstrate favorable association between neighborhood walkability and the CVD risk factors burden in large population of about 1 million individuals. These robust findings support multilevel health system stakeholder engagements and investments in walkable neighborhoods as a viable tool for mitigating growing burden of modifiable CV risk factors.
Abstract 13514: Associations Between Plasma Metabolites With Body Composition Traits and Their Responses to Exercise Training
Authors: Dev Prasun , Barber Jacob L , Clarkson William A , Robbins Jeremy M , Rao Prashant , Mi Michael , Ghosh Sujoy , Katz Daniel H , Clish Clary , Bouchard Claude , Gerszten Robert E , Sarzynski Mark A
Published: June 2023

INTRODUCTION:
Although exercise training can improve body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated.

HYPOTHESIS:
We hypothesized that distinct metabolite signatures exist for both baseline levels and exercise responsiveness of body composition traits, with substantial overlap across traits.

METHODS:
Measurements were taken before and after 20 weeks of endurance training in self-identified Black and White adults of the HERITAGE Family Study (n=652). 300 targeted plasma metabolites were measured using LC-MS. Underwater weighing, CT scans, and anthropometric measurements were used to derive the 11 body composition traits included in this study: BMI, body surface area, fat mass, fat free mass, %fat, waist circumference, waist-to-hip ratio, body weight, and abdominal visceral, subcutaneous, and total fat. Linear mixed models were used to test the association between plasma metabolites and each body composition trait at baseline and in response to training with full covariate adjustment. Significance was set to FDR<0.05.

Results:
On average, subjects were [mean and (SD)] 35 (14) years old, 33% Black, 54% female, and had BMI of 26.2 (5.2) kg/m
2
. The number of metabolites significantly associated with body composition traits at baseline ranged from 57-141 (
Table 1
). DMGV was among the top 3 associated metabolites at baseline for all 11 traits, while SM(d18:1/16:1) was associated with 8 of 11 baseline traits. Few if any significant associations were found between change in metabolites and change in body composition measures in response to exercise training (range: 0-10) (
Table 1
).

CONCLUSIONS:
Although numerous metabolites were associated with body composition traits at baseline, few associations were observed with trait responses to training. These results suggest that intrinsic body composition and its response to exercise training may have differing underlying metabolic signatures.
Abstract 13516: Natural History, Penotypes and Clinical Outcomes in Desmin Related Arrhythmogenic Cardiomyopathy
Authors: Bermudez-Jimenez Francisco Jose , Protonotarios Alexandros , Rampazzo Alessandra , Zorio Esther , Brodehl Andreas , Arias Miguel Ángel , Fernández Armenta Juan , Macías-Ruiz Rosa , Garcia-Pavia Pablo , Gimeno Juan Ramón , Lopes Luis R , Elliott Perry M , Jimenez-Jaimez Juan
Published: June 2023

Background:
Mutations in DES gene, encoding the intermediate filament desmin, have been related to arrhythmogenic cardiomyopathy (AC). Our aim is to describe the clinical phenotype, natural history and outcomes in a multicentric international cohort of desmin-related AC patients.

Methods:
Probands and relatives (85 individuals from 11 families (45% men; mean age 35 [IQR] 23.5-53.5 years old)) carrying a DES mutation from 8 European centers were included. Clinical, electrocardiographical and advanced cardiac imaging data were retrospectively collected and analysed. DES mutations were transfected into cell lines and analyzed by confocal microscopy.

Results:
Disease penetrance in individuals ≥30 years was 80.8% and 71.4% in individuals <30 years; A left dominant or biventricular form of AC was the main clinical phenotype (69 cases, 81 %). More than half of the patients presented low voltage on the ECG, the mean LVEF was 48.9±16% and the mean RVEF was 53.8±10%. A high prevalence of patients with magnetic resonance imaging (n=30) presented fibrosis (65,2%), with a particular circunferencial (“ring-like”) pattern in 46.4% (Figure A). After a median follow-up of 6 years, 24.7% died (mean age 62[33-76]) (Figure B) and 8.2% suffered appropriate shocks (age 47[31-69.5]) or SD (age 33 [24.5-49]). Finally, there were 6 heart transplants (age 54 [33-68]). A LVEF<50% and male sex were associated with major cardiovascular events. In three DES mutations (E401D, L115E and R415Q) desmin aggreggates were observed (Figure C)

Conclusions
AC due to DES mutations have a high clinical penetrance as a left dominant or biventricular form of the disease, with an early onset and a high burden of cardiovascular events. A LV “ring-like” LGE pattern was particularly common. Male sex or mildly depressed LVEF were predictors for SD. DES mutation may be pathogenic by causing desmin aggregates. A) Annular pattern of fibrosis B) Carriers free-of-events survival curve. C) Desmin aggregates
Abstract 13517: Simple Noninvasive FIB-4 Index is Associated With Increased Risk for Spectrum of Atherosclerotic Cardiovascular Diseases: Insights From the Houston Methodist CVD Learning Health System Registry
Authors: Nguyen Ryan T , Gullapelli Rakesh , Nicolas Charlie , Yahya Tamer , BOSE BUDHADITYA , Nwana Nwabunie , Lahan Shubham , Jones Stephen , Aneni Ehimen , Patel Kershaw , Soliman Ahmed , Cainzos Achirica Miguel , Quigley Eamonn , Abraham Bincy , Victor David , Nasir Khurram
Published: June 2023

Introduction:
Non-alcoholic fatty liver disease and liver fibrosis (LF) are associated with atherosclerotic cardiovascular disease (ASCVD). In this study, we aim to assess if the Fibrosis-4 index (FIB-4), a surrogate marker for liver fibrosis that is easily calculated from information within electronic medical records, is associated with composite and subgroups of ASCVD across a wide range of demographics and risk profile in a large integrated healthcare system.

Methods:
This cross-sectional study analyzed data on 606,056 individuals (>18 years old) from the Houston Methodist Cardiovascular Disease Learning Health System Registry (June 2016-April 2022). We implemented the FIB-4 score for patients based on simultaneous presence of 4 variables (age, AST, ALT, and platelet count). LF risk was categorized according to previously described cutoffs: Low (<1.3), Intermediate (1.3-2.67), and High (>2.67). ASCVD (CAD, PAD, and Stroke) were identified using ICD-10-CM codes.

Results:
In the final study population (mean age: 54 years, 60% females, 16% Non-Hispanic Black, and 16% Hispanic adults), 27% of individuals were at moderate-risk and 8% at high-risk for LF based on the FIB-4 index. Moderate-high risk LF is associated with higher age-adjusted prevalence of both composite and subcategories of ASCVD (CAD, PAD, Stroke). Accounting for demographics, CV risk factors, and ASA/statin use, moderate and high-risk LF was associated with a 1.32 (95% CI 1.30-1.35) and 1.67 (95% CI 1.62-1.72) odds of prevalent composite ASCVD, respectively, compared to low-risk LF. Similar associations were noted for increasing LF risk and prevalence of ASCVD subcategories.

Conclusions:
In a large integrated health system, a moderate-high risk of liver fibrosis (based on FIB-4 index) is significantly associated with a spectrum of ASCVD conditions. FIB-4 index based early identification and management of these high-risk individuals need to be evaluated in further implementation studies.
Abstract 13558: Opening the Black Box of Artificial Intelligence: Visualization of Detecting Heart Failure Subtypes Using Electrocardiography
Authors: Lee Hak Seung , Jang Jong-Hwan , Kang Sora , Jo Yong-Yeon , Son Jeong Min , Lee Min Sung , Kwon Joon-Myoung
Published: June 2023

Objectives:
To evaluate and visualize how artificial intelligence (AI) recognizes electrocardiography (ECG) characteristics of each heart failure (HF) subtype. We developed a visually explainable and interpretable AI-ECG algorithm for various HF subtypes to meet this need. This study proposes the ShapeExplainer (SE) to interpret models.

Methods:
From 33,920 patients at two hospitals, we trained a convolutional neural network to identify patients with HF subtypes using ECG and clinical diagnosis. HF subtypes include heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF, and heart failure with preserved ejection fraction (HFpEF) (
Figure a
). To interprete each HF classifier model, SE, which converts non-HF group data to be recognized as each HF subtype by each classifier, was trained. The converted fake ECG shows what the change is for the classifier to recognize as each HF subtype. SE from the non-HF group of the external validation set shows the result by comparing the shape before and after transformation.

Results:
When tested on an independent set of 6,784 patients, the network model yielded values for the area under the curves of HFrEF of 0.945, HFmrEF of 0.884, and HFpEF of 0.859, respectively. The results of each classifier were visualized by overlapping the original and newly generated ECGs. Comparing each subtype and its fake ECG, there was no clear trend of electrocardiographic features. However, fake ECG showed a tendency of qrs amplitude as it progressed to non-HF, HFpEF, HFmrEF, and HFrEF, especially in T wave or ST-change (
Figure b
).

Conclusions:
The proposed fake ECG generating method is a new approach for interpreting the AI-ECG model, helping physicians understand how AI recognizes HF subtypes.
Abstract 13566: Predictors of Progressive QRS Duration in Left Bundle Branch Block
Authors: Patel Nimai , Grondin Christopher , Nicklas J Matthew , Makki Tarek , Nicklas John M
Published: June 2023

Introduction:
QRS duration in patients with left bundle branch block (LBBB) predicts adverse clinical outcomes and response to cardiac resynchronization therapy (CRT). Changes in LBBB QRS duration over time have not been reported.

Hypothesis:
QRS duration in patients with LBBB changes over time and may be predicted by patient demographics and comorbidities.

Methods:
We retrospectively identified 450 patients with LBBB on an index ECG (QRS ≥120 msec) recorded between 1992 and 2000 and examined any follow-up ECGs recorded after approximately 1, 2, 3, 5, and 10 years. Piecewise linear interpolations were performed, and separate generalized linear models (GLM) with Schwartz Bayesian Criterion effect selection were used to relate baseline clinical variables to changes in QRS duration at follow-up.

Results:
The cohort was 53.1% male, average age 66.7 yr, and mean index ECG QRS duration 144.7 msec. Although there was significant variability, the duration of the mean QRS increased as a tapering exponential function of time (p<0.0001) with progressively less increase at later follow-up. Three additional variables strongly and independently predicted progressive lengthening of the QRS within the overall GLM: heart failure with reduced ejection fraction (HFrEF) (p<0.0001), index ECG QRS duration (neg) (p<0.0001), and male gender (p=0.0063).

In a subgroup of patients with an index ECG QRS <150 msec, these four GLM model variables also predicted the increase in QRS: time (p=0.0129), index QRS duration (p=0.0042), HFrEF (p=0.0001), and male gender (p=0.0084). (Equation, Figure below)

ΔQRS(t;i) = 50.22 - 9.71*e
-0.29*t
- 0.344*QRS(0;i) + 7.62*
1
HFrEF
(i) +5.12*
1
Male
(i) Adjusted R
2
= 0.103

Conclusions:
QRS duration progressively prolongs with time in patients with LBBB especially in patients with relatively narrow QRS and can be predicted by the presence of HFrEF and male gender. These predictors may be useful in better informing clinical prognosis and decisions regarding CRT.
Abstract 13568: Characterization of the Maladaptive QTc Response During the Treadmill Exercise Test in Untreated Patients With Long QT Syndrome
Authors: Neves Raquel , Bains Sahej , Bos Johan M , MacIntyre Ciorsti , Giudicessi John , Ackerman Michael J
Published: June 2023

Background:
Long QT syndrome (LQTS) is a genetic heart disease affecting about 1 in 2000 persons. Around 40% of patients with LQTS can have a nondiagnostic, normal QTc at rest. The treadmill exercise stress test (TEST) can help unmask patients with concealed LQTS with a characteristic maladaptive, paradoxical increase in QTc ( 460 ms) during the recovery phase. In fact, the recovery phase QTc value has been added to the latest diagnostic score for LQTS.

Objective:
To characterize the TEST-derived QTc profile of untreated patients with LQTS and determine its diagnostic and prognostic utility.

Methods:
Retrospective analysis was performed on TEST data derived from 249 patients with LQTS (129 LQT1, 64 LQT2 and 56 LQT3) untreated at the time of their TEST compared with 236 controls. The Bazett’s corrected QTc was calculated at rest (sitting, supine, and standing), during exercise at 1 min, 3 mins, and peak exercise, and during recovery phase at 1, 3 and 5 mins.

Results:
The mean resting QTc was significantly higher in LQTS patients (457 ± 30 ms) compared to controls (420 ± 24 ms; p<0.0001) as well as at every stage during the TEST (p<0.001). For LQT1 patients, highest QTc was observed at peak exercise (mean 496 ± 38 ms) and during the third minute of recovery phase (mean 500 ± 40 ms). In contrast, LQT2 patients showed the lowest QTc (mean 452 ± 48 ms) during peak exercise but the greatest QTc latency (QTc at 5 min - QTc at 1 min recovery; mean QTc latency 33 ± 77 ms; p=0.005) compared to controls. For LQT3, the mean QTc was greatest at rest compared to controls (p<0.001), and there was no difference during exercise and recovery phases. Among 162 LQT1 and LQT2 patients that presented with concealed LQTS, 119 (73%) showed a maladaptive QT response. ROC analysis showed that in patients with LQT1, a maladaptive QTc
>
523 ms at 3 min of recovery was highly predictive of breakthrough cardiac events (AUC 0.84; sensitivity 100%, specificity 72%); no such association was identified for LQT2 or 3.

Conclusions:
This comprehensive characterization of the QTc response before, during, and after a TEST in the largest untreated cohort of patients with LQTS provides important genotype-specific characteristics and can be used as a predictor for potential LQT1-triggered cardiac events after diagnosis and treatment.
Abstract 13579:
TAX1BP3
-Encoding TAX1-Binding Protein 3 is a Novel Genetic Cause of Autosomal Recessive Arrhythmogenic Cardiomyopathy and Causes Pro-Arrhythmic Ryanodine Receptor 2-Mediated Calcium Leak
Authors: Perelli Robin M , Cope Heidi , Behura Alexander S , Ponek Anna Q , Moya-Mendez Mary , Sun Bo , Kurzlechner Leonie , Ezekian Jordan E , Yang Qixin , Campbell Michael J , Spector Zebulon Z , Rehder Catherine , Goldstein David B , Tang Paul C , Shashi Vandana , Landstrom Andrew P
Published: June 2023

Introduction:
Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease where fibrofatty tissue replaces healthy myocardium. AC predisposes to ventricular arrhythmias and sudden cardiac death. We identified biallelic variants in the
TAX1BP3-
encoded tax1-binding protein 3 (TAX1BP3) in a genetically elusive family with AC. TAX1BP3 has putative roles in canonical Wnt signaling, but its function in the heart is unknown. Our goal is to identify novel mechanisms of AC development to develop therapeutics to mitigate or reverse disease progression.

Hypothesis:
We hypothesize that genetic loss of
TAX1BP3
suppresses normal canonical Wnt-signaling in the heart, allowing pathologic remodeling and arrhythmogenesis associated with AC development.

Methods:
Whole exome sequencing of an AC genotype-negative family was performed. Induced pluripotent stem cells generated from peripheral blood mononuclear cells (PBMCs) from were differentiated into cardiac myocytes (iPSC-CMs) for 3 kindred. Line scans using CAL-520-labeled calcium were conducted with a Zeiss confocal microscope to capture calcium sparks after pacing iPSC-CMs. Sarcoplasmic reticulum store was measured after adding 10mM caffeine to iPSC-CMs. Adipogenesis in iPSC-CMs was visualized by immunofluorescence with Nile Red stain.

Results:
TAX1BP3
M78T/del
variant co-segregates with AC in an autosomal recessive inheritance mode in an AC genotype-negative family. TAX1BP3
M78T/del
PBMCs had reduced proliferation and qPCR from whole blood identified decreased canonical Wnt signaling. iPSC-CMs
M78T/del
have decreased intracellular calcium store, increased adipogenesis, and increased calcium leak associated with spontaneous calcium release events. Small molecule Wnt-activator BML-284 normalized calcium leak in iPSC-CMs
M78T/del
.

Conclusions:
Our results demonstrate that loss-of-function of TAX1BP3 is pro-arrhythmic and driven by calcium leak in iPSC-CMs which can be rescued by Wnt activation. We identified a new AC-associated gene, TAX1BP3, that has not been studied in the heart. Further studies are needed to explore the impact of TAX1BP3 on cardiac Wnt signaling, but our findings implicate Wnt activation as a possible treatment for AC - currently an untreatable, deadly disease.
Abstract 13581: Prognostic Value of Left Ventricular Global Longitudinal Strain for Early Prediction of Cancer Therapy-Related Cardiac Dysfunction
Authors: Kar Julia , Bryant A'Mere , Chouhdry Anam , Cohen Michael , Revere Cherie , McQuiston Samuel , Malozzi Christopher
Published: June 2023

Introduction:
This prospective study aimed to determine if MRI-imaging and Artificial Intelligence (AI)-based computation of global longitudinal strain (GLS) in the left ventricle (LV) is an early predictor of cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients.

Hypothesis:
To show with risk analysis that GLS is an independent prognosticator of CTRCD when compared to LV ejection fraction (LVEF) with the patient cohort administered antineoplastic chemotherapy treatment.

Methods:
Motion-encoded data with Displacement Encoding with Stimulated Echoes (DENSE) MRI were acquired on 32 breast cancer patients at baseline and 3- and 6-months follow-ups after chemotherapy. Automated image segmentation for chamber quantification and phase-unwrapping in the LV occurred with two DeepLabV3+ fully convolutional networks (FCNs), and 3D strains computed with the meshfree Radial Point Interpolation Method. CTRCD (including adverse cardiac events and cardiotoxicity) risk analyses with the measured clinical, chamber quantification, and strain parameters were conducted with univariable and bivariable Cox proportional hazard (PH) regressions.

Results:
GLS worsened from baseline to the 3- and 6-months follow-ups (-19.1 ± 2.1% vs. -16.0 ± 3.1% vs. -16.1 ± 2.9%, P<0.001) (Fig. 1). With univariable Cox regression, the 3-months follow-up GLS was independently associated as an agonist (hazard ratio [HR]-per-SD: 2.1; 95% CI: 1.4-3.1, P<0.001) and LVEF as protector (HR-per-SD: 0.8; 95% CI: 0.7-0.9, P<0.001) for CTRCD occurrence. In bivariable regression, GLS (HR-per-SD: 2.0; 95% CI: 1.2-3.4, P=0.01) was an independent predictor of CTRCD regardless of LVEF (HR-per-SD: 1.0; 95% CI: 0.9-1.2, P=0.9) as covariate.

Conclusions:
The end-point risk analyses show that LV GLS is an early CTRCD predictor independent of LVEF in breast cancer patients treated with antineoplastic chemotherapy. GLS should be a standard metric for the clinical diagnosis of CTRCD.