bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16900: Predictors of Cardiovascular Health Trends in College Students
Authors: Alshurafa Nabil , Jain Jayalakshmi , Spring Bonnie , Pfammatter Angela
Published: April 2024

Introduction:
The American Heart Association (AHA) Life’s Simple 7 (LS7) is a metric that is known to predict cardiovascular disease. What is unknown are the factors that predict cardiovascular health (CVH) scores over time, and what patterns of CVH scores are most common. Machine learning algorithms can identify these patterns using a data-driven approach. Our objective was to identify most common risk patterns over time and assess smartphone usage statistics to identify their predictors.

Methods:
We recruited 303 Northwestern University undergraduates and cluster randomized them to one of two health intervention groups. The intervention group focused on cardiovascular health behaviors (n=130) were provided with an app that delivered an intervention targeting the LS7 metrics smoking, physical activity, fruit and vegetable consumption, and weight. All participants reported levels of four behaviors weekly. Health scores were calculated as the sum of metrics meeting ideal criteria; CVH behaviors scored per the AHA LS7. Behavioral patterns over time used in the K-means unsupervised clustering algorithm include the mean, slope and variance of trends. K-Silhouette was used to determine optimal number of clusters, and predictors from the CVH intervention app use data were examined to determine which contributed to distinguishing between clusters.

Results:
We identified four clusters using K-silhouette criteria (Figure 1). Of the smartphone meta-data collected, 2 were significantly different between clusters. We observed greater number of interactions/week (p < .0001) and greater number of app-use days/week (p < .0001) for both “healthy-steady” and “improvers” as compared with “decliners” and “unhealthy-steady” clusters.

Conclusions:
Our findings suggest that frequency and consistency in health behavior monitoring predict healthier trends over time. These usage behaviors may be targets for behavioral interventions. Further work will investigate if these factors meaningfully predict CVH at the end of a 2 year intervention. In the future, predictors could be used as signals that an individual needs behavioral intervention.
Abstract 16908: Valve Calcium Severity is Unrelated to Diet in Severe Aortic Stenosis
Authors: Du Run , Williams Mathew , Taylor Zachary , Zhao Zhen-Gang , Staniloae Cezar , Saric Muhamed , Pushkar Illya , Neuburger Peter , Querijero Michael , Vainrib Alan , Hisamoto Kazuhiro , Amoroso Nicholas , Collins Tara , Clark Emily , Sin Danielle , Shah Binita , Lee Hanah , Vidal Samantha , Bamira Daniel , Benenstein Ricardo , Jilaihawi Hasan
Published: April 2024

Introduction:
Diet and hyperlipidemia are correlated to coronary atherosclerosis, whose progression may be modulated by statin therapy. Aortic stenosis and calcification are atherosclerotic processes but they are not influenced by statin therapy. Limited data is available on the influence or correlates of diet on aortic valve calcification.

Hypothesis:
We hypothesized that diet may be related to aortic valve calcification (AVC) on computed tomography (CT).

Methods:
Consecutive patients with severe or critical aortic stenosis (AS) were evaluated in a busy Heart Valve Clinic and underwent both detailed dietary evaluation with a rate your plate (RYP) questionnaire and a high resolution CT as part of their work-up for valvular intervention (medical therapy, surgical or transcatheter aortic valve replacement). AVC volume was quantified using a validated method based on a higher threshold of detection from the contrast CT (850 Hounsfield Units, HU-850). Dietary data was separated according to patients in the highest tertile of AVC.

Results:
A total of 117 patients were evaluated. The upper tertile threshold of AVC was identified as 284.5 mm
3
(figure: examples above and below this threshold are shown). Higher scores on RYP identify heart-healthy choices. There were no differences in the overall total RYP score or percentages of specific heart-healthy dietary choices according to AVC severity (table).

Conclusions:
AVC severity is unrelated to heart-healthy dietary choices in patients with aortic stenosis.
Abstract 16945: Identification of Peripheral Blood Mononuclear Cell Subpopulations in Chronic Left Ventricular Dysfunction Patients With Improved Functional Outcomes: A Biorepository Evaluation From the CCTRN FOCUS Trial
Authors: Chacon Lourdes I , Resende Micheline M , Gahremanpour Amir T , Perin Emerson C , Sampaio Luiz C , Moye Lem T , Willerson James T , Taylor Doris A
Published: April 2024

Background:
Although cell therapy could potentially slow or reverse progression of chronic ischemic heart failure (HF), clinical trials of bone marrow-derived mononuclear cells (BM-MNC) have met with minimal success. It is unknown why some patients improve (i.e. improvers) and others do not (i.e. non-improvers). B cell numbers, in fact, have been associated with improvement after acute myocardial infarction (MI). We hypothesized that improvers have a higher percentage of B cells in peripheral blood (PB) vs. non-improvers after study treatment.

Methods:
We used flow cytometry to evaluate temporal changes in the frequency of PB subpopulations after BM-MNC or placebo therapy in HF patients enrolled in the FOCUS-CCTRN trial. PB was collected at day 0 (baseline) and days 1, 30, 90, and 180 from consented participants. Cohort 1 (n=17) patients, who improved in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (ESV), and maximal oxygen consumption (VO
2
max) during the 6-month course, were compared to patients who declined in the above three outcomes, cohort 2 (n=11). Linear mixed model was used to determine the changes over time in each cell population. The difference between each time point to day 0 was calculated as linear contrast.

Results:
Cohort 1 had a higher frequency of B cells (CD45+CD19+) at day 0 (15.24±7.55 vs. 8.95±3.49, p=0.002), day 1 (14.67±5.53 vs. 8.78±4.51, p=0.003), day 90 (14.98±6.64 vs. 8.49±4.33, p=0.006) and day 180 (13.44±7.85 vs. 8.07±4.34, p=0.033) and regulatory B cells (CD19+CD11B+) at day 0 (2.06±1.20 vs. 1.09±0.58, p=0.011) and day 90 (2.49±1.50 vs. 1.32±0.62, p=0.016) when compared to cohort 2. Both cohorts had an increase in CD11B+ at day 1 when compared to baseline (91.53±3.43 vs. 93.09±3.69, p=0.020) (92.01±3.63 vs. 94.60±8.70, p=0.005), which remained higher in cohort 2 until day 30 (92.01±3.63 vs. 93.92±1.91, p=0.020).

Conclusion:
A higher frequency of B cells and subsets was observed in PB of patients who improved independent of treatment. These data support prior findings of the importance of B cells in recovery after MI and suggest an important relationship between the humoral immune system and HF.
Abstract 16946: Proteomics Identifies Inflammatory, Lipid, and Cell Proliferative Pathways in Diastolic Dysfunction in HIV: A CHART Substudy
Authors: Shah Svati H , Kwee Lydia , McNulty Steven , Hsue Priscilla , Desvigne-Nickens Patrice , Shah Sanjiv J , Hernandez Adrian F , Braunwald Eugene , Butler Javed
Published: April 2024

Background:
Anti-retrovirals have shifted the epidemiology of heart failure in HIV from one of systolic dysfunction to that of diastolic dysfunction (DD), but the underlying mechanisms are incompletely understood. We hypothesized that a proteomics analysis could identify novel biomarkers of DD in HIV.

Methods:
The NIH-funded Characterizing Heart Function on Anti-Retroviral Therapy (CHART) study enrolled HIV-infected individuals through the Heart Failure Network (HFN) with the goal of identifying clinical, imaging, and molecular markers of DD in HIV. Using the Olink platform (proximity extension assay technology), we profiled 977 proteins in frozen plasma samples from the 195 individuals enrolled in CHART. Logistic regression was used to compare protein levels between DD cases (N=94) and controls without DD (N=101).

Results:
We observed differences in many proteins between DD+ and DD- including inflammation (EDA2R, TNF-R1, TNFRSF19, VSIG4), lipid metabolism (leptin, FABP4, CLMP, PON3, PLIN1), cell proliferation and cell-cell adhesion (IGFBP6, TGFBR2, NOV, INHBC), and extracellular matrix (COL18A1, PRELP, HSPG2, COL1A1) proteins (p= 1.4x10
-3
– 1.2x10
-4
). Of these, eight met false discovery rate (FDR) adjustment (EDA2R [tumor necrosis factor receptor superfamily member], leptin, FABP4 [fatty acid binding protein 4], CLMP [cell-cell adhesion, adipocyte differentiation], IGFBP6 [IGF binding protein involved in cell proliferation], TGFBR2 [transforming growth factor binding receptor 2], NOV [cell proliferation and adhesion], INHBC [member of TGF-β superfamily involved in cell development], and adrenomedullin, all FDR p<0.05). Adjustment for BMI, SBP, age, creatinine attenuated results (nominal p=0.24 – 1.3x10
-3
). Pathway analysis identified extracellular space, TNF activated receptor activity, cytokine-cytokine receptor interaction, collagen trimer, glycosaminoglycan binding, and response to chemical stimulus pathways (FDR P=5x10
-4
- 5x10
-7
).

Conclusions:
Using a high throughput proteomics platform we have identified proteins that differentiate HIV-infected individuals with DD from those without DD, highlighting potential biomarkers and molecular mechanisms mediating DD in HIV for further investigation.
Abstract 17000: Concomitant Transthyretin Cardiac Amyloidosis and Aortic Stenosis: A Systematic Review and Meta-Analysis
Authors: Sleiman Jose , Khan Mohammad S , Usman Muhammad S , Munoz Ezequiel , Ranka Sagar , Muhammad Hassan N , Ijeli Anthonia , Fatima Kaneez , Raza Sajjad , Deo Salil
Published: April 2024

Background:
Concomitant aortic stenosis (AS) and transthyretin cardiac amyloidosis (TTR-CA) in elderly population remains poorly described. Moreover, prognosis in patients with TTR-CA who undergo aortic valve replacement (AVR) is uncertain. We conducted a systematic review and meta-analysis to gain further insight.

Methods:
Medline, Scopus and Embase were searched from inception of these databases to May 2018 for studies reporting prevalence of TTR-CA in AS patients (surgical or trans-catheter) or prognosis of TTR-CA patients who received AVR. Pooled estimates were calculated using a random-effects model.

Results:
Eight studies comprising of 598 patients with AS (mean age: 75.1; males: 57.5%) were included. 63 cases had concomitant TTR-CA, with a pooled prevalence of 11.5% [6.6, 17.4]; I
2
=74%. Four studies (mean age: 76.5; males: 72.7%)] reported prognosis in patients with TTR-CA after AVR. Over a mean follow-up duration of 2.4 years, 14 of 37 patients suffered all-cause mortality (pooled incidence of mortality: 37.5% [22.8, 53.4]; I
2
=0%).

Conclusion:
Current meta-analysis suggests that TTR-CA in AS patients is relatively common, and has high risk of all-cause mortality after AVR. However, low event rates with wide confidence interval limit us from making conclusive statements. Further studies are needed to explore this association.
Abstract 17004: Right Bundle Branch Block (RBBB) is Associated With Poor Prognosis in Patients With Anterior Wall ST Elevation Myocardial Infarction (AWMI): A Nationwide Study Using the National Inpatient Sample (NIS)
Authors: Shrivastav Rishi , Pati Prateeth , Perimbeti Stuthi , Tamis-holland Jacqueline
Published: April 2024

Introduction:
Blood supply to the right bundle comes from the left coronary circulation, which also supplies other major dominant areas of the myocardium. Intuitively, RBBB in the setting of AWMI would indicate more extensive myocardial involvement and thus portend a worse prognosis. Limited previous studies on RBBB in AWMI have demonstrated adverse outcomes, however large scale observational studies are still lacking. We hypothesized that as compared to patients without RBBB, the presence of RBBB in patients with AWMI would be associated with increased morbidity and mortality.

Methods:
The NIS was analyzed to identify adult admissions (>18 years of age) with a primary diagnosis of AWMI (ICD-9 codes 410.0 and 410.1) between 1999 and 2014 (N=219,302 weighted N=1,075,874). Using ICD-9 code 426.4, these admissions were further stratified for RBBB. Using Chi-Square test, we performed bivariate analysis to determine in-hospital mortality across various categorical variables. Multivariate analysis using Cox Proportional Hazard regression was then performed to control for confounders and determine the hazard of acute heart failure (428.21 and 428.23), complete heart block (426.0), implantation of a permanent pacemaker (37.71, 37.81,37.82, 37.83 and 00.51) and in-hospital mortality for patients with AWMI and RBBB as compared to patients with AWMI and no RBBB.

Results:
Out of the 1,075,874 admissions with primary diagnosis of AWMI, about 1.78% (19,153) had RBBB. The mean age of patients with and without RBBB was 69.49 years and 68.46 years (p<0.001) respectively. As compared to patients with AWMI and no RBBB, mortality was significant higher for patients with AWMI and RBBB [9.19% (97,138) vs 15.30% (2930); p<0.0001]. After adjustment, RBBB in the setting of AWMI was associated with a 60% percent increase in the risk of in-hospital mortality (Hazard Ratio 1.60, 95% CI 1.54-1.66; p<0.001) and a higher likelihood for other complications (Table 1).

Conclusions:
The presence of RBBB in the setting of an AWMI is a significant independent predictor of poor prognosis, including a higher rate of acute heart failure, complete heart block and the need for a permanent pacer, as well as a higher in-hospital mortality
Abstract 12361: Yelp Data on Fast Food and Exercise Facilities Predict Cardiovascular Events
Authors: Cabrera Javier , Wang Jin , Zinonos Stavros , Kostis William J , Subramanian Krishnamurthy , Kostis John B ,   For the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: April 2024

Introduction:
Yelp includes information on nearly all businesses and socioeconomic data in any region of the United States. This database maybe used to obtain socio-economic data that may affect the incidence of cardiovascular disease. This project focuses on access to poor quality food such as fast food and lack of exercise that may have a negative impact in cardiovascular disease. A dataset including the number of fast-food restaurants, non-fast-food restaurants, grocery stores, gyms, other fitness facilities, nursing homes, and pharmacies were aggregated by zip code. In addition, demographic variables such as gender, age, and comorbidities were included. Cardiovascular outcomes were obtained from the Myocardial Infarction Data Acquisition System (MIDAS) database of all hospitalizations in New Jersey. Ten percent of the zip codes that did not have sufficient data were excluded.

Hypothesis:
Yelp variables will predict the occurrence of stroke, myocardial infarction and heart failure requiring hospitalization.

Methods:
The yelp data were used to predict three outcomes as identified by the MIDAS database: stroke, myocardial infarction and heart failure requiring hospitalization. Linear models followed by stepwise selection of the predictors were used to define the final models used in these analyses.

Results:
The results of the regressions in the table show that the number of fast-food restaurants and nursing homes were associated with increased frequency of all 3 outcomes controlling for population size. Access to grocery stores, gyms, and other fitness facilities are associated with lower rate of stroke, myocardial infarction and heart failure requiring hospitalization.

Conclusions:
Socioeconomic variables obtained from the yelp database predicted the occurrence of stroke, myocardial infarction and heart failure requiring hospitalization with high degree of accuracy.
Abstract 12379: Distal Waveform Patterns in the Fontan Circulation Are Related to Pulmonary, Liver and Cardiac Function
Authors: Ferrari Margaret R , Schafer Michal , Hunter Kendall S , Di Maria Michael V
Published: April 2024

Introduction:
The lack of a sub-pulmonary ventricle in patients with a Fontan circulation leads to irreversible circulatory decline. Our group has determined that single-site waveform analysis correlates to clinical features of Fontan patients. The goal of this study was to determine if multi-site waveform analysis contributes to detecting early cardiovascular decline.

Methods:
Patients with a Fontan circulation that underwent cardiac MRI were included in this retrospective study. Hemodynamic flow curves were measured in the ascending aorta (AAo N=94), superior vena cava (SVC N=82), inferior vena cava (IVC N=91) and left pulmonary artery (LPA N=85). Flow curves were interpolated to equal temporal phases and were used to create three data matrices of proximal and distal waveforms. Principal component analysis (PCA), a data transformation method used to obtain a wieldy number of ranked components (the PCs) representing the variance of the input data, was performed on each matrix. PCs were correlated to clinical measures of current patient status.

Results:
PCs that accounted for more than 20% of the variance in a data matrix are reported (Pearson’s
r, p
) in Table 1.

Conclusions:
These results indicate that increased liver enzyme levels, with a possible link to Fontan associated liver disease, are related to increased diastolic SVC flow and increased volume in the SVC and IVC throughout the cardiac cycle. An increased diastolic SVC flow profile relates to worsening pulmonary function and oxygen consumption during exercise. A decreased ventricular-vascular coupling ratio is related to increased IVC volume and low oxygen saturations may be indicative of increased LPA volume. Little variations were apparent in the AAo waveforms, suggesting cardiovascular decline may appear distally prior to proximal presentation. We have, for the first time, evaluated multi-site flow patterns and correlated them to functional status in one of the largest Fontan patient cohorts to date.
Abstract 12408: Fragmented QRS is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study
Authors: Chan Jeffrey Shi Kai , Zhou Jiandong , Lee Sharen , Li Andrew , Tan Martin , Leung Keith S , Jeevaratnam Kamalan , Liu Tong , Zhang Qingpeng , Tse Gary
Published: April 2024

Introduction:
Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure.

Hypothesis:
fQRS is predictive of adverse clinical outcomes.

Methods:
This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2000 and 31st December 2019 at a tertiary center in Hong Kong. The baseline ECG was analysed. QRS complexes (<120 ms) with fragmented morphology in ≥2 contiguous leads were defined as fQRS. The primary outcome was a composite of cardiovascular mortality, VA, and sudden cardiac death (SCD). The secondary outcomes were the components of the primary outcome, myocardial infarction, and new-onset atrial fibrillation.

Results:
In total, 2192 patients were included, of whom 179 (8.20%) exhibited fQRS. The follow-up duration was 5.63±4.09 years. fQRS in any leads was associated with a higher risk of the primary outcome (adjusted hazard ratio (HR) 1.541 [1.185, 2.004], p=0.001; Figure A), but not myocardial infarction or new-onset atrial fibrillation. fQRS in >2 contiguous leads was an independent predictor of the primary outcome (HR 1.841 [1.119, 3.029], p=0.016; Figure B), driven by a higher risk of SCD (adjusted HR 2.679 [1.252, 5.729], p=0.011). In patients without ischaemic heart disease (N=1396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.336 [1.343, 8.282], p=0.009, and 1.928 [1.135, 3.278], p=0.015, respectively), but not cardiovascular mortality (adjusted HR 1.049 [0.662, 1.662], p=0.839).

Conclusions:
fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies.
Abstract 12409: Two-Dimensional Speckle Tracking of the Ascending Aorta: A Novel Approach to Evaluate Arterial Stiffness in Pediatric Patients With Repaired Conotruncal Abnormalities
Authors: Goyal Anmol , Parthiban Anitha , White David A , Forsha Daniel E , Aly Doaa
Published: April 2024

Introduction:
Children with repaired conotruncal abnormalities (rCTA) are at risk for progressive aortic dilation and arterial stiffness even after surgical correction. Pediatric data regarding use of 2D speckle tracking echocardiography (STE) for assessment of arterial stiffness is lacking. Our aim was to assess the feasibility and utility of 2D-STE derived ascending aorta (AAo) stiffness in children with rCTA.

Methods:
This was a prospective study, where pediatric patients with rCTA were included and compared to age and sex matched healthy controls. AAo strain, stiffness index and distensibility were measured using M-mode echo across the short axis of the AAo at the level of the right pulmonary artery. Peak AAo global circumferential strain (GCS) was measured using the left ventricle dedicated GCS algorithm by TomTec software version 4.6 SP3, CPA.

Results:
Total of 19 cases [13 (68%) with Tetralogy of Fallot, 4 (21%) with transposition of great arteries and 2 (10.5%) with truncus arteriosus], with mean age of 10.6 ± 4.2 yr and 17 matched controls have been enrolled to date. No subjects were excluded due to poor strain tracking. Patients with rCTA showed statistically significantly lower AAo GCS (8.2 ± 1.4 vs 15.2 ± 1.3), M-mode AAo strain (12.2 ± 5.3 vs 19.6 ± 3.8), AAo distensibility (3.6 ± 1.1 vs 6.1 ± 1.2), and higher AAo stiffness index (5.5 ± 2.1 vs 3.1 ± 0.6) than controls; fig 1. AAo GCS had strong correlation with age since surgical repair (r -0.8, p<0.001); fig1. AAO distensibility and AAo stiffness index had moderate correlation (r -0.5; P<0.05, r 0.4; P<0.05 respectively) while M-mode AAO strain had weak correlation (-0.3 p=0.2) with age.

Conclusions:
2D-STE measured AAo arterial stiffness is technically feasible in pediatric patients post rCTA and controls with significant between-group difference and a stronger correlation with age than the traditional measures of aortic stiffness. This may represent a new index in evaluating vascular biomechanics in pediatrics.
Abstract 12426: Influence of Body Mass Index in Donor Recipient Size Mismatch in Pediatric Heart Transplantation
Authors: Lowrey Laura , Trivedi Jaimin , Ramakrishnan Karthik , Sinha Pranav , Deshpande Shri
Published: April 2024

Introduction:
Body weight has been the traditional metric for matching donor and recipient size for pediatric heart transplantation (pHT). However, the impact of such mismatch is not well established. We hypothesized that mismatch in compound measures such as body mass index (BMI) or body surface area (BSA) rather than weight, may impact outcomes of pHT and therefore should be used for donor-recipient size matching.

Methods:
Analysis of the United Network for Organ Sharing database limited to pHT recipients was performed. Donor and recipient mismatch tertiles were created for weight, BMI, and BSA ratios. Differences in recipient characteristics between each tertile were studied using univariate analysis. Multivariable analysis was used to assess the impact of each mismatch on one-year survival. Kaplan Meier analysis was used to assess overall survival.

Results:
A total of 4,465 pHT patients were available and included in the analysis of which 43% had congenital heart disease (CHD). Overall, those with low donor-recipient ratio for BMI were more likely to be younger recipients, less likely to be Caucasian and be on ECMO (all p<0.01). In both CHD and non-CHD cohorts, multivariable regression analysis showed that use of ECMO (CHD OR 3.97; non-CHD OR 3.24), presence of liver dysfunction (CHD OR 1.10; non-CHD OR 1.11), and low donor to recipient BMI ratio (compared to normal) (CHD OR 1.70; non-CHD OR 2.28) were the only predictors of one-year mortality (all p <0.001). Low BMI ratio was also associated with worse long-term survival in non-CHD groups, but not in the CHD cohort. This finding probably reflects inferior overall outcomes in the CHD cohort. Weight and BSA ratio did not predict one year or long-term survival.

Conclusions:
Traditional matching practice using weight may be inadequate and use of BMI matching may provide improved donor-recipient matching. Use of low BMI donors compared to recipients may predict poor early and long-term survival and therefore should be avoided in pediatric heart transplantation. Further refinement of matching may be needed in specific recipient populations.
Abstract 12427: Insertable Cardiac Monitors for Atrial Fibrillation Detection in Patients With Ischemic Stroke: A Meta-Analysis of Randomized Clinical Trials
Authors: Kheiri Babikir , Sanghai Saket , Alhamoud Hani , Osman Mohammed , Stecker Eric , Henrikson Charles , Nazer Babak
Published: April 2024

Introduction:
The benefits of insertable cardiac monitor (ICM) in patients with recent strokes remains unknown..

Objective:
To evaluate the role of ICM for AF detection in patients with recent stroke.

Methods:
Database search was performed for RCTs. The primary outcome was the time to first detection of AF at 1-year follow-up. Secondary outcomes included the rates of recurrent stroke/TIA and deaths. We calculated the hazards ratios from the extracted Kaplan-Meier curves reported by each trial. Cox proportional hazards model was analyzed following testing of the proportional-hazards assumption (residual Schoenfeld test).

Results:
We included 3 RCTs with a total of 1,233 patients (613 ICM group vs 620 control group who received routine clinical care of ECGs and ambulatory ECG monitoring ranging from 24 hour to 30 days). The mean age was 64.5 ± 11.3 yrs, 37.9% female, 69.3% hypertensive, and 25.9% diabetic with CHA
2
DS
2
-VASc score of 4.6 ± 1.6. The time from index event to randomization was 31.8 ± 42 days. The threshold for AF detection was >30 sec. At 1-year, AF was detected in 12.9% of patients in the ICM group versus 2.4% in the control group (HR=5.3; 95% CI=3.1 - 9.2; p<0.01; NNT 10). There were no significant differences between groups in terms of recurrent stroke/TIA and death (p>0.05). Of the 94 patients with detected AF, 83 patients (88.3%) received oral anticoagulants. Among the 560 ICMs that were inserted, 6 (1.1%) devices were removed due to infection at the insertion site or pocket erosion.

Conclusions:
Among patients with ischemic stroke and no prior evidence of AF, ICM was associated with a significantly higher rate of AF detection over 1-year follow-up. Further large trials with long-term follow-up are needed to establish the association of ICM-detected AF with recurrent strokes, to determine the effect of subsequent anticoagulation in this scenario, and to validate their cost-effectiveness.
Abstract 12435: Impact of Non-Cyanotic Congenital Heart Disease in the Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide In-Patient Sample Analysis
Authors: Patel Neel , Amgai Birendra , Hajra Adrija , Sandipan Chakraborty , Patel Zeel , Aryal Binit , Khalid mazin , Paul Prodip Kumar , Singh Sukhvir , Aronow Wilbert S
Published: April 2024

Introduction:
Reported total congenital heart disease (CHD) birth prevalence has increased substantially over time. It varies from 1.9 to 9.3 per 1000 live births based on geographic location. Aortic stenosis(AS) is a common pathology associated with advanced age. It is found to be in the 11.7-15.0% population over 75-year-old cohort. TAVR is the preferred intervention for severe AS patients. It is now being performed in extreme- to low-risk patients. We sought to determine the impact of non-cyanotic CHD in the patients undergoing TAVR.

Method:
We reviewed National Inpatient Sample (NIS) database from 2016-2018 using Stata 16.0. The NIS is the ICD-10-CM code-based healthcare database. Patients who underwent TAVR were identified and divided into with and without CHD. Multivariate logistic regression, linear regression, and student t-tests were used for analysis.

Results:
Among 134,195 patients who underwent TAVR, 1,135(0.9%) were having NCHD. Patients with NCHD were younger (77.9±11.2 vs. 79.6±8.4 with P=0.02) with equal gender distribution. NCHD patients had longer lengths of stay than others (5.9±6.3 vs. 4.3±5.4 with P=<0.001) and were associated with higher co-morbidities such as anemia, atrial fibrillation, and pulmonary hypertension. 55 (4.9%) patients died in the NCHD group, whereas 1956 (1.5%) patients died in the other. The difference was found to be statistically significant on multivariant logistic regression analysis. (OR:2.9, 95%-Confidence Interval: 1.6-5.3, P=<0.001). Complications such as post-operative shock, AMI, AKI, bleeding requiring transfusion, acute respiratory failure, cardiogenic shock, and pacemaker implantation were comparable between both groups. The mean total charge for the NCHD group was $68688, whereas others were $ 54794.

Conclusion:
NCHD was associated with higher in-patient mortality and LOS in the patients undergoing TAVR for severe AS. However, Complications were comparable in patients with and without NCHD.
Abstract 12442: Extracellular Vesicles Engineered to Target Cardiomyocytes Demonstrate Improved Cardioprotection in a Mouse Model of Myocardial Infarction
Authors: Mentkowski Kyle I , Manzanero Cody A , Eagler Lisa A , Lang Jennifer K
Published: April 2024

Background:
Cardiomyocyte (CM) cell death plays a significant role in left ventricular (LV) remodeling and cardiac dysfunction following myocardial infarction (MI). While extracellular vesicles (EVs) secreted by cardiosphere-derived cells (CDCs) have shown efficacy in promoting cardiac repair in large animal models of MI, their translational potential is limited by their biodistribution. To improve cardiac uptake, we previously engineered CDC-derived EVs to express a CM-specific binding peptide (CMP) on their surface. CMP-EVs demonstrated improved cardiac retention
in vivo
and decreased CM apoptosis
in vitro
when compared with non-targeted EVs. We hypothesized that targeting therapeutic EVs to CMs would result in further reduction of CM cell death
in vivo
and improvement in cardiac function post-MI.

Methods:
EVs were isolated from serum-free media as previously described and characterized by established protocols for size, morphology, and protein expression. To determine if CMP-EVs could enhance cardioprotection
in vivo
, we induced acute MI in adult C57BL/6 mice and randomized them to receive 1) EVs, 2) CMP-EVs or 3) vehicle control by IV and intramyocardial delivery according to approved institutional protocols. LVEF was assessed by echo at 1- and 28-days post-MI and tissue samples processed for assessment of EV biodistribution and histological endpoints.

Results:
CMP-EVs demonstrated superior cardiac targeting (IV route) and retention (intramyocardial route) when compared with control EVs 24 hours post MI (fold change of 1.8 ± 0.23 and 4.8 ± 2.3 respectively; n=8-10 mice/group, mean ± SEM, p<0.05, t-test). Intramyocardial administered CDC-derived EVs improved LVEF compared with vehicle control treated animals 4 weeks post-MI (55 ± 2% vs 44 ± 2%). Mice treated with CMP-EVs demonstrated a statistically significant improvement in LVEF (64 ± 5%) compared with non-targeted EVs (n=6-8 mice/group, mean ± SEM, p<0.05, one-way ANOVA).

Conclusions:
Targeting CMP-EVs to CMs post-MI improved cardiac function compared with control EVs, highlighting the potential importance of CMs as a target cell for CDC-derived EV therapy and demonstrating a strategy to further optimize therapeutic EV delivery to increase efficacy and decease off-target effects.
Abstract 12481: Automated Assessment of Video Quality and Ejection Fraction in Emergency Department Point-of-Care Echocardiograms
Authors: He Bryan , Dash Dev , Duanmu Youyou , Tan Ting Xu , Ouyang David , Zou James
Published: April 2024

Introduction:
Bedside point of care ultrasound (POCUS) has greatly improved bedside emergency medicine through improved cost-effectiveness, prompt availability to augment physical exams, and the ability to evaluate unstable patients at the bedside. While most emergency rooms have ultrasound machines, there is severe underutilization of this bedside imaging modality, in part due to the lack of formalized ultrasound training in most emergency room physicians. Accuracy of bedside assessment of cardiac function remains variable and operator dependent.

Methods:
To aid with interpreting and improving the quality of emergency room transthoracic echocardiograms (TTEs), we train a deep learning algorithm to take POCUS videos and identify patients with a reduced ejection fraction. Our algorithm also identifies which POCUS videos are low quality and need to be retaken. We curated all patients who received POCUS echocardiograms in the apical 4 chamber view from Stanford ED between July 2020 and November 2020, including 927 videos from 574 patients recorded from three different machines (Phillips, GE venue, and Mindray). Each video is annotated with their ejection fraction (775 normal, 152 reduced) and their quality (768 sufficient, 159 low).

Results:
Using these videos, we trained and evaluated our model using 10-fold cross-validation over patients, achieving an AUROC of 0.92 (0.89 - 0.94) for predicting ejection fraction on videos of sufficient quality and an AUROC of 0.81 (0.78 - 0.85) for predicting video quality. We use our model to identify videos with qualities ranked in the top quartile and find that on these videos, our model achieves an AUROC of 0.94 (0.91 - 0.97).

Conclusions:
This algorithm can be run on commodity hardware in real-time, aiding in ultrasound education and significantly decreasing the barrier to entry into ED POCUS for TTEs. the quality predicted by the model can be given as feedback to physicians to aid with improving video quality and image acquisition.
Abstract 12563: The Trajectory of Platelet Factor 4 in Acute Myocardial Infarction and the Impact of PCSK9-Inhibition
Authors: Ziogos Efthymios , Williams Marlene S , Vavuranakis Michael , Blaha Michael J , Jones Steven R , Schulman Steven P , Lai Shenghan , Gerstenblith Gary , Leucker Thorsten M
Published: April 2024

Introduction:
Increased platelet activity during the peri- and early post-infarction period may contribute to adverse outcomes during that time. Platelet factor 4 (PF4) promotes coagulation and inflammation. The trajectory of PF4 and the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on that trajectory are unknown.

Hypothesis:
Early administration of the PCSK9 inhibitor evulocumab, added to dual anti-platelet therapy, inhibits a rise in PF4 during the early post-infarction period.

Methods:
Participants from the Evolocumab in Acute Coronary Syndrome trials (EVACS; NCT03515304, NCT04082442), with a NSTEMI and a troponin-I of
>
5 ng/ml or a STEMI were randomized to placebo or to 420 mg SQ of evolocumab within 24 hours of hospitalization. We performed serial ex vivo serum PF4 levels obtained at baseline (prior to study drug administration), and at days 1 and 30 and PF4 values were normalized to total platelet count. Normally distributed data were summarized using means and standard deviations and non-normally distributed data using medians and interquartile ranges.

Results:
Twenty-three participants were randomized to placebo and 23 to evolocumab. Mean age was 60±13 years, 48% were women, 22% were African American and 96% were on dual anti platelet therapy. Baseline PF4 concentrations (expressed as ng/1k platelets) did not differ between the two groups (placebo: 9.3 [4-12] vs evolocumab 8.0 [4-12], p=0.8). There was no significant change in PF4 in the placebo group from baseline to day 1 but a significant increase to 13.0 [11-14], p<0.01 (baseline vs 30 days) at 30 days (+32%). In contrast, there were no significant changes from baseline in the evolocumab group at either of the timepoints. At 30 days PF4 was higher in the placebo group 13.06 [11-14] than the evolocumab group 10.7 [6-13], p=0.04. Further analysis of results in the evolocumab group did not show any significant changes in PF4 based on the type of P2Y12 inhibitor used and no association with the change in LDL-cholesterol.

Conclusion:
A rise in PF4 levels was observed during the early post-infarction period in acute myocardial infarction patients. This rise was reversed by a single 420 mg SQ dose of evolocumab administered within 24 hours of hospital admission.
Abstract 12567: Reduced Myocardial Strain is Associated With Myocardial Inflammation and Fibrosis on Cardiovascular Magnetic Resonance Imaging in Collegiate Athletes Recovering From SARS-CoV-2 Infection
Authors: Heyniger John , Varghese Juliet , Chandrasekaran Preethi , Gil Katarzyna , Lee Simon , Lee Marc , Hor Kan N , Daniels Curt , Simonetti Orlando P , Rajpal Saurabh
Published: April 2024

Introduction:
Myocarditis is an important cause of sudden cardiac death in competitive athletes. There have been reports of myocardial inflammation on cardiovascular magnetic resonance (CMR) in athlete and non-athlete populations after SARS-CoV-2 infection; however, their clinical and functional significance is not known. We sought to investigate the relationship between left ventricular (LV) strain and other CMR markers suggestive of myocardial inflammation or fibrosis.

Hypothesis:
Reduced myocardial strain is associated with the presence of CMR abnormalities suggestive of inflammation, fibrosis, or necrosis in athletes recovering from SARS-CoV-2 infection.

Methods:
Collegiate athletes (N = 123) underwent a comprehensive CMR exam including strain encoded (SENC) imaging. We analyzed LV global longitudinal strain (GLS) across five groups defined by the presence or absence of late gadolinium enhancement (LGE), and T1 or T2 abnormalities. Myocarditis diagnosis on CMR required both abnormal T1 or LGE, and abnormal T2, in the same LV segment.

Results:
We enrolled 11 COVID negative control athletes (Group 1). Among COVID positive athletes, 42 had no abnormalities on CMR (Group 2), 31 had isolated right ventricular insertion point (RVIP) LGE (Group 3), 28 had LGE beyond RVIP (Group 4), and 11 athletes had myocarditis (Group 5). GLS was significantly lower in Groups 3, 4, and 5 compared with negative controls (p<0.05, Figure 1). There was a deterioration in GLS as CMR abnormalities progressed from control athletes to those with LGE and myocarditis. There was no significant difference in LV ejection fraction between the 5 groups.

Conclusions:
In conclusion, SARS-CoV-2 infection in collegiate athletes leads to subtle abnormalities in cardiac function detected by GLS that correlate with abnormal mapping and LGE suggestive of myocardial inflammation and fibrosis. The clinical significance of these abnormalities remains to be determined.
Abstract 12585: Human Heart Progenitors Regenerate Porcine Hearts via Migration and Fibroblast Repulsionhuman Heart Regeneration by Cardiac Pmigration and Fibroblast Repulsion
Authors: Poch Christine M
Published: April 2024

Human heart regeneration is one of the most critical unmet clinical needs at a global level. Muscular regeneration is hampered both by the limited renewing capacity of adult cardiomyocytes and the onset of cardiac fibrosis, resulting in reduced compliance of the tissue. Pluripotent stem cell strategies have proven efficacious for heart regeneration in rodents, pigs and primates, but approaches to specifically drive cell migration to the site of injury and inhibit subsequent fibrosis have been elusive. By virtue of human cardiac progenitor lineage tracing and single-cell transcriptomics, we uncover coordinated muscular regeneration in injured non-human primate heart bio-mimics. Remuscularization occured
via
directed migration of human ventricular progenitors to site of injury, concomittant fibroblast repulsion targeting fibrosis, and ultimately functional replacement of damaged cardiac muscle by differentiation and electromechanical integration. Single-cell RNAseq captured distinct capabilities, such as migration towards a CXCL12 gradient and fibroblast repulsion regulated by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Injection of human cardiac progenitors into hypo-immunogenic CAG-LEA29Y transgenic porcine hearts following radiofrequency ablation injury proved their chemotactic response and ability to generate a remuscularized scar
in vivo
. Transplantation of ~500 million cryopreserved human embryonic stem cell-derived progenitors
vs
cadiomyocytes similarly enhance cardiac function in pigs with myocardial infarctions. However, the risk of graft-associated ventricular arrhythmias from ectopic pacemaker automaticity shown by electroanatomical mapping is significantly lower in progenitor- compared to cardiomyocyte-treated hearts. Moreover, progenitor grafts exhibit larger CD31
+
blood vessel networks and lower CD68
+
immune cell infiltration. Our study demonstrates that inherent developmental programs within cardiac progenitors are sequentially activated in the context of disease, allowing the cells to sense, counteract injury and integrate into the host environment. As such, they may represent an ideal bio-therapeutic for functional heart rejuvenation.
Abstract 12626: Valvosoft Non-Invasive Ultrasound Therapy (NIUT) in Patients With Severe Symptomatic Aortic Valve Stenosis: First-in-Human Study - Twelve-Months Safety Update
Authors: Messas Emmanuel , Goudot Guillaume , Ijsselmuiden Alexander , den Heijer Peter , Trifunovic Danijela , Olga Petrovic , Puymirat Etienne , CHOLLEY Bernard , Spaulding Christian , Marijon Eloi , van Gameren Menno , Velinovic Milos , Kovacevic-Kostic Natasa , Terzic Dusko , Milicevic Vladimir , Karan Radmila , Rémond Mathieu , Penot Robin , Pernot Mathieu , Tanter Mickael , BERTRAND Benjamin , Spaargaren Rene
Published: April 2024

Background:
While aortic valve replacements (AVR) generally present favorable outcomes in severe calcific aortic stenosis (CAS), not all patients are eligible for an invasive treatment.Cardiawave
©
developed a novel non-invasive ultrasound therapy (NIUT) device, Valvosoft, to treat CAS. A prospective first-in-human study was conducted in two centers (Hôpital Européen Georges-Pompidou, France and Heart Center, Amphia Hospital, Netherlands) in 10 patients and a second study (University Clinical Center of Serbia) involving brain-MRI in 4 patients. All patients had symptomatic severe CAS and were ineligible for SAVR or TAVR according to local heart teams.

Methods:
Transthoracic NIUT was delivered on all 14 patients with Valvosoft. Clinical and echocardiographic evaluation was performed at baseline, discharge, 1-, 3-, 6- and 12-months follow-up (FUP). Additionally, the 4 patients of the second study had a brain-MRI performed before and after treatment.

Results:
Patients were advanced in age (82.4±5.3 years) with severe comorbidities (57% with heart failure and 50% with coronary heart disease). No adverse events (AE) occurred during the procedure other than isolated ventricular extrasystoles. No serious AE were adjudicated by a Clinical Event Committee (CEC) as device- or procedure-related at 1-month FUP. No death, stroke or transient ischemic attack or deterioration of neurological status were observed at 1-month FUP.During 12-months FUP, 5 deaths were reported (between 2 to 7 months after the procedure), all were adjudicated by CEC as non-procedure related. The survival rate was 100%, 93%, 79%, 64% at 1-, 3-, 6 and 12-months (to compare to the classic natural evolution of the disease survival rate of 94%, 73%, 73%, 54% respectively). No sign of cerebrovascular accident was detected in any of the 4 patients who had a brain-MRI before and after treatment.

Conclusions:
NIUT was feasible and safe in this small cohort of very frail, severe symptomatic CAS patients with severe comorbidities. Brain-MRIs performed before and after treatment ruled out silent cerebrovascular events. The survival rate of this cohort suggests that NIUT is beneficial for these patients and serves an unmet medical need.
Abstract 12658: Does Cell-Free DNA Rise With a Higher MFI Titer of DSA?
Authors: Babalola Olayiwola , Patel Jignesh , Kittleson Michelle M , Patel Nikhil , Singer-Englar Tahli , Kim Seong Kyu , Czer Lawrence , Kobashigawa Jon A
Published: April 2024

Introduction:
The use of donor-derived cell-free DNA (dd-cfDNA) has been demonstrated to detect heart transplant rejection as the donor has different DNA from the recipient. dd-cfDNA has also been correlated to the detection of donor-specific antibodies (DSA). It is believed that these DSA do cause injury to the donor heart, thus exposing the donor DNA to the recipient’s bloodstream. It is not known whether the degree or binding capacity of the dd-cfDNA correlates to the binding intensity of the DSA, characterized by mean fluorescence intensity (MFI).

Methods:
Between 2017 and 2020, we assessed 32 heart transplant patients who were sensitized and had a dd-cfDNA level drawn. Positive dd-cfDNA was defined as ≥0.25% and was then correlated to MFI binding of the DSA categorized as weak binding (MFI 2500-5000), moderate binding (MFI 5000-10000), and strong binding (MFI >10000). 62 dd-cfDNA and associated HLA blood draws were used for this study. The Luminex Single Antigen Neat test was used to determine MFI binding of DSAs.

Results:
Positive dd-cfDNA did not correlate to the presence of DSA. However, there was a trend for positive dd-cfDNA correlating to DSA with higher MFI levels (see table).

Conclusion:
dd-cfDNA might signal the presence of DSA with higher MFI levels. This might suggest that these higher levels of DSA might be involved in injury to the donor heart. Larger number of patients will be needed to confirm this finding.
Abstract 12669: Precision Phenotyping of Left Ventricular Hypertrophy With Echocardiographic Deep Learning
Authors: Duffy Grant , Cheng Paul , He Bryan , Yuan Neal , Ebinger Joseph , Zou James , Patel Jignesh K , Witteles Ronald M , Cheng Susan , Ouyang David
Published: April 2024

Introduction:
Left ventricular hypertrophy (LVH) results from chronic remodeling caused by broad range of systemic and cardiovascular disease including hypertension, aortic stenosis, hypertrophic cardiomyopathy, and cardiac amyloidosis. Early detection and characterization of LVH can significantly impact patient care but is limited by under-recognition of hypertrophy, measurement error and variability, and difficulty differentiating etiologies of LVH.

Methods:
To overcome this challenge, we present EchoNet-LVH, a deep learning workflow that quantifies ventricular hypertrophy precision equal to human experts, identifies patients with LVH, and predict etiology of hypertrophy. Trained on 28,201 echocardiogram videos, our model was implemented in Pytorch and evaluated on an independent dataset from an international healthcare system. Human expert annotations of anatomic structures in parasternal long axis echocardiogram videos were used as labels for supervised training.

Results:
EchoNet-LVH accurately measures ventricular dimensions with an R
2
of 0.97 compared to expert annotations. EchoNet-LVH accurately evaluated intraventricular wall thickness (mean absolute error 0.14cm), left ventricular diameter (MAE 0.24cm), posterior wall thickness (MAE 0.12cm) and classifies cardiac amyloidosis (area under the curve of 0.83 on held-out test data) from other etiologies of LVH. In an external dataset of 1,791 echocardiogram studies, EchoNet-LVH reliably quantified ventricular parameters with R
2
of 0.90 and MAE 0.22cm, 0.36cm, and 0.17cm respectively for IVS, LVID, and LVPW.

Conclusions:
Leveraging measurements across multiple heart beats, our model can rapidly identify subtle changes in LVH, is more reproducible than human evaluation, and lays the foundation for precision diagnosis of cardiovascular disease.