bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12589: Fetoscopic Selective Laser Photocoagulation of Placental Anastomoses Leads to Early Reduction of Cardiovascular Burden in the Twin-Twin Transfusion Syndrome
Authors: Chaszczewski Kasey J , Perelman Sarah , Falkensammer Christine B , Khalek Nahla , Pang Chengcheng , Tian Zhiyun , Rychik Jack
Published: April 2024

Background:
Twin-twin transfusion syndrome (TTTS) occurs with an incidence of 10-15% in monochorionic pregnancies. The Children’s Hospital of Philadelphia (CHOP) TTTS Cardiovascular Score (CVS) is a 20-point scale and encompasses evaluation of five domains: Recipient (R) abnormalities of 1) ventricular hypertrophy/systolic dysfunction, 2) atrioventricular valve insufficiency, 3) diastolic ventricular inflow, ductus venosus and umbilical vein flow patterns and 4) right ventricular outflow/pulmonary obstruction; Donor (D) abnormalities of 5) umbilical arterial (UA) flow. We explore the early impact of selective fetoscopic laser photocoagulation (SLPC) of placental anastomoses on fetal cardiovascular (CV) burden.

Methods:
Fetal echocardiograms performed prior to and one week post SLPC from 11/2012 to 6/2018 were reviewed. Pulsatility indices (PI) of the UA and middle cerebral artery (MCA), cerebroplacental ratio (CPR) and CHOP CVS elements were analyzed pre and post SLPC using paired t-tests.

Results:
SLPC was performed in 198 subjects; 17 excluded due to one twin demise post SLPC. Of the 181 analyzed, mean gestational age at SLPC was 19.8 (95% CI: ±0.3) weeks. Following SLPC, R demonstrated an increase in MCA PI and decrease in UA PI, with increase in CPR. D demonstrated a similar magnitude decrease in both MCA PI and UA PI, yielding no change in CPR. Following SLPC, mean CHOP CVS decreased. CHOP pre SLPC CVS was ≥6 in 62 (34%). The magnitude of change was greater in the subgroup with greater pre SLPC CV burden (CVS
>
6). Most common elements to improve were systolic dysfunction, tricuspid inflow, ductus venosus and umbilical vein flow patterns; least likely to improve was ventricular hypertrophy.

Conclusions:
Improvement in CV burden is seen as early as 1 week post SLPC, which supports acute alteration of loading conditions as contributing to the disease. Further study of the trajectory of CV alterations may provide insight into the complex mechanisms underlying TTTS.
Abstract 12601: Higher Arterial Stiffness Predicts Chronic Kidney Disease in the ELSA-Brasil Cohort Study
Authors: Sosa Antunes Candido Julia , Brant Luisa C , Barreto Sandhi Maria , MILL JOSE GERALDO , Camelo Lidyane
Published: April 2024

Introduction:
Arterial stiffening can directly affect the kidneys, which are passively perfused by a high flow. However, whether the relation between arterial stiffness and renal function is completely mediated by diabetes and hypertension (HTN) is a matter of debate.

Objective:
To investigate the relationship between arterial stiffness and the incidence of chronic kidney disease (CKD) in individuals without cardiovascular disease, and verify whether this association is mediated by HTN and diabetes.

Methods:
Baseline data of 13,068 adults from the ELSA-Brasil cohort (2008-2010, mean age 51 ± 9 years, 55% female) with validated carotid-to-femoral pulse wave velocity (cfPWV), estimated glomerular filtration rate (eGFR) estimated by the CKD-EPI equation, and albumin-to-creatinine ratio (ACR) were followed for 4 years (3.8 ± 0.42 years) to investigate the incidence of CKD. Arterial stiffness was measured by cfPWV, per quartile. CKD was defined as eGFR < 60ml/min/1.73m
2
and/or RAC ≥ 30mg/g. Logistic regression models were adjusted for age, sex, race, schooling, smoking, cholesterol/HDL, body mass index (BMI), diabetes, use of antihypertensive, mean arterial pressure, and heart rate. The same analyses were performed in the subsample free of HTN and diabetes at baseline.

Results:
In individuals in the upper quartile of cfPWV (10.1 to 27.9 m/s), the chance of incident CKD increased by 79% (CI 95%: 1.20; 2.68) and by 60% (CI 95% 1.01;2.52) when ACR was used. In the group free of HTN and diabetes, there was twice the chance of eGFR<60ml/min/1.73m
2
(OR 2.08 95%CI 1.17;3.69) and no association when CKD was measured by ACR.

Conclusion:
Our data indicate that higher values of cf-PWV is associated with incident CKD in adults, independent of diabetes or HTN.
Abstract 12617: Acute Myocardial Infarction in Cocaine Users: Prognosis, Outcomes and Clinical Characteristics
Authors: Salguero Lopez Douglas , Donatelle Marissa A , Rogers Everett , Torres Christian , Vedantam Karthik , Beohar Nirat
Published: April 2024

Introduction:
Cocaine use is rising in the USA. It is linked to high cardiovascular morbidity, mortality and increases ischemic events. Little epidemiological data exists exploring the relationship between NSTEMI & STEMI in cocaine users. We sought to examine the National Inpatient Sample (NIS) database to describe demographics & in-hospital outcomes of this cohort.

Methods:
The NIS database was queried from 2016-2018 to identify adults admitted with an MI & stratified by cocaine exposure using ICD-10 codes. Weights were applied to produce national estimates. Chi-square & logistic regression were used to calculate odds ratios. Multivariate analysis was applied to control for confounders.

Results:
A total of 25,000 cocaine positive patients were identified. These patients were younger (NSTEMI 53 vs 68-yo; STEMI 51-yo vs. 63-yo; p<.05), more likely to be male (NSTEMI 78% vs. 59%, p<.05; STEMI 81% vs. 69%, p<.05) & African American (NSTEMI 54% vs. 12%, p<.05; STEMI 45% vs. 8%, p<.05). Common comorbidities included hypertension, smoking, & coronary artery disease. Cocaine users presenting with NSTEMI were less likely to have CAD (70% vs. 81%, p<.05), but more likely to abuse alcohol (NSTEMI 23% vs. 3%, p<.05; STEMI 22% vs. 3%, p<.05). Age, sex, & race did not affect mortality despite the higher prevalence of young, male, & African American subjects. In the cocaine users’ group, pre-existing heart failure raised mortality rates 2.4-fold (p<.05) in those with STEMI & ESRD increased the odds of mortality 4.9-fold (p<.05) in those with NSTEMI. Rates of revascularization within 24-hours of admission were lower in cocaine users (NSTEMI 11% vs. 18%, p<.05; STEMI 45% vs. 53%, p<.05).

Conclusions:
Patients with an MI who were cocaine positive represent a diverse group distinct from the larger cocaine negative group. The use of cocaine should be investigated in patients with certain pre-existing medical conditions, as they had the highest risk of mortality in our study.
Abstract 12619: Macrophage-Dependent Interleukin-1 Beta Secretion (IL-1β) Induces Diabetic Diastolic Dysfunction
Authors: Liu Hong , Huang Yimao , Kang Gyeoung-Jin , Feng Feng , Dickey Deborah , Dudley Samuel C
Published: April 2024

Introduction:
Diabetes mellitus (DM) is a main risk factor for diastolic dysfunction (DD), the underlying pathological condition of heart failure with preserved ejection fraction (HFpEF). Nevertheless, the mechanism linking DM and DD is unclear. DM causes a low level inflammatory response, and we tested whether macrophage-dependent IL-1β secretion was the cause of DM-associated DD.

Methods:
Type II diabetic mice were induced by feeding 60% kcal high fat diet (HFD) for at least 20 weeks. Cardiac macrophage accumulation was assessed by flow cytometry. Diabetic mice were subjected to IL-1β suppressing treatment with IL-1 receptor antagonist (IL-1RA) or macrophage depletion by Clodronate liposome, and mouse cardiac diastolic function was evaluated by echocardiogram (E/E’). To determine the role of macrophage-dependent IL-1β in the DD development, fatty acid binding protein 4 knockout (FABP4 KO) mice were employed, and the secretory profile of isolated macrophages was examined by microarray and ELISA. The relation between IL-1β and the cardiac mitochondrial oxidative stress was investigated to explore the potential mechanism of IL-1β mediated DD.

Results:
Diabetic mice presented DD (E/E’, 19.6 ± 0.8 in control vs. 26.8 ± 0.8 in DM, p<0.05), higher IL-1β level (3.7 ± 0.6 pg/ml in control vs. 9.1 ± 0.8 pg/ml in DM, p<0.05), and increased macrophage accumulation in the hearts (F/80
+
cells, 15.7 ± 0.8% in control vs. 19.6 ± 1.3% in DM, p<0.05). DD was significantly ameliorated by suppressing IL-1β (E/E’, 22.2 ± 1.5, p<0.05 vs. control) or depleting macrophages (E/E’, 15.8 ± 0.7, p<0.05 vs control) in DM mice. Confirming the central role of macrophages and IL-1β, mice with fatty acid binding protein 4 knockout (FABP4 KO) were unable to secrete IL-1β and were resistant to diabetes-induced DD (E/E’, 17.2 ± 1.3 in KO+HFD vs. 22.1 ± 1.1 in wildtype+HFD, p<0.05). IL-1β regulated the mitoROS generation in cardiomyocytes, and a mitochondrially targeted antioxidant (mitoTempo) prevent diabetic-associated DD (E/E’, 20.7 ± 1.6, p<0.05 vs. control).

Conclusions:
DM-associated DD was mediated by macrophage-dependent IL-1β secretion. MitoROS provided a mechanistic link between macrophage secreted IL-1β and diabetic DD.
Abstract 12639: The Disparities of Gender-Based Out of Hospital Cardiac Arrest Characteristics and Outcomes: Comparing Rural to Urban Vancouver Island
Authors: Al Assil Rahaf
Published: April 2024

Introduction:
The relationship between the “chain of survival” metrics of Out of Hospital Cardiac Arrest (OHCA) and survival rates in rural settings has not been fully examined. In previous studies, low survival rate was attributable to the modifiable prehospital metrics and Return Of Spontaneous Circulation (ROSC).

Hypothesis:
Gender-based disparities in the modifiable and non-modifiable OHCA characteristics and outcomes are significant between rural and urban settings.

Methods:
We did a post-hoc analyses of data from the British Columbia cardiac arrest registry, which enrolled all emergency medical system (EMS)-treated OHCAs. All non-EMS-witnessed OHCAs on Vancouver Island from Jan. 2019 to Oct. 2020 were included. The independent variable of interest was rural versus urban settings. Rural areas were defined as all areas outside the urban clusters (population ≥ 1000 and a population density of ≥ 400/km2). Our outcomes were 1. Post resuscitation ROSC, and 2. Survival to hospital discharge. We reported gender-mediated measures and adjusted odds ratios using logistic regression models.

Results:
We included 1172 OHCA patients, with 23% in rural settings, 33% female, 30% had ROSC, and 23% survived to hospital discharge. The median EMS response time, from 911-call to first EMS arrival, was prolonged [10.5 mins (IQR 7.5-15)] in rural settings compared to urban settings [6.5 mins (IQR 5-9)] (p value<.001). Among females, rural settings were associated with higher odds of bystander CPR compared to males [(OR 1.86; 95% CI 1.04-3.35), (OR 1.42; 95% CI 0.95-2.13)], respectively. After adjusting for all covariates, rural settings were associated with lower odds of ROSC among males compared to females [(OR 0.53; 95% CI 0.31-0.90), (OR 0.70; 95% CI 0.34-1.41)], respectively; however, not associated with survival to hospital discharge.

Conclusions:
There are significant disparities in the modifiable prehospital OHCA characteristics, and post resuscitation ROSC between rural and urban Vancouver Island. An officially integrated rural CPR community-based program, and innovations focused on gender-based implementation may significantly improve OHCA survival rates and subsequent prognostication.
Abstract 12646: Cryoablation vs. Radiofrequency Ablation in Persistent AFib: An Updated Meta-Analysis
Authors: Balasubramanian Senthil S , siddamsetti sisir , GAUTAM SANDEEP
Published: April 2024

Introduction:
Catheter ablation is recommended for drug-refractory atrial fibrillation (AF). Cryoablation (CBA) has shown to be equivalent to radiofrequency ablation (RFA) in paroxysmal AF. However, there is a paucity of evidence regarding the efficacy and safety of CBA compared to RFA in persistent AF. An updated meta-analysis was conducted comparing CBA to RFA in persistent AF.

Methods:
A systematic literature review was performed in Embase, PubMed and SCOPUS for all the related articles until May 2021 yielding 112 publications. Eight studies fulfilled inclusion criteria including 1 randomized clinical trial and 7 observational studies. The Mantel- Haenszel random-effects model was used to calculate odds ratio (OR) and 95% confidence intervals (CI). Outcomes analyzed were rate of freedom from atrial arrhythmias, conversion to sinus rhythm during ablation, need for repeat ablation, total complications, vascular injury, phrenic nerve palsy, and cardiac tamponade.

Results:
CBA was performed in 500 patients and RFA was performed in 533 patients. There was no difference in the rate of freedom from atrial arrhythmias (OR = 1.12, 95% CI [0.87-1.46], P=0.38), need for repeat ablation (OR = 0.73, 95% CI [0.44-1.23], P=0.24), total complications (OR = 1.00, 95% CI [0.56-1.76], P=0.99), vascular injury (OR = 1.06, 95% CI [0.45-2.50], P=0.89), phrenic nerve palsy (OR = 3.09, 95% CI [0.86-11.11], P=0.08) and cardiac tamponade (OR = 0.43, 95% CI [0.11-1.77], P=0.24). The rate of conversion to sinus rhythm during ablation was higher in the CBA arm (OR = 2.33, 95% CI [1.41-3.87], P=0.001).

Conclusions:
Cryoablation is a safe and effective alternative to RFA in patients with persistent AF.
Abstract 12648: Improvements In Post-operative Cardiac Surgery Arrhythmia Identification Using The Atriamp Signals
Authors: Brown Diane , Al-subu Awni , Zhang Xiao , VonBergen Nick
Published: April 2024

Background:
Following cardiac surgery, as many as 60% of patients will experience an arrhythmia. These arrhythmias are associated with increased morbidity and occasional mortality. Therefore, rapid and accurate identification is paramount to the improvement of patient outcome. Unfortunately, until now monitoring was limited by lack of timeliness or clarity. Here we evaluate the confidence and accuracy of rhythm diagnosis using the AtriAmp, a UW device that allows continuous arrhythmia monitoring.

Methods:
An ongoing IRB approved prospective observational study of children less than or equal to 18 years of age admitted to the PICU with atrial pacing wires following congenital heart surgery. The AtriAmp was connected to atrial pacing wires and the atrial ECG (AEG) was displayed along with a surface ECG on GE monitors. Nine different types of arrhythmias were collected over the course of the first five months of the study. A 20-question online survey was given to critical care and cardiology providers. Ten questions displayed signals from only the surface leads, the other ten showed the same arrhythmias with AtriAmp signal also displayed. Answers were evaluated for confidence and accuracy.

Results:
40 providers were given the survey with 72% completing at the time of this abstract submission. Paired t-tests and mixed effects modeling were used to assess the data. The overall accuracy of diagnosis increased when using the Atriamp signals along with the surface ECG, but it was not statistically significant (p=0.07). Improvements in accuracy were most notable with atrial ectopic tachycardia (AET), Ventricular tachycardia (VT) and junctional ectopic tachycardia (JET). Provider confidence in diagnosis increased significantly when using the Atriamp signals (48%) compared to using only the surface ECG (62%) to diagnose arrhythmias (p<0.001).

Conclusion:
Use of the AtriAmp increased provider confidence in the diagnosis of post-operative arrhythmias when compared to the same arrhythmias seen on surface electrograms. Future research among a larger sample of providers is needed to further evaluate the use of AtriAmp in arrythmia diagnosis.
Abstract 12653: Cardiologist Perspectives on Cardiac Point-of-Care Ultrasound
Authors: Liu Linda , Pattock Andrew , Kersey Cooper , Huang Gary , Mazimba Sula , Wiley Brandon , kirkpatrick james , Kwon Younghoon
Published: April 2024

Background:
The use of cardiac point-of-care ultrasound (c-POCUS) for patient care has been on the rise in many non-cardiology specialties. Perspectives on c-POCUS by cardiologists, the predominant user of comprehensive echocardiograms, have not been explored.

Methods:
A 19-item online survey was developed to evaluate respondents’ echocardiography experience as well as their current practices and perspectives on various aspects of c-POCUS. The survey was distributed to attending cardiologists at quaternary academic medical centers.

Results:
A total of 96 survey responses were collected from participants at 13 institutions. Majority of the respondents worked in an inpatient setting (97.9%) and formally practiced echocardiography (72.6%). C-POCUS use was common, with 37.9% of cardiologists using it more than twice per inpatient week. Cardiologists that practiced echocardiography used c-POCUS at higher frequency (43% vs. 23%, p=0.07). About half of respondents (47.9%) agreed that c-POCUS changed their clinical management. However, more than half agreed that c-POCUS should be further incorporated in practice (68.1%) and in formal fellowship education (71.3%). Few expressed time and labor intensiveness or impact on volume of comprehensive echocardiograms as major concerns. Major barriers to c-POCUS implementation included device availability, image documentation infrastructure, and reimbursement.

Conclusion:
This study demonstrates that the rising enthusiasm for c-POCUS also extends to cardiology. However, several barriers remain to more thorough utilization of this rapidly adopted diagnostic tool by cardiologists. Interventions to overcome these barriers would likely encourage further integration of c-POCUS use in clinical practice and fellowship training.
Abstract 12659: Associations Between Patient Demographic Characteristics and Odds of Repeat Ablation for Atrial Fibrillation
Authors: Taylor Brittany N , Slotwiner David J , Castanos Yelitza , Wilson Monica L , Reading Turchioe Meghan
Published: April 2024

Introduction:
Atrial fibrillation (AF) affects over 3 million adults in the United States and has an estimated direct healthcare cost of $6 billion. Between 2000 and 2013, there was an eightfold increase in the number of ablations for AF performed. However, success rates vary from 35%-80%. Because AF recurrence is common, patients may require repeat ablations, but less is known about which patients are at high risk for repeat ablations. The objective of this study was to investigate the prevalence of repeat ablations by patient demographic characteristics.

Methods:
From electronic health records, we identified all patients with an admitting diagnosis of paroxysmal AF using International Classification of Diseases billing codes who were treated at NewYork-Presbyterian Hospital from 2010 through 2019. We then identified patients who underwent ablation at the institution using Current Procedural Terminology codes and extracted ablation dates, age at first ablation, gender, race, and ethnicity. We summarized patient characteristics using standard descriptive statistics and evaluated associations between demographics and repeat ablations using logistic regression modeling.

Results:
Of the 1,799 patients studied, 31.0% were female, 54.0% were white, 4.0% were Hispanic or Latino, and 17.9% had at least one repeat ablation. At the first ablation, 19.7% of patients were under age 55, 26.4% aged 55 to 64, 33.4% aged 65 to 74, 16.3% aged 75-84, and 4.2% aged 85 and older. Subjects aged <55 were significantly more likely to undergo repeat ablation compared to (
>
85 (OR 2.03 [95% CI 1.01-4.54]). The odds of repeat ablation did not significantly differ by gender, race, or ethnicity.

Conclusion:
Younger age is associated with increased odds of repeat ablations. Age and other potential predictors of repeat ablations should be further studied in larger, more diverse samples controlling for relevant covariates.
Abstract 12684: Transcriptional Features Of Biological Age Maintained In Cultured Cardiac Interstitial Cells
Authors: Echeagaray Oscar E , Kim Taeyong , Casillas Alex , Monsanto Megan M , Sussman Mark A
Published: April 2024

Introduction:
Ex vivo expansion of cells is necessary in regenerative medicine to generate large populations for therapeutic use. Adaptation to culture conditions prompt an increase in transcriptome diversity and decreased population heterogeneity in cKit+ cardiac interstitial cells (cCICs).

Hypothesis:
Age and/or condition of origin is impacts the transcriptional phenotype as well as population heterogeneity characteristics of cCICs undergoing in vitro expansion.

Methods:
cCICs isolated from neonatal and adult cardiac tissue (Left Ventricular Assist Device; LVAD). Single cell libraries from
in vitro
expanded cells were prepared following five passages. “Transcriptional memory” was surveyed via bioinformatic analysis including unsupervised clustering, differential expression analysis, gene ontology and pathway analysis. Transitional states were assessed through pseudotime analysis.

Results:
Cell cycle imprint associated with biological age after culture was observed in Neonatal cCICs via upregulation of G2M genes. LVAD derived cCICs retained a widespread senescent profile, in particular high expression of interleukins and elements of the senescence associated secretory phenotype (SASP). Nuclear pore complex TPR and UBC9 and translation initiation factors, displayed age-associated downregulation of elements in the RNA transport and processing pathway. Pathway and co-expression analysis of fibroblast markers Ddr2, Tcf21, Vimentin, Periostin and Collagen deposition markers indicated a primed fibrotic phenotype in senescent cells. A small subset of cCICs exist in a transcriptional continuum between “youthful” phenotype and the damaged microenvironment of adult tissue in which they were embedded.

Conclusions:
The influence of age, pathology and the cellular stress associated to the
in vivo
tissue microenvironment persist after culture adaptation, influencing targets of 1) cell cycle, 2) senescence associated secretory phenotype (SASP), 3) RNA transport, and 4) ECM-receptor/fibrosis. The connate transcriptional phenotypes offer fundamental biological insight and highlights cellular input as a consideration in culture expansion and adoptive transfer protocols.
Abstract 12691: Comparison of Deep Learning and Radiomic Features to Differentiate Non-Ischemic and Ischemic Cardiomyopathy Using Cardiac MRI Cine Imaging
Authors: Nakashima Makiya , Chen David , Basnet Ramesh , Benovoy Mitchel , Hwang Tae Hyun , Geschke Robert , Grimm Richard A , Kapadia Samir R , Svensson Lars G , Griffin Brian P , Flamm Scott D , Tang Wai Hong W , Kwon Deborah H
Published: April 2024

Introduction:
Cardiac magnetic resonance (CMR) is frequently utilized to characterize etiology of cardiomyopathy (CM), but there is need for improved disease classification, standardization in the interpretation of findings, and throughput in analysis. Radiomics has been shown to classify disease in a semi-automated manner. Alternatively, deep learning (DL) provides the ability to identify unknown features in image data. Therefore, we sought to compare DL and radiomic approaches to differentiate ischemic vs non-ischemic cardiomyopathy (ICM vs NICM), using cardiac magnetic resonance (CMR) short axis cine images.

Methods:
We selected 291 patients with cardiomyopathy (CM) who underwent a CMR exam at Cleveland Clinic between 2008 and 2018, of which 249 had NICM (positive label) based on expert review of the CMR exam and electronic medical record documentation. We compared a radiomic and end-to-end DL approach to identify CM etiology from short axis cine images. Automatically generated radiomic features describing myocardial shape, texture, thickness, and motion in the cine images were used to train several machine learning classifiers. In the DL approach, we directly used the cine images to train several DL classifiers, without extracting radiomic features. We evaluated the classifiers through 5-fold cross validation using the area under the curve (AUC), F1-score, and accuracy metrics. Statistical significance was evaluated using paired 2-tailed t-test at 0.05 level.

Results:
Support vector machine (SVM) and DenseNet121 achieved the best metrics for radiomic and DL approaches respectively. The radiomic and DL approach achieved similar AUCs of 0.852 and 0.858 respectively, but DL approach achieved statistically significant higher F1-score of 0.758 vs 0.585 of the radiomic approach.

Conclusions:
An end-to-end DL approach more accurately identified NICM vs ICM compared to a radiomics approach, using only cine CMR images.
Abstract 12753: Convolutional Neural Networks Are Non-inferior To Expert Assessment For The Evaluation Of Left Ventricular Systolic Function And Mass In Chronic Heart Failure - Results From The Myovasc Study
Authors: Troebs Sven , Hauptmann Tony , Velmeden David , Soehne Jakob , Schuch Alexander , Mueller Felix , Heidorn Marc , Göbel Sebastian , Schulz Andreas , Münzel Thomas , Prochaska Juergen , Kramer Stefan , Wild Philipp
Published: April 2024

Introduction:
Convolutional neural networks (CNN) can determine markers of cardiac function and structure from echocardiographic imaging datasets. A comparison of measurement results between a CNN and conventional echocardiographic experts with regard to clinical outcome in chronic heart failure (HF) is not available.

Methods:
Data from the MyoVasc Cohort Study (n=3,289; NCT04064450) on chronic HF were analyzed. Comprehensive clinical phenotyping was performed during an investigation in a dedicated study center. Left ventricular ejection fraction (LVEF) and left ventricular mass (LVM) were measured by a CNN published by Zhang et al. Clinical outcome was assessed by a structured follow-up with subsequent validation and adjudication of endpoints.

Results:
Data from automatic and human measurements were available in 2,815 subjects with a median follow-up of 5.5 [4.2/6.6] years. The correlation of both measurements was dependent on image quality, ranging between 0.6 and 0.8. In multivariable Cox regression adjusted for age and sex, human and automated LVEF and LVM measures per changes in one standard deviation demonstrated comparable risks for all-cause mortality (LVEF: HRhuman 0.57 [0.52/0.63] vs. HRauto 0.60 [0.55/0.66]; LVM: HRhuman 1.56 [1.42/1.70] vs. HRauto 1.58 [1.43/1.76]) and for worsening HF (LVEF: HRhuman 0.55 [0.51/0.59] vs. HRauto 0.58 [0.53/0.63],; LVM: HRhuman 1.56 [1.45/1.69] vs. HRauto 1.59 [1.47/1.73]). C-indices of both prediction models did not differ significantly (P=0.19). Sensitivity analysis demonstrated no significant differences in model performance for both asymptomatic and symptomatic HF, as well as among HF phenotypes (all P>0.05).

Conclusions:
CNN-based assessment of LVEF and LVM was non-inferior to conventional expert measurement in predicting all-cause mortality and worsening of HF. This underlines the potential of an CNN-based pipeline for automated evaluation of echocardiography in high-throughput.
Abstract 12761: Association of Medical Non-Adherence to Health Status Outcomes in the ISCHEMIA Trial
Authors: Garcia R. Angel , Spertus John , Jones Philip , Mark Daniel B , Newman Jonathan D , Bangalore Sripal , Boden William E , Stone Gregg W , Reynolds Harmony , Hochman Judith S , Maron David J
Published: April 2024

Introduction:
In the ISCHEMIA trial, participants managed invasively (INV; guideline-directed medical therapy [GDMT] + angiography ± revascularization) had better health status outcomes than those managed conservatively (CON; GDMT alone). It is unknown whether adherence to prescribed medications affects health status outcomes in chronic coronary disease (CCD).

Hypothesis:
Patient-reported medication non-adherence more adversely impacts health status outcomes in those treated with a CON, but not an INV, strategy.

Methods:
Self-reported adherence was assessed at randomization with a modified Morisky-Green-Levine medication adherence measure and patients were dichotomized into adherent (never skipping meds) and non-adherent (occasionally skipping meds). Twelve-month health status outcomes were assessed with the 7-item Seattle Angina Questionnaire (SAQ) Summary Score (SS; range 0-100, higher = better) using adjusted mixed effects cumulative probability models within a Bayesian framework to estimate differences between adherent and non-adherent patients, stratified by study arm.

Results:
Among 4480 randomized patients in the SAQ cohort, 1245 (27.8%) reported non-adherence at baseline. These patients had worse SAQ scores at baseline (CON: 72.9 ± 19.3 vs. 75.6 ± 18.4; INV: 71.0 ± 19.8 vs. 74.2 ± 18.7) and follow-up (CON: 81.2 ± 18.3 vs. 85.4 ± 15.0; INV: 84.3 ± 17.4 vs. 88.2 ± 13.9). The Figure shows similar posterior distributions of better SAQ scores with adherence in both arms (Mean difference = 1.63 (95% CrI 0.33, 2.89) in CON; 1.93 (95% CrI 0.80, 3.06) in INV).

Conclusions:
Medication non-adherence—as was reported in over 1 in 4 patients—was associated with worse 12-month health status, an effect that was similar in CON and INV strategies. While causation cannot be established, improving adherence may improve health status outcomes in CCD, regardless of treatment strategy.
Abstract 12793: Characterization of Isogenic Human IPSC Engineered Cardiac Tissue Deficient in Cardiac Myosin Binding Protein C Indicates a Primary Calcium-Handling Abnormality
Authors: De Lange Willem J , Farrell Emily T , Ralphe John C
Published: April 2024

Mutations that cause truncation of cardiac myosin binding protein C (cMyBP-C) are common causes of hypertrophic cardiomyopathy (HCM), and cause disease through a mechanism of haploinsufficiency. Recent studies in isogenic iPSC-cardiomyocyte (CM) heterozygous for cMyBP-C truncation, show normal cMyBP-C protein levels, suggesting a different mechanism. Though rare, cases of patients homozygous for cMyBP-C truncations, present with early postnatal cardiomyopathy rapidly progressing to heart failure.

We postulated that human iPSC-ECTs would present with a hypercontractile phenotype with accelerated contractile kinetics, similar to cMyBP-C
-/-
mouse ECTs.

We introduced homozygous (-/-) and heterozygous (+/-) frameshifts in cMyBP-C in iPSCs by CRISPR gene editing followed by differentiation into CM which were incorporated into ECTs.

Although cMyBP-C protein levels were similar in +/- and +/+ 2D CM, the level of cMyBP-C was reduced in +/- ECTs (0.25 vs. 0.49; p = 0.007; N ≥ 8,) and was absent in -/- ECTs. Functional characterization revealed slow Ca
2+
-handling that became more pronounced with prolonged time in culture (Ca
2+
T
100
: 110.9 vs. 76.0 ms; p = 0.0006; N ≥ 7) and normal Ca
2+
-sensitivity, without pronounced differences in contractile function in +/- ECTs. In addition to slow Ca
2+
-handling, -/- ECTs (Ca
2+
T
100
: 133.3 vs. 76.0 ms; p < 0.0001; N ≥ 8) also present with decreased Ca
2+
-transient (0.24 vs. 0.65 F
340
/F
380
; P = 0.002; N ≥ 8) and twitch (3.93 vs. 10.30 mN/mm
2
; p < 0.0001; N ≥ 21) amplitudes, and slow late relaxation (RT
50-90
120.0 vs. 95.1 ms; p < 0.0001; N ≥ 21) that became more pronounced with prolonged time in culture. When permeabilized, -/- ECT displayed a right-shift in Ca
2+
-sensitivity (pCa
50
5.87 vs. 5.98; p < 0.0001; N ≥ 11) and a decrease in Hill-coefficient (2.24 vs. 2.98; p = 0.0006; N ≥ 11).

In our living 3D
in vitro
tissue culture system, heterozygous truncation of cMyBP-C causes haploinsufficiency and demonstrates a slow Ca
2+
-release with minimal contractile abnormalities, while -/- ECTs present with a hypocontractile phenotype, likely mediated by aberrant Ca
2+
handling and sensitivity. These findings reinforce that Ca
2+
-mishandling is a primary defect in cMyBP-C HCM, and therefore represents a target for therapeutical intervention.
Abstract 12798: Somatic Mosaicism in Blood Cells is a Risk Factor for Incident Heart Failure in 200,628 UK Biobank Participants
Authors: Satterfield Benjamin A , Saadatagah Seyedmohammad , Dikilitas Ozan , Kullo Iftikhar J
Published: April 2024

Introduction:
Somatic mutations accrue in hematopoietic stem cells with age and can lead to selective clonal expansion, a process termed Clonal Hematopoiesis of Indeterminate Potential (CHIP). CHIP has been associated with increased risk of coronary heart disease (CHD) and myocardial infarction (MI). Whether CHIP is a risk factor for incident heart failure is unclear.

Methods:
The presence of CHIP was assessed in exome sequence data from 200,628 UKB participants using the Genome Analysis Toolkit pipeline and filtering somatic mutations from a pre-specified list within
DNMT3A
,
TET2
, and
ASXL1
. CHIP was defined as somatic mutations in these 3 genes with variant allele fraction (VAF) >10%. We ascertained incident heart failure (overall, ischemic, and non-ischemic), death, cardiovascular death, and coronary heart disease (CHD defined as of MI and/or coronary revascularization) as determined by UKB algorithms, self-report, and diagnosis/procedure codes. Cox proportional hazard models adjusted for age, sex, self-reported race/ethnicity, diabetes, hypertension, smoking, and BMI were used to assess whether CHIP was associated with incident adverse events.

Results:
We identified 3,885 participants with CHIP in
DNMT3A
,
TET2
, and
ASXL1
at a VAF of >10%. Over a median follow-up of 9 years, 2,055 participants developed incident heart failure. CHIP was associated with both ischemic and non-ischemic heart failure. We replicated previously reported associations of CHIP with death and incident CHD (
Table
).

Conclusions:
CHIP was associated with increased risk of both ischemic and non-ischemic heart failure. The association with ischemic subtype is likely mediated by the increased risk of CHD. The basis for the increased hazard of non-ischemic heart failure is unclear but may be due to an inflammatory milieu in CHIP carriers.
Abstract 13015: Rates and Predictors of Treatment With Oral Anticoagulant in Patients Newly Diagnosed With Atrial Fibrillation at High-Risk for Stroke
Authors: Manning Evan , Burns Kelley , Laurie Melissa , Luke Patten , Ho Michael , Sandhu Amneet
Published: April 2024

Introduction:
Atrial fibrillation (AF) is the most common arrhythmia in adults and increases risk of stroke. Guidelines recommend treatment with oral anticoagulants (OACs) for those at high risk of stroke associated with AF, yet many patients do not receive OAC therapy.

Methods:
Using University of Colorado’s multi-institutional electronic health records (EHR) database, patients newly diagnosed with AF (by ICD-9/10 codes) and CHA
2
DS
2
-VASc score ≥ 2 between 2013-2018 were identified and prescription of an OAC during the first 6 months after AF diagnosis was determined. Logistic regression was used to compare baseline characteristics to the odds of being prescribed an OAC.

Results:
We identified 18,404 newly diagnosed AF patients with a CHA
2
DS
2
-VASc score of ≥2 (mean age 74; 46.6% female; 88.6% white). Of these 18,404 patients, 7,604 (41.3%) were prescribed an OAC in the follow up period and 10,800 (58.7%) were not. The Figure below displays a forest plot of patient-level factors correlating with OAC and lack of OAC prescription. This analysis demonstrated that patient sex, race, comorbidities, risk of stroke/bleeding and other prescriptions may influence the prescribing an OAC.

Conclusions:
Most newly diagnosed AF patients with a CHA
2
DS
2
-VASc score of ≥ 2 were not prescribed an OAC in the first 6 months after diagnosis. Understanding factors associated with not being prescribed an OAC may help efforts to improve anticoagulation rates in those with AF at high risk of stroke.
Abstract 13021: Post-Myocardial Infarction Differences in Cardiac Histopathologic Phenotypes Across Clinical Categories
Authors: Gaddam Meghna , Kim Sarah , Sunderraj Ashwin , Sinha Arjun , Lloyd-jones Don , Thorp Edward B , Lomasney Jon W , Feinstein Matthew J
Published: April 2024

Introduction:
Defining tissue-level phenotypic factors occurring in people with different clinical profiles may yield insights into pathogenesis of post-MI cardiac dysfunction.

Methods:
Two trained adjudicators analyzed reports from autopsies performed on patients with clinical diagnoses of MI who underwent autopsy at a large urban medical center between 10/31/2002 and 4/1/2021 (N=275). Standardized criteria were used to extra whether patients had the following histopathological criteria: 1) cardiomegaly; 2) coronary or large artery atherosclerosis; 3) severe coronary atherosclerosis; histopathologic features of 4) remote and/or 5) acute MI; 6) and myocardial fibrosis; and/or 7) myocardial inflammation. Interobserver agreement for histopathologic phenotypes was 0.929. Chi-squared and ANOVA were used to determine differences in histopathologic phenotypes by demographic and clinical variables. A Bonferroni-corrected p-value of 0.001 was used to determine statistical significance.

Results:
Among patients with clinical diagnoses of MI who underwent autopsy (N=275), not all had evidence of MI observed on histopathology; 185 (67%) had histopathologic evidence of remote MI, 86 (31%) had histopathologic evidence of acute MI (including 50 who had evidence of both acute and remote MI), and 55 (20%) had no histopathologic evidence of prior MI (Table). Patients with MI diagnoses who had chronic inflammatory diseases were significantly more likely than those without chronic inflammatory diseases to have myocardial tissue inflammation at autopsy (78% vs. 23%; p=0.0008). Patients with LVEF >=50% were substantially less likely than those with LVEF <40% and 40 to <50% to have histopathologic evidence of remote MI (51%, 69%, and 87% in each group, respectively; p=0.0002).

Conclusion:
Chronic inflammatory disease status and LVEF strata were associated with different myocardial tissue-level phenotypes at autopsy among patients with clinical diagnoses of MI.
Abstract 13028: Cannabis Use Disorder Adversely Affects Outcomes of Diabetics Hospitalized With Prior Myocardial Infarction and Revascularization: A National Propensity-Matched Analysis
Authors: Desai Rupak , Patel Viralkumar , Patel Divyank , Zalavadia Dipen , Jain Akhil , Kumar Gautam , Sachdeva Rajesh
Published: April 2024

Background:
Increasing unmonitored use of recreational cannabis in the United States is alarming especially among patients with known cardiovascular disease (CVD) risk. Considering mixed reports of cannabis use and its impact on diabetes mellitus and associated outcomes, we aimed to assess the impact of cannabis use disorder (CUD) on outcomes of diabetics hospitalized with prior myocardial infarction (MI) and revascularization [PCI and/or CABG].

Methods:
We queried the National Inpatient Sample (2015Oct-2017Dec) to identify admissions among diabetics with prior revascularized MI and CUD. Propensity score-matched analysis (1:1) was performed adjusting for demographic and hospital characteristics to obtain CUD+ & CUD- cohorts which were then compared for comorbidities and in-hospital outcomes. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE: all-cause mortality, acute MI, cardiac arrest and stroke) and subsequent revascularization and secondary outcomes were median hospital stay and charges.

Results:
Each diabetic cohort with prior MI and revascularization consisted of 190 patients with and without CUD (CUD+ vs. CUD-). Both matched cohorts were comparable in terms of demographics
(Table 1)
and had balanced distribution of most of the CVD risk factors except hypertension (92.1% vs. 97.4%; p=0.022) and renal failure (18.4% vs. 28.9%; p=0.016) which were lower in the CUD+ cohort. The rates of MACCE (28.9% vs. 10.5%) and revascularization (23.7% vs. 7.9%, p<0.001) were significantly higher in the CUD+ cohort (p<0.001). Furthermore, the CUD+ cohort was less often routinely discharged (63.2% vs. 76.3%) with higher length of stay (4 vs. 3 days) and hospital charges.

Conclusion:
This nationwide propensity-matched analysis revealed that the CUD increases the rates of MACCE, subsequent revascularization with higher healthcare resource utilization in diabetics hospitalized with a prior history of MI and revascularization.
Abstract 13033: Cavin/Caveolin Interaction Modulates BMP/Smad Signaling in Pulmonary Artery Endothelial Cells
Authors: Tomita Shinya , Nakanishi Naohiko , Ogata Takehiro , SUGA TAKAOMI , Tsuji Yumika , Higuchi Yusuke , Matoba Satoaki
Published: April 2024

Background:
Pulmonary hypertension (PH) is a progressive disease associated with poor prognosis. Caveolin-1 (Cav1) and Cavin-1 are components of caveolae, and both interact with each other and influence the composition and stabilization of caveolae. Cav1 is identified as a related gene of pulmonary arterial hypertension (PAH). Gene mutation of bone morphogenetic protein type II receptor (BMPRII) is the most common cause of PAH. BMPRII is localized in caveolae and associates with Cav1. However, the role of the Caveolin-Cavin system on the BMP/Smad signaling and the PAH progression has not been well-known.

Methods and Results:
As in previous reports, Cav1 knockout mice exhibited PH with pulmonary vascular remodeling and right ventricular hypertrophy. Caveolae disappeared in pulmonary microvascular endothelial cells of Cav1 knockout mice. We then examined the role of Caveolin-Cavin and the association with BMP/Smad signaling in human pulmonary artery endothelial cells (hPAECs). Cav1 knockdown in hPAECs reduced BMPRII at the plasma membrane and Smad 1/5/9 phosphorylation. Cav1 knockdown also significantly increased hypoxia-induced apoptosis in hPAECs. Cav1 was associated with BMPRII at the membrane of hPAECs. In addition, Cavin-1 inhibited the interaction of BMPRII with Cav1 and reduced BMPRII localization on the membrane of hPAECs. Cavin-1 knockdown reversed BMPRII localization at the plasma membrane and Smad 1/5/9 phosphorylation induced by Cav1 knockdown. Both Cavin-1 and BMPRII were associated with the Cav1 scaffolding domain. These results suggest that Cavin-1 interacts with Cav1 and inhibits the association of Cav1 with BMPRII, resulting in modulating Smad signaling pathway.

Conclusions:
Cavin-1 and BMPRII are competitively associated with Cav1 at the plasma membrane and modulating BMP/Smad signal transduction in PAECs. Our findings reveal a previously undescribed mechanism via Cavin-Caveolin interaction in BMP/Smad signaling-modulated PH development.
Abstract 13039: Putative Protective Effects Of Caffeine And Its Metabolites On Coronary Heart Disease In The Middle East
Authors: Ullah Ehsan , Kunji Khalid , El-Menyar Ayman , Elsousy Reem , Al-Nesf Maryam , Beotra Alka , Al-Maadheed Mohammed , Mohamed-Ali Vidya , Saad Mohamad , Al Suwaidi Jassim
Published: April 2024

Introduction:
Protective association between coronary heart disease (CHD) and caffeine intake and its metabolism has been reported. Some of the caffeine’s beneficial actions may be attributed to its direct effect on the endothelial cell, stimulating the production of nitric oxide (NO), as well as its role as an adenosine receptor antagonist. In the Middle East and Gulf region CHD is rampant, and caffeine consumption is also relatively high. The interaction of the two is of interest and will be investigated in this study.

Hypothesis:
Caffeine is a protective factor for CHD in the Middle East.

Methods:
The Qatar Cardiovascular Biorepository provided 1,001 CHD patients and the Qatar Biobank provided 2,999 control subjects. Metabolites in the caffeine pathway (KEGG, hsa00232) were quantified and curated via liquid chromatography-mass spectrometry by Metabolon Inc. We then subjected data to standard quality control procedures. Association between metabolite levels and CHD was tested by logistic univariate regression, controlling for age, BMI, and sex.

Results:
The caffeine KEGG pathway contains 22 compounds. Eleven were present in our cleaned metabolomics panel, and all of them were reduced in CHD patients (Figure 1). Five were significant at
P
<0.05: caffeine (
P
=5.26x10
-3
), 1,7-dimethyluric acid (
P
=2.96x10
-4
), paraxanthine (
P
=8.67x10
-3
), theobromine (
P
=2.33x10
-5
), and 1-methylxanthine (
P
=1.17x10
-2
). Through pathway enrichment analysis, caffeine metabolism pathway was found to be significantly enriched with an FDR
P
=4.59x10
-34
and an enrichment ratio of 44.23.

Conclusions:
The finding of lower levels of caffeine and several of its metabolites in CHD patients in this study suggests a potential protective effect for this stimulant. However, this is a cross-sectional cohort study, so we are observing only association at a slice in time.
Abstract 13075: Initial Physical Activity Level is a Strong Predictor of Adherence to the Physical Activity Goal: A Secondary Analysis of the SMARTER Weight Loss Trial
Authors: Bizhanova Zhadyra , Sereika Susan M , Kariuki Jacob K , Conroy Margaret B , Brooks Maria M , Rockette-Wagner Bonny , Cheng Jessica , Beatrice Britney , Loar India , Wang Yuhan , Pulantara I Wayan I , Parmanto Bambang , Cedillo Maribel , Burke Lora E
Published: April 2024

Background:
Over a third of excess coronary heart disease mortality in the US is related to inadequate physical activity (PA). Use of wearable activity trackers is beneficial for PA improvement in many populations. However, predictors of long-term adherence to PA remain unknown.

Hypothesis:
The 1
st
week PA levels will be the strongest predictors of long-term adherence to the PA goal in adults with overweight or obesity in a mHealth weight loss intervention trial.

Methods:
A secondary analysis of a 12-month behavioral weight loss trial (SMARTER) that randomized 502 participants to either self-monitoring with tailored feedback messages (SM+FB, n=251) or self-monitoring alone (SM, n=251) was conducted. At baseline, each participant received a Fitbit Charge 2 and PA goal of ≥150 minutes of moderate or vigorous activity (MVPA) per week. The outcome of interest for this analysis was long-term PA adherence, i.e., the number of weeks adherent to PA goal over 12 months. Twenty-six explanatory variables were considered, including treatment assignment; baseline socio-demographics; health history; body mass index (<30 vs. ≥30 kg/m
2
); psychosocial factors; and1
st
week PA levels (<150 vs. ≥150 MVPA min/week). Machine learning methods (i.e., random forest regression trees and lasso regression) were used to identify predictors of long-term PA adherence.

Results:
The sample ranged in age from 19 to 75 years (57% were <50 years old), and was mostly Caucasian (83%), female (80%) and had a mean BMI 33.7 ± 4.0 kg/m
2
. The sample was randomly split 4:1 into training (n=394) and validation subsamples (n=104) which were comparable by treatment assignment. Both random forest and lasso regression identified 1
st
week PA levels as the most important predictor of long-term PA adherence. The findings were confirmed in the validation cohort with an out-of-sample R-square of 40.2% from random forest and a R-square of 47.9% from lasso regression, suggesting good predictive abilities.

Conclusion:
This analysis confirmed higher initial PA levels as the strongest predictor of long-term PA adherence. The findings support screening for PA at study entry and developing tailored interventions for those with lower initial PA levels.