bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18596: Sildenafil Modulates Metabolic Remodeling by Increasing Fatty Acid β-Oxidation in Single Ventricle Congenital Heart Disease
Authors: Pietra Ashley E , Turner Mary E , Sanchez Erin E , Stone Matthew , Stauffer Brian L , Sucharov Carmen C , Miyamoto Shelley D , Garcia Anastacia M
Published: December 2023

Introduction:
Sildenafil, a phosphodiesterase-5 inhibitor (PDE5i), is used to treat heart and circulatory failure (HF) in single ventricle congenital heart disease (SV). We previously demonstrated that human SVHF myocardium is characterized by increased PDE5 activity and impaired mitochondrial energetics, which are improved with PDE5i. Using an in vitro model in combination with SV myocardial tissue, we test the hypothesis that mitochondrial fatty acid β-oxidation (FAO) is improved with PDE5i therapy via activation of sirtuin-3 (Sirt3) and resulting protein deacetylation.

Methods:
Primary cardiomyocytes (neonatal rat ventricular myocytes, NRVMs) were treated with 2% serum from SVHF patients or non-failing (NF) controls +/-PDE5i (72 hours). To mechanistically interrogate whether PDE5i acts via Sirt3, we utilized siRNAs against Sirt3 +/-PDE5i. FAO was directly assessed via the Seahorse Bioanalyzer (Agilent). Mitochondrial protein levels and acetylation profiles were quantified via Western blot. Sirt3 activity was measured in isolated mitochondria from SVHF myocardium using a fluorescent-based enzymatic assay. Statistical analysis was performed using a Welch ANOVA with post-hoc Dunnett’s multiple comparisons test (FAO) or a paired T test (Sirt3 activity).

Results:
NRVMs treated with SVHF serum have impaired mitochondrial FAO and while PDE5i therapy results in improved FAO, siRNA knockdown of Sirt3 abolishes the PDE5i protective effect (A). Mitochondria isolated from SVHF myocardium are hyperacetylated, and ex vivo PDE5i treatment enhances Sirt3 deacetylase activity (B-C), and deacetylates mitochondrial proteins.

Conclusions:
SVHF serum treatment of cardiomyocytes is a novel in vitro platform for mechanistic investigations of SV-related pathophysiology. These data suggest PDE5i directly augments mitochondrial FAO via Sirt3-mediated protein deacetylation and provides important insight into the myocardial specific mechanisms of PDE5i.
Abstract 18608: Using Electronic Medical Record Based Tools to Assess the Prevalence of Iron Deficiency, Iron Deficiency Anemia, and Treatment With IV Iron Among Patients With Decompensated Heart Failure
Authors: Hope Matthew R , Rakita Val , Fleece David , gangireddy chethan
Published: December 2023

Introduction:
Iron deficiency (ID) and iron deficiency anemia (IDA) are common among patients with heart failure (HF). They are associated with increased hospitalizations and all-cause mortality. Intravenous (IV) iron repletion has been associated with significant improvement in these outcomes, but is underutilized during HF admissions. Electronic medical record (EMR) based tools to increase recognition of ID and IDA in patients with HF and promote treatment with IV iron have not been described.

We developed an EMR based tool to identify patients admitted with HF with ID and IDA who were candidates for IV iron repletion in an urban academic medical center.

Hypothesis:
ID and IDA are underdiagnosed and undertreated among patients admitted for HF. EMR based tools can be used to systematically identify patients with ID, IDA, and increase appropriate use of IV iron in patients with HF.

Methods:
Retrospective analysis of patients admitted with HF between March and May 2023. The EMR based tool defined HF by encounter diagnosis and use of IV diuretics, anemia by hgb of < 13 g/dl (male) and < 12 g/dl (female), ID by ferritin < 100 ng/ml or ferritin < 300 ng/ml and iron saturation < 20%, IDA by presence of ID and anemia, and if the patient received IV iron. Presence of HF, anemia, ID, IDA, and use of IV iron were confirmed by manual chart review.

Results:
The EMR based tool identified 116 patients admitted with a diagnosis of HF who received IV diuretics. In total, 103 (89.6%) had clinically decompensated HF by chart review. Three patients were excluded due to leaving AMA or on hospice. The average patient age was 63.8 years, 49 (50%) were male, and 50 (50%) were female, and 72 (73%) were African American (AA). In this sample, 81 (82%) had anemia, of which 47 (58%) had both ferritin and iron saturation levels collected during the admission. A total of 15 (19%) had no record for ferritin, iron saturation, or both. By including labs from prior admissions, a total of 64 (65%) of the 99 patients had ID while 57 (58%) had IDA. In total, 22 received IV iron (34% of patients with ID, 39% of patients with IDA).

Conclusions:
An EMR based tool can be used to identify patients with HF, ID, IDA, and the use of IV iron. ID and IDA are prevalent among patients with HF but remain underdiagnosed and undertreated.
Abstract 18621: Platelet Aggregation is Heightened in Those With Metabolic Syndrome and Less Effectively Mediated by Aspirin Therapy
Authors: Mata Vivas Maria Teresa , Garshick Michael , Drenkova Kamelia , Berger Jeffrey
Published: December 2023

Background:
Patients with metabolic syndrome (MetS) are at a higher risk of developing cardiovascular disease (CVD); however, interventions to mitigate this risk are not fully known. Platelets play a significant role in atherothrombosis, and aspirin is an important, yet controversial therapy used for the primary prevention of CVD. In this study, we examined platelet phenotype in MetS and degree of inhibition from ex vivo aspirin administration.

Methods:
In a study examining the mechanisms of atherothrombosis in pro-inflammatory conditions, patients without clinical CVD were enrolled and underwent phenotyping. Patients with MetS (n = 34, age 53.3 ± 13 years, 59% male) were compared to patients with no MetS (n = 63, age 41.1 ± 16 years, 52% male). Platelet aggregation of freshly isolated platelets was measured via light transmission aggregometry (LTA) in resting and stimulated conditions, in response to agonists adenosine diphosphate (ADP), high and low dose of arachidonic acid (AA), and after ex vivo aspirin (ASA) administration.

Results:
MetS patients were older and similar in sex and race (Figure 1A). As expected, patients with MetS had higher individual components of MetS, yet similar LDL-C (Figure 1A). Platelet aggregation to low dose ADP (p=0.09) and AA (p=0.04) was significantly increased in MetS (Figure 1B). Platelet aggregation in response to AA and coincubation with ASA was significantly lower in the no MetS cohort (Figure 1C). The efficacy of aspirin therapy was significantly lower in MetS (Figure 1D). In response to high dose AA after ASA treatment, platelet aggregation increased as number of MetS parameters also increased (Figure 1E). However, no individual metabolic syndrome parameter appeared to be driving these findings (Figure 1E).

Conclusion:
Among MetS patients, platelet aggregation is heightened and less inhibited by aspirin than those with no MetS. Additional research is warranted to explore possible anti-platelet strategies in patients with MetS.
Abstract 18627: The Relative Contribution of Perfusion vs. Congestion in Predicting Adverse Outcomes in Heart Failure With Preserved Ejection Fraction
Authors: Jani Vivek P , Vaishnav Joban , Vungarala Soumya , Hahn Virginia S , Kass David A , Sharma Kavita
Published: December 2023

Background:
Heart Failure with Preserved Ejection Fraction (HFpEF) constitutes greater than half of all heart failure (HF) patients with limited therapies. There are limited data on the role of congestion versus perfusion in prognosticating outcomes.

Methods:
A total of 243 patients seen at the Johns Hopkins HFpEF Clinic between 2011-2023 with HFpEF and RHC were included for analysis. Subjects were stratified into congestion and perfusion groups based on the median PCWP and CI, which were 15 mmHg and 2.44 L/min/m
2
, respectively. Groups were assigned as follows: dry-warm (PCWP < 15 mmHg, CI ≥ 2.44 L/min/m
2
), wet-warm (PCWP ≥ 15 mmHg, CI ≥2.44 L/min/m
2
), dry-cold (PCWP < 15 mmHg, CI < 2.44 L/min/m
2
), and wet-cold (PCWP ≥ 15 mmHg, CI < 2.44 L/min/m
2
), seen in
Figure 1A
.

Results:
Subjects with hypoperfusion (wet-cold and dry-cold) were older (p=0.01), more likely to have atrial fibrillation (p<0.0001), had worse RV function (p=0.002), and had elevated NT-proBNP (p=0.0001) compared to subjects with normal perfusion. Congested patients were more likely female (p=0.002), had higher BMI (p=0.02), higher creatinine (p=0.005), evidence of metabolic syndrome, including elevated fasting glucose (p=0.0008), elevated cholesterol (p=0.01), and LVH on echocardiography (p=0.002). Kaplan-Meier survival analysis of the hemodynamic profiles for a combined end point of all-cause mortality and HF hospitalization revealed that congested profiles exhibited the lowest event free survival compared to the dry profiles (logrank p=0.008;
Figure 1B
) and of these, the wet-warm subjects had the lowest event-free survival at 36 months.

Conclusion:
Unlike in prior HF studies, congestion in HFpEF appears to be concomitant with obesity and metabolic syndrome. Moreover, while consistent with prior studies that congestion drives outcome differences compared to perfusion, wet-warm HFpEF patients appear to have the lowest event free survival as opposed to wet-cold patients as in other forms of HF.
Abstract 18630: Variance In Endocardial Voltage Between The Sinus Node And Other Bi-atrial Regions In Patients With Atrial Fibrillation
Authors: Srivastava Viren , Ganesan Prasanth , Goyal Jatin , Deb Brototo , Azizi Zahra , Narayan Sanjiv M
Published: December 2023

Background:
The mechanisms for atrial fibrillation (AF) are unclear but correlate with substrates such as low voltage and CHADS2VASc risk factors, which is a target for AF ablation after the recent ERASE trial. Experimental models of AF show that fibrosis increases near the sinus node, which may explain the link between AF and sinus node dysfunction. However, such data are less clear in patients without global mapping of all regions simultaneously.

Hypothesis:
We hypothesize that there is a difference in regional endocardial voltages in AF patients mapping globally, specifically between the sinus node and other atrial regions.

Methods:
We studied N = 57 patients undergoing AF ablation with bi-atrial global endocardial voltage data (19 females, LVEF 58 ± 1.5%). Electrograms were collected using 64 pole basket catheters in the right (RA) and left (LA) atrium for 1 minute. We used custom software to analyze 3D electroanatomic maps (NavX, Abbott, IL) for voltages in 3 predefined regions in the RA near and remote from the sinus node, and in the LA (Fig 1).

Results:
Patients exhibited lower voltages in the lateral RA (0.43 ± 0.05 vs 0.66 ± 0.06 mV; p < 0.05), and the RA septum (0.46 ± 0.04 vs 0.66 ± 0.06 mV; p < 0.05) compared to the sinus node, respectively. Patients also exhibited lower voltages in the lateral RA compared to the LA roof (0.43 ± 0.05 vs 0.57 ± 0.05 mV; p < 0.05). The difference between the sinus node and the LA roof (0.66 ± 0.06 vs 0.57 ± 0.05; p > 0.05) and other regions failed to reach significance. No difference between combined right atrial voltage and left atrial voltage was found. Differences were maintained for successive time windows over 1 minute.

Conclusion:
We observed consistent regional variations in atrial voltage in AF patients, and higher voltage in the sinus node than other regions. Future studies should determine if this underlies the link between AF and sinus node dysfunction, and if this varies in comorbidities such as diabetes mellitus.
Abstract 18644: Disparities in Inpatients’ Perceptions, Evaluation, and Responses to Worsening Heart Failure Symptoms- Racial and Financial Status
Authors: Hammash Muna , Alkawaldeh Mohammad , Lin Chin-Yen , Moser Debra K
Published: December 2023

Background:
Most patients with heart failure (HF) exhibit a broad symptom profile, sporadically marked by periods of acute exacerbation and readmission that can be prevented by symptom monitoring and adequate self-care. Yet, patients are frequently unable to adhere to appropriate self-care measures. Reasons for non-adherence are multifactorial including disparities related to race and financial status, and are insufficiently investigated. Thus, a secondary analysis study was conducted to 1) compare HF inpatients’ knowledge, cognitive function and HF self-care based on their race (Black and White), and financial status (higher if they reported having “enough or more than enough to make ends meet” and lower if they “did not have enough to make ends meet”), and 2) investigate disparities in patients’ perception and evaluation of symptoms, and actions taken during HF exacerbation based on their race and financial status.

Methods:
A total of 185 patients (62 years ±13, 49 % female, 76% white) admitted for acute HF exacerbation completed standardized instruments measuring cognitive function, HF knowledge, HF self-care, perception of, and responses to HF symptoms. Chi-square and independent samples t-test analyses were used.

Results:
Black patient with HF had lower levels of HF knowledge, cognitive function, and engagement in self-care maintenance behaviors than White patients (p <.05). Black patients believed medication nonadherence, excessive fluid intake, hypertension, and overeating were causes of their worsening symptoms (p <.05). Black patients tended to call an ambulance in response to worsening symptoms while White patients took their water pill (p = 0.03). Patients with lower financial status reported higher body mass index than those with higher financial status (p = .03). Patients with lower financial status linked their symptoms to depression and lung problems (p =.02), but they did nothing to manage symptoms and hoped their symptoms would go away (p < .05).

Conclusions:
Interventions that take into account culture and financial status are needed to mitigate racial disparities, improve symptom perception, and promote appropriate responses in HF patients.
Abstract 18653: Long Term Outcomes in Patients With Systemic Lupus Erythematosus Undergoing Cardiac Surgery: A Propensity Analysis
Authors: wassif heba , Kramer Benjamin , Honnekeri Bianca , Lowry Ashley , Blackstone Eugene H , Gad Mohamed M , Littlejohn Emily , Menon Venu , Roselli Eric E , Braghieri Lorenzo
Published: December 2023

INTRODUCTION
The burden of cardiovascular diseases, including coronary artery disease and valvular disease, is greater in patients with systemic lupus erythematosus (SLE) than in the general population. There is a paucity of robust data on short- and long-term outcomes after cardiac surgery in patients with SLE.

AIM To evaluate early (<30 days) and late post-operative morbidity and mortality in patients diagnosed with SLE who underwent valve repair or replacement with or without coronary artery bypass grafting (CABG) compared to non-SLE patients.

METHODS
This retrospective propensity matched comparative effectiveness study examined outcomes of patients who underwent valve repair or replacement with or without CABG, from 1/2000-1/2021. Outcomes in non-SLE and SLE surgical population were compared using 2:1 propensity score matching, accounting for baseline patient and procedural characteristics. Primary end points were 30-day and time-related mortality. Additional outcomes included occurrence of stroke, dialysis, blood transfusions, surgical re-exploration, and duration of intensive care unit (ICU) and hospital length of stay.

RESULTS
A total of 275,827 patient-years of follow-up information was available; median follow-up for death was 4.3 years. After matching, 265 patients with SLE were compared to 529 without SLE. Both cohorts demonstrated similar in-hospital mortality (2.8% SLE vs. 1.5% Non-SLE,
P
=.25), one-year survival (90% SLE vs. 89% Non-SLE) and 5-year survival (76% SLE vs. 71% Non-SLE). Length of post-operative ICU stay was shorter in the SLE cohort (
P
=.007).

CONCLUSION
In patients with SLE selected to undergo cardiovascular surgery, in-hospital, 1 and 5-year morbidity and mortality were similar to the general operative population. A jeopardy for a diagnosis of SLE was not present.
Abstract 18666: SR-BI and Tyrosine Kinase Inhibitors: A Novel Pathway for Atherosclerotic Cardiovascular Disease Therapeutic Development
Authors: Sucharski-Argall Holly C , Jurs Sallie J , Argall Aaron D , Williams Jordan L , Dewali Revati S , Dudley Emma K , Comisford Luke , Gulik Nondyce C , Lah Alaina A , Stanford Kristin I , Mohler Peter J , Koenig Sara N
Published: December 2023

Introduction:
Cardiovascular disease (CVD) is the leading cause of death in the U.S., where coronary artery disease (CAD) accounts for 42.1% of all CVD deaths. Current therapeutics focus on lowering LDL-C, as previous attempts to raise HDL-C were not successful in altering CVD outcomes. However, the therapeutic potential of HDL has not been fully explored. Variants in SCARB1, the gene that encodes HDL receptor Scavenger Receptor B1 (SR-BI), are associated with dyslipidemia and atherosclerotic CVD (ASCVD), and we first to identified Mendelian inheritance of SCARB1 variants that cause severe early-onset CAD and dyslipidemia. Limited clinical evidence suggests imatinib reduces total cholesterol in chronic myeloid leukemia (CML). Additionally, TKI treatment in atherosclerotic mice reduced total cholesterol (imatinib) and atherosclerotic lesions (dasatinib). Yet, no data is available on the effects of TKIs on HDL and RCT.

Hypothesis:
Our findings suggest that HDL function (vs. HDL-C concentration) in reverse cholesterol transport (RCT) may be a promising target for cholesterol-based therapy and studying TKIs in RCT may provide a novel mechanism for therapeutic development.

Methods:
We performed a high throughput drug screen with 788 FDA-approved compounds, using HepG2 cells to measure endogenous HDL binding. We identified four compounds that significantly increased HDL binding, of which, imatinib was the only one to increase SR-BI. Wildtype C57Bl/6 mice on a high fat, high cholesterol diet, underwent imatinib treatment for 4 weeks and measured biweekly serum lipids.

Results:
We have found that imatinib and dasatinib significantly enhance HDL binding, where imatinib increased SR-BI, ABCA1, and ABCG1 in vitro. Furthermore, in vivo imatinib treatment decreased plasma total cholesterol, HDL-C and triglyceride levels, and elevated hepatic SR-BI. Knockdown of SR-BI in HepG2 cells ameliorated the imatinib-induced HDL binding increase suggesting an SR-BI-specific mechanism. Mass spectrometry revealed a novel SR-BI methionine oxidation site with imatinib treatment.

Conclusions:
Our data supports the exploration of TKI-mediated SR-B1 regulation, HDL metabolism, and RCT mechanism to identify new therapeutic targets for dyslipidemia and ASCVD.
Abstract 18673: Lack of Influence of Comorbidities on NT Pro-BNP/BNP Ratio in ATTR-CA: A Prospective, Single Sample, Paired Data Analysis
Authors: Satyavolu Bharadwaj , Bittencourt Marcio , Vasilakis Georgia M , Al Ahmad Majd F , Medoff Brent , Soman Prem
Published: December 2023

Introduction:
Scores to stage amyloidosis include laboratory values of NT pro-BNP and BNP. However, no prior data on the correlation between the two markers is available for the same sample in ATTR patients with a spectrum of co-morbidities. While established staging systems for cardiac amyloidosis use NT-pro BNP, many centers routinely measure BNP. To facilitate universal staging, we explored the relationship between NT-pro BNP and BNP measured from a single blood sample in ATTR patients with a spectrum of co-morbidities.

Hypothesis:
The ratio of NT pro-BNP to BNP is influenced by atrial fibrillation, BMI, left ventricular and renal function.

Methods:
ATTR-CA patients had serial NT pro-BNP and BNP measured from a SINGLE blood sample. Ratios were compared in patients stratified by co-morbidities. A regression equation to derive BNP from NT pro- BNP was created.

Results:
Among 101 patients, (85% men, 84% Caucasian), co-morbidities were prevalent (atrial fibrillation: 56%, LVEF < 50%: 46%, GFR <60 mL/min/1.73 m
2
: 51%, BMI ≥ 27: 51%); 4% were on ARNI. A strong correlation (r = 0.83) and a ratio of the log transformed data of 1.32 (95% CI: 1.29 - 1.34) was found between NT-pro BNP and BNP levels, which was not different among patients stratified according to co-morbidities. The relationship between NT pro-BNP and BNP was defined by ln(BNP) = 0.59 + 0.69 ln(NT pro-BNP).

Conclusions:
Our study suggests a robust correlation between NT-pro BNP and BNP in ATTR-CA patients and a constant ratio among patients with different co-morbidities. A regression equation may facilitate deriving BNP levels from NT- pro BNP and must be validated independently.
Abstract 187: Diabetes is Associated With Mortality Among Comatose Survivors of Cardiac Arrest but Does Not Interact With Blood-Pressure Targets
Authors: Josiassen Jakob , Beske Rasmus Paulin , Schmidt henrik , Kjaergaard Jesper , Moller Jacob , Hassager Christian
Published: December 2023

Introduction:
The prevalence of diabetes (DM) is increasing and associated with cardiovascular morbidity and mortality. Whether patients with DM may benefit from other treatment targets after cardiac arrest remain sparsely described.

Aim:
This study aimed to assess blood-pressure targets among patients with and without DM successfully resuscitated from out-of-hospital cardiac arrest (OHCA).

Methods:
In a large double-blind RCT, a mean arterial blood-pressure (MAP) of 63 mmHg (Low) vs 77 mmHg (High) was targeted among OHCA patients with a presumed cardiac cause. Patients were stratified according to DM and the primary endpoint was all-cause 365-day mortality. In addition, a Cox regression model with DM and treatment allocation interaction was used and adjustment for age and sex was additionally performed.

Results:
A total of 789 patients were included of which 110 (14 %) had DM. The DM patients were older (median 67 vs 63 years) and had more comorbidities including hypertension (75 vs 41 %) and ischemic heart disease (31 vs 20 %) p<0.05 for all. The DM and non-DM patients showed similar characteristics with regards to prehospital management including bystander CPR (87 vs 88 %), time to advanced life support (median 7 vs 7 min), shockable rhythm (87 vs 90 %) and time to ROSC (median 19 vs 18 min), p NS for all. Upon hospital arrival the DM patients presented with higher lactate (median 6.7 vs 4.6 mmol/L p<0.001) and higher blood glucose (median 17.4 vs 12.8 mmol/L p<0.001). An increased 365-day mortality was observed among DM patients, Figure. Adjusted p=0,07. In the Cox model no modifying effect of the MAP targets was observed (p DM x MAP =0.24). Hazard ratio CI 95 % High vs Low for DM 0.81 [0.46;1.44], p= 0.48 and non DM 1.18 [0.91;1.53], p= 0.21. Upon adjustment (p DM x MAP =0.27).

Conclusion:
Diabetes was associated with mortality among OHCA patients which was partly driven by age. No difference was however observed whether a MAP of 63 mmHg or 77 mmHg was targeted.
Abstract 18715: A Cardiovascular Health Literacy Intervention Targeting Arab Women
Authors: Greenberg Keren , Saifi Aisha , Nubani Husseini Maha , Karjawally Mayada , Agbaria Nisreen , Zwas Donna
Published: December 2023

Health Literacy (HL) is defined as an individual's motivation and ability to gain access to, understand and use information in ways which promote and maintain good health. Low health literacy is associated with increased cardiovascular risk factors. Arab women in Israel are at high cardiovascular risk with cardiovascular mortality that exceeds the mortality in Jewish women by 60%, and may have reduced health literacy.

Objectives:
To assess HL in Arab women in East Jerusalem and to design, implement and evaluate an interactive HL intervention in Arab women that will lead to an Increase in the percentage of women who utilize effective patient-doctor communication skills, increased self efficacy with regards to the patient-doctor interaction, improved comprehension of test results and increased cardiovascular knowledge.

Methods:
Tailored 3 session workshop. Questionnaires were administered before and 3 months after the intervention.

Results:
267 women participated. 12.1% had inadequate health literacy and 24.2% had problematic health literacy. Of these women, there were matched pre/post questionnaires for 195 women. Matched participants reported increased preparatory behaviors before doctor visits including preparing symptom lists, question lists, medication lists, and medical documents (all p<.001.) They reported increased scores on the Perceived Efficacy in Patient-Physician Interactions scale (7.25 to 7.95, p<.001) , in particular in low efficacy participants who increased from 5.6 to 7.7, p<.001. Health literacy as measured on the HLS-EU-16 increased from 12.6 to 14.33 (p<.001), and 84.5% were in the sufficient range.

Conclusions:
A three session, tailored interactive HL workshop improved patients’ pre-visit preparation skills, self-efficacy and HL in a convenience sample of Arab women from East Jerusalem. HL can be improved with intervention and as such can be considered a modifiable risk factor for cardiovascular disease.
Abstract 18718: A Deep Learning Model for Classifying Left Ventricular Enlargement Using Transthoracic and Point-of-Care Echocardiograms
Authors: Malins Jeffrey G , Anisuzzaman DM , Jackson John , Lee Eunjung , Naser Jwan , Rostami Behrouz , Bird Jared , Friedman Paul , Lopez-Jimenez Francisco , Attia Zachi , Pislaru Sorin , Kane Garvan
Published: December 2023

Background:
Enlargement or dilation of the left ventricle (LV) is associated with increased cardiovascular morbidity and mortality, and is an established precursor of ventricular dysfunction and heart failure in almost all major cardiovascular conditions. Although there are existing artificial intelligence frameworks that make use of deep learning to detect LV enlargement, many entail LV segmentation, which can be error-prone especially for point-of-care ultrasound (POCUS) images.
Goal:
To develop a fully end-to-end deep learning framework that takes as input either transthoracic echocardiographic (TTE) or POCUS 2D image clips, and classifies directly (i.e., without first segmenting the LV) whether a patient has an enlarged LV.

Methods:
Using a sample of retrospective TTE data enriched for LV enlargement (out of 13,868 patients total, 3,351 had an enlarged LV defined using sex-specific guideline-directed criteria), we trained a classifier that takes as input apical 2-chamber and parasternal long axis videos, and provides as output a binary label denoting whether a patient has an enlarged LV. Then, we evaluated the trained model using a holdout testing dataset of retrospective TTE data (2,087 patients) as well as data from a prospective cohort of 428 patients from whom TTE and POCUS were collected simultaneously.

Results:
For the retrospective TTE testing dataset, the AUC was 0.851 (95% confidence interval (CI) of 0.830-871). For the prospective cohort, the model performed comparably for both TTE and POCUS video clips (TTE: AUC of 0.865, 95% CI of 0.823-0.906; POCUS: AUC of 0.840, 95% CI of 0.797-0.883).

Conclusions:
The current deep learning model performed comparably well for both TTE and POCUS echocardiograms. We regard these results as a proof-of-concept of the potential utility of this model in helping point-of-care clinicians make decisions regarding whether patients should receive further evaluation for LV enlargement and associated conditions.
Abstract 18768: Diagnosis of Occult Atrial Fibrillation in Patients With Embolic Stroke of an Undetermined Source Based on Left Atrial Strain
Authors: Maqsood Hamza , Jumani Laraib , Wazir Momna , Raza Samina , Munir Maryam , Noor Nabeeha , Mehmood Saad , Neelam FNU , Gulraiz Azouba , Saleem Hamza
Published: December 2023

Introduction and Hypothesis:
A late electrocardiographic evaluation of patients with embolic stroke of an undetermined source (ESUS) can show atrial fibrillation as a potential cause of embolic stroke. Existing literature has highlighted that left atrial dysfunction can lead to the development of paroxysmal atrial fibrillation (PAF) and subsequent embolism. Our study sought to evaluate the diagnosis of occult atrial fibrillation in patients with embolic stroke of an undetermined source based on abnormalities in the left atrial strain.

Methods:
230 patients were included in our multi-center, observational study with the mean age as 56.4 years and 26% females. We followed up on these patients for the occurrence of paroxysmal atrial fibrillation and recurrent ischemic stroke. Trans thoracic echocardiography (TTE) was done, and images were subsequently analyzed for spackle tracing deformation patterns. Primary and secondary outcomes included plotting these atrial strain values against PAF and recurrent ischemia, respectively.

Results:
198 patients completed the study. Patients with newly diagnosed PAF had more abnormal left atrial reservoir strain (LASr; 27.3% ± 12.2%, P<0.05) and left atrial conduit strain (LAScd; -13.7% ± 6.2%, P<0.05) compared with patients who had normal rhythm. Multivariable logistic regression analysis showed that LAScd was associated with occult PAF (adjusted odds ratio [aOR] = 1.212, 95% CI, 1.043-1.314, P<0.05) and the composite outcome of AF and recurrent ischemic stroke (OR = 1.146, 95% CI, 1.023-1.185, P<0.05).

Conclusions:
Our study concluded that abnormal left atrial strain is associated with the detection of occult AF in patients admitted with embolic stroke of undetermined origin. Early detection of etiology by determining left atrial strain can lead to better prognosis and good clinical outcomes.
Abstract 18778: Patient-Derived Stem Cell Models of Pediatric Restrictive Cardiomyopathy Exhibit Increased Resting Tension and Cardiomyocyte Calcium Sensitivity
Authors: Staudt David , Serrano Ricardo , Ozaki Tan Sho , Feyen Dries , Mercola Mark
Published: December 2023

Introduction:
Pediatric Restrictive Cardiomyopathy (RCM) is a genetic cardiomyopathy resulting from profoundly increased stiffness of the wall of the cardiac ventricle with normal or low normal contractility. Treatment options are limited, with most patients necessitating heart transplant. Therapies that can improve diastolic function are needed for this severe disease. However, development of novel therapies has been limited by a paucity of models of this rare disease. Here, we develop two novel models of pediatric RCM and use novel high-throughput functional analysis to measure diastolic dysfunction and defects in calcium handling.

Hypothesis:
Patient-derived human induced pluripotent stem cell (hiPSC) models of pediatric RCM will exhibit increased resting tension indicative of diastolic dysfunction, as well as increased calcium sensitivity.

Methods:
Cardiomyocytes were differentiated from hiPSCs derived from two pediatric patients with RCM, as well as a paired isogenic CRISPR-corrected lines. Cells were replated onto polyacrylamide gels and stained with calcium sensitive dyes, and contractility, resting tension, and calcium sensitivity were measured using a novel high-throughput functional imaging platform.

Results:
RCM cells from both patients showed elevated contractility, resting tension, and calcium sensitivity compared to their isogenic controls.

Conclusions:
Patient-derived RCM cells show alterations in calcium sensitivity and resting tension that recapitulate and explain the diastolic dysfunction seen in patients. These lines, combined with the high-throughput measurement platform described here, will provide a powerful platform for exploring novel therapeutic strategies for this severe disease.
Abstract 18791: Sex Differences in the Phosphorylation of Argonaute 2 Result in Reduced Translocation of Micro RNA-181c Into the Mitochondria and Cardioprotection in Pre-Menopausal Females
Authors: Quiroga Diego T , Roman Barbara , Garbus Haley , Ebenebe Obialunanma , O'Rourke Brian , Kohr Mark J , Das Samarjit
Published: December 2023

Introduction:
MicroRNAs (miRNAs) play a crucial role in regulating gene expression and have been implicated in various aspects of cardiovascular health and disease. miR-181c is known to be upregulated in obesity, and its translocation into cardiomyocyte mitochondria leads to excessive production of Reactive Oxygen Species(ROS). ROS-mediated degradation of Sp1, a transcription factor for MICU1, results indecreased MICU1 expression and subsequent mitochondrial [Ca2+] accumulation, leading to heart failure. We hypothesized that phosphorylation of Argonaute 2 (pAGO2) at Ser 387could inhibit the translocation of miR-181c into mitochondria by enhancing the stability of the RNA-induced silencing complex in the cytoplasm. Estrogen (E2) could provide cardioprotection in pre-menopausal women against the consequences of mitochondrial miR-181c upregulation by phosphorylating AGO2.

Hypothesis:
We hypothesize that sex differences in pAGO2 levels lead to reduced translocation of miR-181c into mitochondria, thereby influencing the cardiac response observed in pre-menopausal females compared to males.

Methods:
This study utilized male, female, and ovariectomized (OVX) mice as
in
vivo
model. AC16 cardiomyocyte cell line was treated with E2 and transfected with miR-181c to mimic conditions of miR-181c upregulation. qRT-PCR was performed to assess miR-181c, SP1, and MICU1 expression levels. Western blot analysis was employed to detect protein levels.

Results:
Our results revealed significantly higher levels of pAGO2 in pre-menopausal female mice compared to males. This increased pAGO2 phosphorylation was associated with decreased translocation of miR-181c into mitochondria in pre-menopausal females, and this condition was reversed in OVX mice. In AC16 cells, E2 treatment normalized the aberrant degradation of Sp1 and the dysregulation of MICU1 induced by miR-181c overexpression.

Conclusion:
This study provides evidence of sex differences in pAGO2 levels, suggesting that reduced translocation of miR-181c into mitochondria contributes to the observed cardiac effects in pre-menopausal females.
Abstract 18795: Low Density Lipoprotein Cholesterol Levels at Baseline and the Need for Additional Non Statin Lipid Lowering Therapy for Attaining Lipid Targets in Patients Presenting With Acute Coronary Syndromes- A Retrospective Study
Authors: Pradhan Akshyaya , Singh Ajit Pratap , Rana pradeep , Bhandari Monika , Vishwakarma Pravesh , singh Abhishek , Shukla Ayush , Kumar Sharma Akhil , Chaudhary Gaurav K , Chandra Sharad , sethi rishi , Dwivedi Sudhanshu K
Published: December 2023

Introduction:
CAD is the leading cause of death globally, with more than 17.3 million deaths per year. Multiple modifiable and non-modifiable factors may contribute to cardiovascular risk; among them, LDL-C levels play a crucial role in the pathophysiology of ACS.

Objectives:
To study the baseline LDL in ACS patients and Predict the need for additional lipid lowering therapies other than high-dose statins for attaining LDL-C goals.

Methods:
This is a single-centre retrospective study analysing LDL-C levels at the time of admission for ACS.

Results:
A total of 1880 ACS patients were enrolled (75.3% STEMI & 19.7% NSTEMI) with a mean age of 56±11.79 years (82% males).The mean LDL-C was 74.73mg/dL, with 79 % of patients having LDL less than 100 mg/dL and 89% of patients having LDL-C levels less than 130 mg/dL. Patients less than 40 years of age had a mean LDL of 88.01 mg/dL, while individuals over 60 years had 69.03 mg/dL (p- <0.001). No significant correlation was observed between angiographic severity and LDL-C levels in 1259 patients who underwent coronary angiography. Most patients (96%) received high-dose statin (Atorvastatin 80 mg and Rosuvastatin 40 mg) on discharge. Considering the expected LDL-C reduction by 50 % with high intensity statins alone, the target LDL-C goals as prescribed by ESC guidelines (< 55 mg/dl) and ACC/AHA guidelines (< 70 mg/dl) would be attained by 79% & 89% of patients respectively on follow up. With high intensity statin plus ezetimibe combination (with an expected 65% LDL-C reduction), 89% patients could achieve LDL-C goal by ESC guidelines criteria and > 99% would attain LDL targets set by ACC/AHA guidelines.

Conclusions:
In this south Asian cohort of ACS patients, the LDL-C levels at presentation were lower compared to western studies and more than three quarters could potentially achieve their LDL-C targets by high intensity statin alone. The results could have potential implications for non-statin therapy utilization.
Abstract 18817: Dysregulation of Key Calcium Cycling Genes Does Not Drive Right Heart Maladaptation in a Porcine PH Model
Authors: Ravichandran Anjali J , Mazurek Renata , Mavropoulos Spyros , Sakata Tomoki , Ishikawa Kiyotake , Marx Jonas
Published: December 2023

Introduction:
Pulmonary hypertension (PH), a complex disease characterized by an elevated pulmonary artery pressure, causes maladaptation in patients. Maladaptation, or the hemodynamic and functional changes involved in RV/PA uncoupling, leads to poorer outcomes in patients. Dysregulation of calcium cycling controlled by SERCA2a and modulators, PLN and SUMO1, has been shown to cause left heart failure (HF), however its role in right heart maladaptation is unclear.

Hypothesis:
The dysregulation of the key calcium cycling genes, SERCA2a, PLN, and SUMO1 contributes to the maladaptation in PH.

Methods:
In this retrospective study, tissues of a porcine Yorkshire model of post-capillary PH were analyzed to understand molecular differences in right ventricular (RV) remodeling resulting in refractory symptom presentation (maladaptive group,
n
=6) or symptom absence (adaptive group,
n
=5). Pulmonary and cardiac hemodynamics, functional assessment, echocardiography, and pressure-volume relationship data were collected. Sham control group, (
n
=5) received left thoracotomy only.

Results:
Calcium cycling genes known to be dysregulated in left HF did not display significant differences in group or spatial expression across RV, septal, and LV tissues (Figure). Other significant findings include increases in RV hypertrophy (p<0.001) and stroke work (p=0.0036) when comparing maladaptive and sham group (
n
=5) with RV dilation only in maladaptive group (p=0.0004).

Conclusions:
Dysregulation of calcium cycling genes in the RV does not explain symptom presentation in the maladaptive group and suggests different processes underlie left and right HF. RV dilation is likely a key driver of maladaptive symptom presentation in a porcine model of PH.
Abstract 18831: The Protective Effect of Duffy Antigen Receptor for Chemokines Gene Deletion on Abdominal Aortic Aneurysm Formation: Role of Lysyl Oxidase
Authors: Aboud Ghaith , Harb Ragheb , Kim David , Goo Brandee , OGBI Mourad , Veerapaneni Praneet , Chouhaita Ronnie , Coffey Philip , Lee Richard , Benson Tyler W , Owens Phillip P , Bogdanov Vladimir , Guha Avirup , Shi Hong , Kim Ha Won , Weintraub Neal L
Published: December 2023

Introduction:
Epidemiologic studies indicate that Blacks are protected against abdominal aortic aneurysm (AAA), despite similar risk factors as Caucasians. Approximately 70% of Blacks harbor a variant in the Duffy Antigen Receptor for Chemokines (DARC), a non-signaling receptor expressed primarily on erythrocytes which binds and regulates inflammatory chemokines. Since chemokines play a critical role in AAA, we tested the hypothesis that lack of DARC expression on erythrocytes protects against AAA, and we investigated the mechanisms.

Methods:
Mice lacking DARC on hematopoietic cells were created by mating DARC flox/flox mice with Vav1-Cre mice. At 10-14 weeks of age, both Vav1-Cre positive (DARC
HKO
) and Vav1-Cre - mice [wild type (WT) littermate controls] received PCSK9 adeno-associated virus injection and were started on high fat diet. After 1 week, mice were infused with angiotensin II (AngII, 1,000 ng/kg/min) via osmotic minipump for 26 days to induce AAA.

Results:
Compared to WT, there was no difference in blood pressure or cholesterol levels in AngII-infused DARC
HKO
mice, which were confirmed to lack DARC on erythrocytes by flow cytometry. Aortic diameter and AAA incidence were significantly decreased in DARC
HKO
compared to WT mice (n=16-20, p=0.0257), in conjunction with reduced elastin degradation and macrophage infiltration. We did not find differences in levels of DARC-bound chemokines that could account for the protection against AAA. Interestingly, we found that the level and activity of lysyl oxidase (LOX), a cytokine-like enzyme that crosslinks extracellular matrix proteins and protects against AAA, were higher in DARC
HKO
mice compared to WT mice.

Conclusions:
Loss of DARC on hematopoietic cells protects against AAA formation, likely by upregulating aortic LOX. These findings provide novel insight into ethnic differences in susceptibility to AAA.
Abstract 18846: A Noninvasive Smartphone Assessment of Aortic Arch Pulse Wave Velocity and Total Arterial Compliance
Authors: Niroumandi Soha , Rinderknecht Derek , Bilgi Coskun , Wolfson Aaron , Vaidya Ajay , King Kevin S , Pahlevan Niema M
Published: December 2023

Introduction:
Several clinical studies including a large multiethnic population (Dallas Heart Study) have shown that total arterial compliance (TAC) and aortic arch pulse wave velocity (PWV
aa
) are predictors of cardiovascular disease (CVD) events. Dallas Heart Study also showed that PWV
aa
predicts brain white matter hyperintensity volume independent of cardiovascular risk factors. Recently, Intrinsic Frequency (IF) analysis of carotid pressure waveform from the Framingham Heart Study was used to predict heart failure (HF) events and CVD (Hypertension, 2021 PMID: 33390053).

Aim:
Our goal was to show the IF method can determine PWV
aa
and TAC when applied on carotid pulse waveforms obtained from a standard iPhone camera.

Methods:
The clinical cohort consisted of 120 individuals (40% women) with ages from 20-92 yrs (mean 53 ± 18), including 54 healthy and 66 patients with CVD (22 HF). Phase-contrast magnetic resonance imaging (PC-MRI) and carotid pressure tonometry data were used to compute TAC. PWV
aa
values were obtained using PC-MRI flow in ascending and descending aorta (not achieved in 1 patients). A custom Apple iPhone 5S application was used to obtain carotid pulse waves by holding the camera against the neck. IF parameters of iPhone waveforms (calibrated by cuff brachial pressures) were used in machine learning algorithms (IF-iPhone). The models of TAC and PWV
aa
were developed using 100 participants (99 for PWV
aa
) and blindly tested on an additional 20 individuals.

Results:
In blind tests, iPhone-IF models showed Pearson correlations of r=0.89 and r=0.84 with the measured values of TAC and PWV
aa
, respectively (Fig.1).

Conclusions:
Assessment of PWV
aa
and TAC can be accurately achieved using an unmodified smartphone (iPhone). PWV
aa
evaluation with an iPhone can be used to identify, predict, and quantify risk of vascular brain damage. A Noninvasive iPhone-based method can be used in a clinical or home setting to routinely assess TAC in the general population or in HF.
Abstract 18850: Impact of Intravascular Imaging-Guided versus Coronary Angiography-Guided Percutaneous Coronary Intervention on Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Yasmin Farah , Jawed Kinza , Moeed Abdul , Hassan Omer , Rahman Saad Ur U
Published: December 2023

Background:
Intravascular imaging (IVI) namely intravascular ultrasound (IVUS) and optical coherence tomography (OCT), presents as a promising imaging modality for drug-eluting stent (DES) implantation compared to the gold-standard conventional two-dimensional angiography. IVI provides detailed information on vessel lumen, lesion length, and degree of calcification. For this purpose, we conducted a meta-analysis by pooling recently conducted randomized control trials (RCTs) to compare IVI with angiography for DES implantation.

Hypothesis:
IVI is associated with a significant reduction in CV events for DES implantation.

Methods:
Fourteen RCTs reporting CV outcomes with IVI versus angiography-guided stent implantation in CAD patients undergoing PCI were included in MEDLINE, and Scopus databases (Inception till May 2023). The primary outcome of interest was target-lesion revascularization (TLR). The outcome measures were summary random effects risk ratio (RR) with 95% confidence intervals.

Results:
A total of 8,946 patients (IVI 4,751 vs. angiography 4,195; mean age 61.7 years) were included. Over a median follow-up of 15 months (12-24.3), IVI was associated with significantly reduced TLR (RR 0.63 [0.49, 0.79]; Figure 1), target vessel revascularization (RR 0.66 [0.53, 0.83]), and major adverse cardiovascular events (MACE) (RR 0.69 [0.58, 0.78]) vs. conventional angiography for PCI. However, no significant difference was observed in all-cause mortality between the two imaging modalities (RR 0.85 [0.63, 1.15]). Meta-regression analysis showed no significant impact of follow-up duration, baseline comorbidities such as hypertension, smoking status, previous myocardial infarction, and stent length on TLR incidence.

Conclusion:
IVI was associated with improved CV outcomes in terms of reduced TLR, TVR, and MACE incidence when compared with traditional angiography in CAD patients for stent implantation.
Abstract 18857: Association Between Physical Activity and Risk of Incident Cardiovascular Disease in Women With Novel Risk Factors: Evidence From the UK Biobank Cohort
Authors: Ataei Zhaleh , Ruiz-Carmona Sergio , Wright Leah , Howden Erin
Published: December 2023

Introduction:
Early menopause and complicated pregnancy are associated with a higher risk of cardiovascular diseases (CVD), such as coronary heart disease (CHD) or heart failure (HF). Physical activity (PA) is a modifiable behaviour that typically reduces the risk of CVD; however, it is unclear if this is the case for these novel risk factors.

Hypothesis:
We hypothesised that PA could moderate the risk of incident CVD in women with novel risk factors.

Aims:
This study sought to investigate the effect of PA on the risk of incident CVD in women with a history of early menopause and/or complicated pregnancy.

Methods:
We included 55,930 women (median age 59) with novel risk factors and free from CVD (HF, CHD, arrhythmia, and ischemic stroke) from the UK Biobank Study. Novel risk factors were defined as complicated pregnancy (n=23,627, median age=56), described as a history of any stillbirth or ≥2 miscarriages, gestational diabetes, or hypertensive disorders of pregnancy, and early menopause (n=35,838, median age=60), defined as natural or surgical (bilateral oophorectomy) menopause <47age. Women were categorised into three groups of high (≥1,500 MET-minutes/week), moderate (≥600 MET-minutes/week) and low levels of PA according to their responses to the International Physical Activity Questionnaire (IPAQ). Multivariable Cox proportional hazard models were performed, and the results were adjusted for traditional CVD risk factors such as smoking, alcohol consumption, obesity, diabetes, hypertension, hyperlipidaemia, and cancer.

Results:
At a median follow-up of 13 years, there were 6636 events. A high level of PA was significantly associated with a lower risk of incident HF (hazard ratio [HR] 0.76, 95% CI[0.63 0.90], n= 1374), arrhythmia (HR 0.79, 95% CI[0.70 0.88], n=2699), and stroke (HR 0.77, 95% CI[0.61 0.97], n=797), compared to low levels of PA. We also observed a significant association between moderate levels of PA and reduced risk of incident arrhythmia (hazard ratio 0.78, 95% CI 0.70 0.87) compared to low levels of PA.

Conclusion:
High levels of PA can significantly reduce the risk of most incidents of CVD in women with novel risk factors. Thus, higher PA should be strongly encouraged to women with novel risk factors to lower the risk of CVD.