bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13109: Epigenetic Regulation and Function of Pleiotropic GWAS Locus
LRP1
in Human Induced Pluripotent Stem Cells Derived Contractile Smooth Muscle Cells
Authors: LIU LU , ZAHRA HAIMOUD Fatima , HENRY Joséphine , BERRANDOU Takiy , GEORGES Adrien , BOUATIA-NAJI Nabila
Published: April 2024

Introduction:
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction in young and middle-aged women. A common genetic variant, rs11172113, located in LRP1 (low density lipoprotein receptor-related protein 1) first intron, was associated with several vascular diseases, including SCAD, and regulation of LRP1 expression in arterial tissues. However, the biological mechanisms through which rs11172113 influence LRP1 function in the context of non-atherosclerotic arterial lesions are not known.

Hypothesis:
We hypothesized that rs11172113 genotype affects LRP1 expression through specific mechanisms in contractile smooth muscle cells (SMCs), leading to alterations of their physiological function.

Methods:
We differentiated 4 human induced pluripotent stem cells (iPSCs) lines (2 males, 2 females) towards either contractile or synthetic SMCs using a recently optimized 24-day protocol. We performed RNA-Seq and ATAC-Seq at 6 time points during differentiation. We silenced LRP1 using siRNAs in differentiated SMCs and used CRISPR-Cas9 to induce deletions of the enhancer region containing rs11172113 or frame-shift indels in exons 2 or 5 of LRP1 in iPSCs.

Results:
iPSCs derived SMCs presented the expected morphology and expression of SMC markers. Transcriptomic analyses showed that contractile SMCs harbored SMC properties during late differentiation and resembled SMCs of artery tissue, whereas genes involved in cell stress were upregulated in synthetic SMCs at the end of differentiation. In particular, LRP1 expression and DNA accessibility at rs11172113 were higher in contractile SMCs. The deletion of rs11172113 enhancer region led to a decrease in the expression of LRP1 in both contractile and synthetic SMCs. LRP1 inactivation decreased the proliferation and increased the migration capacity of contractile SMCs. Detailed characterization of the influence of LRP1 on extracellular matrix maintenance and cellular contraction is ongoing.

Conclusions:
We confirmed rs11172113 to regulate LRP1 expression in iPSCs derived contractile SMCs. Our results support LRP1 influence on SMCs phenotype as a causal factor in the genetic susceptibility to SCAD and related vascular diseases.
Abstract 13122: STK25 Regulates the Cardiac PKA Pathway in Human Cardiomyocytes
Authors: Zhang Xiaokan , Wang Bryan Z , Kim Michael , Tamargo Manuel , Nash Trevor , Soni Rajesh , Li Eric , Rao Jenny , Liu Bohao , Lock Roberta I , Vunjak-Novakovic Gordana , Fine Barry
Published: April 2024

Hypothesis:
STK25 regulates cell survival, metabolism and cardiac function through phosphorylating PKA R1α and modulating PKA signaling pathway in human cardiomyocytes.

Background:
Dysregulation of cardiac kinases are related with many cardiovascular diseases including hypertrophy, remodeling and ischemia injury. STK25 is a stress response kinase that regulates cell survival through modulating several signaling pathways and is involved in the metabolism regulation. However, the direct substrates and mechanism of STK25 remain undefined.

Methods:
CRISPR-Cas9 was used to generate a homozygous knockout (KO) of STK25 in induced pluripotent stem cell (iPSC) which were then differentiated into cardiomyocytes (iPSC-CMs) and used for engineered human cardiac tissue generation. Role of STK25 in gene expression, cell proliferation/apoptosis, metabolism and cardiac function were characterized. STK25 was quantified in human left ventricular tissue from heart failure (HF) patients.

Results:
In iPSC-CMs, phospho-proteomic analysis identified PKA signaling as the most significantly upregulated pathway by STK25 deletion. PKA regulatory subunit I α (R1α) was identified as a downstream substrate of STK25 and validated by IP. Loss of STK25 resulted in elevated PKA kinase activity and decreased phosphorylation of PKA targets implicated in cardiac contractility and Ca2+ handling, such as cardiac myosin-binding protein C (cMyBPC), cardiac troponin (cTnT), ryanodine receptor-2 (RyR2) and L-type calcium channel (CaV1.2). Further mechanistic studies revealed that STK25 mediates PKA activity through phosphorylation of the R1α regulatory subunit at S77/83 sites, leading to inhibition of PKA kinase activity. In functional assays, STK25 modulated cell cycle progression, proliferation, hypoxia induced apoptosis, beta adrenergic response, and mitochondrial respiration in iPSC-CMs. We also detected significant increase in STK25 expression and PKA R1α phosphorylation in HF patients versus normal control, demonstrating STK25 altered regulation in heart diseases.

Conclusions:
STK25 kinase is a critical regulator of the PKA pathway in human cardiomyocytes modulating cell growth, metabolism and cardiac function and is aberrantly expressed in heart failure.
Abstract 13132: A Community Program to Prevent Cardiovascular Disease: The Ask About Aspirin Project
Authors: Luepker Russell V , Eder Milton , Finnegan John R , Vant Hof Jeremy R , Duval Sue
Published: April 2024

Objectives:
To test a statewide population and clinic education project to improve guideline-based (2009 USPSTF) appropriate use of low-dose aspirin for the primary prevention of cardiovascular disease (CVD).

Methods:
Minnesota was the education target and the four adjacent Upper Midwest states were controls. The 2015-2020 Ask About Aspirin campaign used digital and traditional media to encourage eligible adults to ask their clinicians about aspirin use for CVD prevention. The clinical strategy included professional education and clinical support tools to improve aspirin candidacy identification and appropriate use indications.Three cross-sectional random telephone surveys of men age 45-79 and women age 55-79 (5,626 in MN, 2,716 controls) evaluated aspirin use.

Results:
The Ask About Aspirin website had over one million visits (Figure 1). Over 1000 clinicians were trained in 124 primary care clinics. The project resulted in small but non-significant changes in campaign awareness (5.3% to 4.7%) and discussions with clinicians (34.1% to 36.5%). After the release of new guidelines (2016) and several controversial aspirin trials (2018-20), the overall use of aspirin fell (41.3% to 34.2%) (Figure 2). Appropriate aspirin use also declined (50.3% to 38.9%) (Figure 2). These changes did not differ significantly from controls.

Conclusions:
A multiyear statewide campaign failed to increase guideline-based aspirin use for CVD prevention. Contextual factors including guideline change and public controversy over aspirin use likely influenced this finding.
Abstract 13136: Immune Cell Mitochondrial Function and Diastolic Function in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Bohmke Natalie J , Chavez Domenico A , Carper Moriah C , Billingsley Hayley E , Del Buono Marco G , Markley Roshanak , Carbone Salvatore , Abbate Antonio , Kirkman Danielle L
Published: April 2024

Background:
Systemic, multimorbidity-driven inflammation may promote diastolic dysfunction in HFpEF. In this regard, anti-inflammatory therapies have been an attractive treatment strategy in clinical trials of HFpEF. Metabolic reprogramming of immune cells that alter the mitochondrial bioenergetic profile may be an upstream mediator of inflammation. Our aim was to investigate the relationship between the immune cell bioenergetic profile and diastolic function in HFpEF.

Methods:
Nine female patients with a diagnosis of HFpEF (4 Black, 5 White; Median [IQR]: Age 60 [46-67] yrs; BMI 37 [34-42] kg/m
2
) were enrolled. The mitochondrial bioenergetic profile was assessed in isolated peripheral blood mononuclear cells by respirometry coupled with modulators of cellular respiration to obtain basal respiration, ATP-linked respiration, maximal respiration and non-mitochondrial respiration. Transthoracic echocardiographic Doppler measures of diastolic function were performed and included mitral inflow velocities (E wave) and early diastolic mitral annular velocity (e’).

Results:
Diastolic function, represented by E/e’ (Median [IQR]: 10 [8-10] was inversely associated with basal respiration (
r
=-0.78, p=0.01), maximal respiration (
r
=-0.87,
p
=0.002), ATP linked respiration (54 [40-105] pmol/min,
r
=-0.75,
p
=0.02), non-mitochondrial oxygen consumption (24 [20-35] pmol/min,
r
=-0.82,
p
=0.007) and spare respiratory capacity (r=-0.82, p=0.007) as shown in Figure 1.

Conclusion:
There is a strong negative association between the immune cell mitochondrial bioenergetic profile and diastolic function in HFpEF. Patients with greater impairment in diastolic function, as shown by higher E/e’ ratios, have lower immune cell respiration and reduced respiratory reserve. The relationship between immune cell mitochondrial function, inflammation and diastolic function in HFpEF patients warrants further investigation.
Abstract 13139: Single Gene Cardiopoiesis Induced in Human Pluripotent Source
Authors: Kargaran Parisa , Li Mark , Terzic Andre , Behfar Atta
Published: April 2024

Introduction:
The process of engaging stem cells towards a cardiopoietic (CP) state was established using a protein-based cocktail consisting of multiple growth factors. Although this regenerative enhancement protocol has been successfully tested in advanced clinical trials, it remains resource-intensive. Recent efforts have focused on streamlining cardiopoiesis through a protein-independent alternative that leverages a transfection-based mRNA approach. Microencapsulated modified messenger RNA (M3RNA) was utilized to deliver brachyury (T), an early mesodermal transcription factor to provoke early lineage specification in pluripotent cells.

Hypothesis:
Transfection of a human pluripotent stem cell source with T induces early expression of CP transcription factors to accelerate cardiac differentiation.

Methods:
Human pluripotent stem cells were transfected with T and maintained for 14 days. Expression of the cardiopoietic markers MEF2C, GATA4, and Nkx2.5 was analyzed using RT-qPCR, in tandem with MYH6 at days 10 and 20. Differentiation proficiency was independently corroborated by assessing Mef2c and Nkx2.5 expression by IF.

Results:
Following transfection with T, Nkx2.5, MEF2C and GATA4 were significantly induced at 72h (60-, 20- and 40-fold, respectively, p<0.01 for all 3 markers vs baseline), reflecting timing of differentiation initiation. At 5 days post differentiation, expression of the cardiac-specific Nkx2.5 increased by 5 fold vs control and the cell cycle regulator CHIR (p<0.01), suggesting successful persistent induction of cardiopoeisis. At 10 and 20 days of differentiation, RNA expression of MYH6 was 10-15 times induced in human pluripotent cells transduced with T (p < 0.0001, and p < 0.001 vs control, respectively), compared to 2 times (p<0.05, p<0.01 vs control, respectively) in CHIR treated cohorts. Accordingly, at 42 days post-induction of differentiation, a greater number of cells expressed MLC2V and cTnT (p<1e-05, <1e-07, respectively vs control), driving a robust beating pattern.

Conclusion:
This study implements a single gene T M3RNA-based approach to readily induce cardiac differentiation from pluripotent sources, exceeding available commercial platforms.
Abstract 13145: Impact of Chronic Obstructive Pulmonary Disease and Smoking on Clinical Outcomes After Percutaneous Coronary Intervention
Authors: Nardin Matteo , Cao Davide , Chiarito Mauro , Nicolas Johny , Pivato Carlo Andrea , Tavenier Annerieke , Sartori Samantha , Zhang Zhongjie , Qiu Hanbo , Krishnan Prakash , Barman Nitin , Sweeny Joseph , Dangas George , Mehran Roxana , Sharma Samin K , Kini Annapoorna
Published: April 2024

Background:
Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide and often coexists with cardiovascular disease. Smoking is a common risk factor which promotes both respiratory and atherosclerotic disease. Whether COPD patients are at higher risk for cardiovascular events irrespective of smoking habit is poorly understood.

Hypothesis:
To investigate the additive prognostic impact of COPD and smoking in a cohort of patients undergoing percutaneous coronary intervention (PCI).

Methods:
Consecutive patients undergoing PCI at Mount Sinai Hospital, NY, between 2012-2019 were included and stratified by the presence of COPD at baseline. Active smoking was defined as the presence of smoking anytime during the year prior to admission. There were no formal exclusion criteria, except for the absence of information on COPD and smoking status. The primary endpoint was the composite of all-cause death or myocardial infarction at one year of follow-up.

Results:
Of the 16,313 patients included in the analysis, 1,295 (7.94%) had COPD. Patients with COPD were older, more often Caucasian, and had higher burden of comorbidities including hypertension, cancer, chronic kidney disease, heart failure. Active smoking was more common in COPD patients compared to those without COPD (27.3% vs. 15.4%, p<0.001). The primary endpoint occurred more frequently in COPD patients (4.6% vs. 2.0%; HR 2.3, 95% CI 1.7-3.1; p<0.001), with a graded risk by smoking status (
FigureA
). Findings were consistent after multivariable adjustment (
FigureB
).

Conclusion:
In a large and contemporary cohort of patients undergoing PCI, those with COPD were at higher risk of death or myocardial infarction compared to those without COPD, and this risk was further enhanced among COPD patients who smoked.
Abstract 13152: Circulating Endothelial Extracellular Microvesicles Increase With Advancing Age And Are Associated With Endothelial Dysfunction
Authors: DeSouza Christian , Stockelman Kelly A , Bammert Tyler D , Hijmans Jamie G , Lincenberg Grace , Greiner Jared , Stauffer Brian L , Desouza Christopher
Published: April 2024

Background:
Aging is associated with a progressive increase in risk and prevalence of cardiovascular disease (CVD). Endothelial cell dysfunction is considered to be a central mechanism underlying the age-related increase in vascular risk and disease. However, the direct, and indirect, effects of aging on endothelial cell biology are diverse and not completely understood.Clinical interest in circulating extracellular vesicles, particularly endothelial cell-derived microvesicles (EMVs), has intensified due to their involvement in the development and progression of endothelial dysfunction and CVD. The purpose of this study was to determine: 1) if circulating EMV levels increase with age, independent of other cardiometabolic risk factors; and if so, 2) whether circulating EMVs are associated with age-related endothelial vasodilator dysfunction.

Methods:
Thirty-six healthy, non-obese, normotensive, sedentary men were studied: 12 young (age: 27
+
1 yr); 12 middle-aged (51
+
1 yr) and 12 older (67
+
2 yr). EMV identification (CD31
+
/42b
-
) and concentration in peripheral blood was determined by flow cytometry. Forearm blood flow (FBF: via plethysmography) was assessed in response to intra-arterial infusions of acetylcholine (4.0, 8.0 and 16.0 μg/100 mL tissue/min) and sodium nitroprusside (1.0, 2.0 and 4.0 μg/100 mL tissue/min) in 8 young, 8 middle-aged and 8 older men.

Results:
Circulating EMV levels were significantly and progressively higher across the young, middle-aged and older groups (57
+
5 vs 102
+
9 vs 134
+
16 EMV/μL, respectively). FBF response to acetylcholine was significantly and progressively lower (~35%) in the young (from 5.2±0.4 to 17.2±1.8 mL/100 mL tissue/min) vs middle-aged (4.5±0.3 to 13.2±1.2 mL/100 mL tissue/min) vs older (4.2±0.3 to 11.3±0.8 mL/100 mL tissue/min) group. Circulating EMVs were positively associated with age (r=0.67; P<0.01) and inversely associated with the vasodilator response to acetylcholine (r=-0.43; P<0.01).

Conclusions:
Aging, independent of other cardiometabolic risk factors, is associated with progressive elevated circulating levels of EMVs. Circulating EMVs may serve as a biomarker of, and contributor to, age-related endothelial dysfunction and vascular disease risk.
Abstract 13172: Using Machine Learning to Identify Transcriptomic Biomarkers That Differentiate Early vs Late Stage of Atherosclerosis
Authors: Price Colin , Hixson James , Kim Do-Kyun , Vander Heide Richard , Wang Yue , Van Eyk Jennifer E , Herrington David M , Warren Andrew , Mao Chunhong
Published: April 2024

Introduction:
We used a machine learning approach to explore the transcriptomic signaling component of atherosclerosis. This approach can be viewed as complementary to classical differential-expression-based RNA-Seq approach while defining some of its limitations and providing insight into the cellular basis of atherosclerosis.

Methods:
Abdominal aorta specimens (n=242) from 128 Coroner’s autopsy cases were graded by pathologists and classified as normal (nl), fatty streak (fs), fibrous plaque (fp), or complex fibrous plaque (fc). The pathology samples were sorted into two groups for comparison: normal/early (nl/fs) vs late stage (fp/fc) of atherosclerosis. The RNA-Seq data were analyzed using an ensemble of machine learning methods to identify a set of genes that differentiate the normal/early and late pathology stages. Three feature selection algorithms (recursive feature elimination, random forest optimization and regularized linear regression) were employed to assign a total ranking to the importance of genes for pathology classification. Five different classifiers (Naive Bayes, Logistic Regression, Random Forest, Support Vector Machine and Decision Tree) were trained and XGboost model was used for ensemble learning. We used the resulting performance characterization relative to the clinically established ground truth to validate the characteristic genes and abundances selected by this model.

Results:
The ensemble machine learning approach identified a set of gene features that best explain late versus normal/early stage of atherosclerosis in a 5-fold cross validation experimental design. XG-boosting shallow learners give stable performance across sample splits and more consistently high F1 scores. We found that the performance of the resulting model was highly correlated with the degree of the disease severity, indicating a relationship between concerted transcript abundance and the presentation of disease phenotype.

Conclusions:
Our machine learning approach identifies ensemble biomarkers that differentiate early vs late stage atherosclerosis. Our results also indicated a potential transcriptomic basis for the severity of disease phenotype as embodied by histopathology grading not included in the training data.
Abstract 13177: Performance of Google Translate for Spanish Translations of Cardiac Care Unit Discharge Instructions
Authors: Duvalyan Angela , Subramanian Vinayak , Morales-Oyarvide Vicente , Álvarez Concejo Bruno , Sumarsono Andrew
Published: April 2024

Introduction:
Providing written discharge instructions (DIs) to non-English speaking patients is often challenging. Providers often must decide whether to write DIs in English or use online or in-person translation services. Prior studies evaluating the overall efficacy of Google Translate (GT) in the emergency department setting demonstrated mixed results, however the accuracy of GT for cardiology-specific diagnoses has not been studied. We evaluated the accuracy of GT for DIs for patients discharged from the inpatient cardiac care unit (CCU).

Methods:
We conducted a single-center, retrospective study of patients discharged from the CCU at Parkland Hospital. We extracted DIs along with the number of medication changes and procedures performed. We analyzed each sentence by content, Flesch-Kincaid Grade Level and Flesch-Kincaid Reading Ease formula. Using GT, we translated each sentence to Spanish and had two translators back-translate to English. The back-translated English was compared to the original English and graded for accuracy, meaning, fluency adequacy, and severity using a 5-point Likert Model. All scores were summed, with a maximum score of 20. We used univariate and multivariate logistic regressions to evaluate factors associated with perfect translation (score = 20).

Results:
Of the 44 DIs, 859 sentences were extracted. 769 (90%) of sentences were translated perfectly (score = 20) and 817 (95%) scored greater than or equal to 18. Thirty four sentences received a score of 3 or lower in any category. 2.6% (22 of 859) had severity scores of 3 or lower. In a multivariate logistic regression, sentence content of follow-up instructions was the only factor associated with higher risk of incorrect translation (OR 2.25, 95% CI: 1.05-4.84, P = 0.038), while Flesch-Kincaid Grade Level (95% CI: 0.97-1.05), Flesch-Kincaid Reading Ease (95% CI: 0.996 - 1.02), medication changes (95% CI: 0.93-1.04), and procedures performed (95% CI: 0.89-1.26) were not.

Conclusion:
GT perfectly translated 90% of DIs, but incorrectly translated 2.6% of instructions to a degree that may impair patient care. GT may be a useful tool to provide written DIs for cardiac care patients, but should still be used cautiously and in conjunction with verbal instructions.
Abstract 13186: A Machine Learning Evaluation of Patient Characteristics Associated With Guideline-Directed Prescribing for Heart Failure and Reduced Ejection Fraction
Authors: Trinkley Katy , Suresh Krithika , Kim Rachel , Rosenberg Michael , Tan Malinda , Anderson Heather , Allen Larry A , Kao David P , Tiwari Premanand , Malone Daniel
Published: April 2024

Introduction:
Patients with heart failure and reduced ejection fraction (HFrEF) are consistently under-prescribed guideline-directed medications. Many barriers to prescribing are known, including patient characteristics (e.g., higher potassium values within normal limits predict under-prescribing of some medications). However, identification of these barriers has relied on traditional
a priori
hypotheses or qualitative methods. To overcome the limitations of traditional methods, we used a supervised machine learning (ML) approach to identify potential new barriers to prescribing.

Methods:
We used electronic health record data to evaluate characteristics of adults with HFrEF within the UCHealth system. Characteristics evaluated included insurance type, medications, diagnoses and lab values. We evaluated the predictive performance of ML algorithms and statistical models based on area under the receiver operating characteristic curve (AUC) to predict prescription of 4 types of medications: angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACE/ARB), angiotensin receptor-neprilysin inhibitor (ARNI), beta blocker (BB), or mineralocorticoid receptor antagonist (MRA). We identified top characteristics associated with prescribing each medication type from the models with the best predictive performance.

Results:
For 3,835 patients meeting inclusion criteria, 70% were prescribed an ACE/ARB, 8% an ARNI, 75% a BB and 40% a MRA. The best-predicting model for each medication type was a random forest. Figure 1 describes the top characteristics associated with each medication type.

Conclusions:
In this hypothesis generating ML study, we identified additional patient characteristics that may be associated with under-prescribing for HFrEF. These results also align with some patient characteristics that are known barriers to prescribing. Additional research is needed to further elucidate barriers to prescribing for HFrEF.
Abstract 13190: Evidence of Occult Global and Regional Myocardial Strain Abnormalities in Adolescent Athletes After COVID-19 Infection
Authors: Lee Marc , Hor Kan N , Rajpal Saurabh , Heyniger John , Simonetti Orlando , Tran Andrew H , Wright Lydia , L'Italien Kaitlin E , Nandi Deipanjan , Lee Simon
Published: April 2024

Introduction:
There is increased scrutiny on cardiac screening of competitive athletes after COVID-19 illness, and cardiac magnetic resonance (CMR) is frequently undertaken. Limited reports with echocardiography-based strain techniques suggest occult abnormalities in collegiate athletes after COVID-19. Cardiac involvement in the adolescent athlete has not been well characterized. The purpose of this study is to describe CMR findings, including strain encoded (SENC) imaging, in adolescent athletes after COVID-19 (C19+AA).

Methods:
Retrospective review was performed of ambulatory C19+AA patients who underwent CMR (Group A). Healthy athletes (Group B) and nonathlete healthy controls (Group C) underwent CMR with SENC for comparison. Myocardial strain was evaluated by MyoStrain (Myocardial Solutions, Morrisville, NC). LV global (GLS) and regional strain (from modified AHA-16 segment model) were compared between the three groups with abnormal defined as magnitude <17 and statistical significance set at p < 0.05.

Results:
Group A patients were younger (n = 87, 52% male, age 15.4±1.8 yrs) than Group B (n = 19, 63% male, age 21.3±1.6 yrs) and Group C (n = 9, 52.6% male, age 19.3±1.1 yrs) with no difference in LVEF between the three groups (Group A = 59.1±3.9%, Group B = 60.3±6.2%, Group C = 61.0±4.1%). Despite preserved global function, Group A had significantly lower GLS (-17.6±2.3% vs Group B = -20.8±1.4%, p <0.04 and Group C = -19.1±2.4%, p = 0.02) with no difference between the latter groups (p = 0.07). Higher numbers of abnormal segments were observed in Group A (6.9±3.7, 43.1%) vs Group B (2.4±1.9, p < 0.0001) and Group C (3.7±3.5, p < 0.0001) with no difference between the latter groups (p = 0.1).

Conclusions:
Global and regional strain abnormalities were common in C19+AA in the setting of normal LVEF. This may represent occult myocardial abnormalities in adolescents after COVID-19. Future longitudinal studies with age matched controls are needed to monitor for progression.
Abstract 13194: Regional Disparities in Clinical and Socioeconomic Characteristics of African-American Patients With Cardiac Amyloidosis Served by Two Inner City Hospitals
Authors: Murthi Mukunthan , Asif Talal , Gupta Aman , Vega Karen , Pinelo Coll Cardenas Anna P , Fernandez Stanley F , Malhotra Saurabh
Published: April 2024

Introduction:
The highest prevalence of cardiac amyloidosis (CA) in the United States (US) is reported among African American (AA) individuals, with a significant regional variation in this prevalence. We aimed to study the clinical, demographic and socioeconomic differences among AA patients diagnosed with CA from inner city hospital located in different regions of the US.

Methods:
Demographic, clinical and socioeconomic data on patients diagnosed with CA was collected from Buffalo General Medical Center, Buffalo, NY (Northeast region; Erie County) and Cook County Health, Chicago, NY (Midwest region; Cook County). CA was diagnosed based on a combination of pyrophosphate scintigraphy and assessment of paraproteinemia. Socio-economic data from zip code of patient’s residence was obtained from publicly available 2010 census summary data.

Results:
Overall, 80 patients were tested for CA in Erie County and 150 patients in Cook County, of which 58 (72.5%) and 128 (85.3%) were AA, respectively. Among AA patients, 16 (28%) from Erie County and 29 (23%) from Cook County were diagnosed with CA (Table). Despite younger age, and a lower prevalence of male gender, CAD, hypertension and aortic stenosis, Cook County patients had more severe cardiomyopathy, given a significantly lower ejection fraction at presentation. Additionally, patients from Cook County had lower socioeconomic status as evident by a lower average income, fewer social security beneficiaries, greater unemployment and a greater prevalence of uninsured population.

Conclusions:
Despite similar racial background, there are significant demographic, clinical and socioeconomic differences among AA patients with CA from two different regions in the US. Within race disparities, that could be influenced by regional socioeconomic differences, may drive clinical outcomes of AA patients with CA.
Abstract 13654: Can a Novel Earbud Technology Detect Severe Aortic Stenosis? Modernizing the Wiggers Diagram Through Infrasonic Hemodynography Synchronized With Echocardiography and Cardiac Catheterization
Authors: Waldman Carly E , Patel Siddarth , Wheeler Carmen M , Panchal Jal , Sidhu Rajbir , Krol Monika , Szepieniec Tomasz , Shakya Pratistha , Gupta Saumya , Shahinyan Karlen , Barnacka Anna , Engstrom Hayley , Southard Kayla , Daniel Misty , Stinis Curtiss , Romero Steven , Bridges Charles , Bhavnani Sanjeev
Published: April 2024

Introduction:
Severe aortic stenosis (AS) produces a typical systolic ejection sound detected by clinical auscultation with a characteristic feature on Doppler echocardiography (ECHO) & hemodynamics at cardiac catheterization (CC). We propose a new assessment of AS through ‘infrasonic hemodynography’ (IH) - cardiovascular monitoring by infrasound (<20 Hz) measured by a novel digital device. To assess AS, we aim to compare IH to standard ECHO & CC measurements.

Methods:
We report an N-of-1 analysis from an ongoing prospective clinical trial to validate IH on cardiac function. A study subject with severe AS wore the IH ear-bud (MindMics, Figure A) & underwent simultaneous measurements with IH-ECHO & IH-CC-ECG, with IH waveforms (in-ear acoustic pressure in Pascals) synchronized (via cross-correlation), stacked (11 heart beats), & averaged over the QRS complex of the ECG. The QRS complex was then used as a reference to generate a quantitative Wiggers diagram, aligning IH & CC waveforms with the aortic valve on ECHO. Time of aortic valve opening (AVO) & closure (AVC) were determined from the ECHO image. The systole & diastole were assessed by creating Wiggers diagrams from the LV outflow & mitral valve inflow ECHO images.

Results:
The peak systolic pressure in CC occurred close to the AVC derived from ECHO (Figure B), as is typical of the delayed peak pressure in severe AS. This was captured in the IH waveform & visualized by overlaid LV & AO pressures simultaneously collected during CC (Figure C). Additionally, the blood pressure increase seen on CC in response to AVC (the dicrotic notch) was also delayed & aligned with the drop in flow & the start of the E wave on ECHO, consistent with severe AS, & detected on IH.

Conclusions:
We describe in-ear IH as a new method for non-invasive measurement of severe AS. Infrasound assessment of cardiac function represents a potentially important development to modernize the Wiggers Diagram & to detect valvular disease that is independent of ECHO & CC.
Abstract 13657: Malignant Multivessel Coronary Spasm
Authors: Inashvili Ana , Yang Ruifang , Kilpatrick Benjamin , Goldgrab David , Garza Hector , Patel Devansh , Khan Tehreen , Dewhurst Robert M , Mester Stephen , Bugni William
Published: April 2024

Objective:
Management of multivessel coronary spasm is challenging.

Case:
A 59-year-old female with a medical history of CAD status post coronary stents presented with atypical chest pain.The following morning the patient suffered a PEA arrest, from which she was resuscitated. Retrospective review of telemetry revealed frequent episodes of transient ST segment elevations in inferior leads, lasting minutes, eventually followed by sinus bradycardia and episodes of high-degree AV block with pauses up to 20 seconds.Two weeks earlier the patient presented at another institution with similar complaints. Inferior STEMI was diagnosed, she received 2 DES, in proximal OM1 and Mid LAD. She represented 6 days later with continued symptoms and repeat catheterization revealed patent stents. She was reassured and discharged on Isosorbide Mononitrate in addition to Carvedilol.

Management and Decision Making:
Coronary angiography at our facility demonstrated 90% stenosis of proximal LCX and 60-70% of proximal LAD. These stenosis resolved with intracoronary nitroglycerin. The stents were patent. Therefore, she was diagnosed with coronary spasm. During her hospital stay, the patient did have four more episodes of ST elevations associated with complete heart block. Since she developed high degree AV block after a coronary spasm, a temporary pacemaker was placed. Norvasc as well as nitroglycerin drip were used to treat her coronary vasospasm. Pure B-blocker medications were avoided to prevent unbalanced alpha effect.The patient was extubated 4 days later and fully recovered neurologically. A permanent pacemaker was placed and discharged home.

Conclusion:
High suspicion is important for diagnosis of coronary vasospasm. Treatment with coronary vasodilators is cornerstone of management. We also avoided pure alpha agonists during resuscitation measures, as well as pure B-blocker medications after recovery.
Abstract 13661: Low Organ Perfusion Pressure Indexed To Body Surface Area
Predicts Poor Sur
vival Even After Heart Transplantation If The Right Atrial Pressure Is High
Authors: RATNAGIRI RAVIKUMAR , BALAKRISHNAN KOMARAKSHI R , Rao K G Suresh , Muralikrishna T , Veena Ramanan
Published: April 2024

Introduction:
Increased Right Atrial pressure (RAP) is associated with impaired renal function and mortality in patients with heart failure. Reduced renal perfusion pressure is associated with deranged renal function.

Hypothesis:
The effect of high RAP on survival may persist even after heart transplantation if the organ perfusion pressure indexed to body surface area (OPPI) is low. OPPI is more sensitive than organ perfusion pressure (OPP) in predicting survival.

Methods:
277 patients who had a heart transplant between October 2012 to march 2020 were included in the study . OPP was calculated as : Mean arterial pressure (MAP) - RAP . OPPI was calculated as : (MAP-RAP) / body surface area .

Results:
There was a more significant negative correlation between OPPI and creatinine (r = -0.4015,p =0.000) than OPP and creatinine (r = -0.0335,p = 0.6187) (fig 1a) .

The effect of OPPI on MELD score was also more significant than OPP.( r = -0.2973, p = 0.000 vs r = -0.0335, p = 0.6187).

The 90 day mortality after transplantation was more with higher RAP (23.5 % vs 11.5 %, p ~ 0.012 RAP > & < 15) , but
not if
OPPI was > 40.(10.8 % vs 9.4 %,p ~ 0.817). The 90 day survival was worse with lower OPPI but improved with lower venous pressures.(Fig 1b)

The effect of RAP on medium term survival was significantly worse for RAP > 15 (p = 0.0143).(Fig 1c). The effect was absent if OPPI was > 40.(Fig 1d). Survival at 5 years was worse if the OPPI was low . This effect was absent if the RA pressure was low.(1 e,f). Medium survival for mean pulmonary artery pressure more than 40 mm hg was worse but not if OPPI > 40.(Fig 1 g,h).

Conclusions:
Short and medium term survival after transplantation are worse with high RAP
if
OPPI is low. OPPI ,a hemodynamic parameter easily measurable, is more sensitive in predicting survival than OPP . OPPI < 40 appears to be deleterious. With high RAP, excessive vasodilatation must be avoided
Abstract 13663: Safety and Possible Effectiveness of Paclitaxel Associated to LDL-Like Nanoparticles (LDE) in the Treatment of Patients With Chronic Ischemic Heart Disease
Authors: MARINHO LUCAS L , Rached Fabiana H , Tavoni Thauany , Cardoso Ana Paula T , Torres Roberto Vitor A , Serrano Carlos V , Nomura Cesar H , Maranhao Raul C
Published: April 2024

Introduction:
Experimental studies have shown that anti-proliferative chemotherapeutic agents such as paclitaxel (PTX), associated to solid lipid nanoparticles (LDE), have marked anti-atherosclerotic effects. The combination with LDE nearly abolishes PTX toxicity.

Hypothesis:
Treatment with LDE-PTX in patients with chronic ischemic heart disease (CIHD) is tolerable and safe, and favorably changes plaque characteristics, as denoted by coronary computerized tomography angiography (CCTA).

Methods:
In this prospective, randomized, double-blind, placebo-controlled study, patients with multivessel CIHD received IV infusions of either LDE-PTX (n=20; PTX dose: 175 mg/m2 body surface) or LDE alone (n=20; placebo group). Infusions were administered every 3 weeks for 6 times. Analysis of cardiovascular risk and inflammatory biomarkers and CCTA data was performed at baseline and at the end of the study. Clinical and laboratorial safety evaluations were made before each infusion.

Results:
Overall, patients aged 65.6 ±8 yrs, 58% had diabetes, 50% had history of myocardial infarction and 91% were under statin and aspirin therapy. Baseline demographics, risk factors and laboratory data were similar between infusion groups. There was no statistical difference regarding the levels of hsCRP, IL-1β, IL-6, IL-8 and TNF-α from baseline to follow-up between groups, but there was a trend for decrease in IL-6 levels in the LDE-PTX group (-16%), not observed in the placebo group. Regarding the CCTA high-risk plaques, a tendency for reduction of the napking-ring signal after infusion was observed in the LDE-PTX group (figure 1) compared to placebo (p=0.098). No clinical or laboratorial toxicities were observed.

Conclusions:
This study shows that LDE-PTX was safe in CIHD patients and showed signs of benefits in reducing inflammatory biomarkers and modification of high-risk plaque characteristics.
Abstract 13664: Identification of Myocardial Scar Using Deep Residual Network Integration of CMR Images in Ischemic Cardiomyopathy
Authors: Udin Michael , Ionita Ciprian , Kai Alice , Pokharel Saraswati , Sharma Umesh C
Published: April 2024

Introduction:
Ischemic scar development is a potential precursor of lethal arrhythmias and heart failure, conditions with exceptionally high mortality rates. Contrast-enhanced cardiac magnetic resonance imaging (CMR) is frequently used in clinical practice to quantify myocardial scar. With the advance of machine learning, increasing amounts of information can be garnered from CMR scans, including information that has both diagnostic and prognostic value for patients with ischemic cardiomyopathy.

Hypothesis:
We hypothesize that deep residual network integration combined with an augmented CMR scan selection can more accurately differentiate between patients with and without myocardial ischemic scarring.

Methods:
CMR scans from 170 patients, 138 with ischemic scarring and 32 controls without myocardial scarring, were collected from a tertiary care facility. CMR scans were selected to include those that had a clear visualization of the left ventricle and the surrounding myocardium. This region of interest (ROI) was then cropped. Images from patients with no myocardial scarring were additionally rotated 3 times to improve class balance. The final dataset was composed of 9,840 images from the patients with no myocardial scarring and 10,480 images with ischemic scarring.

Results:
Applying a ResNet-50-based convolutional neural network machine learning algorithm, we were able to identify patients with ischemic scarring at an accuracy of 75.9%. Sensitivity and specificity were 76.2% and 75.7%, respectively, with an F1 Score of 76.7%. By introducing targeted ROI selection, we were able to further improve accuracy to 81.7% with an F1 score of 82.4%. Sensitivity and specificity were also higher at 83.4% and 79.8%, respectively. The data acceptance rate of the short axis images for this implementation was 22.0%.

Conclusion:
Application of our residual network integration algorithm- along with targeted ROI selection- can significantly enhance the accuracy of myocardial scar detection in patients with ischemic cardiomyopathy. When tested in larger samples this is expected to aid clinical adjudication and enhance workflow.
Abstract 13667: Earlier Onset in Homozygous Val122Ile Hereditary Transthyretin Cardiac Amyloidosis Allows for Advanced Therapies
Authors: Rim Austin , Yalamanchili Sreeram , Bigham Thomas , Brown Matthew , Bhatt Kunal
Published: April 2024

Introduction:
Transthyretin cardiac amyloidosis (TTR-CM) is a progressive disease characterized by the misfolding and deposition of amyloid fibrils extracellularly in the myocardium. The most common mutation in the U.S. is Val122Ile, which is estimated to occur in 3.4% of all African Americans. While this mutation is believed to have a more malignant phenotype, the differences in homozygous vs. heterozygous carriers of this autosomal dominant disease are not known.

Methods:
We conducted a retrospective chart review of patients enrolled in Emory University's Cardiac Amyloidosis Clinic between January 2014 and April 2021. Patients who carried one or more alleles for the Val122Ile mutation were included in this study. Means testing was performed and all data reported as mean ± standard deviation or count (percentage). Kaplan-Meier analysis was performed with Breslow test.

Results:
Among 74 patients who had the Val122Ile mutation, 6 were homozygotes and 68 were heterozygotes. Homozygotes were significantly younger than heterozygotes at diagnosis (61±6.5 vs. 74±7.1 years, p < 0.01) and were more likely to present with stage 4 heart failure (p = 0.02). Compared to patients with heterozygous mutation, patients with homozygous mutation were more likely to receive heart transplantation (p = 0.04). Kaplan-Meier analysis revealed lower rate of survival for homozygotes when compared to heterozygotes (p = 0.04). Extracardiac manifestations of amyloidosis including carpal tunnel syndrome, lumbar stenosis, polyneuropathy, and autonomic dysfunction did not differ significantly between the two groups.

Conclusion:
Val122Ile homozygotes were diagnosed at a younger age than Val122Ile heterozygotes, presented more frequently with advanced stage heart failure, and had worse survival time. There was no difference in extracardiac manifestations of amyloidosis between the two groups.
Abstract 13675: Temporal Trends and Prognostic Significance of Coronary Artery Disease in Patients With Critical Limb Ischemia: Insights From the National Inpatient Sample
Authors: Chunawala Zainali , Chew Christopher , Hendrickson Michael , Arora Sameer , Mishkel Gregory , Tafur Alfonso J , Levisay Justin p , Ricciardi Mark , Lee Cheong Jun , Qamar Arman
Published: April 2024

Background:
It is uncertain whether presence of CAD has a prognostic implication in patients (pts) with CLI. We sought to compare the trends and outcomes of pts with CLI based on presence of history of CAD.

Methods:
Temporal trends in hospitalization for CLI based on history of CAD were determined using the 2000-2018 NIS database. A multivariable regression analyses of outcomes was performed based on the CAD status and revascularization type. Propensity score matching was used to compare outcomes based on type of revascularization. Primary outcome of interest was in-hospital mortality.

Results:
Among 13,570,000 pts with CLI (41% female, 69% whites, mean age 69 years), 23% had concomitant CAD and 9.6% underwent revascularization (42.6% endovascular & 57.4% surgical). In pts with CLI, there was an increasing trend in the prevalence of CAD (Figure; Panel A). Furthermore, in pts with CLI + CAD, the frequency of endovascular revascularization increased from 15% to 48% while there was a decreasing trend of surgical revascularization (85% to 52%). After multivariate adjustments, CLI + CAD was associated with increased risk of in-hospital mortality (OR: 1.40; CI: 1.32-1.47) & bleeding requiring transfusion (OR: 1.10; CI: 1.06-1.12) than those with CLI without CAD (Figure; Panel B). Among both patients with CLI + CAD & CLI without CAD, endovascular revascularization was associated with lower likelihood of in-hospital mortality (OR: 0.69; CI: 0.63- 0.76 & OR: 0.71; CI: 0.67-0.76) & bleeding requiring transfusion (OR: 0.40; CI: 0.38- 0.43 & OR: 0.44; CI: 0.43- 0.46) than surgical revascularization.

Conclusions:
Increasing prevalence and poor prognosis of CAD among patients with CLI warrants immediate attention to optimize preventive and treatment strategies.
Abstract 13690: Complex Clinical Course of Unsuccessfully Revascularized Right Coronary Artery
Authors: Inashvili Ana , Yang Ruifang , Kilpatrick Benjamin , Goldgrab David , Garza Hector , Gomez Mauricio , Perzanowski Christian , Khan Tehreen , Bugni William , Mester Stephen
Published: April 2024

Objective:
Since onset of reperfusion era, ventricular aneurysms have become a rare complication of acute myocardial infarction, with incidence of LV inferior wall aneurysm around 5%. Guidelines recommend an ICD placement for sustained V tach after 48 hours of MI, however management of persistent V tach associated with ventricular aneurysm is uncertain.

Case:
The patient is a 60 year old male who presents with persistent palpitations, occurring after a mechanical fall. EKG demonstrated slow persistent V tach with HR of 121.Two and a half months prior, the patient suffered from inferior wall STEMI, unsuccessfully reperfused at another institution, secondary to iatrogenically dissected RCA. He presented at our institution 3 weeks after complaining of chest pain and diagnosed with moderate pericardial effusion, as well as large LV inferior wall aneurysm. Pericardial fluid was not large enough to drain. He represented two weeks later, with worsening SOB and tamponade physiology by TTE. A total of 2.5 L of pericardial fluid was drained over several days. CT surgery was consulted, coronary angiography was performed and demonstrated multivessel coronary artery disease. Plan was to follow up as an outpatient for surgery.

Medical Decision Making:
During his most recent presentation with V tach, the patient did not respond to Amiodarone infusion but underwent successful synchronized cardioversion with 30 J.He underwent CABGX2 and inferior LV endoaneurysmorrhaphy with 4x6 cm bovine pericardial patch. An ICD was implanted before his discharge.

Conclusion:
This patient’s V tach was likely secondary to LV aneurysm. Per our hypothesis, he would still be prone to develop V tach around the suture lines.Therefore the patient underwent an ICD implantation.
Abstract 13706: Expanded Coverage for Cardiac Rehabilitation in Heart Failure Patients Accelerated Annual Rates of Use
Authors: Guduguntla Vinay , Hou Hechuan , Sukul Devraj , Keteyian Steven J , Aaronson Keith D , Thompson Mike P
Published: April 2024

Introduction:
Cardiac rehabilitation (CR) reduces morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). In an effort to improve enrollment, Medicare expanded coverage for CR to include HFrEF patients in 2014, but the impact of this policy change is unknown.

Methods:
A 20% sample of Medicare inpatient, outpatient, and carrier claim files (2008 to 2017) were used to identify 849,054 patients with HFrEF, defined as having ≥ 2 outpatient claims or ≥ 1 inpatient hospitalization for chronic systolic heart failure during a calendar year. Patients who died within the calendar year of diagnosis were excluded. CR participation was identified using CPT and revenue center codes. We performed an interrupted time-series analysis to estimate annual rates of CR use over the ten year period, annual changes in CR use in the pre- (2008-2013) and post-policy (2014-2017), and the differences in annual trends pre- vs. post-policy. Results were risk adjusted by age, sex, race, dual eligibility, and Charlson comorbidities.

Results:
A total of 34,179 (4.0%) beneficiaries with HFrEF attended CR during the study period. Annual trends in CR enrollment are shown in Figure 1
.
From 2008 to 2014, CR utilization increased from 3.30% to 4.30% at an annual absolute change of 0.15% per year (p<0.001). After Medicare expanded coverage, rates of CR enrollment went from 4.30% in 2014 to 5.54% in 2017, at an annual absolute change of 0.31% (p<0.001). Comparing trends in participation before and after the change in policy, the annual rate of change in CR enrollment was 0.16% higher on an absolute scale (p<0.001).

Conclusions:
Although the absolute enrollment rate of patients with HFrEF in CR remains low, expanding coverage in 2014 was associated with a doubling in the annual rate of increase of CR use. Interventions beyond coverage changes, at the individual, provider, and system level, are needed to improve CR participation in HFrEF patients.