bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16730: Neighborhood Deprivation and Left Ventricular Mass in Women, NGHS Longitudinal Cohort Analysis
Authors: Baker-Smith Carissa M , Woo Jessica G , Urbina Elaine M
Published: December 2023

Left ventricular hypertrophy is an independent predictor of cardiovascular disease. Neighborhood level deprivation is a risk factor for increased morbidity and mortality for a variety of diseases and conditions. However, to date, no study has assessed the relationship between neighborhood level deprivation and left ventricular hypertrophy.

Methods:
The NHLBI National Growth and Health Study (NGHS) is a 36-year longitudinal study of 871 women (50% white/50% Black). All participants were enrolled between 9-10 years of age in 1987. Annual assessments of anthropometric, echocardiographic and neighborhood level deprivation data, between the ages of 20-28 years (visits 11-17), were analyzed. We assessed the relationship between quartiles of deprivation index (DI) (high/worst, moderately high, moderately low, low/best) at ~age 20 years with levels of systolic blood pressure (SBP), body mass index (BMI) and indexed left ventricular mass (LVMI, g/m
2.7
), between ages 20-28, adjusting for race.

Results:
Data from 531 (55% Black) women were examined. Compared to the lowest DI quartile, the highest DI quartile exposure at ~20 years was associated with a 3.37 [1.34, 8.44] greater odds of BMI
>
30 (obesity) at age 28,
p=0.01
. An interaction between visit and DI quartile was significant, such that women in the highest DI quartile at age 20 had greater increases in BMI by age 28 than those in lower DI quartiles (
p=0.001
, Figure 1). There was no significant relationship between SBP and DI quartile in this cohort (data not shown). Compared with women who resided in the lower 2 DI quartiles at age 20, the LVMI of women exposed to higher (worse) DI was significantly greater after age 23 (visit 14
, p<0.05
, Figure 2).

Conclusion(s):
In summary, increased deprivation is associated with increased BMI in young adult women, adjusting for race. In addition, increased deprivation is also associated with greater indexed left ventricular mass, an independent predictor of cardiovascular disease.
Abstract 16731: Post-GWAS Functional Analysis of CBLN2 Locus Reveals the Role of CUX1 in the Inflammatory Pathogenesis of Pulmonary Arterial Hypertension
Authors: Sun Wei , El Khoury Wadih , Jiang Danli , Tang Ying , Wu Ting , Zhang Yingze , Li Gang , Chan Stephen Y
Published: December 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a complex and deadly pulmonary vascular disease highly relevant to genetic susceptibility and acquired inflammatory triggers. Chr18q22.3 near cerebellin 2 precursor (CBLN2) gene is the first genetic locus identified by Genome-wide Association Study (GWAS) that is significantly associated with PAH risk in the European population. This locus includes closely linked non-coding intergenic single nucleotide polymorphisms (SNPs) downstream of CBLN2. Although CBLN2 is upregulated in PAH and causes pulmonary vascular dysfunction, it remains unknown how these non-coding SNPs remotely affect CBLN2 and in turn, alter the genetic susceptibility of PAH.

Methods and Results:
We combined Hi-C chromatin interaction analysis, electrophoretic mobility shift assay, and SNP genotype-PAH correlation analysis with the
All of Us
database (N=20,343). In doing so, we identified rs11151770(A/G) as a PAH-associated functional SNP (fSNP), among 19 haplotype SNPs in linkage disequilibrium with the associated CBLN2 locus. The genomic region containing rs11151770(A/G) exhibited long-range chromatin interaction with the CBLN2 promotor. Proteomic analysis revealed that nuclear transcription factor Cut-like Homeobox 1 (CUX1) binds specifically to the risk allele A of rs11151770 but not to the non-risk allele G, regulating the expression of CBLN2 as an activator in pulmonary arterial endothelial cells. CUX1-CBLN2 was upregulated by acquired inflammatory PAH triggers IL-1β and IL-6. SNP genotyping in PAH patients (N=159) and non-PAH controls (N=87) showed a 2.2-fold enrichment of the risk allele A only in patients with PAH associated with connective tissue disorders (N=77, p=0.036). These findings supported a pathogenic mechanism of an inflammation-sensitive pathway (CUX1-CBLN2) controlled by an fSNP (risk allele A) underlying the reported genetic association of the CBLN2 locus with PAH risk.

Conclusion:
Our post-GWAS functional genomics analysis defined a pathogenic CUX1-mediated, fSNP rs11151770(A/G)-controlled, and inflammation-responsive pathway that provides a mechanistic explanation for the GWAS-identified association between genetic variants in CBLN2 locus and PAH susceptibility.
Abstract 16738: Impact of Remnant Cholesterol Level on Long-Term Outcomes in Patients With Multivessel Disease Undergoing Coronary Artery Bypass Grafting
Authors: Tang Liang , Yang Yuejiao , Hu Xin-qun , Fang Zhen-fei , Liao Xiao-bo , Zhou Xin-min , Zhu Zhao-wei , Zhou Sheng-hua
Published: December 2023

Introduction:
The remnant cholesterol (RC) is being increasingly documented as an important risk factors of coronary artery disease. Thus far, the impact of RC level on the long-term outcomes of patients with multivessel coronary artery disease (MVD) undergoing coronary artery bypass graft (CABG) has not been investigated.

Hypothesis:
Elevated RC level is associated with increased risk of MACCEs in patients with MVD undergoing CABG.

Methods:
All patients who were diagnosed with multivessel coronary artery disease and undergoing CABG between 2011 and 2020 were considered for enrollment. RC was calculated as total cholesterol minus HDL-C minus LDL-C. Patients were categorized by RC thresholds and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) was examined according to the RC level at one-year post-CABG.

Results:
A total of 2,072 patients (60.8 ± 8.3 years; 83.5% men) were included in this study. Patients was divided into four groups: RC < 0.5 mmol /L, RC of 0.5-0.99 mmol/L, RC of 1.0-1.49, mmol/L, and RC ≥ 1.5 mmol/L. During a median follow-up of 4.2 years after the 1-year assessment, 25.0% of the patients had occurrences of MACCEs. The multivariable adjusted hazard ratios (95% CI) for MACCEs, cardiac death, nonfatal myocardial infarction, re-revascularization, cardiac rehospitalization (admission because of angina or heart failure) and nonfatal stroke, were respectively 2.49 (1.99-3.12), 2.20 (1.18-3.86), 3.18 (2.16-5.84), 3.02 (2.12-4.34), 1.93 (1.42-2.87), and 1.37 (0.83-2.27) in patients with RC ≥ 1.50 mmol/L, compared with patients with 1-year RC < 0.5 mmol/L. The 1-year RC level was significantly associated with MACCEs, with the lowest risk of MACCEs reflected in the patients with RC < 0.5 mmol/L.

Conclusions
:
In patients with MVD undergoing CABG, the RC level at one-year after CABG were independently associated with long-term outcomes.
Abstract 16742: Deep-Learning-Derived Retinal Cardiovascular Risk Predictor (Reti-CVD) and 14 Cardiovascular Conditions in UK Biobank
Authors: Kang Hyun Goo , Rim Tyler H , Lee Geunyoung , Yu Marco , Tham Yih-Chung , Cheng Ching-Yu , Lee Chan Joo J , Kim Sung Soo , Park Sung Ha
Published: December 2023

Introduction:
The advent of sophisticated deep learning algorithms has now made it possible to predict the risk of cardiovascular diseases (CVDs) using retinal images. We had previously developed a retina-based deep learning model, Reti-CVD, trained on coronary artery calcium (CAC) data, which successfully predicted future CVD incidents in a longitudinal study.

Hypothesis:
This study aims to investigate the cross-sectional association between Reti-CVD and 13 distinct CVDs, alongside arterial hypertension.

Methods:
Our cross-sectional analysis involved 45,980 participants from the UK Biobank at baseline. To discern the differential cardiovascular risk associated with Reti-CVD, we studied a wide array of CVDs. These included cerebrovascular diseases, aneurysms, thrombo-embolic diseases, other CVDs (coronary artery disease, aortic valve stenosis, atrial fibrillation, heart failure, and peripheral vascular disease), and arterial hypertension. We defined CVD outcomes based on the international classification of disease codes. We used logistic regression, adjusted for hypertension, diabetes, dyslipidemia, and smoking, to estimate the correlations between Reti-CVD and the defined CVD outcomes.

Results:
In the cross-sectional study, after adjusting for CVD risk factors, we found the highest tertile of Reti-CVD scores to be significantly associated with 11 outcomes in comparison to the first tertile (adjusted Odds Ratio [OR], 95% Confidence Interval [CI]). These include: Coronary artery disease (OR=10.37, 95% CI, 7.58-14.18), peripheral vascular disease (9.65, 2.94-31.64), atrial fibrillation (9.36, 6.51-13.45), aortic valve stenosis (8.13, 1.87-35.35), heart failure (7.33, 3.64-14.77), ischemic stroke (4.70, 2.30-9.59), transient ischemic attack (4.17, 2.07-8.40), arterial hypertension (3.17, 2.78-3.61), pulmonary embolism (3.00, 1.86-4.84), deep vein thrombosis (2.54, 1.70-3.80), and cerebrovascular diseases (2.36, 1.63-3.42). Notably, we found suggestive evidence of an inverse association of Reti-CVD tertiles with subarachnoid haemorrhage.

Conclusions:
This study demonstrates that higher Reti-CVD scores correlate with an elevated risk across a broad range of cardiovascular conditions.
Abstract 16745: Continuous Stellate Ganglion Block for Ventricular Arrhythmias: Case Series, Systematic Review and Comparison With Epidural Anesthesia
Authors: morena arianna , Toscano Antonio , Angelini Filippo , Gravinese Carol , Frea Simone , Saglietto Andrea , Balzani Eleonora , cedrone martina , Giunta Matteo , Costamagna Andrea , Anselmino Matteo , Rinaldi Mauro , Brazzi Luca , De Ferrari Gaetano Maria , Dusi Veronica
Published: December 2023

Background:
Percutaneous single bolus injection left stellate ganglion block (PLSGB) and thoracic epidural anesthesia (TEA) have been proposed for the acute management of refractory ventricular arrhythmias (VAs). Data on continuous PLSGB (C-PLSGB) are scant.

Objectives:
to report our single center experience with C-PLSGB and perform a systematic review on C-PLSGB and TEA to preliminary compare these 2 techniques.

Methods:
consecutive patients receiving C-PLSGB were enrolled. The systematic literature review was performed following the latest PRISMA criteria.

Results:
our single-center case series (8 pts, 88% male, 60 ±16 years, all with structural heart disease) supports that C-PLSGB is feasible and safe, even on fully anticoagulated patients and leads to a complete VAs suppression in half and to an overall clinical benefit in all patients. Overall, considering previously published data, 34 patients received C-PLSGB, and 18 TEA for refractory VAs. Most (61%) in the TEA group were on general anesthesia, as opposed to 24% in the C-PLSGB group (p=0.01); 52% of patients were on full anticoagulation at C-PLSGB, none at TEA (p<0.01). C-PLSGB and TEA efficacy was not significantly different (31/34 versus 13/18 had a complete or at least partial response, p=0.1). No major complications occurred, yet the discontinuation rate was significantly higher in the TEA compared to C-PLSGB (22% versus 3%, p=0.037).

Conclusions:
C-PLSGB seems feasible, safe and effective for the acute management of refractory VAs. C-PLSGB efficacy seems to be not significantly different to that of TEA and may be accomplished with less concerns of anticoagulation, and lower discontinuation rate.
Abstract 16746: Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis
Authors: Peng Qianman , Zhu Bo , Lu Yao Wei , Cui Kui , Singh Bandana , Li Kathryn , Wylie-Sears Jill , Osorio Daniel , Sun Liang , Wong Scott , Cowan Douglas B , Bischoff Joyce E , Chen Hong
Published: December 2023

Introduction:
Atherosclerosis is the leading cause of mortality in the United States and most other developed countries. Endothelial cell (EC) activation is a hallmark of the initiation and progression of atherosclerosis; identification of molecular markers of dysfunctional endothelium represents a biological challenge to developing new therapeutic targets. CD45 is a marker of hematopoietic cells, which is rarely expressed in ECs. However, recent studies indicated that CD45 is indispensable in driving the endothelial-to-mesenchymal transition (EndMT) following myocardial infarction. EndMT has also been implicated in the pathogenesis of atheroma progression. Thus, we aim to investigate whether endothelial CD45 contributes to the progression of atherosclerosis by facilitating the EndMT.

Methods and results:
In vitro
, we used CRISPR/inactive Cas9 transcriptional activation system to express CD45 in human endothelial colony-forming cells (ECFCs). Using FACS analyses, we found that CD45+ECFCs upregulate transforming growth factors (TGFβ
1-3
) that implicate EndMT but downregulate FGFR1 expression, which exacerbates EndMT. qRT-PCR and WB showed that CD45+ECFCs downregulate transcription factors KLFs.
In vivo
, we generated a tamoxifen-inducible EC-specific CD45 deficient mouse strain (EC-CD45iKO) in ApoE-deficient (ApoE-/-) background and fed with a Western diet (C57BL/6) for atherosclerosis and molecular analyses. We found that ApoE-/- / EC-iCD45KO mice reduced plaque macrophages, foam cells, expression of adhesion molecule, and lesion development compared to ApoE-/- controls. Interestingly, ApoE-/- / EC-iCD45KO mice showed the reduction of α-smooth muscle actin, which is typical of EndMT, in the aortic plaque. Single-cell RNA-seq analyses have been performed to characterize that endothelial CD45 regulates the expression of pro-inflammatory, EndMT, and endothelial cell markers genes on the aortic ECs.

Conclusion:
These findings demonstrate that endothelial CD45 potentiates atherosclerosis by inducing TGF signaling and mesenchymal phenotype, causing FGFR1 downregulation and attenuating KLFs expression to drive EndMT, highlighting endothelial CD45 may be a new drug target for the treatment of atherosclerosis.
Abstract 16751: Novel Psoriasis Agents Associated Cardiotoxicity: Analysis of FAERS
Authors: Vyas Rahul , Al-Yafeai Zaki , Sondhi Manush , Vadlamudi Kavya
Published: December 2023

Introduction:
Psoriasis is a chronic skin condition characterised by hyper-proliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug Administration (FDA) has approved nine biological agents to address the burden of psoriasis, but their cardiovascular risks remain poorly studied.

Methods:
This retrospective pharmacovigilance study utilised the FDA Adverse Event Reporting System database to analyse adverse events associated with newly approved therapeutic agents for psoriasis. We employed disproportionally signal analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval.

Results:
Among the vast FAERS database, which contained more than 25 million adverse events, a total of 334,399 events were associated with newly approved therapeutic agents for psoriasis. Cardiac adverse events accounted for 3,852 cases, including pericarditis, atrial fibrillation, and coronary artery disease. Secukinumab had the highest number of reported adverse events, followed by brodalumab, while tildrakizumab had the lowest. Coronary artery disease was the most reported adverse event (1,438 cases), followed by pericarditis (572 cases) and atrial fibrillation (384 cases). Secukinumab had the highest incidence of coronary artery disease, pericarditis, and atrial fibrillation. Risankizumab showed a significant association with an increased risk of coronary artery disease and atrial fibrillation, while tildrakizumab and Ixekizumab were associated with atrial fibrillation. Secukinumab was associated with an elevated risk of pericarditis.

Conclusions:
The study uncovers unknown cardiovascular adverse effects related to biologic agents used in psoriasis treatment. These findings emphasise the importance of monitoring and evaluating the cardiovascular safety profiles of biologic agents used in psoriasis treatment.
Abstract 16756: Trends of Cardiovascular Deaths in Patients With Melanoma From 2005 to 2019: An Analysis Based on SEER Program Database
Authors: Prasai Astha , Baral Nischit , Niroula Shailesh , Banjade Prakash , Kandel Kamal , Devkota Amrit , Khan Ejaz ahmad A , Bista Mamata , Mitchell Joshua D
Published: December 2023

Introduction:
Melanoma is the fifth most common cancer diagnosis in the United States. With recent advances in treatment modalities, including immune checkpoint inhibitors (ICIs), targeted therapies, there has been improvement in survival among melanoma patients. However, increasing resistance and treatment related adverse effects (TrAEs) are being reported including cardiovascular side effects.

Objectives:
To evaluate the trend of cardiovascular specific death rate among patients with melanoma.

Methods:
We used Surveillance, Epidemiology, and End Results (SEER) Program database 17 registries from 2000 to 2019 and SEER*Stat Version 8.4.1 software to analyze the data using the rate session. Joinpoint software, version 4.7.1.0 was used to create log-linear time trends annually.

Results:
Our study included 301,632 patients with melanoma from 2005 to 2019. The annual percentage change (APC) of melanoma was 0.46% (95% CI -1.45 to 1.07, p>0.05) annually from 2005 to 2011 and 3.33% (95% CI 1.79 to 4.27, p<0.05) annually from 2011 to 2014 and the incidence rate decreased by 0.06% (95% CI -1.44 to 0.5, p>0.05) annually from 2014 to 2019. Melanoma specific mortality rate increased annually by 2.03 % (95% CI 0.78 to 3.94, P <0.05) from 2005 to 2013 and decreased by 5.49% annually (95% CI -8.65 to -3.65, P <0.05) from 2013 to 2019. Cardiovascular disease specific mortality rate increased by 7.08% annually (95% CI 4.66 to 9.64, P <0.05) from 2005 to 2019. (Figure 1)

Conclusion:
Our study shows that there has been an annual increase in cardiovascular specific mortality rate from 2005 to 2019, while there was annual decrease in melanoma specific mortality rate from 2013 to 2019. Increase in cardiovascular specific death rates could be due to the direct toxicity of newer therapies and prolonged survival, which further could be due to advancement in diagnostics and newer therapies.
Abstract 16767: Utilization Trends and Sex Disparities in Cardiac Magnetic Resonance Imaging for Cardiovascular Diseases: Insights From TriNetX, a Large Database Analysis
Authors: Narendrula Aparna , Issa Rochell , Chen David , Nguyen Christopher , Tang Wai Hong W , Kaelber David , Kwon Deborah H
Published: December 2023

Introduction:
Cardiac magnetic resonance imaging (CMR) is an important imaging modality for diagnosing cardiovascular diseases and optimizing therapeutic management. We assessed CMR utilization and potential sex disparities for myocarditis, Takotsubo cardiomyopathy (CM), heart failure, and amyloidosis.

Methods:
Using the TriNetX database, we conducted a comprehensive analysis, querying adults with diagnoses of these four diseases. CMR risk within 1 year of ICD-10 diagnosis was assessed. Trends in CMR incidence proportion and prevalence between 2015 and 2022 were examined. Odds ratios were used to assess the presence of both sex disparities and temporal differences in CMR utilization for myocarditis in the COVID-19 era.

Results:
Overall increasing prevalence and incidence proportion of CMR for these four diagnoses are presented in Figure 1. CMR utilization for patients with myocarditis (10.4%), remained consistent between 2019 and 2020. However, the odds of CMR slightly increased in 2021 and then declined in 2022. CMR utilization for Takotsubo, heart failure, and amyloidosis diagnoses was lower, 2.4%, 1.3%, and 4.4%, respectively. Odds ratios revealed higher likelihood of CMR ordered for males than females diagnosed with Takotsubo CM [OR 1.352* (1.143, 1.599)], heart failure [ OR 1.248* (1.221,1.277)], and amyloidosis [OR 1.375* (1.261,1.499)].

Conclusions:
Despite CMR's diagnostic and prognostic utility in patients with suspected myocarditis, heart failure, Takotsubo CM, and amyloidosis, CMR utilization is rising but low, with significant sex disparities in referral patterns. Further studies are needed to determine how increased CMR utilization impacts cardiovascular disease diagnosis, patient outcomes, and sex disparities.
Abstract 16776: Recurrent Admission of Acute Decompensated Heart Failure Among Patients With and Without PAD and Its Significance in the CKD Population: The ARIC Cohort Study
Authors: Chunawala Zainali S , Bhatt Deepak L , Qamar Arman , Vaduganathan Muthiah , Mentz Robert J , Matsushita Kunihiro , Grodin Justin L , Pandey Ambarish , Caughey Melissa C
Published: December 2023

Introduction:
Peripheral artery disease (PAD) and chronic kidney disease (CKD) are common comorbidities in patients with heart failure (HF). Importantly, CKD is associated with a greater risk of incident PAD and is a known risk factor for worse outcomes in HF patients. However, it is unclear whether the concomitant existence of PAD and CKD increases the risk of recurrent hospitalization for acute decompensated heart failure (ADHF).

Methods:
Since 2005, the Atherosclerosis Risk in Communities (ARIC) study has conducted hospital surveillance of ADHF with events verified by physician review. Demographics, comorbidities, laboratory data, and medications were abstracted from medical record by trained personnel. Hazard ratios of ADHF readmissions were analyzed using repeat-events Cox regression. Models were adjusted for age, race, sex, year and hospital of admission, coronary artery disease (CAD), COPD, and diabetes mellitus. CKD was defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73m
2
.

Results:
From 2005-2018, there were 1049 index hospitalizations for ADHF (mean age 77 years, 66% white) with measured creatinine, who were discharged alive. Of these, 155 (15%) had a diagnosis of PAD and 66% had CKD stage 3a or worse (GFR ≤60 mL/min/1.73m
2
). Patients with PAD had a greater prevalence of smoking, CAD, myocardial infarction, and stroke. The 1-year ADHF readmission rate tended to be higher in patients with PAD, irrespective of CKD stage, compared to those without PAD (
Figure 1
). After adjustments, PAD was associated with greater hazards of 1-year ADHF readmissions, both in patients with CKD stage 3a or worse (HR, 1.71; 95% CI: 1.25 - 2.32) and without CKD (HR, 1.84; 95% CI: 1.07-3.15).

Conclusion:
Patients with ADHF and concomitant PAD have a higher prevalence of cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of the CKD status. Focused strategies to prevent ADHF readmission in this high-risk group are warranted.
Abstract 16778: Design of a Pan Heart Failure Gene Therapy by Targeting Telomere-p53 Axis
Authors: Zhao Yinlong , Bao Xiaolu , Xiong Weiyao , Liu Yangyang , Ashley Euan A , Han Wei , Chang Alex C
Published: December 2023

Introduction:
Cardiovascular disease and heart failure is among the top causes of morbidity and mortality worldwide with a critical need for innovative therapies to reverse the course of ventricular dysfunction. We established that heart failure cardiomyocytes exhibit telomere uncapping and shortening, which leads to DNA damage p53 activation and inhibition of mitochondrial biogenesis.

Hypothesis:
We hypothesize that reprotection of telomeric ends can prevent p53-induced mitochondrial dysfunction and restore cardiac function.

Methods:
We designed a pan-HF gene therapy (AAV9-modhTERT) - that acts through telomeric reprotection to turn off p53 and restore myocardial mitochondrial biogenesis - and validate safety and efficacy in Ang II and TAC heart failure murine models. Cardiac specificity in human induced pluripotent stem cell derived cardiomyocytes, biodistribution in mice, and dose titration studies on Ang II and TAC mice were performed.

Results:
One dose of AAV9-modhTERT sufficiently improved ejection fraction by ~20%, prevented cardiac fibrosis and expression of HF biomarkers. Molecularly, AAV9-modTERT blocked DNA damage activation, reversed mitochondrial biogenesis, restored mitochondrial ultrastructure and respiration, and reversed transcriptomic profiles.

Conclusions:
These preclinical studies demonstrate considerable potential for the first pan-HF single-dose gene therapy that can reverse cardiac function and prevent myocardial remodeling which would be invaluable clinically and an Investigator Initiated Trial (IIT) (NCT05837143) was launched in April 2023.
Abstract 16786: Integrative Omics in Failing Myocardium Highlights Metabolic Substrate Utilization Defects in Human Heart Failure
Authors: Kwee Lydia C , Truby Lauren K , Page Stephani , Bowles Dawn E , Milano Carmelo , Ilkayeva Olga , Newgard Christopher , Felker Michael , Bristow Michael , Holley Christopher L , McGarrah Robert W , Shah Svati H
Published: December 2023

Introduction:
Changes in substrate utilization may be a biomarker of, or a contributor to, heart failure with reduced ejection fraction (HFrEF). Previous work has described circulating metabolites, proteins and transcripts that reflect myocardial bioenergetics, but direct assessment in relevant tissues is lacking. Here, we leverage integrative omics to identify tissue-level biomarkers and pathways of HFrEF that may play a role in pathogenesis.

Methods:
Myocardial tissue was obtained from 27 HFrEF donors and 21 non-failing hearts (noHF) from Duke University and the University of Colorado Medical Centers. Targeted (n=139 metabolites) and nontargeted (Metabolon, n=817) metabolic profiling was performed; in addition, 496 proteins were assayed (Olink) and ~31,000 transcripts were quantified via RNA sequencing. Individual metabolites were tested for association with HFrEF in models adjusted for age, sex and diabetes. Metabolomics, proteomics and RNA-seq data were integrated using block sparse partial least squares discriminant analysis (sPLS-DA) to identify correlated biomarkers that discriminate HFrEF from noHF hearts.

Results:
The targeted metabolomics platform primarily assayed metabolic fuel substrate pathways; 71 analytes (51%) were associated with HFrEF after controlling the false discovery rate (FDR) at 5%. Medium- and long-chain acylcarnitines (C10s-C18s) were significantly lower in tissue from failing hearts, while branched-chain amino acids (BCAA) and ketoacids were higher. In the nontargeted set, 293 metabolites (36%) differed between HFrEF and noHF. BCAA and acylcarnitine associations were recapitulated along with a decrease in malonylcarnitine. The sPLS-DA model selected 25 targeted and 50 nontargeted metabolites, 35 proteins and 35 transcripts, and successfully discriminated HFrEF from no HF (balanced error rate = 3.2%). 39/186 tested KEGG pathways were overrepresented in these analytes, including fatty acid metabolism (FDR q=0.002).

Conclusions:
Analysis of tissue-level metabolites suggests both decreased use of fatty acids as a fuel and disrupted enzymatic breakdown of BCAAs in the failing heart, while integrative omics pathway analysis also supports the association of disrupted fatty acid metabolism with HF.
Abstract 16795: Blood Pressure Lowering Therapeutical Strategies Have Different Impact on Brain Functional Connectivity
Authors: Carnevale Lorenzo , maffei angelo , landolfi alessandro , Carnevale Daniela , Lembo Giuseppe
Published: December 2023

Hypertension is a major risk factor for cognitive impairment and dementia. Using functional MRI, researchers have been able to study the brain’s functional connectivity in hypertensive patients. This has revealed that even before showing signs of vascular dementia, hypertensive patients have altered brain connections compared to normotensive patients. Our aim is now to characterize whether different classes of antihypertensive drugs, which vary in their mechanism of action and ability to cross the blood-brain barrier, have different effects on the brain’s functional organization. In this study, 42 hypertensive patients with controlled blood pressure underwent resting-state functional MRI. The data was analyzed using CONN to build functional connectivity network matrices and analyze the amplitude of spontaneous brain activity fluctuations (fALFF). These results were then evaluated using general linear models to identify connections that were modulated by specific classes of antihypertensive drugs. We applied regression models taking into account age, sex, BMI, alcohol, smoke and BP levels as covariates. Our results show that treatment with diuretics was associated with a large connectivity network among several brain networks (A). Treatment with ACE inhibitors (B), ARBs (C), and beta-blockers (D) was also associated with significant modulation of specific connections (all highlighted connections p<0.05, statistics in figure). Overall, diuretics had the greatest impact on brain function, possibly due to their effect on blood volume and cerebral circulation, with the effect further confirmed by fALFF analyses, showing a widespread reduction of the BOLD-signal intensity of spontaneous cerebral activity (all highlighted clusters p<0.05, statistics in figure E). These findings may help inform the choice of antihypertensive treatment for individual patients, taking into account the potential cognitive and functional impact of different drugs.
Abstract 16815: Outcomes of Cardiac Sympathetic Denervation via Cautery Ablation for Ventricular Arrhythmia: A Single Center Study
Authors: Yoo David H , Allan James S , Mansour Moussa C , Heist Edwin Kevin , Sharif Zain , Mela Theofanie
Published: December 2023

Introduction:
Cardiac sympathectomy denervation (CSD) has been demonstrated to reduce ventricular arrhythmia (VA) burden and to improve arrhythmia-free survival. Early evidence for the clinical antiarrhythmic benefits for CSD was established in patients with long-QT syndrome and catecholaminergic polymorphic VT (CPVT). Its benefit has subsequently been shown to extend to other undifferentiated cardiomyopathies.

Hypothesis:
Literature on CSD for VA has been limited due to a small number of patients. Our retrospective study is to review patients who underwent CSD for VA at our center via cautery ablation.

Methods:
We identified 9 patients who underwent CSD from 4/2018 to 2/2022. Electronic medical record was reviewed for clinical history and outcomes.

Results:
Mean age was 52±17 and 5 patients (55.6%) were male. Seven patients (77.8%) had nonischemic cardiomyopathy (NICM) and 2 patients (22.2%) had CPVT. Mean LVEF was 43±19% and 5 patients (55.6%) had heart failure with NYHA class 3±0.7. Five patients (55.6%) underwent CSD in outpatient setting and 4 patients (44.4%) had polymorphic VT. Six patients (66.7%) had prior catheter-based VT ablation, 1 patient (11.1%) had prior ganglion block, and 4 patients (44.4%) had history of VT storm. All patients were on antiarrhythmics ranging from a beta blocker monotherapy to a combination of class Ic, class III, and a beta blocker. Seven patients (77.8%) had a defibrillator prior to CSD. All patients underwent CSD (7 with bilateral and 2 with left only) without any procedural complication. Five patients (55.6%) had recurrence of VA in 423±567 days with follow-up duration of 729±478 days. Three patients (33.3%) underwent heart transplant or LVAD and three patients (33.3%) died in 426±396 days since CSD. Overall, 3 patients (33.3%) including 2 CPVT patients and one NICM patient with normal EF were free of death, sustained VT, or advanced heart failure therapies.

Conclusions:
CSD via cautery ablation is safe and effective for patients with refractory VA to antiarrhythmics and/or VT ablation. Success rate appeared to be higher in patients with CPVT and normal EF. Lower rate of survival and freedom from VT or transplant/LVAD compared to published literature may reflect our sick population.
Abstract 16817: Comparison of Diagnostic Performance of Quantitative Perfusion Stress Myocardial Perfusion Imaging With Cardiac Magnetic Resonance Between Different Vasodilators
Authors: Rodriguez-Lozano Patricia , Wang Shuo , Wang Haonan , Ng Ming-Yen , Kim Paul , Singh Amita , Mushtaq Saima , Tsun Hei Sin , Tada Yuko , Hillier Elizabeth , Østergaard Mariager Christian , Salerno Michael , Pontone Gianluca , Urmeneta Javier , Saeed Ibrahim M , Patel Hena , Martinez Vicente , Maceira Alicia , Monmeneu Jose , Pazhenkottil Aju P , Benovoy Mitchel , Amir-Khalili Alborz , Janich Martin A , Arai Andrew E , Friedrich Matthias G , Patel Amit R
Published: December 2023

Introduction:
Adenosine and regadenoson are commonly used vasodilators in myocardial perfusion imaging for assessment of suspected coronary artery disease.

Hypothesis:
The aim of this study is to determine the difference between the different vasodilators by quantifying stress and rest myocardial perfusion using cardiovascular magnetic resonance (CMR).

Methods:
Subjects with known or suspected CAD from 10 centers undergoing invasive coronary angiography or CT angiography were enrolled for rest and stress first-pass perfusion images using dual sequence. First-pass stress perfusion images were acquired on 1.5T or 3.0T GE scanner during adenosine or Regadenoson. Fully quantitative perfusion values were determined using Fermi deconvolution. Significant CAD was defined by: presence of≥50% stenosis in the left main coronary artery or ≥70% in the one major vessel. Diagnostic performance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) was measured using receiver operating characteristics curves.

Results:
A total of 89 subjects were recruited with a median age of 66 yrs, 69% men, 55% significant CAD, history of hypertension in 78%, diabetes in 48%, and hyperlipidemia in 74%. 36 subjects used adenosine, while 53 used regadenoson as the vasodilator agent. Stress MBF had a good area under the curve for adenosine vs. regadenoson [ 0.89 (0.78-1.00) vs. 0.82 (0.66-0.98), p=0.43], sensitivity (100% vs. 84%), and specificity (80% vs. 80%). MPR had a higher area under the curve for adenosine than regadenoson [0.87 (0.75-0.98) vs. 0.68 (0.52-0.84), p=0.06], sensitivity (100% vs. 61%), and specificity (68% vs. 73%). (Figure)

Conclusions:
Our study showed that fully quantitative perfusion using CMR, regadenoson, and adenosine have similar good diagnostic accuracy when stress MBF was used as the diagnostic parameter. However, adenosine outperformed regadenoson for the detection of significant CAD when MPR was used as the diagnostic parameter.
Abstract 16827: Safety and Efficacy of Cangrelor in Acute Coronary Syndromes: A Systematic Review and Network Meta-Analysis
Authors: Mostafa Mostafa R , Eid Mohamed , Takla Andrew , Najim Mostafa , Mohamed Sarah , Barssoum Kirolos , Al-azizi Karim M , Goldsweig Andrew M , Jneid Hani
Published: December 2023

Introduction and Hypothesis:
Cangrelor is a potent intravenous non-thienopyridine P2Y12 inhibitor. We conducted a network meta-analysis to study the efficacy and safety of cangrelor compared to oral P2Y12 inhibition or placebo in acute coronary syndromes.

Methods:
This meta-analysis followed the Cochrane collaboration guidelines and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. Outcomes of interest included all-cause mortality, myocardial infarction, stent thrombosis, major bleeding, minor bleeding, and the need for blood transfusion.

Results:
In a network meta-analysis of 6 studies comprising 26,444 patients, Both cangrelor and clopidogrel showed no statistically significant difference compared to placebo in all-cause mortality (P= 0.46, I
2
= 22%) [Figure 1], myocardial infarction (P= 0.50, I
2
= 24%) [Figure 2], stent thrombosis (P= 0.84, I
2
= 0%) [Figure 3], major bleeding (P= 0.73, I
2
= 11%) [Figure 4], or the need for blood transfusion (P= 0.43, I
2
= 17%) [Figure 6]. Additionally, clopidogrel did not show a significant difference in the occurrence of minor bleeding compared to placebo. However, cangrelor was linked to an increased risk of minor bleeding (P=0.04, I2=54%) [Figure 5].

Conclusion:
Cangrelor has comparable outcomes to clopidogrel in patients with acute coronary syndromes and can be used as a reliable alternative in this population.
Abstract 16833: Native Pulmonary Valve Infective Endocarditis in the Absence of Typical Risk Factors
Authors: Goldstein Jake , Wieschhaus Keaton , Poellinger Nicholas , Gussak Georg , Malas Kaled , Kashlan Besher , Diaz Gabriel , Paterick Timothy , Malas Waddah , Dajani Khaled
Published: December 2023

Introduction:
Isolated Pulmonary valve endocarditis (PVE) is a rare subset of right sided endocarditis associated with high mortality. We describe a case of PVE without typical risk factors.

Case:
A 53-year-old male with a history of controlled type 2 diabetes, coronary artery disease and recent minor trauma to the foot presented with 1 week of intermittent fevers, night sweats, and decreased appetite. Vital signs revealed a temperature of 103°F. Exam was significant for a grade II diastolic murmur best heard on the left sternal border and a healed wound on the left 5th metatarsal. Blood cultures taken grew Methicillin-Resistant Staphylococcus Aureus. A trans-thoracic echocardiogram revealed an echo dense material on the pulmonary valve measuring 1.0 x 0.3 cm. Differential diagnosis included endocarditis, pulmonary fibroelastoma, thrombus, or a cardiac tumor. A trans-esophageal echocardiogram later obtained revealed an echogenic lesion on the pulmonic valve measuring 2.1 x 1.2 cm with severe pulmonic insufficiency. An echodensity adherent to the right ventricular wall was also visualized. Tricuspid valve appeared normal. Due to persistent bacteremia despite appropriate antimicrobial coverage and significant valvular insufficiency, a decision was made to proceed with cardiac surgery. Patient received debridement to both pulmonary valve and right ventricular vegetations and underwent pulmonary valve replacement. Intraoperative pathology was consistent with endocarditis. The nidus for infection was attributed to the patient’s recent traumatic wound. The patient was discharged home with 6 weeks of daptomycin therapy.

Conclusion:
Right sided endocarditis involving the pulmonic valve is rare but can occur in individuals without an obvious predisposing cardiac structural abnormality. In our case, the patient developed severe valvular insufficiency therefore was successfully treated with surgical intervention and a prolonged course of antibiotics.
Abstract 16836: A View-Invariant Deep Learning Model for Estimating Ejection Fraction From Any Valid Echocardiogram Videoclip, Including Point-of-Care Ultrasound (POCUS)
Authors: Anisuzzaman DM , Malins Jeffrey G , Jackson John I , Lee Eunjung , Naser Jwan , Rostami Behrouz , Bird Jared G , Friedman Paul A , Lopez-Jimenez Francisco , Pislaru Sorin V , Kane Garvan C , Attia Zachi
Published: December 2023

Background:
Recently, our team developed an end-to-end artificial intelligence (AI) framework that can successfully estimate left ventricular ejection fraction (LVEF) from echocardiogram videos. However, this framework requires specific views (A2C and PLAX), and cannot estimate LVEF for studies from which these views are missing.

Goal:
To develop a deep learning model to estimate LVEF from any type and number of echocardiogram video(s).

Methods:
We built a deep learning model for B-mode echocardiogram videos of the left ventricle (A2C, A3C, A4C, or PLAX views), using retrospective transthoracic echocardiography (TTE) data. The model was evaluated with two test datasets: one with random valid (i.e., showing the left ventricle) views, and one with preselected views (both having 433 patients). Later, the model was tested with a prospective patient cohort that had both TTE and point-of-care ultrasound (POCUS) data collected simultaneously (393 patients).

Results:
On the retrospective TTE test set, we observed excellent performance (five random valid views per study: RMSE of 6.87% and Pearson correlation (PC) of 0.82 on LVEF estimation, and an AUC of 0.96 (95% CI: of 0.94-0.98) on low LVEF classification (<=40%); preselected views: RMSE of 6.75%, PC of 0.83, and an AUC of 0.96 (95% CI: 0.94-0.98)). For both TTE and POCUS data from the prospective cohort, we also observed strong performance (TTE: RMSE of 5.62%, PC of 0.87, and an AUC of 0.97; POCUS: RMSE of 6.12%, PC of 0.84, and an AUC of 0.96). For the prospective test sets as well as for the retrospective TTE test set with preselected views, results reflect the estimated LVEF average of A2C, A3C, A4C, and PLAX videos from each patient.

Conclusions:
For both TTE and POCUS data, the current model showed strong performance which was comparable to that of our previously established view-specific model. Alongside this comparable performance, the current model surpasses our previous model in terms of flexibility, as it isn't dependent on view classification and allows a broader selection in terms of the number and types of videos per study or patient. This innovative approach could prove particularly beneficial in point-of-care situations in which it may not be feasible to obtain high-quality, view-specific videos.
Abstract 16868: Genetic Regulation of Branched-Chain Amino Acid Levels Does Not Increase Type 2 Diabetes Risk
Authors: Agamasu David I , Shi Mingjian , Vaitinadin Nataraja Sarma S , Murthy Venkatesh L , Shah Ravi V , Bagheri Minoo , Ferguson Jane F , Mosley Jonathan
Published: December 2023

Introduction:
The branched-chain amino acids (BCAAs) valine, leucine, and isoleucine are associated with incident type 2 diabetes (T2D). Prior genetic studies have provided conflicting results as to whether the BCAAs are causally related to T2D but are limited by a small number of genetic instruments associated with BCAA levels.

Hypothesis:
We hypothesized that polygenic predictors that capture a broad set of genetic mechanisms regulating BCAA levels would clearly define the etiological relationship with T2D.

Methods:
We constructed and validated instrumental variables for each BCAA using well-powered datasets and tested their association with T2D using two-sample inverse variance weighted (IWV) Mendelian randomization (MR). Sensitivity analyses were performed to ensure the accuracy of the findings. We also tested whether instrumental variables for T2D, fasting insulin, and body mass index (BMI) were associated with BCAA levels. Finally, logistic regression was used to test whether a polygenic risk score (PRS) for T2D was associated with measured BCAA levels among 1220 participants in the Framingham offspring study (FOS) without prevalent T2D.

Results:
There were no significant associations with T2D for valine (beta=0.17 change in log-odds per standard deviation change in valine, [95% CI, -0.28 - 0.62], p=0.45), leucine (beta=0.19 [-0.30 - 0.68] p=0.45) or isoleucine (beta=0.02 [-0.54 - 0.59], p=0.94). In contrast, T2D was associated with each BCAA (valine: beta=0.08 per standard deviation change in levels per log-odds change in type 2 diabetes, [0.05 - 0.10], p=1.8x10
-9
), (leucine: beta= 0.06 [0.04 - 0.09], p=4.5x10
-8
) and isoleucine (beta= 0.06 [0.04 - 0.08], p=2.8x10
-8
). The T2D associations were replicated in an independent population but not in a second population where T2D cases were removed. Similarly, a T2D PRS was associated with measured BCAA levels in the FOS study but not when incident T2D cases were removed. Positive associations were seen for fasting insulin and BMI, and the BCAAs by MR, and, in multivariable MR analyses, T2D and fasting insulin had independent associations with each BCAA.

Conclusions:
These data suggest that BCAAs are not mediators of T2D risk but may rather serve as biomarkers of T2D and higher insulin levels.
Abstract 16870: Short-Term Risk Prognostication for All-Cause Mortality After Endovascular Revascularization in the Medicare Claims-Linked VQI Registry
Authors: Cleman Jacob , Romain Gaelle , Callegari Santiago , Scierka Lindsey , Jacque Francky , Provance Jeremy B , Smolderen Kim G , Mena-Hurtado Carlos
Published: December 2023

Background:
Patients with chronic limb-threatening ischemia (CLTI) have high mortality rates after revascularization. Balancing short-term mortality risk against limb salvage gains is important when triaging patients with CLTI to revascularization. Data for risk stratification is limited. We aimed to develop machine learning models to rank predictive variables for 30-day and 90-day all-cause mortality for CLTI after peripheral vascular intervention (PVI).

Methods:
Patients undergoing PVI for CLTI between 2017 and 2018 in the Medicare-linked Vascular Quality Initiative (VQI) were included. Sixty-six preprocedural variables were included in random survival forest (RSF) models. RSF models were constructed for 30-day and 90-day all-cause mortality in the training sample (80% of data) and evaluated in the validation sample (20% of data). Predictive variables were ranked based on frequency that they caused branch splitting nearest the root node. Goodness of fit was assessed by Harrell’s C-index.

Results:
A total of 10,114 patients (mean age 72 ± 11, 59% male, 74% white) were included. The mortality rate was 4.4% at 30 days and 10.6% at 90 days. The RSF model for 30-day mortality identified stage 5 chronic kidney disease (CKD), dementia, and urgent procedures as the most predictive variables. For the 90-day mortality prediction model, the most important variables were stage 5 CKD, dementia, and poor functional status
(Figure)
. For both models, 8 of the top 10 variables were either medical history or functional status variables. The C-index was 0.72 for the 30-day model and 0.73 for the 90-day model.

Conclusion
Using data from the claims-linked VQI registry, medical comorbidities and functional status variables were identified as the most predictive variables for 30-day and 90-day all-cause mortality using RSF models. Results may help guide individualized risk conversations regarding PVI versus conservative therapy for the highest risk patients.
Abstract 16872: Sex Differences in Acute Decompensated Heart Failure: A Pooled Analysis
Authors: Gupta Prerna , Kao David P
Published: December 2023

Introduction:
Sex differences in heart failure physiology, presentation, and symptoms have been well established across the heart failure spectrum. Sex differences in presentations of acute decompensated heart failure (ADHF) have not yet been well explored. We pooled data from 5 clinical trials to assess sex-based differences in presentation of ADHF.

Methods:
Patient clinical variables, hemodynamic parameters, patient-reported outcomes, and clinical outcomes were compared among trial data from ATHENA, CARRESS, DOSE, ESCAPE and ROSE. Baseline characteristics, physiologic variables, and medications were compared between men and women in aggregate as well as by study. Echo and invasive hemodynamics were assessed in ESCAPE only. Correlations were assessed in a stepwise manner assess relationships between clinical parameters. We also compared weight change and net fluid balance between sexes.

Results:
Among 1,649 patients pooled across trials, 466 (28%) were women. Men had significantly lower LVEF, pulse pressure, systemic vascular resistance, and body mass index. Women had lower natriuretic peptide, intracardiac filling pressures and six-minute walk distance. Women had higher pulse pressure and systemic vascular resistance (Table). Women had much higher rates of LV hypertrophy (71% vs 43%, p = 0.007) using sex-specific criteria whereas men had much higher rates of anemia using sex-specific criteria. At discharge women had a lower net fluid balance and less weight loss both in absolute terms and adjusted for body weight.

Conclusion:
The results above demonstrate significant sex-based differences in presentation for ADHF. Despite generally similar signs and symptoms of congestion, women presented with less fluid accumulation, lower filling pressures and preserved peripheral hemodynamics. These differences suggest warning signs for ADHF and treatment goals during hospitalization may be different in women than men.