bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12390: Machine Learning Model Predicts One-Week Blood Pressure Average and Trajectory From One Drop Data
Authors: Sears Lindsay , Harvey Colin , Sears Lindsay , Goldner Dan , Dachis Jeff
Published: April 2024

Introduction:
Self-monitoring of blood pressure (BP) is associated with better BP management. Studies to date have focused on monitoring historic or real-time BP values, which are not inherently informative for prospective health decisions. Having a prediction of next week’s average BP gives both immediate feedback on current activity and an opportunity to take action to prevent a predicted rise in BP. Using BP and other tracking and clinical data from One Drop, an app that integrates digital therapeutics, health predictions and health sensing data, we developed a machine learning model to forecast weekly average systolic and diastolic BP.

Method:
One Drop has collected over 25 billion data points from people in all 195 countries, including BP, glucose, weight, medication, food, physical activity, heart rate, comorbidities, other behaviors such as sleep, and biographic data such as gender and age. Data through June 2020 were used to train two supervised learning models: 1) a regression model to predict next week’s average BP, and 2) a classification model to predict next week’s BP trend direction: rising, falling, or steady, with steady defined as a change in weekly average of less than 5 mm Hg. The trained models were used to predict hold-out values collected after June 2020 and were evaluated using mean absolute error (MAE) and AUC.

Results:
This study was based on a sample of 17 million BP measurements over 150,000 person-weeks from 6,600 One Drop members (46.7% male, 16.0% female; 37.3% unreported). The MAE of the regression model was 4.55 mm Hg, 22.2% less than assuming persistence (MAE = 5.85 mm Hg). For the classification model, one-vs-rest AUCs were 88.9% (rising); 80.3% (steady), 89.2% (falling) with a weighted AUC of 84.5%.

Conclusion:
Machine learning models based on app-collected health and self-care data can provide accurate short-term forecasts of changes in average BP. Timely feedback of this kind may empower people to make healthier choices that prevent predicted rising BP and potentially reduce overall CVD risk.
Abstract 12391: Association of Left Ventricular Global Longitudinal Strain With Poor Clinical Outcome in COVID-19: A Systemic Review and Meta-Analysis
Authors: Limpruttidham Nath , Riangwiwat Tanawan , Prasitlumkum Narut
Published: April 2024

Introduction:
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared a global pandemic by the World Health Organization (WHO) in March 2020. Although left ventricular global longitudinal strain (LV-GLS) has been validated as a prognostic marker in other disease processes, the utility of LV-GLS in risk stratification of coronavirus disease 2019 (COVID-19) remains controversial. This study aimed to investigate the prognostic value of echocardiographic findings, including LV-GLS in patients with COVID-19.

Hypothesis:
LV-GLS is associated with poor clinical outcomes in patients with COVID-19.

Methods:
We comprehensively searched the databases of MEDLINE and EMBASE from inception to June 2021. Included studies were published observational studies that reported an association between echocardiographic findings and prognostic valve in COVID-19. Data from each study were combined with random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled odds ratios and their 95% confidence intervals at 0.05 significance level. Sensitivity analysis and funnel plot were assessed for the validity of the results.

Results:
Six observational studies from August 2020 to May 2021 were included in this meta-analysis. The pooled odds ratio for COVID-19 mortality for each 1% change in LV-GLS was 1.452 (95% confidence interval 1.186 to 1.778, P < 0.001). There was moderate heterogeneity with an I-square value of 49.9%. Sensitivity analysis showed no significant deviation from pooled odds ratios. There was no evidence of publication bias from the funnel plot and Egger’s test.

Conclusions:
LV-GLS measurement has prognostic value in risk stratification among COVID-19 patients. Low LV-GLS is independently associated with poor clinical outcomes.
Abstract 12394: Development of a Heparin Dosing Algorithm to Maintain Therapeutic Anticoagulation During Atrial Fibrillation Ablation
Authors: Martini Matthew , Mahnke Marcus , Modaff Daniel S , Fleeman Blake , Kipp Ryan T , Wright Jennifer , Meadow Joshua , Kalscheur Matthew
Published: April 2024

Introduction:
Therapeutic anticoagulation during atrial fibrillation (AF) ablation reduces the risk of cerebral thromboembolism during ablation. Heparin dosing strategies vary and can result in sub-therapeutic anticoagulation.

Hypothesis:
We hypothesize that a heparin dosing algorithm will improve maintenance of guideline-based therapeutic activated clotting times (ACT) during AF ablation.

Methods:
Starting from published guidance on heparin dosing during AF ablation, an artificial intelligence algorithm based on a decision tree and other mathematical considerations was developed. The algorithm launches directly from the electronic medical record and captures deidentified data for future improvements. The rules were modified over several months to establish the tested algorithm. The strategy utilized heparin boluses and an infusion. Dosing was adapted based on an individual patient’s response to the first heparin bolus. Goal ACT was 300-350 s. Outcomes from a month prior to algorithm introduction were compared to those from one month using the developed algorithm. The measured outcomes included time from first bolus to therapeutic ACT (>300 s), number of heparin boluses to achieve goal ACT, time in left atrium below therapeutic ACT, and ACT value when below goal in left atrium.

Results:
Data from seventeen pre-algorithm procedures were compared to fourteen procedures completed using the dosing algorithm. Compared to procedures using typical dosing, procedures using the dosing algorithm reached goal ACT faster (16.1 ± 5.3 min compared to 26.2 ± 14.5 min, p = 0.02) with fewer heparin boluses (1.1 ± 0.3 boluses compared to 1.6 ± 0.9 boluses, p = 0.04). The ACT did drift below goal in some cases (n = 4 using algorithm and n = 5 using typical dosing). The time below goal was not different between dosing strategies (16.5 ± 8.7 min for algorithm compared to 22.4 ± 7.9 min for typical dosing). However, when the ACT drifted below goal with the dosing algorithm, it was significantly closer to goal than with typical dosing (295 ± 3 s compared to 268 ± 21 s, p = 0.02).

Conclusion:
An artificial intelligence algorithm based on a decision tree and adaptation to individual patient kinetics may improve maintenance of guideline based therapeutic ACT during AF ablation.
Abstract 12399: Don’t Burst My Blood: Ticagrelor Induced Thrombotic Thrombocytopenic Purpura
Authors: Medamana John L , Laljee Saif , Kiefer Nicholas , Brejt Shelly
Published: April 2024

Background:
Dual antiplatelet therapy, a fundamental component of the treatment of acute coronary syndromes (ACS), increases bleeding risk. Patients with thrombocytopenia and ACS are difficult to manage as thrombocytopenia increases the risk both of bleeding and ischemic events.

Case:
A 47 year old male with a medical history most significant for coronary artery disease (requiring multiple stents) and stroke who presented with chest pain and was found to have a NSTEMI. Notably, the patient stopped his ticagrelor six weeks prior to presentation. The initial CBC demonstrated clumped platelets. The patient was loaded with aspirin and ticagrelor, placed on a heparin drip and admitted.

Decision Making:
Exam on the morning after presentation demonstrated jaundice as well as petechiae on the patient’s extremities. He then exhibited altered mental status concerning for a seizure. Repeat labs demonstrated new severe thrombocytopenia, confirmed on a dedicated platelet count, anemia and indirect hyperbilirubinemia. A peripheral smear did not demonstrate schistocytes; however, the PLASMIC score indicated a high risk of thrombotic thrombocytopenic purpura (TTP) and he was started on plasmapheresis and steroids. His ADAMTS13 activity level returned low, confirming TTP. Common causes of TTP were excluded and Ticagrelor was deemed responsible. With continued plasmapheresis and steroids, his platelets normalized. A diagnostic left heart catheterization demonstrated patent prior stents as well as a 90% mid circumflex lesion. The patient was discharged on aspirin and rivaroxaban per the COMPASS trial, and was advised to avoid further P2Y12 inhibitors.

Conclusion:
This case demonstrated ticagrelor induced TTP, which has been infrequently reported in the literature. The patient was likely previously sensitized to ticagrelor and then developed TTP when he was loaded on presentation. It also demonstrates the importance of not ignoring clumped platelets and obtaining a true platelet count prior to starting triple therapy. In normal circumstances, his circumflex lesion would likely have been intervened upon; however, the patient’s intolerance of P2Y12 inhibitors limited management options during this presentation and will likely limit future interventions.
Abstract 12401: Cardiovascular Risk Profile and Gestational Diabetes Mellitus by Maternal Nativity and Length of US Residence in Racially Diverse, Urban, Low Income Population in the United States
Authors: Shah Lochan M , Boakye Ellen , Ogunwole Michelle , Bennett Wendy L , Wang Xiaobin , Blumenthal Roger S , Hays Allison , Minhas Anum , Blaha Michael J , Nasir Khurram , Zakaria Sammy , Sharma Garima
Published: April 2024

Introduction:
Gestational diabetes mellitus (GDM) is independently associated with increased cardiovascular disease (CVD) risk. GDM disproportionately affects non-Hispanic Black (NHB) women in the United States (US). The prevalence of GDM by nativity (US born versus foreign born) and duration of US residence is not well known in other race/ethnicities.

Methods:
We analyzed 6088 women with data on GDM from the Boston Birth Cohort. We performed multivariable logistic regression to investigate the association of nativity and duration of US residence (<10 versus ≥10 years residence) with GDM by race (NHB, Hispanic, and White). Covariates included sociodemographic characteristics and CVD risk factors.

Results:
In our sample, 44.3% were NHB, 39.3% Hispanic, and 16.4% White. Foreign born NHB and Hispanic women with duration of US residence <10 years had lower prevalence of CVD risk factors (multiparity, severe stress, chronic hypertension, smoking in pregnancy, obesity BMI ≥ 30 kg/m2) than those with ≥10 years US residence and US born women. Foreign born NHB with duration of US residence <10 years had higher odds of GDM (adjusted OR, aOR: 1.6, 95%CI 0.99-2.6, p=0.05) compared to US born NHB women, while in contrast foreign born Hispanic women with duration of US residence <10 years had lower odds for GDM (aOR 0.54, 95%CI 0.32-0.91, p=0.021). The odds of GDM in Hispanic and NHB women with US residence ≥ 10 years was not significantly different from their US born counterparts.

Conclusions:
GDM prevalence is higher in foreign-born NHB women with shorter duration of US residence, despite better risk factor profiles. GDM is lower in foreign-born Hispanic women with shorter duration of US residence, mirroring their better risk factor profile. Thus, the “healthy immigrant effect” (health advantages for foreign-born women), appears to not apply to GDM in NHB. Further research is needed to examine why GDM burden in NHB women is not well explained by risk factor burden or environmental stress.
Abstract 12407: A Comparison of Hemodynamic and Cardiopulmonary Exercise Stress Variables for Advanced Heart Failure Prognosis
Authors: Cochran Matthew K , Belkin Mark N , Siddiqi Umar , Nguyen Ann , Chung Bow , Smith Bryan , Sarswat Nitasha , Kim Gene H , Pinney Sean P , Grinstein Jonathan , Kalantari Sara
Published: April 2024

Introduction:
Both invasive hemodynamics as measured by right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET) are used for prognostication in advanced heart failure patients. We aimed to compare the prognostic performance of these variables in patients with advanced heart failure with a particular focus on defining the incremental prognostication of advanced hemodynamic metrics compared to CPET variables.

Methods:
We retrospectively analyzed patients who underwent both a RHC and CPET within one year of each other from January 2013 to January 2019 at our institution. The CPET variables of peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2), oxygen pulse (VO2/HR), and the RHC variables of left ventricular stroke work index (LVSWI), cardiac power output (CPO), and aortic pulsatility index (API) were used. The primary outcome was death, left ventricular assist device, or heart transplant at one year following the RHC.

Results:
A total of 55 patients were included in the analysis: 35% women, 51% Black, and 27% ischemic cardiomyopathy. Overall, using Spearman’s analysis, there were no significant correlations between the RHC and CPET variables. On Kaplan-Meier analysis, lower LVSWI was significantly associated with the primary outcome when compared to lower VO2/HR, HR 5.3 (95% CI 1.2-23, p = 0.02.), lower VE/VCO2, HR 3.7 (95% CI 1.3-10.4, p = 0.014), and lower peak VO2, HR 7.0 (95% CI 0.9-56, p = 0.06).

Conclusion:
LVSWI is more associated with one-year outcomes in patients with advanced heart failure than other prognostic hemodynamic or CPET variables. Furthermore, advanced hemodynamic metrics are more prognostic than CPET measurements when these values are discordant.
Abstract 12410: The Critical Role of Mitochondrial Dysfunction in the Impaired Angiogenesis Associated With the Pulmonary Hypertensive Phenotype
Authors: Niihori Maki , James Joel , Philip Rohit C , Rafikov Ruslan , Rafikova Olga
Published: April 2024

Introduction:
Mitochondrial dysfunction (MD) is known to be tightly associated with the pathobiology of pulmonary arterial hypertension (PAH). Recently, we discovered that rats reproducing a human mutation in NFU1 (NFU1
G206C
) have a severely altered mitochondrial function and spontaneously develop PAH characterized by increased right ventricle (RV) systolic pressure, RV hypertrophy, and severe obliterative disease of small pulmonary arteries.

Hypothesis:
In this study, we investigated whether MD induced by NFU1 mutation is sufficient to impair pulmonary angiogenesis contributing to PAH pathogenesis.

Methods:
Angiogenesis was assessed by micro-computed tomography of the pulmonary vasculature, microangiography of small pulmonary arteries (PAs), and histological evaluation of pulmonary capillary density. The angiogenic capacity was also investigated
in vitro
using cell migration and tube formation assays and analysis of EC tip cell population by flow cytometry.

Results:
MD significantly reduced the complexity of the pulmonary vascular network and prevented its further advancement (PA density (mean intensity/pxl) in WT vs. NFU1
G206C
at 6 and 10 wks of age is 0.07±0.004 vs. 0.03±0.002 and 0.1±0.004 vs. 0.04±0.003; p<0.0001; N=5). NFU1
G206C
rats had a reduced number of PA branches and junctions and impaired PA capillary density. PA endothelial cells isolated from NFU1
G206C
rats demonstrated a strongly attenuated cell migration (~30% of WT) and tube formation capacity and a ~2.2 fold decrease in the number of CD-304 positive EC tip cells. Supplementation of NFU1
G206C
rats with lipoic acid (LA, 1.70 mM in drinking water) aimed to attenuate the LA-synthase insufficiency secondary to NFU1 mutation, restored mitochondrial function, preserved the complexity of PA vascular network at WT level, and averted the PAH phenotype.

Conclusions:
We conclude that MD plays a causative role in the impaired pulmonary angiogenesis. Indeed, the lungs of NFU1
G206C
rats fully reproduced the “dead-tree” picture of pulmonary vasculature described in PAH patients. At the same time, normalized mitochondrial function was sufficient to preserve pulmonary angiogenesis and prevent the PAH, suggesting the protective role of MD ameliorative approaches.
Abstract 12419: Internalized Weight Stigma Linked to Greater Visceral Adiposity for Women, but Not Men
Authors: Keirns Natalie G , Keirns Bryant H , Sciarrillo Christina , Emerson Sam , Hawkins Misty A
Published: April 2024

Introduction:
As visceral adipose tissue (VAT) is an important predictor of CVD risk, it is necessary to understand psychosocial factors possibly related to VAT accrual. Weight stigma is a chronic stressor which particularly impacts women and is associated with increased cortisol secretion. Given that chronically elevated cortisol is linked to VAT increase, weight stigma may lead to accumulation of visceral fat. This study investigated relationships between internalized weight stigma (IWS), VAT, and gender.

Hypothesis:
We hypothesized that IWS would be positively associated with VAT, and that this relationship would be moderated by gender. We predicted that the relationship between IWS and VAT would be stronger for women than for men.

Methods:
Participants (
N
=70, 81% white, 53% women,
M
age
=30.4±7.8 years,
M
BMI
=28.7±5.5 kg/m
2
,
M
BF%
=32.4±8.9%) completed in-lab measures of demographic factors (age, gender, race/ethnicity), IWS (Weight Bias Internalization Scale-Modified; WBIS-M) and visceral adiposity. VAT mass (g) was measured via DXA scan (Hologic Horizon A DXA system). Primary moderation analysis investigated the effect of gender on associations between IWS and VAT mass. Covariates were age, race/ethnicity, and total BF%.

Results:
Participants represented a broad range of total BF% (15-48%) and BMI (19.6-45.2 kg/m
2
). Women displayed greater WBIS-M scores (
M
=3.5,
SE
=0.2) than men (
M
=2.7,
SE
=0.2;
p
<.01). Differences between VAT mass (g) for women (
M
=429.4,
SE
=39.7) and men (
M
=480.1,
SE
=30.5) were non-significant (
p
=.32). After adjusting for covariates in the primary moderation analysis, WBIS-M scores displayed a positive association with VAT mass (
b
=31.5,
p
=.03). The relationship between WBIS-M scores and VAT mass was moderated by gender (
b
=74.7,
p
=.01); no relationship between WBIS-M scores and VAT mass was observed in men (
b
=-8.0,
p
=.68), whereas a positive association between WBIS-M scores and VAT mass was observed in women (
b
=66.7,
p
<.01).

Conclusions:
Internalization of weight stigma was associated with greater visceral adiposity in women across the BMI spectrum, implicating it as a chronic stressor. Future studies should investigate directionality and causality of this relationship to mitigate stigma-associated CVD risk.
Abstract 12432: Hypertension is Associated With Increased Hospitalization and Not Mortality Among COVID-19 Patients
Authors: Douen Aaron , Romney Wesley , Oh Jeremy , Panetti Ryan , Ramdass Prakash , Lee Winston , Toreli Aleksandre , Juang George
Published: April 2024

Introduction:
Hypertension (HTN) is associated with cardiovascular mortality risk. The risk of mortality or hospitalization amongst COVID-19 patients with HTN remains unclear.

Hypothesis:
There is increased risk of hospitalization and mortality amongst COVID-19 patients with HTN.

Methods:
The electronic health database at Coney Island Hospital was queried retrospectively for a cohort of patients, 18 or older, between 3/1/2020 and 4/1/2020. We included SARS-CoV-2 positive patients divided into two groups, hypertensive and non-hypertensive. We examined baseline characteristics including comorbidities. The primary outcomes were all-cause mortality and hospitalization. The secondary outcomes were acute kidney injury, ventricular arrhythmia, myocardial infarction, heart failure, and intubation. We also examined the use of antihypertensives.

Results:
We identified 23,102 patients positive for SARS-CoV-2; 3,507 with HTN and 19,595 without. Patients in the HTN group had a higher incidence of underlying comorbidities (p<0.001). The mean age in years was 64.69 +- 16.2 (SEM 0.109) and 41.9+-15.3, (SEM 0.273) for HTN and non-HTN respectively (p<0.117). The unadjusted odds of death, OR 59.54 (46.51-76.22), p<0.001, and hospitalization, OR 41.781 (37.6-46.2), p<0.001, were significantly higher in the HTN group, however only hospitalization was significantly higher in the HTN group, OR 8.86 (7.61-10.32), p<0.001, when adjusted for comorbidities using multivariate logistic regression; mortality was not significant, OR 1.16 (0.83-1.62), p=0.391. For the secondary outcomes, hypertensive patients had significantly increased unadjusted odds of all outcomes (p<0.001).

Discussion:
In this cohort of patients, the unadjusted odds of death for COVID19 patients with HTN is significantly increased compared to non-hypertensive patients. Despite the increased age, using multivariate logistic regression, we found that HTN does not significantly increase mortality. Hospitalization remains significantly elevated with multivariate regression in hypertensive patients.

Conclusions:
This retrospective cohort study suggests that HTN alone does not increase the odds of death amongst COVID-19 patients, however hospitalization may be increased.
Abstract 12444: Smooth Muscle-Specific Deletion of Perk Prevents Atherosclerotic Plaque Formation in Mice
Authors: Chattopadhyay Abhijnan , Majumder Suravi , Guan Pujun , Zhang Chen , Kaw Anita , Zhou Zhen , Kaw Kaveeta , Kwartler Callie , Lemaire Scott A , Shen Ying H , Milewicz Dianna M
Published: April 2024

Introduction:
Lineage tracing and single cell RNA sequencing (scRNA-Seq) studies have identified a subset of phenotypically modulated vascular smooth muscle cells (SMCs) that appear with atherosclerotic plaque formation in hyperlipidemic mice. These modulated SMCs (mSMCs) are de-differentiated, and increase expression of macrophage, fibroblast and stem cell markers. We previously showed that SMCs exposed to free cholesterol
in vitro
activate an endoplasmic reticulum unfolded protein response (UPR) and assume an mSMC phenotype, and blocking Perk specifically abolishes this SMC modulation.

Methods:
Here, we sought to define the role of Perk in atherosclerotic plaque formation using SMC-specific Perk knockout in C57BL6 mice (

Perk
SMC-KO

) and inducing hyperlipidemia by

PSCK9
DY

overexpression and a high fat diet for 12 weeks.

Results:
Aortic Oil Red O staining and
en face
aortic analysis revealed no plaque formation in the

Perk
SMC-KO

aorta, with the exception of some small plaques in the root, whereas the wild-type (WT) aortas had extensive plaque, especially in the aortic arch (N = 10, p<0.0001,
Fig. 1A
). scRNA-Seq analysis of aortic tissue from the root to the arch from these mice showed no major differences in cell clusters between

Perk
SMC-KO

and WT mice at baseline (
Fig. 1B
). In hyperlipidemic WT mice, SMC-derived cluster 8 expands and a new cluster 7 appears (circled in red,
Fig. 1B
). In

Perk
SMC-KO

mice, cluster 8 is similarly expanded with hyperlipidemia, while cluster 7 is completely absent (
Fig. 1B
, bottom right). Cluster 7 in the WT atherosclerotic aortas is the only cluster with Perk expression and has significantly increased expression of macrophage markers and a subset of fibroblast-specific markers when compared to cluster 8.

Conclusions:
These data indicate that SMC phenotypic modulation plays a major role in atherosclerotic plaque formation and Perk is a key regulator of the SMC modulation that specifically contributes to atherosclerotic plaque burden.
Abstract 12458: Protein L-isoaspartyl O-methyltransferase Attenuates Endothelial Activation Through Inhibitory Interaction With TRAF6 and ICAM1
Authors: Zhang Chen , Yi Bing , Sun Xiaobo , Kazama Kyosuke , Sun Jianxin
Published: April 2024

Introduction:
Endothelial activation provokes expression of cell surface adhesion molecules to facilitate circulating leukocyte diapedesis, which demands rigorous surveillance to prevent excessive inflammation response and host damage. As a repair enzyme, protein L-isoaspartyl O-methyltransferase (PIMT) methylates and converts isoaspartyl (isoAsp) residuals back to conventional form to avoid protein damage and aging. However, the role of PIMT in vascular homeostasis remains to be delineated.

Methods and Results:
Murine acute lung injury (ALI) model was deployed to investigate the significance of PIMT in endothelial activation and vascular inflammation. Results showed that mice harboring heterozygous deletion of PIMT displayed exacerbated pulmonary vascular inflammation. Ectopic overexpression of PIMT protected endothelial cells against endotoxin stimulated endothelial activation, as characterized by attenuated expression of inflammatory cytokines, chemokines, cell adhesion molecules and monocytic adherence to activated endothelial cells. Mechanistically, we found that PIMT inhibits lipopolysaccharide (LPS)-induced endothelial NF-κB transactivation. Tumor necrosis factor receptor-associated factor 6 (TRAF6) was identified as a dynamic binding partner and substrate of PIMT in regulating NF-κB signaling. PIMT catalyzed methylation at an asparagine derived isoAsp residual of TRAF6 directly prevented its oligomerization and auto-ubiquitination. Strikingly, we also found that PIMT specifically impeded N-glycosylation at multiple sites of endothelial intercellular adhesion molecule 1 (ICAM1). The hypo-glycosylated ICAM1 elicited impaired interaction with cell skeletal and reduced stability, which further diminished endothelial activation.

Conclusions:
PIMT negatively modulates endothelial activation through restricting activation of TRAF6 and inhibiting N-glycosylation of adhesion molecules. Our study provides a novel insight into the role of protein O-methylation in regulating endothelial inflammation and suggest that targeting PIMT may have potential therapeutic applications in treating inflammatory vascular disorders.
Abstract 12460: The Effect of Alirocumab on the Plasma Metabolome and Lipidome in End-Stage-Renal Disease
Authors: Bottiglieri Teodoro , Mehta Ankit , East Cara
Published: April 2024

Introduction:
Atherosclerotic disease is the major cause of morbidity and mortality among patients maintained on dialysis for end-stage renal disease (ESRD). Cardiovascular disease specifically accounts for almost 50% of deaths of these patients. In a pilot study to determine the safety of Alirocumab we investigated the plasma metabolome and lipidome in patients on dialysis and after treatment with a PCSK9 inhibitor.

Methods:
We recruited 14 subjects (10 male/4 female) from outpatient nephrology practices on hemodialysis (n=12) or peritoneal dialysis (n=2) for 3 months without complications. Subjects received Alirocumab (150 mg, i.m.) every 2 weeks. Blood was drawn from 13 subjects at baseline and after 12 weeks (6 injections) at completion of the trial. In addition, blood was drawn from 21 healthy controls. Plasma obtained was stored at -80
o
C for biomarker analysis. Targeted metabolomic analysis allowed quantitative detection of 542 metabolites including 480 lipid species in 13 lipid classes. This analysis was performed by liquid chromatography mass spectrometry using the Quant 500 metabolomic kit.

Results:
Metabolomic analysis identified 152 metabolites significantly different (FDR p<0.05) between control and ESRD subjects. Notably, various elevated metabolites as well as lower triglyceride and phosphatidylcholine lipid species. Twenty-three metabolites were significantly decreased after Alirocumab treatment (FDR paired t-test, p<0.05), all of which were lipid species from the following classes: cholesterol esters, ceramides, hexosylceramides and sphingomyelins (Figure 1).

Conclusions:
Subjects with ESRD have dysregulation of lipid metabolism that may contribute to atherosclerosis. The effect of Alirocumab on plasma ceramides and sphingomyelins is of particular interest since increased levels in these lipid species have been shown to be associated with vascular disease and increased mortality.
Abstract 12467: Maternal Vaping Effects on Cerebrovascular Function in Offspring
Authors: Mills Amber , Plants Rachel , Nassabeh Sydney , Bruce Alex , Robinson Madison , Chantler Paul D , Olfert I. Mark
Published: April 2024

Electronic cigarettes (E-cigs) are traditionally marketed as a safer alternative to smoking even during pregnancy. Previous studies have shown cerebrovascular dysfunction from direct chronic E-cig exposures, but little is known about the effect of indirect exposure to offspring while in utero. We hypothesize maternal vaping would induce cerebrovascular impairment in offspring, and that vaping at 30 watts would have greater effect compared to 5 watts. Female Sprague Dawley rats (N=8) were time mated, and once pregnant, the dams were randomly assigned to the following groups 1) 5 watts (N=3), 2) 30 watts (N=3), 3) and ambient air (control, N=2). Exposure (consisting of 20 puffs, 1hr/day, 5 days/week) began on gestational day 2-3 using whole-body chambers. E-liquid was 50% vegetable glycerin (VG), 50% propylene glycol (PG) and contained no nicotine or flavor. One male and female offspring per dam were studied 30-days after birth, where the middle cerebral artery (MCA) was isolated and reactivity assessed using dose response (10
-9
M to 10
-4
M) to acetylcholine (ACh), Serotonin (5-HT), L-arginine methyl ester (L-NAME), and sodium nitroprusside (SNP) via pressure myography. Maximal MCA dilation to ACh (10
-4
M) was impaired in both 5 and 30 watts compared to air (33±3% and 56±6%, respectively, p<0.05), and 30-watt group was greater than 5 watt (p<0.05). MCA vasoconstrictory response to 5-HT in both 5 and 30 watts were impaired compared to control (39±3% vs 52±8%, respectively, p<0.05), but 5 and 30 watts were not different from each other (p=0.08). SNP was only different for 30 watts compared to control (19±7%, p<0.05), and not for 5 watts (9±9%, p=0.07). Changes observed with 5 and 30 watts using L-NAME were not statistically different compared to control (7±11% vs 27±16%, respectively, p=0.15). These data show maternal vaping during pregnancy results in cerebrovascular impairment involving endothelial–dependent and –independent pathways in 1-month old offspring, and suggests that the magnitude of impairment is greater with increasing vaping wattage.
Abstract 12468: Atlas of Human Cardiac Promoters Reveals Regulatory Shift Between Healthy and Failing States
Authors: Gams Anna , Deviatiiarov Ruslan , Roman Syunyaev , Tatarinova Tatiana V , Singh Ramesh , Shah Palak , Gusev Oleg , Efimov Igor R
Published: April 2024

Introduction:
Genome regulatory elements capture transcription networks across diverse biological states. We aimed to identify and compare active promoter networks in healthy and failing human hearts in all four chambers.

Methods:
Samples were collected from the left and right atria and ventricles of 21 healthy and 4 ischemic (ICM) and 6 non-ischemic (NICM) human hearts. Cap analysis of gene expression (CAGE) was used to identify transcription start sites (TSS) with one nucleotide resolution. This method allows identifying promoter regions located directly upstream of TSS. Analyses performed included differential gene expression and pathway enrichment.

Results:
We identified over 10,000 novel promoter clusters
(Fig A)
. Additionally, atria express over 1,000 more genes compared to ventricles
(Fig B)
. We also showed that over 300 single nucleotide polymorphisms related to cardiac disease are located in the regulatory region
(Fig C)
. Contrary to the previous RNA-sequencing findings, we found a clear distinction between ICM and NICM, the former having upregulation in metabolism-related genes and the latter in the immune system
(Fig D)
. We also showed that the sets of genes related to sex dimorphism are different in healthy vs failing states
(Fig E)
. CAGE analysis allows studying alternative usage of promoters which can result in different binding of transcription factors. Several electrophysiology-related genes showed atrioventricular TSS alternatives
(Fig F)
. For example, failing hearts lost a second TSS location compared to healthy in KCNIP2 (KChIP2) while in KCNJ4 (IK1) they showed an increased expression of the second TSS relative to annotated TSS
(Fig G)
.

Conclusion:
We present evidence of the importance of the cardiac regulatory element database since it allows to explore transcription factor binding sites and regulatory networks or find specific targets for drug development in a specific biological context, such as ICM or NICM.
Abstract 12473: Seasonal Differences In Management And Outcomes Of Cardiac Arrest Complicating Acute Myocardial Infarction
Authors: Kanwar Ardaas , Vallabhajosyula Saraschandra , Patlolla Sri
Published: April 2024

Introduction:
The role of seasons in the outcomes and management of acute myocardial infarction (AMI) patients with cardiac arrest (CA) remains understudied.

Methods:
We used the National Inpatient Sample (2000-2017) to identify adults AMI admissions with concomitant CA. Admission month was used to classify them into- Spring (March-May), Summer (June-August), Fall (September-November) and Winter (December-February) admissions. We evaluated seasonal variation in the prevalence of CA among AMI admissions and associated in-hospital mortality. Use of cardiac and non-cardiac procedures, hospital length of stay, hospitalization costs and discharge disposition were also analyzed.

Results:
Between 2000-2017, of the 10,880,856 AMI admissions with information on admission month available, CA was identified in 546,334 (5.0%). Incidence of CA was 4.9% in spring, 5.0% in summer, 5.1% in fall, and 5.1% in winter AMI admissions. Adjusted trends identified a steady increase in STEMI-CA admissions with a relatively stable or declining trend for NSTEMI-CA admissions across all seasons. AMI-CA admissions admitted in summer were less often female, had lower comorbidity, more often presented with STEMI and had higher rates of cardiogenic shock and shockable rhythms compared to AMI-CA admissions in spring, fall and winter. Compared to AMI-CA admissions in other seasons, those admitted in winter had slightly lower rates of coronary angiography (61.4% vs. 63.3%-64.3%) and PCI (45.6% vs. 47.2-48.4%) (p<0.001). Compared to those admitted in the spring, adjusted in-hospital mortality was higher for winter (OR 1.08 [95% CI 1.06-1.10]; p<0.001), lower for summer (OR 0.96 [95% CI 0.94-0.98]; p<0.001) and comparable for fall (OR 1.00 [95% CI 0.98-1.02]; p=0.91) AMI-CA admissions. Length of hospital stay, total hospitalization charges, and discharge dispositions for AMI-CA admissions were comparable across the seasons.

Conclusions:
Lower use of guideline directed therapies and higher in-hospital mortality was identified in winter AMI-CA hospitalizations. The role of pathobiology and/or impact of environmental conditions across seasons in AMI-CA remains to be evaluated.
Abstract 12474: Acute Myocardial Infarction Following Hospitalizations for Gastrointestinal Bleeding: Incidence, Predictors, Management, and Outcomes
Authors: Rubinfeld Gregory , Berger Jeffrey , Smilowitz Nathaniel
Published: April 2024

Introduction:
Patients hospitalized with gastrointestinal bleeding (GIB) are at risk for acute myocardial infarction (AMI). Clinical characteristics of patients with AMI after a GIB are poorly characterized. We sought to evaluate the incidence, management and outcomes of AMI following hospitalization for GIB.

Methods:
Patients admitted with a diagnosis of GIB were identified in the 2014 United States Nationwide Readmission Database using ICD-9 diagnosis codes. Hospital readmissions for AMI within 90 days of GIB were identified. Patients with AMI after GIB were compared to those without a prior GIB to determine differences in management and in-hospital outcomes. Invasive management of AMI was defined as invasive angiography or coronary revascularization. Logistic regression models were used to estimate odds of invasive management and all-cause, in-hospital morality after adjustment for clinical covariates.

Results:
A total of 644,622 patients with GIB were identified, of which 7,523 (1.2%) were readmitted for AMI within 90 days. Older age, diabetes mellitus, chronic kidney disease, coronary and peripheral artery disease, unknown GIB source, and AMI during the index GIB hospitalization were associated with 90-day AMI readmission. Compared to AMI patients without a recent GIB, patients with AMI within 90 days after GIB were older (74.4 vs. 68.4 years, p<0.01), more likely to be women (47% vs. 41.1%, p<0.01), have kidney disease (43.2% vs. 22.4%, p<0.01), present with non-ST segment elevation MI (82% vs. 73%, p<0.01), and were less likely to undergo invasive management of AMI (28% vs 63%, P<0.01; adjusted odds ratio [aOR] 0.40, 95% CI 0.37-0.44). Recent hospitalization for GIB within 90 days was associated with higher all-cause in-hospital AMI mortality (22% vs 9%, P<0.01; aOR 1.86 [1.68-2.06]).

Conclusion:
In the first 3 months after hospitalization for GIB, 1 of every 83 patients was readmitted with AMI. Patients with AMI after GIB were less likely to undergo invasive management of AMI and had higher mortality than those without recent GIB. Strategies to reduce morbidity and mortality of GIB-associated thrombosis are needed.
Abstract 12480: Establishing Safety and Risk Profile of Right Heart Catheterization
Authors: Hull Jocelyn V , Padkins Mitchell , El Hajj Stephanie C , Al-hijji Mohammed A , Lennon Ryan , Crusan Daniel , Behfar Atta , Gulati Rajiv , Kanwar Amrit , Farhat Salman , Jain Vaibhav , El Sabbagh Abdallah , Singh Mandeep
Published: April 2024

Introduction:
We aim to elucidate the incidence of major complications related to right heart catheterization (RHC) and ascertain if there are unique risks with right ventricular biopsy.

Methods:
Diagnostic RHC procedures from 1/1/2002 through 12/31/2013 were identified using the clinical scheduling system at Mayo Clinic, Rochester. Major complications were identified through electronic records using International Classification of Diseases, Ninth Revision billing codes. All events were recorded and adjudicated. Analysis was performed on four separate patient categories (RHC/RV angiography alone, RV biopsy alone, multiple RHC procedures, and concurrent RHC/LHC procedures) and the overall group. Primary outcomes are described in Table 1. Outcomes were measured within 7 days of the procedure, except for death (same day events) and tricuspid regurgitation (variable time endpoints).

Results:
There were 17,696 RHC procedures (5,556 RHC/RV angiography, 3,846 RV biopsy alone, 776 multiple RHC procedures, and 7,518 combined RHC/LHC). Patient population had a mean age of 56.5 years (15.3) and was predominantly male (58.5%). Same-day death related to RHC procedure occurred in 1 procedure or 0.6 of 10,000 RHCs. There was no significant difference in the risk of complications across RHC procedure categories except for worsening tricuspid regurgitation, which was significantly (p<0.001) more prevalent with RV biopsy (392 cases, 6.0%) than without (136 cases, 1.2%).

Conclusion:
The incidence of major complications related to right heart catheterization is rare. Worsening tricuspid regurgitation is the most frequently identified change with a significantly higher prevalence with biopsies.
Abstract 12499: Risk of Venous Thromboembolism in Autoimmune Connective Tissue Diseases: A Population-Based Retrospective Study
Authors: Desai Parth V , Akhtar Tauseef , Patel Axi , De Sirkar Sovik , Walsh Kevin , Krepostman Nicolas , Collins Matthew , manadan augustine , Fareed Jawed , Darki Amir
Published: April 2024

Introduction:
Autoimmune Connective tissue diseases (CTD) are known to induce systemic and intravascular inflammation, endothelial damage, and the resulting surge in the prothrombotic milieu. However, the literature describing the correlation between various CTD and risk of Venous thromboembolism (VTE) is limited.

Objective:
We sought to assess the association of VTE and CTD in a nationwide larger population-based database.

Methods:
We conducted a retrospective analysis on all adults (aged >=18 years) admitted with an index diagnosis of either acute Pulmonary Embolism (PE) or deep venous thrombosis (DVT) from the National Inpatient Sample (NIS) database (2017) using ICD 10 codes. Logistic regression models were used to adjust for the potential confounders of VTE including factors related to admission, hospital, and patients’ comorbidities.

Results:
Out of more than 30 million hospital admissions, a total of 285,650 patients (mean age 63±17 vs 57±20 yrs, p<0.01; Females 51% vs 57%, p<0.01) were identified with a primary diagnosis of VTE. Advancing age and black race (OR 1.38, 95% CI 1.35-1.42, p<0.001) had a higher risk of VTE, whereas females had a lower risk of VTE compared to men (OR 0.82, 95% CI 0.8-0.83, p<0.001). Out of twenty-one, autoimmune CTD evaluated in this study, eight diseases [antiphospholipid antibody syndrome (APS), ANCA vasculitis, dermatopolymyositis, giant cell arteritis (GCA), Polymyalgia rheumatica (PMR), Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and sarcoidosis] were independently associated with risk of VTE. APS (OR 4.4, 95% CI 3.8-5.1, p<0.001), GCA (OR 1.8, 95% CI 1.4-2.3, p<0.001), and SLE (OR 1.6, 95% 1.4-1.7, p<0.001) had the highest risk of VTE based on their odds ratio.

Conclusions:
In our study, various autoimmune connective tissue diseases were significantly associated with the risk of VTE. Further studies are warranted to identify the underlying mechanism and preventive strategies in this population.
Abstract 12525: TEAD1 is a Novel Regulator of NRF2 and Oxidative Stress Response in Cardiomyocytes
Authors: Jagannathan Rajaganapathi , Lee Jeongkyung , Liu Ruya , Devallance Evan , yang ping , Negi Vinny , LI FENG , Pagano Patrick J , Yechoor Vijay , Moulik Mousumi
Published: April 2024

Introduction:
TEAD1, the Hippo pathway-regulated transcription factor, has a critical non-redundant role in cardiomyocyte (CM) homeostasis, and its loss-of-function results in acute lethal dilated cardiomyopathy. However, the functional pathways regulated by TEAD1 in CMs remain unclear.

Hypothesis:
TEAD1 plays an essential role in CM oxidative stress response (OSR) via the regulation of NRF2, the master regulator of antioxidant response.

Methods and Results:
Conditional CM-specific TEAD1 deletion in adult mice results in acute heart failure (HF) and altered expression of OSR genes. In silico analysis of publicly available RNA-seq data revealed significant downregulation of TEAD1 in dilated and ischemic cardiomyopathy patient hearts and a positive correlation between TEAD1 and NRF2 expression. ChIP-seq with TEAD1 antibody and ATAC-seq revealed that TEAD1 occupied open promoter/enhancer regions of multiple OSR genes, including NRF2 and its targets in adult mouse hearts. Mosaic deletion of TEAD1 in ~50% CMs, which allowed assessment of TEAD1 LOF in CMs without confounding HF effect, reduced NRF2 expression, and increased myocardial oxidative stress indicated by 8OHdG staining (DNA oxidative damage) and cellROX only in TEAD1-deficient CM, but not in CM with normal TEAD1 expression. Ex vivo and in vitro TEAD1 knockout in primary murine adult and neonatal CMs and H9C2 cells resulted in significantly elevated total cellular (Boronate assay) and mitochondrial (mitoSOX) ROS due to reduced NRF2 expression and promoter activity (ARE reporter assay). TEAD1-deficient CM had a lower tolerance to chemically (Angiotensin II, DMNQ, or AntimycinA)-induced oxidative stress. Furthermore, hTEAD1 overexpression was sufficient to significantly increase NRF2-ARE activity and rescue the elevated ROS production in CMs.

Conclusions:
TEAD1 is a novel cell-autonomous direct transcriptional regulator of NRF2 and CM oxidative stress response.
Abstract 12572: Low Incidence of Cardiovascular Events in Patients With Metastatic Sarcoma Using Upfront Dexrazoxane and High-Dose Doxorubicin
Authors: Mitchell Joshua D , Van Tine Brian , Hirbe Angela C , Oppelt Peter , Frith Ashley , Rathore Richa , Wan Fei , Berry Shellie , Landeau Michele , Heberton George , Gorcsan John , Huntjens Peter , Soyama Yoku , Vader Justin M , Alvarez-Cardona Jose , Zhang Kathleen , Lenihan Daniel , Krone Ronald
Published: April 2024

Background:
Prognosis for soft tissue sarcoma (STS) remains poor with a progression free survival of 4.6 months. Doxorubicin is a central and effective treatment option, though cardiotoxicity frequently limits dosing. Dexrazoxane has been shown to protect the heart but questions of possible reduced tumor efficacy have limited dexrazoxane to be used only after administration of 300 mg/m2 of doxorubicin. We explored the use of up-front dexrazoxane to mitigate the cardiotoxic effects of doxorubicin in a single-arm non-inferiority trial patients with STS.

Methods:
Patients with metastatic or unresectable STS without prior anthracycline treatment were eligible for enrollment. The study was powered to demonstrate that dexrazoxane does not prevent a decrease of progression free survival (PFS), with a PFS more than 3.7 months considered non-inferior. Secondary aims included cardiac related mortality and the incidence of heart failure or cardiomyopathy. Patients were allowed to continue on doxorubicin beyond 600mg/m2 if they were deriving benefit and were not demonstrating evidence of cardiac dysfunction. Patients with concerns about cardio-toxicity were referred to a cardio-oncologist.

Results:
62 patients were started on study treatment and had at least one year of follow-up. Patients received a median of five cycles (375 mg/m2, range 75-3075 mg/m2) of doxorubicin. The upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 5.5 months (95% CI 4.2-8.4 months). No patients required cardiac hospitalization on protocol. Two patients developed new LV dysfunction with LV ejection fraction below 50% on core lab evaluation with recovery in one and persistent LVEF < 50% in one. There were no deaths attributed to doxorubicin.

Conclusion:
Up-front dexrazoxane prevented severe cardiac systolic dysfunction in patients receiving high cumulative doses of doxorubicin without reducing progression free survival (5.5 months vs 4.6 months in historical controls).