bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13287: Reading Nutrition Labels, and Self-Regulatory Lifestyle Behaviors Improves Cardiovascular Health: A Structural Equation Modeling Approach - Nhanes 2017-2018
Authors: Parameswaran Vijaya , Wang Yunmei , Cola Phillip , Nambisan Priya , Dash Rajesh
Published: June 2023

Introduction:
Recommendations for self-regulatory lifestyle behaviors - SRLB, such as reducing salt, or calories, often focus on reading nutrition labels. While these are correlated with cardiovascular outcomes, their causal effects are underexplored.

Hypothesis:
As covariance-based structural equation modeling - SEM, examines multivariate causal relationships in one model while considering measurement error, we propose using SEM to hypothesize that label reading and SRLB will improve cardiovascular outcomes (Figure1a)

Methods:
SEM was applied to National Health and Nutrition Examination Study 2017 - 2018 data in adults over 18 years of age, adjusted for education, age, gender, and ethnicity. Label reading included the use of calorie and sugar information. SRLB included weight loss, increasing exercise, and reducing salt and fat.

Results:
Of 4260 adults, 51.9% were female, with a mean age of 51.46 ± 17.5 (Table 1b). Extensive effects of SRLB, on HDL-C (β= .12, p <.01), Total Cholesterol - TC (β= -.17, p <.001); and label reading, on Blood Pressure - BP (β = -.73, p <.001), Triglycerides - TG (β = -.49, p <.001) were noted. BMI (β = -.10, p <.01) and Hba1c (β = -.13, P<.001) improved with SRLB, but label reading showed no effect. Higher education increased BP (β =.1, P<.001), but decreased Hba1c (β = -.07, P<.001) and ethnicity had a negative effect on BMI (β = -.1, P<.001) (Table 1c).

Conclusions:
Using SEM, we demonstrate the causal effects of dietary and lifestyle behaviors on cardiovascular outcomes. The extensive impact of label reading illustrates its efficacy in managing hypertension and dyslipidemia, but the absence of effect on weight and blood sugar management, and the varied effect of education, and ethnicity, need to be explored. In addition, our findings may underscore the need for culturally tailored lifestyle recommendations that achieve caloric balance by interpreting calorie and sugar information in the context of serving size and caloric expenditure.
Abstract 13291: Virtual Pharmacist Approach to Comprehensive Medication Management in Post-Discharge Heart Failure Patients: A Randomized Quality Improvement Initiative
Authors: Thai Tram , Downing Greg , Plotke Melanie , Olmsted Eric , Jafri Farrukh
Published: June 2023

Introduction:
Successful management of Heart Failure (HF) patients post-discharge requires a multi-faceted approach including close medication management to decrease preventable readmissions.

Methods:
We conducted a one-year single center, single-blinded randomized trial of HF patients post-discharge comparing standard of care vs. intensive virtual care on HF readmission rates. The intensive virtual care included comprehensive medication management by a Virtual Clinical Pharmacist (VCP).

Results:
Among the 591 participants, the median age was 73.2 years, 52.5% male, and 56.2% white. There were 308 patients randomized into the intervention group of which 165 (53.5%) enrolled. During VCP visits, 155 patient concerns were identified including active symptoms (45.2%), lack of clarity of medication regimen (40.6%), concurrent uncontrolled hyperglycemia or hypertension (9%) and non-adherence with provider follow up appointments (5.2%). There were 625 VCP interventions in 165 HF patients. Of these patients, VCPs increased access to medical care (33.9%), optimized guideline directed medical therapy (17.6%), addressed symptoms of HF exacerbations (7.9%), and other impactful interventions (Table). VCP recommendations had a 59% acceptance rate into the patient’s treatment plan when clinicians were contacted directly. A 6.9% decrease in 30-day readmission rates was demonstrated (p=0.03) in the intervention group, in addition to a decrease from 24.4% to 19.2% in emergency department visits (p=0.15). For patients readmitted, the intervention arm had a shorter length of stay, 5.6 days, when compared to control, 6.8 days (p=0.14).

Conclusion:
This single center randomized trial demonstrated that Virtual Clinical Pharmacist-led comprehensive medication management identified key interventions with high-level clinician engagement for post-discharge HF patients that resulted in a 6.9% reduction in HF readmissions.
Abstract 13293: Albuterol and Hyperthyroidism as Potential Causes of Stress Cardiomyopathy
Authors: Lombo Luque Santiago , Leon William , Venugopal Sandhya
Published: June 2023

Introduction

Takotsubo cardiomyopathy (TCM) is a recognized reversible process associated with emotional or physical stressors characterized by left ventricular apical ballooning in the absence of obstructive coronary artery disease. We present a unique case of TCM after albuterol use in the setting of hyperthyroidism.

Results

A 74-year-old woman with history of hyperthyroidism and asthma presented with acute substernal chest pain and progressive dyspnea. She was diagnosed with an asthma exacerbation, started oral prednisone 3 days before presentation, and reported using 16 puffs of her albuterol inhaler the day before. Examination revealed blood pressure 157/100 mmHg, heart rate 135 beats per minute, respiratory rate of 35 breaths per minute, and SpO2 94% on a 5-liter nasal cannula. Lung exam revealed bilateral end-expiratory wheezes, and she appeared in respiratory distress. The remainder of the exam was unremarkable, including cardiac exam. ECG revealed atrial tachycardia with ST elevations in the anterolateral leads concerning for injury. High sensitivity troponin was 1484 ng/L (ref <19), free T4 level 3.63 ng/dL (ref 0.56-1.64 ng/dL), TSH <0.02 μU/mL (ref 0.35-3.30 μU/mL ) with TSH-receptor Ab 8.62 IU/L (ref <1.75 IU/L) consistent with worsening hyperthyroidism when compared to one month prior (free T4: 1.19 ng/dL; TSH: 0.84 μU/mL/mL). Emergent cardiac catheterization showed non-obstructive coronary artery disease and reduced ejection fraction (EF) of 30% with akinesia of the anterolateral, apical, and diaphragmatic segments consistent with TCM. She had a full recovery of systolic function noted on repeat echocardiogram 10 weeks after treatment with guideline-directed therapy.

Conclusion

TCM is primarily driven by a high catecholamine state that, paradoxically, increases β-2 adrenergic receptor inhibitory signaling, thus, causing preferential depression of apical myocardial function possibly due to topographic receptor distribution. Hyperthyroidism mimics a state of adrenergic excess partially mediated by the upregulation of β-adrenergic receptors by thyroid hormones, and the use of β-2 agonists potentiated the development of TCM.
Abstract 13301: Rasa3 is a Novel Candidate Gene in Sickle Cell Disease-Associated Pulmonary Hypertension and Pulmonary Arterial Hypertension
Authors: Prohaska Clare C , Zhang Xu , Schwantes-An Tae-Hwi , Stearman Robert , Aldred Micheala A , Lutz Katie , Pauciulo Michael , Nichols Bill , Desai Ankit A , Gordeuk Victor , Machado Roberto F
Published: June 2023

Introduction:
Pulmonary hypertension (PH) is associated with significant morbidity and mortality. RASA3, a GTPase-activating protein, is integral to processes highly relevant to PH. We explore the association of RASA3 genetic variation with PH risk in patients with sickle cell disease (SCD)-associated PH and pulmonary arterial hypertension (PAH).

Methods:
Using peripheral blood mononuclear cells (PBMC) from 3 cohorts of subjects with SCD, cis-expression quantitative trait loci (eQTL) were queried for
RASA3
. Genome-wide single nucleotide polymorphisms (SNP) near or in the
RASA3
gene that associate with lung RASA3 expression were identified using Genotype Tissue Expression project data, reduced to 9 tagging SNPs for
RASA3
and associated with PH markers. Associations between the top
RASA3
SNP and PAH severity were tested using whole genome genotype data from PAH Biobank subjects. Using RNAseq samples aligned with SNP arrays from lung tissue from the Pulmonary Hypertension Breakthrough Initiative (PHBI), we evaluated the frequency of the risk allele at our SNP of interest.

Results:
PBMC
RASA3
expression was significantly lower in patients with SCD-associated PH using elevated TRV≥2.5m/s and RHC data and associated with significantly higher mortality. One eQTL for RASA3 was identified, rs9525228, with the risk allele correlating with PH risk and severity in patients with SCD-associated PH. Analyzing this SNP in PAH patients based on either European or African ancestry (EA, AA), we found that rs9525228 associated with markers of PH in EA but not AA individuals (Table 1). There was a trend towards decreased survival in EA individuals carrying rs9525228 (p=0.08) that was not seen among AA individuals. Using PHBI samples, individuals homozygous for the risk allele had lower RASA3 expression (p=0.05).

Conclusions:
RASA3
is a novel candidate gene in SCD-associated PH and PAH and appears to be protective. Further studies are ongoing to delineate the role of RASA3 in PH.
Abstract 13304: Sox17 Deficiency Induces Pulmonary Hypertension Through E2F1/BRD4 Signaling
Authors: Yi Dan , Liu Bin , Ramirez Karina , Li Rebecca , Pan Jiakai , Lee Won Hee , Kala Mrinalini , Fallon Michael B. , Dai Zhiyu
Published: June 2023

Introduction:
Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients.

Hypothesis:
Genetic SOX17 mutations are associated with PAH. We hypothesized that endothelial SOX17 mutations or loss of function contributes to endothelial dysfunction and the pathogenesis of PAH.

Methods:
Endothelial-specific deletion of Sox17 (
Sox17iCKO
) mice were generated.
Sox17iCKO
and
Sox17f/f
(WT) mice after tamoxifen injection were incubated without or with hypoxia (10% O
2
) for 3 weeks to induce PH. EC proliferation, apoptosis, cell junction assay, Western blotting, QRT-PCR, RNA-sequencing analysis, and luciferase assays were performed to understand the molecular mechanisms of SOX17 deficiency and mutation in ECs. siRNA and inhibitors were used to determine the involvement of E2F1/BRD4 signaling in SOX17 deficiency ECs.

Results:
Sox17iCKO
mice developed spontaneous mild PH and exaggerated hypoxia-induced PH evidenced by the increase of RVSP and RV hypertrophy compared to WT mice. SOX17 knockdown in human PVECs induced cell proliferation, anti-apoptosis, and impaired cell integrity. SOX17 knockdown reduced BMPR2 signaling. SOX17 knockdown and mutations at the HMG domain lost transcriptional activities and its ability to repress -catenin. RNA-seq analysis demonstrated enrichment of cell cycle pathway after the loss of SOX17 in PVECs. iRegulon analysis revealed the involvement of transcriptional factor E2F1. siRNA-mediated E2F1 knockdown normalized SOX17 deficiency-induced PVECs dysfunction. Knockdown SOX17 significantly upregulated E2F1 promoter activity, which was dependent on the binding site in the E2F1 promoter by luciferase and mutagenesis assay. E2F1 or BRD4 inhibitors attenuated SOX17 deficiency-induced PH in mice.

Conclusions:
Our study demonstrated that endothelial loss of SOX17 induces PH in mice. Pharmacological inhibition of E2F1/BRD4 signaling attenuated PH development in
Sox17iCKO
mice.
Abstract 13305: Impact of Small Cajal-Body Associated RNAs in IPSC-Derived Cardiomyocytes From Progeria and Noonan Patients
Authors: Sigamani Vinoth , Perales Selene G , Mani Saiprahalad , RAJASINGH SHEEJA , Johnson Rajasingh
Published: June 2023

Introduction:
Progeria and Noonan syndrome are major genetic disorders that impact the cardiovascular system and lead to congenital heart defects in children. The small Cajal body-associated RNAs (scaRNAs) are a class of H/ACA box non-coding RNAs, which play an important role in the biochemical modification of spliceosomal RNAs and contribute to alternative splicing and maturation of mRNAs. In this study, we aim to elucidate the role of scaRNAs during cardiac differentiation and its effect in Progeria and Noonan Patients-derived induced pluripotent stem cell-derived cardiomyocytes (iCMC).

Hypothesis:
We hypothesize that scaRNAs have a significant role in cardiac development and are associated with cardiovascular development in disease conditions.

Methods and Results:
To elucidate the role of scaRNAs in Noonan and Progeria patients during cardiomyogenesis, we differentiated iCMCs from iPSCs generated from Noonan (c.1654A>G) and Progeria (c.1824 C>T) patients. The differential expression of scaRNAs was performed by qRT-PCR and the result shows that scaRNA6, scaRNA11, scaRNA14 scaRNA20, and scaRNA28 were significantly reduced in Noonan and Progeria patients iCMC compared to normal skin fibroblast (SF)-derived iCMCs and Urinary epithelial cells (UE)-derived iCMC
(Fig.1).
The mRNA expression of the cardiac-specific gene in Progeria and Noonan patient-derived iCMC was significantly reduced when compared with normal iCMC. Furthermore, the scaRNA overexpressed normal iCMCs (scaRNA20-OE-iCMCs) showed significantly increased cardiac-specific mRNA and protein expressions when compared with control iCMC
(Figs.2 & 3)
.

Conclusion:
Our finding indicates that scaRNAs have major impacts on Noonan and Progeria patient-derived iCMC. Targeting the scaRNAs will have efficient therapeutic potential for Noonan and Progeria patients.
Abstract 13311: Risk of Ventricular Tachycardia and Sudden Cardiac Arrest Associated With Drugs Known to Cause Torsades De Pointes in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Huang Chien-Yu , Overholser Brian R , Sowinski Kevin M , Jaynes Heather A , KOVACS Richard , Tisdale James E
Published: June 2023

Introduction:
Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced proarrhythmia. It is unknown whether patients with HF with preserved ejection fraction (HFpEF) are also at increased risk.

Hypothesis:
The risk of drug-associated ventricular tachycardia (VT) and sudden cardiac arrest (SCA) is increased in patients with HFpEF.

Methods:
Using Medicare enrollment in fee-for-service medical and pharmacy benefits (2014 to 2016) and ICD-9/10 codes, we identified patients taking drugs known to cause torsades de pointes (TdP drugs; www.crediblemeds.org) and non-TdP drug users among three groups: HFrEF (n=31,422), HFpEF (n=40,012), and no HF (n=633,558). Multinomial propensity score-matching was performed to minimize baseline differences in covariates (patient demographics, comorbidities, health care utilization and drug history). Cochran-Mantel-Haenszel statistics and standardized differences were used to compare baseline characteristics. A generalized Cox proportional hazards model was used to estimate hazard ratios (HRs) and test the association of VT and SCA among TdP drug users with HFpEF, HFrEF, and no HF.

Results:
Of 23,910 TdP drug users with HFrEF, VT and SCA occurred in 4,263 (17.8%) and 493 (2.1%) patients, respectively. In comparison, among 31,359 TdP drug users with HFpEF, VT and SCA occurred in 1,570 (5.0%) and 340 (1.1%) patients. VT and SCA occurred in 3,154 (0.8%) and 528 (0.1%) of 384,824 TdP drug users without HF. The overall risk of both VT and SCA was increased in patients with HFrEF and in those with HFpEF (Table). The risk of VT associated with TdP drugs was increased across the overall population. Use of TdP drugs significantly increased the risk of VT and SCA in patients with HFrEF, but not in patients with HFpEF.

Conclusions:
The risk of VT and SCA associated with drugs known to cause TdP was increased in patients with HFrEF but not in those with HFpEF.
Abstract 13318: Shared Genetic Architecture of RV-PA Coupling and Measures of Adiposity
Authors: Agrawal Vineet , Bagheri Minoo , Vaitinadin Nataraja Sarma S , Shi Mingjian , Ferguson Jane F , Wells Quinn , Gupta Deepak , Hemnes Anna R , Mosley Jonathan , Brittain Evan
Published: June 2023

Introduction:
The right ventricle’s ability to adapt to load stress, termed RV-PA coupling, is a major determinant of survival in pulmonary hypertension. However, the etiologic drivers of impaired RV-PA coupling are incompletely understood. One approach to identifying etiologic factors is through the study of the genetic architecture underlying impaired RV-PA coupling. We previously showed shared genetic risk between adiposity and RV size. Thus, we interrogated a polygenic predictor of RV-PA coupling to determine whether it shares genetic risk with adiposity.

Methods:
In 3493 adult subjects of European ancestry in Vanderbilt Univ. Medical Center’s de-identified DNA biobank (BioVU) with an available echocardiogram, RV-PA coupling was calculated as the ratio of tricuspid annular plane systolic excursion (TAPSE) to estimated RV systolic pressure (RVSP). The association between three measures of obesity and RV-PA coupling was examined using 2-sample inverse variance weighted (IVW) meta-analysis, and MR-Egger to assess for pleiotropy. Genetic instruments for obesity were constructed using prior summary statistics for body mass index (BMI), waist circumference, and whole body fat mass.

Results:
Median age of cohort was 63, 54% female. Median and IQR of variables were as follows: TAPSE 2.0 [1.6, 2.4], RVSP 31 [25, 40], TAPSE/RVSP 0.6 [0.4, 0.8]. By 2-sample MR, we found a significant negative association between genetically determined waist circumference and RV-PA coupling (β=-0.34, p=0.004) (Figure). We found similar negative associations between RV-PA coupling and BMI (β=-0.41, p=0.01) and whole body fat mass (β=-0.55 p=0.005). Units for estimates were log change in outcome (TAPSE/RVSP) per change in exposure.

Conclusions:
Our findings suggest shared genetic architecture between measures of adiposity and RV-PA coupling, supporting the notion that pathophysiologic mechanisms underlying adiposity may be play a causal role in impaired RV-PA coupling.
Abstract 13328: Mitral Annular Calcification and All-Cause, Cardiovascular, and Non-Cardiovascular Mortality in a Multiracial Cohort: The Multi-Ethnic Study of Atherosclerosis
Authors: Boakye Ellen , Pressman Gregg S , Dardari Zeina A , Jha Kunal , Szklo Moyses , Budoff Matthew , Nasir Khurram , Blaha Michael J , Oni Ebenezer
Published: June 2023

Introduction:
Mitral annular calcification (MAC) may be a potential marker of biological aging. However, the relative association of MAC with mortality, including all-cause, cardiovascular, and non-cardiovascular mortality in a multiracial cohort, is not well studied.

Methods:
We used data from 6814 men and women (mean age 62.2 ±10.2 years; 12% Chinese, 38% White, 22% Hispanic, and 28% African American) without CVD at baseline in the Multi-Ethnic Study of Atherosclerosis. MAC (absent/present and <100/≥100 AU) was assessed with non-contrast cardiac computed tomography at baseline. Using multivariable-adjusted Cox proportional hazard and competing risks regression, we evaluated the association of MAC with all-cause, and cardiovascular and non-cardiovascular mortality, respectively.

Results:
The prevalence of MAC was 9.5% and was higher in women (10.7%) than men (8.0%). Compared to persons without MAC, those with MAC > 0 had higher incidence rate of all-cause (13.6 vs. 41.2 per 1000 person-years), cardiovascular (3.1 vs. 11.0 per 1000 person-years), and non-cardiovascular mortality (9.9 vs. 28.7 per 1000 person-years) over a mean follow-up of 14.4 ± 3.7 years. Persons with MAC > 0 had significantly higher multivariable-adjusted risk of all-cause (Hazard Ratio [HR]: 1.51; 95%CI: 1.32 - 1.72), cardiovascular (SHR: 1.46; 95%CI: 1.09 - 1.95), and non-cardiovascular mortality (SHR: 1.37; 95%CI: 1.16 - 1.61), compared to those without MAC. Similarly, compared to MAC <100 AU, MAC ≥100 was associated with a 1.82 (1.53 - 2.15), 1.55 (1.07 - 2.25), and 1.62 (1.30 - 2.01)-fold increased hazard of all-cause, cardiovascular, and non-cardiovascular mortality, respectively (
Figure
).

Conclusions:
In this multiracial cohort, MAC was associated with all-cause, cardiovascular, and non-cardiovascular mortality. Thus, MAC may be a marker not only for atherosclerotic burden but also for other metabolic and inflammatory factors that increase the risk of death from other causes.
Abstract 13330: Cardiorespiratory Fitness is Associated With Decreased Platelet Reactivity
Authors: Grech Joseph , Nkambule Bongani , Thibord Florian , Chan Melissa , Chen Ming-Huei , Ramachandran Vasan S , Nayor Matthew G , Lewis Gregory , Johnson Andrew
Published: June 2023

Introduction:
Platelets are key mediators in atherosclerotic cardiovascular disease (CVD). Low cardiorespiratory fitness (CRF) is a major risk factor for atherosclerosis. However, little is known about the effects of CRF on platelet function.

Methods:
Platelet assays and cardiopulmonary exercise testing were conducted in the Framingham Heart Study (n= 3001). A linear mixed effects model was used to analyze associations between CRF (assessed by peak oxygen uptake [VO
2
] in participants achieving a respiratory exchange ratio >= 1), and platelet reactivity traits from multiple platelet function assays: whole blood Multiplate impedance aggregometry (MP), Total-Thrombus Formation Analysis System (T-TAS), and light transmission aggregometry (LTA). Statistical models adjusted for relatedness, age, sex, and anti-platelet medications. Bonferroni correction for multiple statistical testing resulted in a significance threshold of p<7.35E-04.

Results:
Of 68 platelet traits analyzed, 31 traits passed the significance threshold, all with a direction of effect indicating higher CRF associated with decreased platelet reactivity. Significant traits spanned multiple platelet agonists. Our strongest associations were seen with MP after TRAP-6 (velocity, p=1.57E-26; AUC, p=2.33E-21; aggregation, p=5.30E-16) and ADP stimulation (velocity, p=1.63E-19; AUC, p=7.64E-17; aggregation, p=1.00E-11), and LTA after ristocetin stimulation (max aggregation, p=5.33E-11; AUC, p=1.11E-10).

Conclusion:
Our research adds to past work that shows CRF to be associated with reduced CVD by suggesting that decreased platelet reactivity may be involved mechanistically. We found significant associations with multiple platelet agonists, indicating higher CRF globally inhibits platelets; however, given the multiple strong associations after TRAP-6 and ADP stimulation, PAR-1 and purinergic signaling, respectively, may be most heavily involved. This is notable since each of these receptor pathways is directly or indirectly tied to anti-coagulant or anti-platelet therapies. Ultimately, our results suggest that CRF may be important for additional consideration in tailoring anti-platelet strategies.
Abstract 13332: Obesity Paradox in Stress Cardiomyopathy When Comparing Outcomes
Authors: Dastmalchi Lily N , Delfiner Matthew S , Oliveros Estefania
Published: June 2023

Introduction:Stress Cardiomyopathy (SCM), is an acute reversible myocardial injury associated with transient left ventricular dysfunction. Risk factors include female sex, post-menopause, anxiety, depression, schizophrenia, asthma and chronic obstructive pulmonary disease, diabetes, and substance use. Obesity has an increased sympathetic tone and state of chronic metabolic stress, both of which are similar in etiology to SCM. We postulate that obesity may have high prevalence in patients with SCM.

Methods:
We queried the Nationwide Inpatient Sample database (2016-2019) to identify adult patients with SCM with and without obesity, along with other common co-morbidities using ICD-10 codes. We compared the categorical and continuous variables by Pearson χ2 and Student t test.

Results:
There were 31,725 patients with SCM. The mean age was 67.15
+
14 years and the population was predominately female, n=26409 (83.2%). Racial distribution consisted of White (n=24713 77.9%), Black (n=24713, 8%), and Hispanic (n=1918, 6%). There were 3816 (12%) who were diagnosed with obesity. When comparing both groups, obese patients were found to be younger than non-obese, 63.3
+
14 years vs. 67.68
+
13 years, p<0.001, respectively. Obese patients had higher incidences of hypertension (n=10317; 38.9% vs. 1485; 37%, p=0.005), chronic kidney disease (n=3874; 17.5% vs. n=668; 13.9%, p<0.001), dyslipidemia (n=1771; 46.4% vs. n=10625; 38.1%, p <0.001), diabetes mellitus (n=373; 9.8% vs n=1278; 4.6%, p<0.001), non-alcoholic fatty liver disease (n=30; 0.8% vs. n=68; 0.2%, p<0.001), and polycystic ovarian syndrome (n= 30; 0.8% vs n=68; 0.2%, p<0.001). Tobacco use was higher in non-obese vs. obese patients (n=311; 1.1% vs. 28; 0.7%, p=0.32). The length of stay for both groups was similar, 7-days. Obese patients had a lower total hospital charges ($95,098 vs. $98,735). There was a lower incidence of mortality among obese patients n=194 (5.1%) vs. non-obese n=1743 (6.2%), p<0.005.

Conclusion:
Despite obese patients having more risk factors for developing SCM than non-obese patients, they were found to have decreased mortality and a lower cost of stay. These findings suggest that obesity may play a paradoxical role in SCM.
Abstract 13335: The Predictive Value of Paced Qrs Frequency Analysis in Achieving Left Bundle Branch Pacing
Authors: Vajapey Ramya , Amuthan Ram , Chung Mina K , Tchou Patrick , Rickard John , Chung Roy , Varma Niraj , Niebauer Mark J
Published: June 2023

Introduction:
Left bundle branch area pacing (LBp) is a newer technique to deliver more synchronous left ventricular activation. Several criteria have been proposed, but not fully validated, to confirm LBp during implantation of pacing lead.

Hypothesis:
We hypothesized that higher frequency content of the paced QRS complex may show predictive value of successful LBp.

Methods:
We evaluated 84 patients with ejection fraction >50%, who underwent LBB lead placement (n=42) using ≥1 current criteria and right ventricular midseptal (RVsp) lead placement (n=42) from 2000-22. Time frequency analysis (Matlab) was used to determine frequency content of paced QRS complex. Centroid Frequency (CF), which is the weighted average QRS frequency, was calculated. Unpaired t-test and Chi Square test were used for continuous and categorical variables, respectively. Multivariate analysis using logistic regression was used for variables with univariate p<0.20. Variables with significant multivariate comparison (p<0.05) underwent receiver operator curve analysis. Sensitivity and specificity for a CF ≥7.0 Hz for LBp was determined.

Results:
Baseline clinical characteristics are listed in Table 1. Patients in RVsp group had longer paced QRS duration (155.6 ± 28.0 vs 127.1 ± 17.2, p<0.002) compared to LBp group. Of all ECG leads, V2 gave greatest difference, with CF of LBp group at 8.8 ± 1.6 Hz vs 5.7 ± 0.7 Hz of RVsp group (fig 1). This difference was significant by both univariate (p<0.003) and multivariate (p<0.010) analysis. Predictive value of CF for successful LBB pacing in lead V2 was highest with an AUC of 0.98. Sensitivity and specificity were 88.1% and 97.6%, respectively.

Conclusions:
Spectral analysis predicts successful LBp with higher frequency content when compared to RVsp pacing. Given the limitations to the current criteria to confirm LBp, intraprocedural use of frequency content analysis of the paced QRS complex in patients may prove a useful means of identifying LBB capture
Abstract 13336: Rasa3 Affects Key Proliferation and Angiogenic Pathways in and Around Pulmonary Artery Endothelial Cells
Authors: Prohaska Clare C , Bai Yang , Gomes Marta T , Lockett Angelia , Machado Roberto F
Published: June 2023

Introduction:
Despite improvements in quality of life and functional status, pulmonary hypertension (PH) remains a highly morbid disease with poor life expectancy with no targeted treatments available. RASA3 is a ubiquitously expressed GTPase activating protein that is integral to angiogenesis and barrier function in endothelial cells (EC). In this study, we sought to explore the differential expression of RASA3 in response to PH-relevant stimuli and downstream markers of EC health when RASA3 expression is lost.

Methods:
Human pulmonary artery cells (PAECs) from Lonza were grown in culture and treated with 1% hypoxia, increasing concentrations of TNF-α for 24 hours or IL-1β for 48 hours and then harvested. Cells were transfected with siRNA directed against RASA3 or non-targeting control and harvested to evaluate downstream markers of EC health, or plated on Matrigel to evaluate angiogenic capabilities. Non-contact co-culture experiments were performed using human pulmonary artery smooth muscle cells (PASMC) with PAECs that were transfected with siRNA against RASA3 or non-targeting control.

Results:
We found that when untreated PAECs were exposed to 1% hypoxia for up to 96 hours, RASA3 expression was significantly decreased (p=0.046). When treated with increasing concentrations of TNF-α for 24 hours, RASA3 expression decreased (p=0.0002). When PAECs were treated with IL-1β 10ng/mL for 48 hours, RASA3 expression significantly increased (p=0.001). Silenced RASA3 PAECs had significantly less PCNA (p=0.0474), a trend towards increased HIF-2α expression (p=0.08) and increased VEGFR2 expression (p=0.0878). Cells that had silenced RASA3 expression when plated on Matrigel were significantly less able to form rings compared to non-targeting control (p=0.0152). PASMCs that had been co-cultured with silenced RASA3 had significantly increased PCNA compared to PASMCs co-cultured with non-targeting control PAECs (p=0.0467).

Conclusions:
RASA3 is essential to PAEC homeostasis, and loss of RASA3 affects endothelial cell health as well as affects its local environment. Further studies are ongoing to determine how loss of RASA3 contributes to the development of PH.
Abstract 13344: Endothelin B Receptor Agonist, Sovateltide, Promotes Neural Regeneration by Improving Mitochondria Function in a Neonatal Rat Model of Hypoxic-Ischemic Encephalopathy
Authors: Briyal Seema , Hurrell Sarah , Prazad Preetha , Gulati Anil
Published: June 2023

Introduction:
Our preliminary studies have indicated the role of Endothelin B receptors (ETBR) stimulation in decreasing oxidative stress and cell death after sovateltide treatment following hypoxic-ischemic encephalopathy (HIE) in rat pups, which suggests the involvement of ETBR in neonatal hypoxic-ischemic injury. However, its mechanism of action is not yet established. Therefore, this study investigated the effect of sovateltide on mitochondrial dysfunction and neurogenesis in a neonatal rat model of HIE.
Hypothesis
: Sovateltide protects neuronal survival via preserving mitochondrial activity.
Methods:
Sprague-Dawley male and female rat pups grouped separately, were divided into 5 different subgroups (1) Control; (2) HIE + Vehicle; (3) HIE + Hypothermia; (4) HIE + sovateltide; and (5) HIE + sovateltide + hypothermia. HIE was induced by ligating the right carotid artery on a postnatal day (PND) 7, followed by hypoxia for 120 min and hypothermia (32-34°C) for 5 h. On PND 7, sovateltide (5 μg/kg, ICV) was injected after hypoxic-ischemic injury. Pups were euthanized on PND 10. Brains were isolated for analysis of markers for mitochondrial fission and fusion as well as neurogenesis in rat brain tissues using western blots.
Results
: Animals receiving sovateltide showed a significantly increased expression of neuronal differentiation marker, NeuroD1 (p<0.0001) and DoubleCortin (p<0.001) along with neural marker for mature neurons, NeuN (p<0.001) compared to vehicle. Additionally, an upregulation (p<0.0001) of mitochondrial fusion-related proteins, Mfn2, and downregulation of fission proteins, Drp1, in the sovateltide group compared to the vehicle was observed. Higher neuronal progenitor cell differentiation along with better mitochondrial biogenesis in the brain of sovateltide alone or as an adjunct to hypothermia in rat pups was noted. Similar findings were obtained in both male and female rats.
Conclusion
: Stimulation of ETBR by sovateltide promotes neural regeneration via maintaining mitochondrial dynamics, indicating a potential neuroprotective effect and may, therefore, offer a legitimate therapeutic target for the treatment of neonatal HI brain injury.
Abstract 13349: Inclusion and Enrollment of Women and Minorities in Left Atrial Appendage Occlusion Clinical Trials: A Meta-Analysis
Authors: Sundaram Kavin , Sabzwari Syed Rafay Ali , Aleong Ryan G , Tumolo Alexis , Rosenberg Michael , Zipse Matthew , Tzou Wendy , Garg Lohit
Published: June 2023

Introduction:
Retrospective studies suggest that women undergoing left atrial appendage occlusion may have worse outcomes and population-based studies suggest racial variations in appendage anatomy and risk of stroke.

Hypothesis:
Randomized controlled trials of LAAO for atrial fibrillation will have low rates of inclusion of women and racial minorities.

Methods:
Databases were queried for all randomized clinical trials of LAAO from inception until May 2022 and included in the analysis
(Figure 1)
.

Results:
The search strategy identified 10 trials for inclusion in the study. Most studies reported rates of participation of women (9/10, 90 percent
Figure 2a
). The inclusion of women in these trials were low and constituted 34% of included patients (29-42%) with high heterogeneity (
Figure 3a).
Among these reports, only two studies (2/10, 20 percent,
Figure 2b
) reported details of the race and ethnicity of participants and 1031 / 1114 (93%) were Caucasians. Meta-analysis showed low heterogeneity
Figure 3b).

Conclusions:
In trials of LAAO for atrial fibrillation, rates of inclusion of women remain low relative to population prevalence. Reporting of participation of ethnic minorities also remains low. Improvement in these areas in future studies may help support the generalizability of the existing literature.
Abstract 13362: Increased Bleeding and Poor Outcomes in Patients Who Require Cardiac Procedures While Receiving P2Y12 Inhibitors
Authors: Pollack Charles V , Erickson Jeffrey , Birchall Jonathan , Lee John , Skaar Jeffrey R , Piazza Tyler , Liu Rachel , Mammadov Kamran
Published: June 2023

Introduction:
P2Y12 inhibitors (P2Y12i) reduce thrombotic risk in patients with acute coronary syndrome and in secondary prevention of atherothrombotic events, but dual antiplatelet therapy with a P2Y12i + aspirin increases bleeding risk. P2Y12i washout is recommended prior to procedures, but when procedures cannot be deferred, washout is precluded, thereby increasing periprocedural bleeding risk, with potential negative outcomes.

Hypothesis:
P2Y12i are associated with increased bleeding risk and poorer clinical and economic outcomes in invasive cardiovascular (CV) procedures.

Methods:
In a retrospective study of hospital chargemaster data (2017-2019), patients receiving P2Y12i (cangrelor, clopidogrel, prasugrel, ticagrelor, or ticlopidine) or aspirin without P2Y12i (control) prior to an invasive CV procedure were identified from hospital charge and ICD-10 codes. Inpatient bleeding, mortality, length of stay (LOS; days), and intensive care unit (ICU) LOS (days) were assessed.

Results:
Among 2,996,051 patients with invasive CT procedures, P2Y12i-treated patients had significantly higher bleeding rates versus control patients (4.2% vs 3.1% p<0.05). Coronary artery bypass graft (CABG) procedures were the most common. Heart valve procedures showed the highest bleeding rates. Both CABG and valve procedures showed significant increases in bleeding for patients with P2Y12i versus control patients (CABG 9.2% vs 5.7%; valve 17.2% vs 8.9%; both p<0.05). P2Y12i-treated patients with bleeding versus those without bleeding had significant increases in in-hospital mortality (CABG 5.0% vs 2.1%; valve 12.4% vs 4.8%), LOS (CABG 11.7 vs 10.7; valve 13.0 vs 11.6), and ICU LOS (CABG 8.4 vs 5.5; valve 11.2 vs 8.3) (all p<0.05). Similar findings were observed for other procedures.

Conclusions:
Invasive CV procedures in patients receiving P2Y12i were associated with increased bleeding rates. Patients with increased bleeding had poorer outcomes, including increased in-hospital mortality. Bleeding avoidance in P2Y12i-treated patients requires an adequate discontinuation period prior to invasive procedures. Delaying CV procedures, however, may result in suboptimal outcomes, highlighting the unmet need for a rapid reversal strategy for P2Y12i.
Abstract 13368: Effect of Peripheral Endothelial Function Assessment in Improving the Risk Stratification of Major Cardiovascular Events Beyond CHA2DS2-Vasc
Authors: Rajai Nazanin , Toya Takumi , Sara Jaskanwal D , Lopez-Jimenez Francisco , Lerman Lilach O , Lerman Amir
Published: June 2023

Introduction:
Peripheral microvascular endothelial dysfunction (PMED) is a marker and precursor of atherosclerosis and is associated with an increased risk of cardiovascular events. The present study aims to identify the best cut-off value of PMED, assessed by the reactive hyperemia index, in predicting major adverse cardiovascular events (MACE). Additionally, we investigate whether integrating PMED to CHA2DS2-Vasc score improves the predicting accuracy of cardiovascular disease.

Methods:
this is a retrospective study of patients who underwent reactive hyperemia peripheral arterial tonometry (PAT). The optimal cut-off value of reactive hyperemia index associated with MACE was calculated using the area under the receiver-operating curve and the maximum Youden index. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, vascular disease were determined to calculate the CHA2DS2-VASc score. MACE was defined as myocardial infarction, heart failure hospitalization, and cerebrovascular events.

Results:
1,690 patients were enrolled (average age 51.1±13.9, 64.1% female). The optimal cut-off value of the reactive hyperemia index was 2.0 in the overall population and females and 2.17 in males. The risk of MACE during 10 (Interquartile range: 4,16) years of follow-up was 15.3%. Multivariable logistic regression revealed that PMED as an independent predictor of MACE (PMED: OR, 3.6, 95% CI, 2.6-4.9, p<0.001) (Table1). Furthermore, integrating PMED to CHA2DS2-VASc significantly improved the predictive accuracy (area under the curve, 0.747 vs. 0.708, p<0.001).

Conclusion:
PMED is a strong predictor of cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.
Abstract 13381: Utility of Transthoracic Echocardiogram in Diagnosing Native Valve Infective Endocarditis
Authors: Chacon-Lutrick Lucas , jones erika , Lopez Erick , Schevchuck Alex
Published: June 2023

Background:
Infective endocarditis (IE) predisposes patients to severe morbidity and mortality. 2D transthoracic echocardiogram (TTE) is the preferred initial imaging modality of choice and frequently is followed by Transesophageal echocardiogram (TEE). Establishing the role of TTE and a TEE in ruling out IE can provide a framework for institutional changes leading to fewer invasive and costly TEE procedures.

Methods:
A retrospective chart review at the University of New Mexico Hospitals included patients diagnosed with IE for which echocardiography was performed. Demographic data, history of IV drug use, prior IE, physical exam findings, microbiology, echocardiographic findings, and post-imaging management changes were recorded.

Results:
We identified 101 patients with clinically suspected endocarditis for review. TTE was performed in all patients and TEE in 23 patients (23%). TTE results were positive for endocarditis in 11 patients (10.89%), negative in 83 patients (82.18%), and indeterminate in 6 patients (5.94%) and did not have surgical features. TEE was performed in 4 out of 11 patients with positive TTE. TEE did not change management in these cases. In the 6 cases of indeterminate TTE, treatment decisions could be made in 4 cases without a TEE. Two of the 101 patients had negative TTE but positive TEE. Both had MSSA bacteremia and a positive Duke score. TEE resulted in a longer antibiotic course. Treatment decisions could be made in 78% of patients with suspected infective endocarditis without a TEE.

Conclusion:
TEE has a small added value for the diagnosis of infective endocarditis, and treatment decisions can often be made in most patients without the use of TEE. In this study, TEE only changed care in 2% of patients with suspected IE without surgical features by increasing the duration of antibiotic treatment.
Abstract 13386: The Association of High Polygenic Risk With Future Coronary Heart Disease Events Diminishes Later in Life
Authors: Dikilitas Ozan , Smith Johanna , Schaid Daniel J , Kullo Iftikhar J
Published: June 2023

Introduction:
Polygenic risk scores (PRS) for coronary heart disease (CHD) are associated with incident CHD events. We assessed whether the strength of this association differs over the life course.

Methods:
We studied 7,958 genotyped participants of European-ancestry without CHD enrolled in the Atherosclerosis Risk in Communities Study (ARIC). Participants were 45-64 years old at the baseline visit occurring 1987-89 with follow up available through 2015. A genome-wide PRS for CHD composed of 1.7 million variants was computed for each participant. Incident CHD was defined as clinically adjudicated myocardial infarction including silent infarction, coronary revascularization, or fatal coronary event. An extended Cox model was constructed with age as the model time scale. The association of PRS with incident CHD was assumed to be log-linear and further modeled as a function of age assuming differing piecewise constant effect sizes across the intervals ≤55, 55-65, 65-80, and ≥80 years. The regression model also included the following covariates: sex, systolic blood pressure, total and HDL cholesterol, history of diabetes, antihypertensive medication use, and smoking status.

Results:
In the ARIC cohort (median enrollment age 54, interquartile range [IQR] 49-59, female 52%), over a median of 24.5 years (IQR 14.4-28.1), there were 1,872 incident CHD events. In comparison to average polygenic risk for CHD (50th percentile of PRS distribution), harboring high polygenic risk (95th percentile) was associated with a 2.9-fold increased risk of incident CHD (95% CI 2.12-3.95) up to age 55 years, independent of conventional risk factors. The strength of association was attenuated later in life (Hazard ratio, age 55-65, 2.5 [2.14-2.84]; age 65-80, 1.87 [1.68-2.07]; age ≥80, 1.78 [1.38-2.31])

Conclusions:
A genome-wide PRS for CHD is more strongly associated with incident coronary events at younger age. The strength of association declined later in life while remaining significant. The age-dependent association of PRS with CHD may need to be accounted for in risk prediction models.
Abstract 13391: Exploring Prognostic Implications of Socioeconomic Status in Patients With Peripheral Arterial Disease
Authors: Leveille Nayla , Chen Mia , Nauche Benedicte , Drudi Laura M
Published: June 2023

Introduction:
This systematic review sought to describe the prognostic implications of SES on clinical outcomes in patients undergoing vascular interventions for claudication and critical limb threatening ischemia (CLTI). 

Hypothesis:

Methods:
Studies were systematically searched across 5 databases from inception to June 2021. Studies focused on patients with claudication or CLTI undergoing open, endovascular, or hybrid procedures. Studies were included if SES was documented and associated with a clinical outcome. Two independent reviewers selected studies for inclusion, extracted data, and assessed risk of bias using ROBINS-I and Newcastle-Ottawa scales. Extracted data included study and clinical characteristics, demographics, interventions, outcome measured, and association of SES with the clinical outcomes.

Results:
Thirty four studies met our inclusion criteria and addressed the impact of SES in patients undergoing interventions for PAD, with 8 articles including only claudication patients, 2 including only CLTI patients, and 24 including a combination of both groups. The way SES was defined varied across studies, with some describing it in relation to insurance status (n=14), household income (n=13), income in area of living (n=8), income in the hospital’s area (n=1) and employment status (n=1). Low SES was associated with higher rates of amputation as a primary intervention, higher rates of above the knee amputation compared to below the knee amputation, higher 30 day postoperative death, longer lengths of stay, higher surgical sites infections, amputations following primary interventions, in-hospital complications, long term major adverse limb events and long term amputation rates. Given the amount of heterogeneity that was present in the designs, populations, and comparators among the included studies, we were unable to statistically pool data across trials.

Conclusions:
Our qualitative findings suggest that low SES is associated with significant adverse outcomes in patients with PAD including higher rates of primary amputation, post-operative mortality, length of stay, among others. Reasons for these disparities should be explored to identify solutions for decreasing and eliminating these health inequities.
Abstract 13394: Primary Perfusion Balloon Angioplasty in Primary Percutaneous Coronary Intervention for St-Segment Elevation Myocardial Infarction - The Novel Cardioprotective Revascularization Strategy
Authors: Nakanishi Toru , Koto Dan , Kasahara Mizuho , Mizukoshi Kei , Takano Makoto , Mizuno Koichi , Matsuda Hisao , Akashi Yoshihiro J
Published: June 2023

Background:
In patients with STEMI, primary PCI reduces the risk of cardiovascular death, whereases following myocardial reperfusion injury indicating poor prognosis. Post-conditioning is expected to limit reperfusion infarction but the long-term outcome is unclear. We investigated whether primary perfusion balloon angioplasty (PPBA) strategy might reduce reperfusion injury and improve prognosis.

Methods:
PPBA is maneuver treating as primary revascularization procedure with perfusion balloon angioplasty undergoing long-inflation (5-minutes or more) as post-conditioning. This study is a retrospective analysis from an observational registry which enrolled all consecutive 49 patients with STEMI undergoing PCI in PPBA strategy or conventional balloon angioplasty (CBA) strategy at a single center from February 2021 to January 2022. The primary outcome of the study was MACE as a composite of all-cause death, cardiac death, MI, CI-TVR, hospitalization because of heart failure, and cerebrovascular disease followed at 6 months. The secondary outcome was the composite of no-reflow or slow flow phenomenon, ST elevation, and VT or VF occurrence immediately after primary revascularization procedure.

Results:
24 patients were treated with PPBA strategy and 25 patients were treated with CBA strategy. At the 6-months, primary composite outcome occurred in 25% treated with PPBA strategy and in 52% treated with CBA strategy (HR, 0.38; P=0.04); the difference was driven by a lower incidence of cardiac death, MI, CI-TVR in PPBA arm. Immediately after primary revascularization, secondary composite outcome occurred in 4.2% treated with PPBA and in 56% treated with CBA (RR, 0.03; P=0.0001); the difference was driven by a lower incidence of no-reflow/slow flow and ST elevation in PPBA arm.

Conclusions:
PPBA strategy as primary cardioprotective revascularization expected post-conditioning reduces lethal reperfusion injury, resulting in a better prognosis in STEMI.