bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11453: Age, Sex, and Outcomes in Heart Failure With Reduced Ejection Fraction: Insights From the VICTORIA Trial
Authors: Pina Ileana L , Zheng Yinggan , Bonderman Diana , Pouleur Anne , Saldariagga Clara , Pieske Burkert , Blaustein Robert O , Nkulikiyinka Richard , Westerhout Cynthia M , Armstrong Paul W , Lam Carolyn S
Published: June 2023

Background:
Both patient age and sex influence heart failure (HF) treatment and outcomes. Given women are generally older in HF trials, we examined the associations of age and sex with clinical characteristics, background HF therapy, and response to vericiguat in VICTORIA. VICTORIA enrolled 5050 patients with HF with reduced ejection fraction (HFrEF) and recent worsening HF, was broadly inclusive without an upper age limit, and included 28% women (n=1208), and 31% (1568 ) were ≥75 years old with event rates exceeding most HF trials.

Methods:
Clinical characteristics were compared across age groups (<65, 65 to <75, ≥75 and <75, ≥75 years) and sex (
Table
).

Results:
More women (37%) than men (29%) were age ≥75 years. Compared with younger patients, those ≥75 had higher EF and class III/IV symptoms, more comorbidities, higher NT-proBNP and lower eGFR, indicative of more advanced disease; however, this age group had the lowest use of triple therapy. Within each age group, women had higher EF and lower burden of some comorbidities (atrial fibrillation, hyperlipidemia, coronary artery disease) compared with men, but similar functional status and NT-proBNP. There were no sex differences in the use of triple therapy by age group; however, women ≥75 years less often achieved target doses of triple therapy than men of similar age. Women were also less likely to receive HF devices across all ages. The incidence of the primary composite endpoint (cardiovascular death or HF hospitalization) increased across age groups and was higher in men than women. Compared with the pre-specified age subgroup analysis (i.e., <75, ≥75 years), the beneficial effect of vericiguat on the primary endpoint was not modified by age (continuous) and sex (3-way interaction; p=0.847).

Conclusions:
Women in VICTORIA were older than men, and while elderly women received less intense background HF therapy, their prognosis was nominally better than elderly men. Vericiguat’s benefit was independent of age and sex.
Abstract 11457: Long Noncoding RNA LncAPAT Promotes Atherosclerotic Plaque Instability by Targeting Ribosomal Protein L22
Authors: Kamili Adalaiti , Li Rongxia , Yang Shujun , Zhang Weili
Published: June 2023

Introduction:
Atherosclerosis is a chronic inflammatory disorder and macrophages play a critical role in the progression of atherosclerosis. Long noncoding RNAs (lncRNAs) participate in the process of macrophage inflammation and atherosclerosis. But the molecular mechanisms underlying the function of lncRNAs in macrophages during the development of atherosclerosis are largely unknown.

Hypothesis:
We hypothesized that lncRNAs may regulate inflammatory response of macrophages and atherosclerotic plaque instability.

Methods and Results:
Subjects with suspected coronary artery disease were examined by coronary computed tomography angiography and divided into control (without >1 mm
2
lesions) and mixed plaque groups (with plaques containing lipid, fibrous and calcified components). With whole transcriptome sequencing and further confirmation of real-time PCR in peripheral bloods, a novel lncRNA (named hereafter, atherosclerotic plaque instability associated transcript,
lncAPAT
), was identified to express at high levels in patients with mixed plaques. A murine model with monocyte-specific knock in of
lncAPAT
was generated. (
LncAPAT
significantly promoted plaque burden by 1.67-fold in the aorta of MØ

lncAPAT

mice compared with control group (MØ

control

mice). Immunofluorescence analysis showed an elevated numbers of macrophage (by 88%) and increased expression of matrix metalloproteinase (MMP) (MMP9 by 7.7-fold and MMP2 by 86%) in plaques of MØ

lncAPAT

mice.
LncAPAT
significantly promoted monocytes adhesion to endothelium
in vitro
and increased the expression of tumor necrosis factor α and intercellular adhesion molecule 1.
LncAPAT
also enhanced the lipid uptake ability of macrophages. Chromatin isolation by RNA purification-sequencing assay showed that
lncAPAT
interacted directly with the promoter region of the ribosomal protein L22 gene (RPL22), and it promoted inflammatory response of macrophages by inhibiting the transcriptional activity of RPL22.

Conclusion(s):
Our findings first identified that lncAPAT was upregulated in patients with coronary vulnerable plaques and promoted the inflammatory response of macrophages by inhibiting the transcriptional activity of RPL22, thereby contributing to plaque instability.
Abstract 11459: The Biochemical and Physiological Pathways From Obesity to Cardiovascular Disease: A Prospective Cohort Study of 404332 UK Biobank Participants
Authors: Zhou Ziyi , Parra-Soto Solange , Petermann-Rocha Fanny , Boonpor Jirapitcha , Welsh Paul , Celis-Morales Carlos , Sattar Naveed , Pell Jill , Ho Frederick
Published: June 2023

Background:
There are limited effective population measures to control obesity even though it is a major risk factor for chronic diseases. We explored the mechanisms linking obesity and cardiovascular diseases (CVDs), including atherosclerotic CVD (ASCVD) and heart failure (HF), which could be more effective targets for disease prevention.

Methods:
This is a prospective cohort study of 404,332 UK Biobank participants of white ethnicity who were free from CVDs, chronic diseases, and respiratory disease at baseline and had body mass index (BMI) ≥18.52. Data was collected at the baseline assessment between 2006 and 2010. Linkage to death registrations and hospital admission records was used to ascertain ASCVD and HF outcomes up to late 2021. Obesity is defined as BMI ≥302. Biomarkers included lipids, blood pressure, HbA1c, liver, and kidney function markers chosen based on results from trials and Mendelian randomisation studies. Cox proportional hazard models were used to estimate HRs and 95% confidence intervals (CIs). Mediation analysis based on g-formula was used to identify significant mediators as well as their relative importance for ASCVD and HF separately.

Findings:
Obesity (BMI ≥30 kg/m2) was associated with an increased risk of ASCVD (HR 1.20, 95% CI 1.16-1.24) and HF (HR 1.75, 95% CI 1.68-1.82) after adjusting for sociodemographic and lifestyle factors and use of statins and medications for blood pressure and diabetes. The strongest mediators for ASCVD were eGFR, blood pressure, and triglycerides, which accounted for 54.63%, 38.15% and 27.69% of the associations respectively; those for HF were eGFR (33.09%), CRP (10.32%), and HbA1c (7.45%). The mediators explained a much higher proportion of excess ASCVD risk than HF risk.

Interpretation:
Interventions that help individuals living with obesity to maintain healthy levels of lipids, blood pressure, HbA1c, and kidney function could potentially alleviate some of the ASCVD burdens. However, the HF burden could not be meaningfully reduced without weight management.
Abstract 11467: Novel Identification Strategy to Increase Diversity in Heart Failure Clinical Trials
Authors: Gilchrist Susan C , Ferrell Joe , Pagel-Langenickel Ines , Shirodaria Cheerag , Flinders JB
Published: June 2023

Introduction:
Women and racial/ethnic minorities remain underrepresented in cardiovascular (CV) clinical trials, thus limiting the generalizability of study findings and the use of novel CV therapeutic testing among those who often have the greatest burden of CV disease. One potential solution is to shift the identification of trial participants from traditional academic centers to large registries. To this end, we tested whether an Emergency Medical Services (EMS) platform could identify patients in the pre-hospital setting who were potential candidates for heart failure (HF) clinical trials. Second, we sought to determine the demographic underpinnings of this population.

Methods:
The Biospatial platform used EMS electronic patient care reports (ePCR) as the foundational data source. Records of pre-hospital patients with an EMS provider impression of HF were identified through Biospatial’s artificial intelligence algorithm. In a subset of patients, ePCR records in Florida were linked to hospital diagnosis codes utilizing the Florida Health Information Exchange.

Results:
Between February 1, 2021 and April 30, 2022, we identified 18,198,085 records in the US with a 911 response and patient disposition requiring EMS transport to a local emergency room. There were 63,595 records in which an EMS provider recorded a primary or secondary impression of HF. Of those, 49% were female, 60.3% were White, 22.7% Black, 3.2% Hispanic/Latino, and 13.8% other or unknown. Next, as a test case, the Florida Health Information Exchange was utilized to determine whether an EMS impression of HF was confirmed by a hospital ICD-10 HF code (I50). There were 5363 records in Florida that met the criteria for a 911 call. Of those, 2355 had linked hospital data and 1560 had a populated diagnosis code. Sixty-four percent (64%) of individuals identified by EMS as having HF in the pre-hospital setting received a hospital diagnosis of HF.

Conclusion:
The utilization of an EMS registry is a novel strategy to identify a diverse population of HF patients for inclusion into clinical trials. Further work is needed to optimize the EMS heart failure algorithm for clinical trial participant identification and to test this strategy for other CV diagnoses such as myocardial infarction and stroke.
Abstract 11479: Adolescents Have Reduced Exercise Capacity After Heart Transplant
Authors: Markiewitz Nathan , Stack Kathryn , Lane-Fall Meghan , HUANG JING , Mercer-Rosa Laura M , Mitchell Jonathan , O'Connor Matthew J , Rossano Joseph , Paridon Stephen , Burstein Danielle , Edelson Jonathan B
Published: June 2023

Introduction:
There are limited data on exercise capacity and its determinants in pediatric heart transplant patients (HT).

Methods:
This single-center, retrospective cohort study of patients (<18yo) includes subjects who received their index HT from 1990-2016 and completed a maximal effort cardiopulmonary exercise test (CPET) during adolescence (12-18yo). The primary outcome was maximum oxygen consumption (VO2). Secondary outcomes included anaerobic threshold (AT) and power consumption (PC). Outcomes were evaluated as percent predicted by sex and age. Wilcoxon rank-sum tests were used to test deviation from predicted exercise capacity. Linear regression models were used to assess association of clinical variables with CPET outcomes.

Results:
Our sample of 86 patients was 53% male (n=46), 68% White (n=53), with a median age at transplant of 10y (IQR [3-14]). The majority had a diagnosis of congenital heart disease (59%, n=51) and 21% (n=18) were supported with VAD prior to HT. The median age at EST was 17y (IQR 14.7, 17.6), mean time from OHT 7.1y (SD 5.3), and most patients were tested using cycle ergometry (87%, n=75). Max VO2 (median=26.3 ml/kg/min, 65% predicted), AT (median=17.5 ml/kg/min, 66% predicted) PC (median 1.8 w/kg, 56% predicted) were significantly lower than 100% predicted (p<0.001 for all, Fig 1). After adjustment for age at transplant and time since transplant, increased BMI (b= -1.32 95% CI [-1.85, -0.79]) and decreased peak heart rate (HR) (b= 0.32 95% CI [0.19, 0.45]) predicted reduced max VO2. Ejection fraction, cardiac index, and pulmonary capillary wedge pressure measured on cardiac catheterization were not associated with max V02.

Conclusions:
Adolescents after HT demonstrate markedly reduced exercise capacity. While impaired chronotropy has been implicated in impaired exercise capacity in HT, the association of BMI is novel. The identification of this modifiable factor has important clinical implications for future interventions.
Abstract 11490: The Role of Breast Milk Extracellular Vesicles on Endothelial Dysfunction
Authors: Cho Young-Eun , Chen Shaoshuai , Crouch Keith , Kim Jeonga
Published: June 2023

Introduction:
Breast milk has abundant extracellular vesicles (EVs), which have strong anti-inflammatory properties. EVs are not degraded in the stomach, thus, orally administered milk exosomes are absorbed into the intestine and then disseminated to other organs via circulation. Circulating milk EVs in the blood have a high chance of interacting with endothelium, however, the impact of milk exosomes on the endothelial cells has not been examined. Endothelial dysfunction is a hallmark of cardiovascular diseases induced by the inflammatory process. In this study, we have tested if orally administered human breast milk EVs (bEVs) can improve endothelial dysfunction in obese mice.

Hypothesis:
Oral administration of bEVs restores the endothelial function in high fat diet-induced obese mice

Methods:
Breast milk was obtained from healthy mothers with normal pre-pregnancy BMI who delivered a baby within the past 30 days (n=24). bEVs were isolated by ultracentrifugation, and the presence of exosomes was confirmed with the expression of CD9, CD81, CD63, and TSG101. C57BL/6J male mice were fed a 60% high-fat diet for 16 weeks, then bEVs were administered weekly via oral gavage for six weeks (3μg of EVs/g). The same amount of PBS was administered to obese and chow diet-fed mice. Glucose tolerance test and insulin tolerance test were performed before and after treatment. Endothelial cell-dependent vasorelaxation was measured in the 1
st
branches of mesenteric arteries.

Results:
Oral administration of bEVs for 6-weeks did not change body weight in obese mice. Glucose tolerance and insulin tolerance were not also affected. However, the fasting blood glucose level was significantly reduced (p=0.0012, n=5-7) in bEV-treated obese mice. In mesenteric arteries, acetylcholine-induced relaxation was significantly improved (p<0.001) in bEV-treated obese mice compared with the PBS-treated obese mice.

Conclusions:
Oral administration of bEVs improved the endothelial cell function in obese mice, although the metabolic parameters were not changed. Further investigation will be followed to understand how bEVs improve the impaired endothelial cell-dependent vasorelaxation.
Abstract 11491: Clinical Time Course of Post-Acute Sequelae of SARS-CoV-2 Cardiovascular Syndrome
Authors: Beatty Mark C , Verma Amanda K
Published: June 2023

Introduction:
Post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) is a heterogeneous disorder of post-COVID syndrome that involves a wide range of cardiovascular symptoms including palpitations, chest pain, dyspnea and dizziness. The clinical time-course of PASC-CVS is not well characterized. We sought to understand predictors of time to symptom improvement for patients with PASC-CVS.

Methods:
Patients with PASC-CVS undergoing evaluation in a dedicated post-COVID cardiology clinic were recruited after informed consent. Information was obtained from chart review and included demographics, comorbidities, symptoms, time of infection to time of presentation to the clinic and time to improvement in symptoms. A multivariate linear regression model was used to determine predictors of time to improvement.

Results:
A total of 144 consecutive patients were included that had complete records available for review. Average age was 46 years, 74% were female and 94% were Caucasian. Comorbities included obesity (49%), mental health disorder (25%), hypertension (24%), hyperlipidemia (24%), pulmonary disease (18%), type II diabetes (9%), atrial arrhythmia (5%) and coronary artery disease (3%). Time from infection to presentation (p <0.001), chest pain (p 0.002) and dyspnea (<0.001) demonstrated significant associations with time to improvement of symptoms and were used in the multivariate regression model (F 27.8, p<0.001). The time to presentation predicted the longest time to symptom improvement, followed by dyspnea, chest pain, and dizziness.

Conclusions:
This analysis of a large group of PASC-CVS patients suggests those who wait longer to seek care for PASC-CVS symptoms may have longer duration of post-COVID symptoms. Additionally, specific symptoms may take longer to improve than others. Patients with PASC-CVS should therefore consider early medical care to mitigate symptoms and reduce duration of post-COVID syndrome.
Abstract 11498: County-Level Social Vulnerability si Associated With Higher Rates of Vascular Amputations in Florida
Authors: Shah Khanjan B , Elzeneini Mohammed , Shah Samir , Strong Adrienne , Li Yujia , Aranda Juan , Winchester David E , Guo Yi , Pepine Carl , Berceli Scott A
Published: June 2023

Introduction:
Peripheral arterial disease (PAD) is a highly prevalent condition that disproportionately affects patients in minority groups and results in high morbidity and mortality. We seek to determine the association between county-level social vulnerability and vascular amputations in Florida.

Methods:
We queried the Florida State Inpatient Database (SID) for hospitalizations with a primary diagnosis of PAD between October 2015 and December 2019. We linked patient-level hospitalizations with the county-level social vulnerability index (SVI). We used multivariable regression models to compare rates of major or minor amputations between SVI quartiles for overall SVI and each of the four SVI themes. We also examined in-hospital mortality, 60-day readmissions, total hospital charges, and other secondary outcomes as stratified by socioeconomic status SVI quartile.

Results:
38,488 hospitalizations for PAD were identified during the study period. Patients in worse overall SVI quartiles were younger, more likely to be racial minorities (53.7% in 4
th
quartile compared to 19.1% in 1
st
quartile, p <0.0001), and more likely to have emergent or urgent hospitalizations. Overall amputation rate during hospitalization was 22%. Patients in the worst overall SVI quartile demonstrated higher rates of amputations (OR 1.30, 95% CI: 1.11-1.53) when compared to the most favorable SVI quartile. Socioeconomic status SVI was associated with a higher risk of amputations (OR 1.40, 95% CI: 1.21-1.64) even after adjustment for patient race (OR 1.32, 95% CI: 1.13-1.54). Worse socioeconomic SVI was also associated with longer hospital lengths of stay and higher costs but was not associated with increased in-hospital mortality or readmissions.

Conclusions:
Patients with worse social vulnerability are more likely to require amputations for PAD in an urgent or emergent clinical setting and have longer lengths of stay and higher costs. Patient socioeconomic status predicts adverse outcomes for PAD even after adjusting for race. Our data suggest a socioeconomic basis for disparities in PAD outcomes. Policymakers should allocate additional resources for areas with worse SVI to design and evaluate interventions to improve care and outcomes.
Abstract 115: Comparison Of Di-block Copolymer-based Cell Membrane Stabilizers To The Tri-block Poloxamer 188 In Protecting Coronary Artery Endothelial Cells Against Hypoxia-Reoxygenation Injury
Authors: Li Zhu , Gupta Mukesh K , Barajas Matthew B , Duvall Craig L , Riess Matthias L
Published: June 2023

The triblock copolymer-based cell membrane stabilizer (CCMS) Poloxamer (P)188 consists of a central hydrophobic poly-propylene oxide (PPO) block that is flanked by two hydrophilic poly-ethylene oxide (PEO) blocks (PEO
75
-PPO
30
-PEO
75
). It has been found to protect against various types of ischemia/reperfusion (IR) injury (e.g. stroke, traumatic brain injury, trauma, myocardial infarction) presumably by preserving membrane integrity and function. Modifications of its structure to di-block compounds (PEO-PPO) with a strongly hydrophobic (t) tert-butyl end-terminal were reported to yield even stronger protection. Recently, we demonstrated the critical importance of endothelial cells in mediating protection against IR injury of cardiomyocytes in a co-culture study.

Here, we compared the protective effects of custom-made di-blocks (PEO
113
-PPO
10
t, PEO
226
-PPO
18
t and PEO
113
-PPO
20
t) at different concentrations (0 to 300 μM) on cell proliferation, lactate dehydrogenase (LDH) leakage and FM1-43 dye incorporation as markers of cell viability and membrane damage, respectively, to P188 in mouse coronary artery endothelial cells (MCAECs) when given upon the beginning of 2 hrs reoxygenation after 24 hrs hypoxia (HR) vs corresponding control normoxia (CN) conditions. Data are mean +/- standard deviation; statistics: ANOVA and SNK post-hoc testing, alpha = 0.05, # vs CN, * vs 0 mM.

P188 as well as all three tested di-blocks significantly attenuated HR-induced cell damage dose-dependently; the figure shows the LDH data. This, for the first time, demonstrates that di-block compounds can protect MCAECs against HR injury as effective and even superior to P188.

If translated clinically, di-block CCMS may become effective new compounds mitigating IR injury.
Abstract 11506: Roles of Mechanical Overload and the Microtubule Network in Mediating T-Tubule Remodeling
Authors: Courelli Vasiliki , Uchida Keita , Vite Alexia , Prosser Benjamin , Margulies Kenneth B , Ibrahim Michael
Published: June 2023

Background:
Mechanical overload is an established contributor to the remodeling of T-tubules (TT) and associated dyssynchronous Ca
2+
release leading to abnormal excitation-contraction coupling in cardiomyopathies. We examined the induction of pathologic TT remodeling in isolated cardiomyocytes and the involvement of microtubules in this process.

Methods:
Normal adult rat ventricular myocytes (aRVMs) were cultured for 48hrs on MREs at either physiological (10kPa) or pathological (50kPa) stiffness. Variable
in vitro
load application was achieved using custom magnetorheologic elastomers (MREs) with tunable stiffness. Cells were stained with Di-8-ANEPPS and Fluo-4-AM and imaged using Airyscan confocal microscopy. Microtubule dependency was investigated by treating cells with 1μM nocodazole, a microtubule depolymerization agent.Structural changes in TT networks were quantified in terms of regularity, luminal dimensions, density, and directionality. Field stimulation of cells allowed for acquisition of [Ca
2+
]
i
transients via line scans and subsequent analysis of key [Ca
2+
]
i
transient parameters. Changes in protein expression were determined via Western blotting.

Results:
Compared to the physiological stiffness group, aRVMs subjected to pathologically increased stiffness exhibited decreased density and regularity of the TT system, and increased luminal dimension. Direction-specific density analysis showed that pathologically loaded cells have more longitudinal tubule elements and fewer transverse tubule elements. This remodeling was attenuated in aRVMs treated with nocodazole in terms of regularity, luminal diameter, and direction-specific density. The observed changes in both Ca
2+
handling parameters and key protein expression resembled those typical of the
in vivo
myopathic phenotype.

Conclusion:
The results suggest that load-induced TT remodeling occurs via a cardiomyocyte autonomous, microtubule-dependent mechanism.
Abstract 11521: Prevalence of Immortal Time Bias in High-Impact Cardiovascular Publications
Authors: Samuel Michelle , Kutcher Stephen , Flatman Leah K , Emmalin Buajitti , Mahmoud Farida , Bandargal Saruchi , Brophy Jay
Published: June 2023

Background:
Immortal time bias (ITB) is a consequence of non-uniform time zeros (ie. start of follow-up) between treatment groups, resulting in misclassification or selection bias in observational cohort studies. ITB poses a substantial problem as its presence favors the treatment, leading to an overestimation of the protective effect or an underestimation of the harmful effects of the treatment group compared to the control group. Depending on the amount of person-time misclassified or excluded, the magnitude of bias due to ITB may be substantially greater than other biases, such as confounding.

Objective:
To determine the prevalence of ITB in observational cohort studies published between 2020 and 2021 in high-impact cardiovascular journals.

Methods:
Observational cohort studies published in Circulation, European Heart Journal, and the Journal of the American College of Cardiology between January 2020 and December 2021 were screened for inclusion. Cross-sectional studies, case series, case-control, time-series analyses, and survey or surveillance studies were excluded. Two independent reviewers (ie. epidemiologists) evaluated each article for the presence and type of ITB.

Results:
Of 1,558 screen articles, 154 published articles were eligible for inclusion. Twenty of 154 (13%) publications had ITB present. ITB was most frequently due to misclassification bias (17 of 20 articles, 85%). ITB due to selection bias was present in 5 of 20 (25%) articles. Two articles had ITB due to both misclassification and selection biases. Most studies (75%) with ITB did not have an active comparator group. Among studies with ITB, event-based cohorts were the most frequent (65%), followed by event-exposure based cohorts (15%), and exposure-based (10%) and time-based (10%) cohorts. ITB was present in studies with various exposures, including medications (7), surgeries or procedures (5), devices (4), and diseases (4).

Conclusion:
A substantial proportion (13%) of published observational cohort studies in high-impact cardiovascular journals had ITB present and may result in an overestimation of treatment effect. As ITB is preventable with study design techniques, researchers need to be cognizant of this bias.
Abstract 11540: Dephospho-Uncarboxylated Matrix Gla-Protein and Adverse Outcomes in Heart Failure: A Mendelian Randomization Analysis
Authors: Vidula Mahesh K , Schurgers Leon J , Qian Chenao , Salman Oday , Jehangir Qasim , Cohen Jordana , Kvikstad Erika , Maranville Joseph , Zhao Lei , Chang Ching-Pin , Gordon David A , Ramirez-Valle Francisco , Cappola Tom , Chirinos Julio A
Published: June 2023

Introduction:
Matrix Gla-protein (MGP) is a known inhibitor of vascular calcification and is activated by vitamin K-dependent carboxylation. Carboxylation is reduced in vitamin K-deficient states, resulting in increased circulating dephospho-uncarboxylated MGP (dpucMGP). Elevated dpucMGP levels have been associated with large artery stiffenning and worse outcomes in heart failure (HF). We assessed the causal relationship between dpucMGP and adverse outcomes in human HF using Mendelian Randomization (MR).

Methods:
We measured dpucMGP among 2379 Penn Heart Failure Study (PHFS) participants and analyzed a subset with genotypic data (n=1334). We constructed a genetic risk score (GRS) using independent single nucleotide polymorphisms (SNPs) associated with dpucMGP levels at genome-wide significance, and utilized MR analysis to assess the association between genetically determined dpucMGP levels and 1) all-cause death, and 2) death or heart failure-related hospital admission (DHFA).

Results:
Measured dpucMGP levels were associated with an increased risk of death (
Figure 1A
) and DHFA (
Figure 1B
). DpucMGP levels were significantly associated with 55 genome-wide SNPs. MR analysis demonstrated a significant relationship between genetically determined dpucMGP and the risk of death (hazard ratio [HR] 1.67,
P
=0.013) and DHFA (HR 1.51,
P
=0.004).

Conclusions:
Elevated dpucMGP levels are associated with increased risk for all-cause death and DHFA in patients with heart failure, and this relationship is likely causal. Further studies are required to determine the role of vitamin K supplementation in this patient population.
Abstract 11548: Gender Disparities After Transcatheter Aortic Valve Replacement With Newer Generation Transcatheter Heart Valves: A Systematic Review and Meta-Analysis
Authors: Trongtorsak Angkawipa , Thangjui Sittinun , Adhikari Pabitra , Shrestha Biraj , Kewcharoen Jakrin , Navaravong Leenhapong , Kanjanauthai Somsupha , Attanasio Steve , saudye Hammad A
Published: June 2023

Background:
Evidence demonstrated gender disparities after transcatheter aortic valve replacement (TAVR) with early generation transcatheter heart valves (THV)s. However, it is unclear whether gender-related differences persist with the newer generation THVs. We conducted this meta-analysis and systematic review to assess gender disparities after TAVR with newer generation THVs

Methods:
We searched MEDLINE, and Embase databases from inception to May 2022 to identify studies that reported gender-specific outcomes after TAVR with newer generation THVs (Sapien 3, Corevalve Evolut R, and Evolut Pro). Outcomes of interests included 30-day mortality, 1-year mortality and vascular complications. Data were pooled using random-effects models to calculate pooled odds ratio (OR) and 95% conference interval (CI).

Results:
Four studies with a total of 47,933 patients (21,073 in females and 26,860 in males) were included. Ninety-six percent received TAVR via transfemoral approach. Females had higher 30-day mortality (OR = 1.53, 95%CI 1.31-1.79, p-value (p) < 0.001) and vascular complications (OR=1.43, 95%CI 1.23-1.65, p< 0.001). However, 1-year mortality was similar between 2 groups (OR=0.83, 95%CI 0.67-1.04, p=0.33).

Conclusions:
Higher 30-day mortality after TAVR in females may be attributed from higher vascular complications. Further research is needed to explore potential causes of increased mortality. While vascular complications may be an etiology, other patient characteristics or procedure-related issues should be evaluated.
Abstract 11555: Risk Factors Associated With Pacemaker Implant Following Hospital Discharge, Within 30 Days of TAVR
Authors: Cao Jessica , Peigh Graham , Charron Jessica , Cantey Eric , Flaherty James , Davidson Laura , Malaisrie S. Christopher , Verma Nishant , Kaplan Rachel
Published: June 2023

Introduction:
Delayed conduction abnormalities can occur after transcatheter aortic valve replacement (TAVR) in a small but significant group of patients and may be associated with out-of-hospital adverse events including syncope and need for urgent permanent pacemaker (PPM) implantation. There are limited data on the factors associated with need for PPM implantation following TAVR hospital discharge.

Methods:
A single-center retrospective analysis of TAVR patients (2011-2019) was performed. Exclusion criteria included presence of a PPM prior to TAVR, PPM implant during index admission for TAVR, and absence of pre-TAVR ECG data. The primary endpoint was PPM implantation occurring after hospital discharge, within 30 days of TAVR (late PPM).

Results:
Of 1148 TAVR procedures performed during the study period, 850 (79.7 ± 9.3 years old, 53.8% male) were included in analysis. There were 16 patients (1.88%) who required late PPM implantation. The median duration of time between discharge and late PPM was 4 (2.8-9.3) days. Univariate analysis revealed that pre-existing right bundle branch block, and change in PR interval from pre-TAVR through day of discharge was associated with late PPM (Figure). Notably, new left bundle branch block was not associated with late PPM. Multivariate analysis demonstrated that change in PR interval from pre-TAVR through day of discharge was independently associated with late PPM. The rate of late PPM increased linearly with greater PR prolongation (y=1.10x-1.01, r2=0.93), and patients with PR increase >20ms had a 4.8% rate of late PPM implantation (Figure).

Conclusions:
PR prolongation through day of discharge independently predicted need for late PPM following TAVR in our single center experience. Patients with PR increase >20ms from baseline are at particularly high risk for late PPM and should be counseled about the potential need for future PPM.
Abstract 11571: Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Quispe Renato , Sweeney Ty , Ndumele Chiadi E , Martin Seth S , Jones Steven R , Allison Matthew A , Budoff Matthew , Elshazly Mohamed B , Michos Erin D
Published: June 2023

Introduction:
The metabolic phenotype of obesity is characterized by high levels of triglyceride (TG)-rich lipoproteins and remnant particles, which are atherogenic. Adipokines are endogenous hormones released from adipose tissue with several metabolic effects. We aimed to assess the association between adipokines and levels of remnant cholesterol (RC).

Methods:
We studied 1,791 MESA participants of an ancillary study who had adipokine levels measured (leptin, adiponectin, resistin) and CT assessment of visceral and subcutaneous adipose tissue at either visit 2 or 3. RC was calculated as non-HDL-C minus LDL-C, measured at the same visit as the adipokines. Multivariable adjusted linear regression models were used to assess the cross-sectional association between adipokines and RC levels.

Results:
Mean ± SD age was 64.5 ± 9.6 years; 52% women, 40% White, 21% Black, 26% Hispanic, and 14% Chinese-American participants. Median (IQR) of leptin, resistin and adiponectin were 13.1 (5.6-28.2) ng/mL, 14.9 (11.9-18.8) ng/mL and 17.5 (11.9-26.4) ng/mL, respectively. Those in the highest tertile of adiponectin had lower levels of TG [89 mg/dL (65-136)] and RC [18.8 mg/dL (15-24.9)] compared to the lowest tertile [TG 130 mg/dL (93-180); RC 23.6 mg/dL (19.1-30.2), p<0.01]. Individuals in the highest tertile of leptin had higher levels of TG [121 mg/dL (83-177)] and RC [22.8 mg/dL (17.8-30)] compared to the lowest tertile [TG 100 mg/dL (69-141); RC 20 mg/dL (15.7-25.4), p<0.01]. Diabetes was more prevalent in lowest tertile of adiponectin (18.8% vs. 9.1%) and highest tertile of leptin (15.8% vs. 10.7%) compared to their lowest tertiles. No significant differences were seen across resistin tertiles. After adjustment, levels of adiponectin and leptin remained significantly associated with higher levels of RC
(Table)
.

Conclusion:
Lower adiponectin and higher leptin levels were associated with worse metabolic profile, and independently associated with higher levels of RC.
Abstract 11579: Clopidogrel Monotherapy Associates With Increased Mortality Compared With Aspirin Independently of Cardiometabolic Risk Factors
Authors: Reddy Rohin K , Wang Brian X. , Gwyther Bethany , Chakraborty Turja , Gothandaraman Balaji
Published: June 2023

Introduction:
Antiplatelet monotherapy is recommended for prevention of ischaemic events and death following acute coronary syndrome, particularly if contraindications preclude the use of dual antiplatelet therapy. We aimed to scrutinise the effects of clopidogrel vs aspirin when given as secondary prevention monotherapy on mortality independent of baseline cardiometabolic risk factors in a large real-world UK cohort.

Methods:
Between 2012 and 2017, consecutive patients (n = 12967) discharged on clopidogrel or aspirin monotherapy were enrolled at our institution in London, UK (median follow-up 244 days, IQR 659). The primary endpoint was all-cause mortality. Kaplan-Meier curves with a log rank test were used to compare all-cause mortality between patients discharged on clopidogrel monotherapy vs aspirin monotherapy. Cox proportional hazards models were constructed to investigate the relationship between antiplatelet monotherapy and all-cause mortality in multivariable analyses.

Results:
Overall, the primary endpoint of all-cause mortality occurred in 2585 (19.9%) patients: 1642 (18.3%) in the aspirin monotherapy group, compared with 943 (23.5%) on clopidogrel monotherapy (log rank
p
< 0.001), depicted in Figure 1. Clopidogrel monotherapy conferred an 16% increased risk of mortality compared with aspirin in the unadjusted Cox model (HR 1.16, 95% CI 1.07 - 1.25,
p
< 0.001). Following adjustment for age, ischaemic heart disease, stroke hypertension, heart failure, atrial fibrillation, diabetes mellitus, chronic kidney disease and chronic obstructive pulmonary disease, clopidogrel remained significantly associated with increased mortality (HR 1.09, 95% CI 1.00 - 1.18,
p
= 0.045).

Conclusions:
In this large UK cohort, clopidogrel monotherapy associated with increased all-cause mortality compared with aspirin independently of common cardiometabolic comorbidities.
Abstract 11582: Implications of Glycoprotein 2b/3a Receptor Antagonist Use During Percutaneous Coronary Intervention
Authors: Sternberg Michael E , WILLIAMS ERIC , Fonner Clifford E , Dehmer Gregory , Sane DAVID C
Published: June 2023

Introduction:
Glycoprotein 2b/3a receptor antagonists (Gp 2b/3a) were once widely used during PCI. However, due to concerns for excess bleeding, the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization downgraded their use during PCI to Class IIa.
Hypothesis
Higher rates of Gp 2b/3a use will be associated with higher bleeding rates, particularly in hospitals that use more femoral arterial access.

Methods:
We investigated the prevalence of Gp 2b/3a use during PCI among 18 PCI centers in a regional cardiac quality collaborative, between January 2017 and June 2021. Since radial access has lower bleeding rates than femoral access, we determined the impact of Gp 2b/3a use on total bleeding as defined by NCDR, stratified by access site.

Results:
During the study period 36,975 PCI were performed. The rate of Gp 2b/3a use among PCI centers ranged from 2.6% to 59.3% (mean ± SD 20.5% ± 18.5%). PCI centers were analyzed according to whether Gp 2b/3a use was above or below the mean frequency, and according to arterial access site preference (femoral > 45% or radial > 55%). Among low Gp 2b/3a use centers, centers that also favored radial access had lower bleeding rates than high femoral access centers (1.84% vs 2.43%, p=0.009). However, the bleeding risk benefit of radial access was lost in the high Gp 2b/3a usage hospitals, with bleeding rates of 4.54% in the high radial centers versus 3.41% in the high femoral centers (p<0.001) (Table). Among high radial access site centers, the rate of bleeding was 2.5-fold greater in high versus low Gp 2b/3a use centers (p<0.001).

Conclusions:
There is a wide range of Gp 2b/3a use during PCI. Above average Gp 2b/3a use increased total bleeding and neutralized the bleeding risk benefit of radial access. Further study is required to determine why bleeding rates in high radial centers were greater than high femoral centers, when Gp 2b/3a use was above average. Adherence to current guidelines for Gp 2b/3a use may reduce bleeding risk during PCI.
Abstract 11583: Impact of Micra Pacemaker Implantation on Echocardiographic Parameters: A Multi-Center Analysis
Authors: Sriramoju Anil , Elbanna Mostafa , Seri Amith Reddy , Fahmy Mostafa Mahmoud , Baqal Omar Javed , KoKo Nway , Ashraf Hasan , Lee Justin , El Masry Hicham
Published: June 2023

Introduction:
Studies on leadless pacemakers (LP) are very limited and they often fail to reflect real population outcomes.

Hypothesis:
We sought to evaluate the effect of leadless pacemaker implantation on the echocardiographic parameters including ventricular function and valvular competence.

Methods:
A retrospective review including 162 patients (81 Micra Leadless pacemaker implant and 81 dual-chamber transvenous pacemakers) from 3 centers were included. Follow-up clinical, echocardiographic, and pacing characteristics were obtained over a median of 14+/-2 months.

Results:
baseline demographics and clinical characteristics were comparable between the 2 groups including age (78.6+/-9.9, Range 35-95) and gender (49 males, 69.5%). Compared to conventional pacemakers, LP patients had worsening tricuspid regurgitation noted on follow-up echo in 59.3% of patients compared to baseline(P<0.001). This difference was independent of the RV pacing percentage and device location. In addition, LP implantation resulted in a reduction of RV function (P=0.003) and left ventricular ejection fraction (P=0.03). The RV Pacing burden in LP patient patients was not associated with a change in LVEF during the follow-up period (95% CI -0.24, 0.20, p = 0.846).

Conclusions:
LP therapy is associated with worsening tricuspid valve regurgitation and biventricular dysfunction over a mean 1 year of follow-up. Additional prospective randomized studies are warranted to further evaluate these findings.
Abstract 11588: Multicenter Development and Validation of a Machine Learning Model to Predict Myocardial Recovery During LVAD Support: The UCAR Score
Authors: Kyriakopoulos Christos P , Taleb Iosif , Wever-Pinzon Omar , Selzman Craig H , Kfoury Abdallah , Bonios Michael J , Wever-Pinzon James , Yin Michael Y , Tseliou Eleni , Stehlik Josef , Alharethi Rami , Caine William , Fang James C , Koliopoulou Antigone G , Sideris Konstantinos , Nelson Marisca , Elmer Ashley , Dranow Elizabeth , Singh Ramesh , Psotka Mitchell , Birks Emma J , Slaughter Mark S , Koenig Steven , Kyvernitakis Andreas , Hoffman Karlee , Guglin Maya , Kotter John , Campbell Kenneth S , Silvestry Scott C , Vidic Andrija , Raval Nirav , Cowger Jennifer , Kanwar Manreet , Shah Palak , Drakos Stavros G
Published: June 2023

Introduction:
Although significant cardiac reverse remodeling is a prerequisite for a left ventricular (LV) assist device (LVAD) patient to be considered for device weaning, multiple factors including patient goals, physician comfort, and center experience, weigh in on this complex decision. Existing predictive models defining recovery as device removal may under detect patients that could benefit from a targeted bridge to recovery strategy. We sought to derive and validate a predictive tool to identify patients prone to reverse remodel, independent of the complex decision of device explant.

Methods:
Heart failure patients (N=782) requiring LVAD were enrolled at the Utah Transplant Affiliated Hospitals (n=537) and 5 US programs (n=245). Baseline characteristics were recorded. The primary outcome was ‘responder’ incidence, defined as follow-up LV ejection fraction (LVEF) ≥40% and LV end-diastolic diameter (LVEDD) ≤6 cm within one year on LVAD support. Bootstrap imputation and lasso variable selection techniques were used to derive a predictive model which was then validated. A predictive calculator was developed and patients were classified into groups with varying potential for reverse remodeling.

Results:
Patients were predominantly white (84%), males (82%), aged 56±1 years. Overall, 14.8% patients were identified as responders. A subset of 10 pre-operative variables associated with reverse remodeling were included in the multivariate model achieving an optimism-corrected C-statistic of 0.75 (95% CI: 0.73-0.84)
(Figure)
.

Conclusions:
The UCAR calculator is a machine learning-based multicenter and validated risk tool, implementing routine pre-operative clinical data, effectively stratifying patients into groups with varying potential for reverse remodeling. This tool can be useful in selecting patients to implement diagnostic and therapeutic protocols to promote reverse remodeling and myocardial recovery.
Abstract 11591: An Artificial Intelligence Approach in Predicting Subsequent Stroke or Death After Ischemic Stroke: Comparison With Conventional Statistical Methods and External Validation of iScore
Authors: Axford Daniel , Sohel Ferdous , Yousufuddin Mohammed
Published: June 2023

Introduction:
Machine learning models (MLM) hold promise for improved risk stratification and to guide personalized care.

Hypothesis:
MLM would outperform conventional statistical (CS) methods and existing iScore for predicting composite of recurrent stroke or death at 90 days and 3 years after ischemic stroke (IS)

Methods:
We built 3 MLM (random forest [RF], support vector machine [SVM], and extreme gradient boosting decision trees [XGBoost]) and two CS models (logistic regression [LR] and least absolute shrinkage and selection operator [LASSO]) to predict composite outcome at 90 days or 3 years after AIS in a retrospective cohort of 721 adults. The performance of these models was evaluated against the existing iScore to predict outcomes after AIS.

Results:
Composite outcome occurred in11% at 90 days and in 34% at 3 years after AIS. Performance metrics for predicting 90-day and 3-year composite outcome were comparable across all study models except SM LR. Measurements for the area under the receiver operating characteristic curve for each model in validation set was as follow. 1) 90-day prediction: 0.779 for RF, 0.771 for SVM, 0.772 for EXBOOST, 0.613 for LR, 0.811 for LASSO, and 0.720 for iScore; 2) 3-year prediction: 0.743 for RF, 0.777 for SVM, and 0.773 for EXBOOST, 0.724 for LR, 0.790 for LASSO, and 0.710 for iScore.

Conclusions:
ML-based algorithms did not improve prediction of composite outcome at 90 days or 3 years after AIS compared with CS-based LASSO. iScore was successfully validated and compared broadening its generalizability and applicability.
Abstract 11600: Characteristics and Outcomes of Statin Use During Pregnancy: A US Real-World Experience
Authors: Anderson Jeffrey L , Le Viet T , Bair Tami L , Ronnow Brianna , Muhlestein Joseph B , Knowlton Kirk U , May Heidi T
Published: June 2023

Introduction:
Statins traditionally have been contraindicated during pregnancy because of a theoretical risk of teratogenicity. However, emerging evidence to suggest relative safety and potential harm in contraindicating statins in high cardiovascular (CV)-risk pregnancies have led the FDA in 2021 to remove the “Pregnancy Category X” label. This has placed a heavy burden on physician-patient (pt) shared decision making in that statins “should be discontinued in most pregnant patients or consider the ongoing therapeutic needs of the individual pt, particularly those at very high risk for CV events during pregnancy”.

Methods:
The objective of this study was to describe the current real-world characteristics of pts prescribed a statin during pregnancy and pregnancy outcomes in a large US healthcare system. Pregnant pts taking a statin were identified by a search of the electronic medical records (eMR) of Intermountain Healthcare, a system of 24 hospitals and 215 clinics in Utah, Idaho, and Nevada, between 1997 and 2021, and pregnancy outcomes determined electronically. Statin pts were matched 1:10 by age (+/- 1 y) with non-statin pts. Characteristics and outcomes were determined, and adjusted odds ratios (aOR) were calculated.

Results:
A total of 63 statin-user pregnancies were matched to 630 controls. Stain pts had more co-morbidities and higher baseline lipids (Table 1). Adverse pregnancy outcomes were more frequent in statin users (Table 2A). However, statin use did not contribute significantly to multivariable risk prediction of miscarriage or congenital anomalies although possibly it did to eclampsia/preeclampsia (Table 2B).

Conclusions:
In a current real-world US experience, pts prescribed statins during pregnancy had more comorbidities and more adverse outcomes, including fetal anomalies. However, after adjustment, statin use did not contribute to multivariable risk prediction of miscarriage or congenital anomalies.