bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14274: Machine Learning-Enhanced Determinants of Oral Anticoagulation in Atrial Fibrillation: Findings From the PINNACLE Registry
Authors: Rodriguez Fatima , Ward Andrew , Lee Donghyun , Gad Sanchit , Beetel Robert , Harrington Robert A , Virani Salim S , Rumsfeld John , Dash Rajesh
Published: April 2024

Introduction:
Current atrial fibrillation (AF) guidelines recommend use of oral anticoagulation (OAC) to reduce the risk of stroke and systemic embolism. Machine learning (ML) techniques may enhance our understanding of factors associated with gaps in real-world prescription of OAC.

Hypothesis:
There will be large variation in county-level OAC prescription rates among ambulatory patients with AF, and geographic and medication factors will be stronger predictors than clinical comorbidities of lack of OAC prescriptions.

Methods:
Between January 2017 and June 2018, we identified patients with AF from the American College of Cardiology’s (ACC) Practice Innovation and Clinical Excellence (PINNACLE) Registry. We examined associations between patient and site-of-care factors and prescription of OAC across U.S. counties. Several ML methods were used to identify factors associated with lack of OAC prescription.

Results:
Among 864,339 patients with AF, 586,560 (68%) were prescribed OAC. County OAC prescription rates ranged from 26.8% (15/56) to 93% (41/44), with higher OAC use in the Western US. Supervised ML analysis (extreme gradient boosting: area under the receiver operating characteristic curve [AUC]: 0.811, 95% confidence interval [CI]: 0.809-0.813) outperformed the CHA2DS2-VASc score (AUC: 0.571, 95% CI: 0.569-0.574) in predicting likelihood of OAC prescriptions and identified a rank order of patient features associated with OAC prescription. In the ML models, use of aspirin, antihypertensives, lipid modifying agents, antiarrhythmic agents, age, inter-normalized ratio, median household income, and clinic size were the most important predictors of OAC prescription.

Conclusions:
In a national cohort of patients with AF underuse of OAC remains high, with notable geographic variation. ML algorithms can identify factors associated with use of OAC.
Abstract 14276: Bridging The Gap To Optimal Dosing For Guideline-directed Medical Therapy For Patients With Heart Failure And Reduced Ejection Fraction
Authors: Azobou Tonleu Franck H , Campbell Martin L , Miller Stephanie C , Steele Nathan R , Arrington Ryon L , Chen ZhenChao , Fatade Yetunde A , Ogunniyi Modele O
Published: April 2024

Introduction:
The key to improving heart failure (HF) outcomes and its ultimate impact on reducing health care costs include the initiation, optimization, and maintenance of guideline-directed medical therapy (GDMT) in patients with Heart Failure and Reduced Ejection Fraction (HFrEF). The ACC/AHA/HFSA guidelines recommend maximum tolerated doses for these patients unless contraindicated. Despite widespread knowledge, there is underutilization of GDMT at recommended target doses in eligible patients.

Hypothesis:
Majority of eligible patients (>50%) in our safety-net HF Clinic are on optimal doses of GDMT.

Methods:
We conducted a retrospective analysis of GDMT use in patients who were diagnosed with HFrEF between January 1 to March 31, 2019, and completed at least two HF clinic visits in 2019. The primary outcomes were the percent of patients on optimal doses of: (1) beta blockers, (2) renin-angiotensin-aldosterone system (RAAS) inhibitors, and (3) mineralocorticoid antagonists (MRAs). Optimal dose was defined >/= 50% of target dose or maximum tolerated dose.

Results:
Our cohort of 227 patients was predominantly male (70%), African American (94%) with mean age of 59 +/- 11 years. Most patients were on beta blockers (96%) and RASS inhibitors (88%). Only 11% were on Angiotensin Receptor-Neprilysin Inhibitors(ARNI), and 30% on MRAs. Only 52%, 43%, and 20% of patients were prescribed target doses of beta blockers, ACEI/ARBs, and MRAs respectively.

Conclusions:
GDMT dosing in our safety-net HF Clinic was suboptimal. Based on these findings, we are implementing a quality improvement process to facilitate early initiation and up-titration of GDMT with the overall goal of reducing the morbidity and mortality in our patient population.
Abstract 14281: Comparative Visualization of Left Ventricular Segments With and Without Intravenous Contrast During Dobutamine Stress Echocardiography in Class III Obese Patients
Authors: Carlino Carl , Kuppuswamy Saravanan , McCray Lerin , Aggarwal Kul , Alpert Martin A
Published: April 2024

Introduction:
Concern exists regarding adequacy of visualization of stress echocardiograms performed without intravenous contrast (IVC) enhancement in patients with Class III obesity (body mass index ≥ 40 kg/m
2
).

Hypothesis:
Use of (IVC) enhancement will significantly improve visualization and interpretability for ischemia of left ventricular (LV) segments during dobutamine stress echocardiography (DSE) at baseline and at peak stress compared to non-use of IVC enhancement.

Methods:
DSE was performed on 128 candidates for bariatric surgery with class III obesity without chest pain or pre-existent coronary artery disease. DSE without IVC was initially performed on 62 patients with class III obesity, then was subsequently was performed with IVC on 66 patients with class III obesity. LV regional wall motion was assessed at baseline and peak stress using the 16-segment model.

Results:
In the IVC group 1046 of 1056 LV segments studied (99.1%) were well-visualized and interpretable at baseline and 1044 of 1056 LV segments studied (98.9%) were well-visualized and interpretable at peak stress. In the non-IVC group 905 of 992 LV segments studied (91.2%) were well-visualized and interpretable at baseline and 886 of 992 LV segments studied (89.3%) were well-visualized and interpretable at peak stress. A significantly greater number of LV segments were well-visualized and interpretable in the IVC group compared to the non-contrast group, at baseline and at peak stress (p < 0.00001 for both). DSE was positive for ischemia in 1 patient. All patients eventually underwent bariatric surgery without cardiovascular complications. Six months after surgery, all patients were alive; none developed cardiovascular events.

Conclusion:
The use of IVC enhancement during DSE significantly improves visualization and interpretability of lLV segments in patients with class III obesity and relatively low cardiovascular risk.
Abstract 14292: Binge-on-Chronic Alcohol-Induced Gut Dysbiosis Results in Reduced Nitric Oxide Bioavailability and Endothelial Dysfunction
Authors: Li Zhen , Gu Min , Welsh David A , Lefer David J , Sharp Thomas E
Published: April 2024

Introduction:
Binge alcohol drinking adversely impacts cardiovascular (CV) homeostasis, leading to increased risk of CV diseases. It is also well-established that chronic alcohol consumption causes gut dysbiosis. However, the effects of alcohol-induced gut dysbiosis on vascular endothelial function remains unknown.

Methods:
We studied C57BL/6 mice at 10 weeks of age for these studies with n = 8-18 mice per group. Mice underwent a binge-on-chronic alcohol (BoCA) feeding protocol for 20-days and received either vehicle or probiotic treatment. Aortic vascular reactivity (acetylcholine and sodium nitroprusside), plasma nitrite (HPLC) and 8-isoprostane levels (ELISA) were measured. Another group of mice (n = 11-12 per group) received broad-spectrum antibiotic treatments followed by gut microbiotic transplants from either pair-fed or BoCA fed donor mice and plasma nitrite levels were measured to assess vascular function.

Results:
BoCA resulted in impaired endothelium-dependent vascular relaxation which was accompanied by reduced plasma nitrite levels. Probiotic treatment significantly attenuated vascular dysfunction, increased plasma nitrite and reduced 8-isoprostane levels. Further, mice receiving gut microbiotic transfer from alcohol-treated donor mice exhibited reduced circulating nitrite levels when compared to those who receiving the transfer from pair-fed donor mice.

Conclusions:
Our data demonstrate that BoCA consumption induced vascular injury resulting in reduced NO bioavailability, impaired vascular relaxation, and elevated oxidative stress which was attenuated by probiotic treatment. Mice receiving gut microbiotic contents from BoCA fed donor mice displayed reduced NO bioavailability, suggesting that gut dysbiosis is involved in the detrimental cardiovascular effects of BoCA. Further studies are underway to define the mechanisms by which alcohol-induced gut dysbiosis promotes cardiovascular disease.
Abstract 14299: Impact of Gender on Hospital Outcomes in Various Types of ST Elevation Myocardial Infarction (STEMI)
Authors: Gangu Karthik , Bobba Aniesh , Avula Sindhu R , Shinn Alexander , Pulimamidi Shruthi , shah jay , marium fnu , Ali Syed
Published: April 2024

Introduction:
Prior evidence demonstrated that women <75 years with acute coronary syndrome hospitalization have higher short-term mortality compared to men. In this study, we investigated gender-related hospital outcomes based on the location of STEMI.

Methods:
We performed a retrospective study utilizing 2016-2018 National Inpatient Sample database. We included patients aged 18 or older admitted to the hospital with the principal diagnosis of STEMI. This was further subdivided into Inferior STEMI (IMI) and Noninferior STEMI (NIMI). Diagnoses were obtained utilizing ICD 10 CM codes. A multivariate logistic regression model was used to analyze the effect of gender on mortality. Poisson regression was used to analyze length of stay (LOS) . Outcomes were adjusted to age, race, insurance status, elixhauser comorbidities, hospital location and characteristics.

Results:
A total of 438,060 patients were included in the study, of which 231,485 had IMI and 206,575 had NIMI. IMI group had 30.65% women compared to 29.45% in NIMI group. Women were significantly older when compared to men (66.8 vs 61.2 and 67.5 vs 61.2). Women younger than 85 yrs had higher odds of in hospital mortality in both the groups when compared to men (Table 1). Adjusted LOS was 0.94 day (p <0.001) higher in both the groups for female sex.

Conclusions:
Our study shows that female gender was an independent predictor of hospital mortality and higher LOS regardless of the location STEMI.
Abstract 14307: Circulating Whole Blood Gene Expression Profiles Correlate With Intracranial Aneurysm Risk Across Multiple Metrics
Authors: Poppenberg Kerry E , Veeturi Sanyasi Sricharan , Rajabzadeh-Oghaz Hamidreza , Snyder Kenneth V , Siddiqui Adnan H , Tutino Vincent M
Published: April 2024

Introduction:
Intracranial aneurysm (IA) rupture is the primary cause of non-traumatic hemorrhagic stroke. Deciding which unruptured IA should be treated is difficult, as rupture rates are low but complication risks of treatment can be high. Thus, there is a critical need for biomarkers of high-risk IAs.

Hypothesis:
Patients harboring high-risk IAs have distinct gene expression profiles in their circulating blood.

Methods:
We collected whole blood RNA, imaging, and data from patients with IA undergoing angiographic imaging. Next-generation RNA sequencing was used to obtain transcriptomes. Based on images and medical data, high-risk IAs were defined by two metrics: 1) IA size (≥5 mm) from UCAS study and 2) morphologic Rupture Resemblance Score, based on IA Size Ratio (RRS≥0.30). We implemented the widely-used bioinformatics pipeline edgeR to identify significantly differentially expressed genes (q-value<0.05) between high-and low risk groups. Pearson correlation analysis was used to identify which significant genes were correlated with each risk metric (r >0.3). These genes were then used to train a multivariate regression model of IA risk, using 500 Monte-Carlo cross-validation iterations with a 70%:30% training:testing split.

Results:
This study included 91 IAs from 70 patients. Differential whole blood RNA expression was able to delineate high- and low-risk IAs on principal component analysis. 16 differentially expressed genes associated with IA size produced a 4-gene classifier with average AUC=0.82, accuracy=71%, sensitivity=67%, and specificity=76%. Conversely, the 14 differentially expressed genes associated with RRS yielded a 7-gene classifier with better performance, with average AUC=0.84, accuracy=79%, sensitivity=39%, and specificity=93%.

Conclusions:
Whole blood transcriptomes have the potential to reflect IA risk. This work lays the foundation to develop minimally invasive, low cost blood diagnostics for IA risk assessment.
Abstract 14321: A Validation Study of Myocardial Elastography Against Coronary Computed Tomography Angiography in Patients With Coronary Artery Disease
Authors: El Harake Jad , Sayseng Vincent , Grondin Julien , Weber Rachel , Lee Changhee , Einstein Andrew J , Konofagou Elisa
Published: April 2024

Introduction:
Myocardial Elastography (ME) is a new quantitative strain imaging method capable of detecting ischemia due to Coronary Artery Disease (CAD). ME has been compared to nuclear perfusion imaging with good agreement. Coronary Computed Tomography Angiography (CCTA) has been shown to have superior accuracy to nuclear perfusion imaging for CAD staging. In this study, ME is compared to CCTA in CAD patients.

Methods:
High framerate (300 fps) echocardiography in five patients presented with chest pain or shortness of breath symptoms, or having prior history of CAD. Standard short-axis views were acquired at the mid-, basal, and apical left-ventricular (LV) levels using a research ultrasound system (Vantage, Verasonics) with a phased array (P4-2, Philips). ME radial systolic strain (ε) was imaged to evaluate wall thickening using 2D cross-correlation and gradient-based methods on the raw (RF) signals. Average ε within each perfusion territory (LAD, RCA, LCX) was then computed N=45. CCTA was performed using an AcquilionOne Scanner (Canon) with Iohexol (Omnipaque, GE) for contrast. Echocardiograms were coregistered with CCTA using anatomical landmarks.

Results:
Good qualitative agreement between ε (ME) and stenosis level (CCTA) was obtained (Fig. 1A). ME was sensitive in detecting moderate to severe stenosis showing reduced ε. At mild stenosis, despite a trend of ε reduction, some territories maintained mechanical functionality, possibly due to collateral engagement, demonstrating that both structural (CCTA) and functional (ME) properties are complementary in informing on myocardial viability and functionality, especially at mild stenosis. Future work will entail incorporation of FFR
CT
measurements as an additional functional reference measurement to validate ME strain.
Abstract 14325: Socioeconomic Conditions Correlate to Reduction in Mortality Rates Attributable to Smoking in Brazil
Authors: Depaivafagundes Ju Antonio , Carvalho Malta Debora , Brant Luisa , Teixeira Renato , Polanczyk Carisi A , Maria Moraes de Oliveira Glaucia , Ribeiro Antonio L
Published: April 2024

Introduction:
Tobacco consumption through different forms of smoking is associated with an increased risk of cardiovascular events. Socio-demographic Index (SDI) is a composite index that measures per capita income, fertility, and education and mirrors socio-demographic development, allowing comparisons between locations

Objectives:
Analyze the association of socioeconomic conditions and trend cardiovascular mortality rates attributable to smoking in Brazil.

Methods:
Using data from the Global Burden of Disease 2019, we analyzed the age-standardized mortality rate attributable to smoking and the correlation between SDI and the percent variation in mortality rates between 1990 and 2019, for Brazil and each state. SDI values range from 0 to 1 and are higher for better socioeconomic conditions.

Results:
There was a reduction of 58.8% (95% CI, 61.1 - 56.3%) in mortality rates attributable to smoking, from 199.9/100,000 inhabitants (95% UI, 189.1-210.6) in 1990 to 82.4/100,000 inhabitants (95% UI, 77.9-87.5) in 2019. Mortality rates due to tobacco decreased in all Brazilian states. Overall, larger reductions in smoking-attributable mortality rates were observed in states with higher SDI and smaller reductions in states located in Brazil's North and Northeast regions, with lower SDIs. (Pearson correlation 0.637; p <0.001).

Conclusions:
The present study points to the improvement of the mortality attributable to smoking in Brazil in the last three decades. However, regional inequities were shown by the association of more significant mortality reductions in states with a better socioeconomic condition.
Abstract 14342: Artificial Intelligence Dramatically Reduces Annual False Alerts From Insertable Cardiac Monitors
Authors: Ousdigian Kevin , Cheng Ya-Jian , Koehler Jodi L , Radtke Andrew , Rosemas Sarah , rogers john
Published: April 2024

Introduction:
Insertable Cardiac Monitors (ICMs) continuously monitor Atrial Fibrillation (AF) episodes and Pause episodes with high sensitivity, however their false detections create clinician review burden. Cloud-based Artificial Intelligence (AI) algorithms for ICM AF and Pause episodes were recently developed and independently validated but their combined impact in widespread use are unknown.

Hypothesis:
To determine the projected annual impact of AF and Pause AI on alerts in real-world patient population.

Methods:
Real-world data was obtained from de-identified LINQ II ICM patients with ≥3 months of follow-up. For practical purposes, the results were extrapolated to a 200 ICM clinic. The previously published AF and Pause AI performance results were projected onto the real-world data controlling for the patient’s reason for monitoring. The endpoints were daily relative true (sensitivity) and false (specificity) alerts since alerts are triggered based on all episodes in a day.

Results:
The dataset consisted of 2,510 ICMs inserted for Known AF (31%), AF Diagnosis (37%), Syncope (21%), and Other (11%) with a mean follow-up of 4 months. The projected annual volume of alerts was 3,965 AF and 740 Pause alerts for a 200 ICM clinic. AI resulted in minimal (0.6%) overall loss in AF and Pause annualized true alerts, with no loss in true Pause alerts and 0.7% for AF. AI reduced annualized false alerts by 83% including nearly all (97.4%) false Pause and 78% of AF (Figure).

Conclusions:
The AF and Pause AI dramatically reduced the annual data review burden by eliminating most false alerts while maintaining very high sensitivity to true alerts.
Abstract 14352: Echocardiographic Findings With Troponemia and Its Correlation in COVID-19 Patients
Authors: Alhusain Rashid , sattar yasar , Song David , Awadelkarim Abdalaziz , Dayco John , Porter Lekiesha , Uddin Mohammed , Zaher Nathan , Kisha Sarah , Ali Mohammed , Zghouzi Mohamed , Ullah Waqas , Alraies M C
Published: April 2024

Introduction:
Echocardiogram findings with Troponemia and its correlation in COVID 19 patients are not well studied

Methods:
Mean and standard deviation (SD) for continuous variables with normal distribution were reported. Pearson chi-square was performed to see the clinical correlation of dependent variables including regional wall motion abnormalities (RWMA), diastolic dysfunction (DF), paradoxical septal wall motion (PSWM) and pericardial effusion in COVID-19. The primary outcome was to observe the effect on in-hospital mortality and 1 year mortality of echocardiographic findings. Our secondary outcome was to retrospectively see the association of gender with echocardiographic findings.

Results:
In this small, retrospective, single-center study from an epicenter city of COVID-19 at the Detroit Medical Center. We included a total of 122 patients with confirmed COVID-19. The mean age of the cohort was 67.3 years SD= 14. The mean troponin (Tn) at baseline admission was 173 ng/l SD±762 (normal=3-17 ng/l), while the peak Tn were 693 SD±2941. The baseline RSVP was 16 SD±20, while the peaked RSVP was 4 SD±13. Statistically significant associations of RWMA are shown in figure 1. We also found statistically significant differences in DF with presence of MVR (21/35; p<0.05), and RWMA (event/total; 14/35; p<0.05). We also found significance for RV dilation on initial echo for RVH (11/31; p<0.05), and peaked MVR (6/31; p<0.05). We also found statistically significant differences of PSWM for inpatient mortality (3/3; p<0.05), RVH ( 2/ 3; p <0.05), and LTVMV (3/3 ; p <0.05). We found statistical significance of pericardial effusion and LTVMV (3/14; p <0.05). We found statistical significant correlation of gender and RVH on admission echocardiogram: (Male 15/79; Female 2/43; p<0.05), and RWMA (Male 7/79; Female 0/43; p<0.05).

Conclusion:
COVID-19 patients have high mortality in the presence of RWMA and PSWM
Abstract 14353: Feminizing Hormone Therapy and Subclinical Indicators of CVD Risk in Transgender Women With HIV
Authors: Fonseca Nogueira Nicholas , Salazar Ana S , Ruixuan MA , Aguilar Natalie , Gonzalez Alex , Porras Valeria , Parker Meela , Mantero Alejandro , Hurwitz Barry E , Alcaide Maria L , Martinez Claudia
Published: April 2024

Introduction:
Transgender women (TW) are at higher risk of HIV infection compared to cisgender groups and HIV is associated with accelerated cardiovascular disease (CVD) complications. A high proportion of TW use feminizing hormone therapy (FHT), particularly estrogen. However, there is a scarcity of data about the cardiovascular impact of FHT in TW with HIV (TWH). Subclinical indicators of CVD risk, arterial stiffness and endothelial progenitor cells colony forming units (EPC-CFUs), were examined in TWH with and without FHT.

Hypothesis:
Estrogen use in FHT reduces arterial stiffness and induces EPC proliferation.

Methods:
This pilot included adults 20-60 years old, identifying as TW, with a documented HIV-1 diagnosis, stable ART ≥ 6 months, and without history of CVD. Sociodemographic questionnaire was completed prior to an in-person blood collection and applanation tonometry assessment. Groups were stratified by estrogen levels (normal: 1-82pg/ml vs high: >82pg/ml) and relationships with EPC-CFUs and arterial stiffness were examined using t-test and Pearson’s correlation.

Results:
Median age was 42 yrs. (IQR 34-52) with mean glucose 105.70 mg/dl (± 58.07), triglycerides 138.52 mg/dl (± 69.61), LDL 82.38 mg/dl (± 35.01), and CRP 3.45 mg/L (±3.57). TW with high (n=5) and normal (n=12) estrogen levels had similar values in EPC-CFUs counts (p=0.99), central augmentation index (cAIx; p=0.27), carotid to radial pulse wave velocity (CR-PWV; p=0.20), and carotid to femoral PWV (CF-PWV; p=0.87). A positive trend appeared in log-transformed estradiol across cAIx (r=0.32, p=0.21); negative trends in CR-PWV (r=-0.11, p=0.70) and CF-PWV (r=-0.19, p=0.48), and no relationship with EPC-CFUs (r=0.05, p=0.86). There were non-significant negative weak trends between EPC-CFUs and cAIx (r=-0.32, p=0.21), CR-PWV (r=-0.2, p=0.48), and CF-PWV (r =-0.29, p=0.27).

Conclusions:
An inverse correlation between EPC-CFUs and arterial stiffness measurements was observed. Considering these test modalities have a strong correlative potential with CVD risk, FHT does not appear to confer higher CVD risk through these mechanisms. Further research to understand the mechanisms underlying HIV related CVD pathophysiology is critically needed especially in TWH.
Abstract 14358: Bacteremia in Continuous-Flow Left Ventricular Assist Device and Increased Risk for Intracranial Hemorrhage: Insights From National Inpatient Sample Database
Authors: Dar Tawseef A , Celli Diego , Abohashem Shady , Alnajar Ahmed , Abbasi Taimur , Mohiuddin Imran , Hanfy Ahmed , Ibrahim Walid , Aldosoky Wesam , FNU Sibghat Tul LLah , Qureshi Waqas
Published: April 2024

Introduction:
Implantable continuous-flow left ventricular assist devices (LVADs) are used in patients with end-stage heart failure as a bridge to transplant or as a destination therapy. In order to prevent pump malfunction as well as strokes, long term warfarin therapy is prescribed which puts them at risk of bleeding at the same time. Small retrospective studies have suggested the relationship between bloodstream infections and increased risk for intracranial hemorrhages (ICH).

Hypothesis:
Accordingly, we sought to test the hypothesis that “bacteremia is associated with increased ICH risk in LVAD dependent patients” in a large national database.

Methods:
National Inpatient Sample (NIS) database was queried to identify LVAD patients admitted between 2011-2018, using Internal Classification of Diseases 9th and 10th Revision Clinical Modification procedure codes. Outcomes of interest were bacteremia and ICH. A logistic regression model was used for the statistical analysis while adjusting for potential confounders using Elixhauser index score.

Results:
Between 2011-2018, a total of 120,050 (median age 58 yrs, 23.4% female) LVAD dependent patients were admitted to hospitals across the United States. Bacteremia was encountered in 4.3 % of patients. A total of 2.4% of patients developed hemorrhagic stroke during the same hospitalization. Presence of bacteremia (vs. no bacteremia) was associated with 2.3-fold increased risk of ICH (Odds ratio [95% CI] =2.38 [1.79, 3.17], p<0.0001.
Fig A
) after adjustment for age, sex, race, and Elixhauser index score. The yearly incidence trends of bacteriemia and ICH in LVAD dependent patients are shown in
Fig B
.

Conclusions:
In LVAD dependent patients, presence of bacteremia is associated with significantly increased risk of ICH. Since these patients are on warfarin, further studies are needed to evaluate if lowering the goal prothrombin time (PT), while septic, would alleviate this increased risk of ICH in such population.
Abstract 14408: An Angiotensin Receptor Blocker in the Presence of SARS CoV2 Pseudovirus Does Not Change Protein Expression of ACE2 in Human Heart Cell Models
Authors: Das Mitali , Schilling Taylor , Lovano Beth , Castel Laurie , Kim Dokyun , Karnik Sadashiva S , Barnard John , Van Wagoner David R , Jung Jae , Chung Mina K
Published: April 2024

Introduction:
ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) use in COVID-19 raised concern due to reported increases in ACE2, the cell receptor for SARS-CoV2. We tested the
hypothesis
that ARB (Losartan) and ACEI (Captopril) do not impact SARS-CoV2 associated ACE2 expression in cardiomyocytes (CMs).

Methods:
Beating monolayer ventricular CMs were generated from human iPSCs and grown as engineered heart tissue constructs (EHTs), which mimic a more mature phenotype than monolayer CMs. Drug treatments (24hrs) without pseudovirus were applied to EHTs: (A) Vehicle, 1μM Losartan (ARB), 1μM Angiotensin II (AngII), 1μM Losartan+1μM Ang II; (B) Vehicle, 1μM Captopril, 1μM Ang I, or 1μM AngI+1μM Captopril with 2-3 replicates for each combination and RNAseq as outcome. Drug treatment A only was repeated in monolayer CMs with a 5-6 day to rVSV-SARS-Cov2Spike-Luciferase-FLAG tagged pseudovirus (2-4 replicates) with immunoblotting for ACE2, Cathepsin B (CTSB) and Furin proteins.

Results:
Immunoblot densitometry showed abundant ACE2 protein in untreated CMs and EHTs. A focused mRNA analysis of 12 genes associated with SARS-Cov2 entry and processing (EHTs) revealed no significant changes in expression of
ACE2, NRP1, CTSB, CTSL
and
FURIN
due to Losartan or Captopril treatment. There was a nonsignificant trend towards Losartan-induced increase in
AGTR1
with attenuation when AngII was administered, while
ITGA5
trended upwards with Losartan+AngII.
AGTRI
also trended upwards with Captopril and AngI+Captopril. Upon pseudoviral challenge, CMs demonstrated increased ACE2 (55%) and slightly decreased Furin (24%) protein, with unchanged CTSB, although results were not statistically significant. Losartan addition, regardless of AngII, did not alter SARS-CoV2Spike pseudovirus mediated changes of ACE2, Furin or CTSB proteins.

Conclusions:
Losartan or Captopril did not substantially alter gene expression of
ACE2, CTSB, CTSL, FURIN
and
NRP1
in EHTs without pseudovirus. Losartan did not show convincing evidence for pseudoviral mediated changes of proteins important for viral entry and processing in CM cell models.
Abstract 14411: Predictors of Delirium Among Hospitalized Older Adults With Cardiovascular Disease
Authors: Lin Kevin , Bhetuwal Rishtina , Bonilla Moreno Miguel , Irizarry-Caro Jorge , Cerra Zachary , Chauhan Siddharth , Jeffrey Chen , Natasha Cigarroa , Datar Saumil , Gandhi Puja , Hollander Jeffrey , Keiser Monika , McAndrews Kristine , Ren Yawen , Arain Salman A , Dhoble Abhijeet , Kwak Min Ji
Published: April 2024

Introduction:
Delirium is an acute confusional state typically seen in patients admitted to the hospital that can affect mentation, cause agitation, and complicate inpatient stays. The number of older adults with cardiovascular diseases is rapidly increasing. When admitted to the hospital, the elderly are at increased risk of developing delirium.

Hypothesis:
We hypothesized that there will be predictors that are associated with delirium among older adults who were hospitalized in acute care units with cardiovascular disease.

Methods:
A retrospective chart review was conducted on patients initially admitted to the coronary care unit (CCU) and cardiac intermediate care unit (CIMU) of a major metropolitan hospital between January 2019 and December 2019. Patients under the age of 65 were excluded. The remaining patients were analyzed with logistic multivariable regression and odds ratios were calculated for factors associated with developing delirium, adjusting for patient characteristics including Charlson’s Comorbidity Index (CCI) and admission reasons.

Results:
A total of 327 patients with a mean age of 75.6 years were analyzed. Of those patients, 227 (69.4%) had a CCI score of 4 or less. There were no significant associations with development of delirium at any CCI score compared to a score of 0; however, certain admission reasons were significantly associated with delirium, including needing a coronary artery bypass graft and minimally invasive valve repair (Table 1).

Conclusions:
Several different admission diagnoses were significantly associated with increased odds of delirium. Although CCI scores were not significantly associated with the development of delirium during the hospitalization, other risk factors such as age, reason for admission, and procedures performed may have stronger associations. The current study will be a foundation to develop a more patient-centered strategy to prevent and manage delirium in the growing elderly population.
Abstract 14421: Limitations of Using Unipolar Signals to Guide Outflow Tract Premature Ventricular Contraction Ablation
Authors: Sabzwari Syed Rafay Ali , Chang Shu , Mann James , Cerbin Lukasz , Barrett Christopher , Tumolo Alexis , Rosenberg Michael , West John J , Sanchez Jose , Sandhu Amneet , Varosy Paul D , Aleong Ryan G , Zipse Matthew , Sauer William , Tzou Wendy S
Published: April 2024

Introduction:
Unipolar electrogram (EGM) signals are universally used to annotate earliest activation and guide ablation (Abl) of focal arrhythmias. However, their utility in mapping PVCs is limited given 3-dimensionality of wave front propagation, especially when the source is intramural.

Hypothesis:
1) earliest onset of bipolar activation would better guide mapping and Abl in these cases, versus maximum unipolar dV/dt or QS morphology; and 2) differences would be greater for intramural outflow tract (OT) PVCs versus those eliminated with RVOT Abl only.

Methods:
Consecutive patients undergoing successful RVOT or RVOT+LVOT PVC Abl at our center from 2017-2020 were retrospectively analyzed. Bipolar and Unipolar EGMs at successful Abl sites were compared.

Results:
Of 71 patients, 41 had only RVOT and 30 had RVOT + LVOT Abl. All had acute and long-term PVC suppression over mean 22.6 ± 11.6 month follow-up. Mean EGM difference was 7.6 ± 4.7 ms in the RVOT group vs 18.9 ± 10.5 ms in RVOT+LVOT group (p<0.01). QS unipolar EGM was seen in 95% of RVOT patients, 88% of which were at the anterior RVOT/crux, vs 40% of RVOT+LVOT patients (p<0.016). Activation was equally earliest from the posteroseptal RVOT and adjacent LVOT site in 73%, and most of these sites did not have a QS unipolar EGM (Figure).

Conclusions:
Bipolar EGM activation timing guided successful ablation of OT PVCs better than unipolar EGM analysis. A QS unipolar EGM did not reliably predict best ablation sites, especially for intramural PVCs.
Abstract 14426: Comparing Performance of MARKER-HF, a Machine Learning Derived Risk Score, and the Seattle Heart Failure Model in Patients With Heart Failure in a Large, Integrated Health System
Authors: Ahmad Faraz S , Ling Hu Ted , Wehbe Ramsey M , Mutharasan Raja K , Wilcox Jane E , Petito Lucia , Campagnari Claudio , Greenberg Barry H , Yagil Avi , Adler Eric D
Published: April 2024

Introduction:
Patients with heart failure (HF) who advance from Stage C to Stage D experience progressively higher morbidity and mortality rates. Cardiovascular societies recommend using 1-year mortality risk (≥20%) as a trigger for evaluation by a HF specialist. Application of available risk scores to identify patients at increased risk using electronic health records (EHR) is challenging. Consequently, we compared the performance of MARKER-HF, a machine-learning risk model that uses readily available structured data in the EHR, to the Seattle Heart Failure Model (SHFM), which requires elements derived from both structured and unstructured data, for estimating 1-year mortality risk.

Methods:
We analyzed an EHR database for ambulatory patients with HF seen in primary care and cardiology clinics from 1/1/10-12/31/19 at Northwestern Medicine. Eligibility criteria included ages ≥18 years old, at least 1-year of follow-up or death within 1-year, no history of heart transplantation or left ventricular assist device implantation, and availability of the 8 variables used to calculate MARKER-HF (diastolic blood pressure, creatinine, blood urea nitrogen, hemoglobin, white blood cell count, platelets, albumin, and red blood cell distribution width). Unavailable or missing variables required for SHFM were imputed. In all HF patients and in those with reduced ejection fraction (HFrEF), we evaluated model discrimination for 1-year mortality using area under the curve (AUC) and compared AUCs with the DeLong test.

Results:
In a sample of 7130 patients, of whom 1012 died within 1-year, 46.9% were female and median age was 71 (IQR 60-82). The AUC for MARKER-HF and SHFM were 0.69 and 0.64, respectively, for all HF patients and 0.69 and 0.67, respectively, for patients with HFrEF (n=1899). The AUCs for MARKER-HF and SHFM were different for the entire HF population (DeLong p-value=0.01) but not in the HFrEF sub-group.

Conclusion:
In patients with ambulatory HF at an integrated health system, MARKER-HF produced 1-year mortality estimates with equal (HFrEF) or higher (all HF) discrimination than SFHM using fewer and more readily available variables. These findings suggest that MARKER-HF may facilitate the identification of patients with advanced HF using EHR data.
Abstract 14462: RBM20 Regulation In Healthy And Diseased Cardiomyocytes: A New Opportunity For Targeted Therapeutics
Authors: Briganti Francesca , Verma Arjun , Amatya Prashila L , Mercola Mark
Published: April 2024

Introduction:
Mutations in the splicing factor RBM20 cause a severe form of dilated cardiomyopathy (DCM) characterized by early onset, fast disease progression, and high risk of sudden death. We have previously shown that modulation of RBM20 expression is a promising strategy for patient with mutations in RBM20. However, our understanding of its endogenous regulation is limited.

Hypothesis:
DCM-causing mutations in RBM20 interfere with phosphorylation of RBM20 RS domain and with localization of the protein. We hypothesize that modulation of RBM20 phosphorylation could be used to normalize function in the presence of mutations that impair it. We sought to uncover the pathways responsible for such regulation and test their therapeutic potential.

Methods:
We developed a fluorescent in vitro reporter system that allows for the quantification of RBM20 expression and localization in human cardiomyocytes. We generated an induced Pluripotent Stem cells (iPSC) line in which the endogenous RBM20 is tagged at the C-term with an in-frame mCherry (RBM20-mCh). The tag leaves the regulatory regions at the 5’ end of the gene intact. RBM20-mCh hiPSC were differentiated into cardiomyocytes (iPSC-CMs) and matured for 4 weeks. We screened 2-month-old matured iPSC-CM on Matrigel-coated 384-well plates against a library of siRNA targeting all human kinases and phosphatases. We tested the hits in a contractility assay

Results:
We identified 35 kinases and 16 phosphatases that alter RBM20 expression and localization. Functional studies showed that the kinases that upregulated RBM20 expression increased cardiomyocyte contractility while downregulating kinases reduced contractility.

Conclusions:
In conclusion, understanding the kinase regulation of RBM20 provides insight into control of mRNA splicing of proteins such as Titin and may point to new targeted therapeutic strategies for RBM20 mutant DCM.
Abstract 6910: Psychosocial Impairments and Frailty, Cognitive Performance, and Quality of Life Among Older Adults With Atrial Fibrillation
Authors: Mehawej Jordy , Saczynski Jane , Tisminetzky Mayra , Abu Hawa O , Soni Apurv , Wang Weijia , Joanne Mathew , Ding Eric , Gagnier Marc , Alrojolah Loay , Goldberg Robert , McManus David D
Published: April 2024

Introduction:
Psychosocial impairments (i.e., depression or anxiety) and geriatric impairments are prevalent among older patients with atrial fibrillation (AF) and adversely impact their long-term outcomes. However, little is known about the association between symptoms of anxiety or depression and various impairments associated with older age.

Hypothesis:
We hypothesize that depression and anxiety would be associated with frailty, cognitive impairment, and low quality of life among older adults with AF.

Methods:
We analyzed data from the Systemic Assessment of Geriatric Elements-AF study. Participants with AF aged 65 years and older, with a CHA
2
DS
2
-VASc≥2, were recruited from multiple clinics in Georgia and Massachusetts. Patient Health Questionnaire-9 and the Generalized Anxiety Disorder-7 Scale were used to assess depression and anxiety symptoms, respectively. We used a GEE model to examine the association between depression and anxiety at baseline with our principal study outcomes over a 2-year follow-up period.

Results:
972 participants (mean age 74 years; 48 % female; 87 % were non-Hispanic White) were included in this study. Participants who met the criteria for anxiety (29%) or depression (26%) at baseline, as compared to those without, were more likely to be frail (
OR = 2.20, 95% CI: 1.58-3.05; OR [OR] = 4.32, 95% CI: 3.16-5.90, respectively)
and to have a lower AF related quality of life over 2 years (
OR= 3.21, 95% CI: 2.52-4.11; OR= 3.71, 95% CI: 2.94-4.69, respectively).
However, there was no association between depression or anxiety and cognitive impairment.

Conclusions:
Anxiety and depression in older adults with AF were associated with increased risk of frailty and decreased AF related quality of life. As such, addressing mental health needs of older adults may improve their clinical outcomes and quality of life.
Abstract 6925: Association of Increased Risk of Atherosclerotic Cardiovascular (ascvd) Event With Progression of Liver Disease to Cirrhosis
Authors: Hashemi Leila , Wenziger Cachet Magdolna , Do Tran , Budoff Matthew , Streja Elani
Published: April 2024

Introduction:
The current data on the association of advanced liver disease with ASCVD outcomes is conflicting.

Hypothesis:
Hyperinflammatory state due to decrease in bioavailability of nitric oxide, gut hyperpermeability, recurrent infection causing persistent immune system deregulation in advanced liver disease could increase the risk of development and progression of ASCVD.

Method:
Our cohort included 486,887 patients with diagnosis of non-alcoholic fatty liver disease, or viral hepatitis liver disease from VA National Database from January 1, 2000 to December 31, 2019. Cohort then further divided into patients with diagnosis of cirrhosis and without cirrhosis. Cox models were used to estimate the association between severity of liver disease (defined as cirrhosis vs no cirrhosis) with time to the first ASCVD event hospitalization defined as myocardial infarction (MI), ischemic stroke (CVA). Model was adjusted for age, sex, hypertension (HTN), diabetes (DM) and smoking history, systolic and diastolic blood pressure (BP), Low Density lipoprotein (LDL) and high- density lipoprotein (HDL).

Results:
The cohort included 4.6% female, 21% African American, 12% diabetes and 23.5% HTN. The prevalence of HTN and DM were higher in patients with cirrhosis but LDL and systolic BP were much lower in cirrhosis. The time to ASCVD event was 37 vs 73 months in cirrhosis vs no cirrhosis. The Kaplan Meier curve for composite ASCVD is shown in figure 1. In a fully adjusted model, risk of first ASCVD hospitalization was 9% higher in patients with cirrhosis (HR: 1.09, 95%confidence interval, CI (1.07-1.11)). In individual event analysis, risk of time to the first MI and CVA hospitalization were also higher in cirrhosis, with HR 1.01 and 1.20 respectively as shown in figure 1.

Conclusion:
As liver disease advances to cirrhosis the risk of ASCVD events increases and time to the first ASCVD decreases. The inflammatory state of advanced liver disease could be a possible explanation.
Abstract 6941: Cardiac Repair With Echocardiography-Guided Multiple Percutaneous Left Ventricular Intramyocardial Injection of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes After Myocardial Infarction
Authors: Wu Xun , Wang Di , Qin Kele , IROEGBU CHUKWUEMEKA DANIEL D , Xiang Kun , Zhou Yuanjing , Guan Qing , Peng Jun , Yang Jinfu , Fan Chengming
Published: April 2024

Objective:
To investigate the cardiac repair potency with echocardiography-guided multiple percutaneous left ventricular intramyocardial injection of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) after myocardial infarction.

Methods:
The surgically induced myocardial infarcted mice were randomly divided into three groups (8 in each) and were injected with echocardiography-guided percutaneous left ventricular infarcted border zone of one shot hiPSC-CMs (single dose, 10ul of 3x10
5
cells), medium, or repeated delivery of hiPSC-CMs at post-MI week 1 and 2 (multiple dose). The sham group of animals underwent all surgical procedures necessary for MI induction except for the ligation step. 4 weeks after the MI, heart function was measured by the transthoracic echocardiography. The engraftment size was evaluated through the detection of human specific cardiac troponin T. Infarcted size and collagen volume were calculated by sirius-red and fast green staining. Angiogenesis was evaluated by the staining of isolectin B4. Cardiac remodeling was evaluated by the cardiomyocyte minimal fiber diameter in the infarcted border zone. Apoptosis was detected via tunel staining in cardiomyocyte from the infarcted border zone.

Results:
No death was detected with echocardiography-guided percutaneous left ventricular intramyocardial injection. The number of hiPSC-CMs was about 9-fold higher in multiple dose group at week 4 compaired to single dose group. The multiple dose transplantation was associated with significant improvement in left ventricular function, infarct size, angiogenesis, cardiac remodeling, and cardiomyocyte apoptosis.

Conclusions:
Echocardiography-guided multiple percutaneous left ventricular intramyocardial injection is a feasible, satisfactory, repeatable, relatively less invasive and effective delivery method for cell therapy and the delivery of hiPSC-CMs indicate a novel therapy for myocardial infarction.
Abstract 6947: Impact of Severe Anemia on Clinical Outcomes Following Left Ventricular Assist Device Implantation
Authors: Imamura Teruhiko , Besser Stephanie , Siddiqi Umar , Jeevanandam Valluvan
Published: April 2024

Introduction:
Patients with concomitant anemia and congestive heart failure have worse outcomes. The prevalence and clinical risk of significant anemia in patients receiving durable left ventricular assist device (LVAD) remain unknown.

Methods:
We retrospectively analyzed patients who underwent LVAD implantation between 2014 and 2018. The association between hemoglobin level at the time of index discharge and the one-year composite endpoint of heart failure readmissions or hemocompatibility-related adverse events was investigated.

Results:
A total of 167 patients (57 [48, 66] years old, 123 males) were included and stratified into a classification of severe anemia (hemoglobin <9.7 g/dL, N = 99) or non-severe anemia (N = 68). The severe anemia group had a higher one-year incidence of the composite endpoint (56% versus 36%, p = 0.013) with a hazard ratio of 1.71 (95% confidence interval 1.07-2.75) after multivariate adjustment (Figure 1). Patients with severe anemia also experienced suboptimal LVAD unloading.

Conclusions:
Severe anemia was prevalent in LVAD patients and associated with a greater risk of heart failure and hemocompatibility-related adverse events. The optimal threshold for therapeutic intervention in response to anemia post-LVAD needs further investigation.
Abstract 6949: Particulate Matter Increases Inflammation and Impairs Electrical Activity in IPSC-Derived Cardiac Organoids
Authors: Argenziano Mariana A , Najari Beidokhti Maliheh , yang jiajia , Burgos Angulo Mariana , Orona Nadia , Bertalovitz Alexander , McDonald Thomas V
Published: April 2024

Introduction:
Exposure to particulate matter (PM) is associated with increased heart failure (HF) hospitalizations and death. Animal models to study PM-related cardiovascular disease (CVD) are complicated by effects on multiple organs and differing physiology from humans. A recent alternative is the generation of patient-specific induced pluripotent stem cells (IPSCs) to study interactions between the patient’s genome and environmental factors. Given that the heart relies on a network of cells that participate in the development of CVD, we propose a cardiac organoid (hCO) model to study the effects of PM
2.5
.

Hypothesis:
We hypothesize that air pollution exposure causes heart remodeling, which exacerbates HF.

Methods:
IPSCs were differentiated to cardiomyocytes (iCMs), cardiac fibroblasts (iCFs), endothelial cells (iECs) and macrophages (iMø). Cell suspensions containing 50% iCMs and 50% nonmyocyte (4:2:1 ratio of iECs:iCFs:iMø) were mixed and seeded in agarose microwells. Beating hCOs were cultured for 5 days before exposure to 100μg/ml of PM
2.5
for 48h. Immunostaining, qPCR, and Multielectrode Array (MEA) were performed in control (CT) and PM-treated hCOs (PM) (n=10 hCO/ group).

Results:
Treatment with PM caused loss of hCO circularity (CT:0.86±0.02 vs. PM:0.56±0.08, p<0.05, n=5), changes in the beat amplitude, and more frequent premature extrasystoles. Gene expression analysis showed downregulation of
SCN5A
and upregulation of
TNNT2
and
GJA1
. Upregulation of inflammatory markers such as
IL6
,
IL1b
,
CD80
, and
TNFa
was also observed in PM-treated hCOs. Moreover, PM caused upregulation of
MMP1
,
CCL2
,
CASP3
,
SOD1
, and
SOD2
. MEA experiments revealed a longer FPD duration and a decrease in spike slope and beating period along with shortening of the action potential (APD90: CT 577±20ms vs. PM 489±16ms, p<0.05, n=10) and higher beat period irregularity (CT 3.2±0.7% vs. PM 13.1±1.6%, p<0.001, n=10).

Conclusions:
We conclude that PM plays a direct role in the development of CVD, increasing inflammation, apoptosis, oxidative stress, and affecting the electrophysiology of the heart. Further studies in hCOs from HF patients will provide evidence of the effects of PM on the phenotype of the disease.