bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15517: Physician-Patient Engagement to Improve Ambulatory Systolic Blood Pressure
Authors: Kapcin Kyle , Shah Aaisha , Mathos Lauren , Johnston Alexandra , Gadani Mrudula
Published: December 2023

Introduction:
Hypertension is a leading cause of death and disability-adjusted life-years globally. Using implementation science of the 2017 ACC/AHA Guideline for High Blood Pressure (BP) in Adults, we posited a quality improvement (QI) project targeting physician education and multidisciplinary patient engagement in two large urban ambulatory clinics to improve patient blood pressures.

Hypothesis:
We hypothesize that direct physician and patient education and engagement improves achievement of hypertension goals within ambulatory clinics.

Methods:
A QI initiative consisting of a half-day of resident hypertension education, patient access to home BP monitors, and direct patient engagement via physician outreach was conducted. Patients not at BP goal defined as systolic blood pressure (SBP) >130 mmHg were followed over 8 months via multidisciplinary approach to ensure adequate follow-up appointments. Data was collected after 8-months and compared descriptively. BP ranges at month 0: Group A <130 mmHg, Group B 130-139 mmHg, Group C 140-159 mmHg, Group D >=160 mmHg. Emphasis was placed on Groups C and D.

Results:
A total of 6,030 patients had follow-up visits in the 8-month study window. At month 0, 874 patients fell within Group C and 301 within Group D. Of those in Group C, 29.5% achieved SBP goal (<130 mmHg), 27.5% improved BP to 130-139 mmHg, and 34.4% remained within 140-159 mmHg at month 8. In Group D, 20.9% achieved goal SBP <130 mmHg, 17.6% reached 130-139 mmHg, and 34.6% improved to 140-159 mmHg. (Figure 1). Limitations included patients without access to BP cuff during telehealth visits.

Conclusions:
Direct physician engagement and multidisciplinary approach to hypertension management led to decreased SBP readings. Further investigation is warranted to determine how these interventions affect long-term cardiovascular outcomes.
Abstract 15521: Wnt Signaling Inhibition Prevents Postnatal Inflammation and Disease Progression in Congenital Myxomatous Valve Disease
Authors: Xu Na , Alfieri Christina M , Yu Yang , Yutzey Katherine E
Published: December 2023

Introduction:
Myxomatous valve disease (MVD) is the most common cause of mitral regurgitation, leading to cardiac dysfunction and heart failure. MVD in a mouse model of Marfan syndrome (MFS) includes valve leaflet thickening and increased immune cell infiltration. However, the underlying mechanisms by which immune cells are recruited in MFS valves remain undefined.

Hypothesis:
Inhibition of Wnt signaling prevents MVD progression in MFS valves.

Methods:
Mice with the Fibrillin 1 variant

Fbn1
C1039G/+

recapitulate histopathological features of MFS and Wnt signaling activity was detected in TCF/Lef-lacZ reporter mice. Single-cell RNA sequencing was performed from mitral valves of WT and

Fbn1
C1039G/+

mice at 1 month-of-age. Inhibition of Wnt signaling was achieved by conditional induction of Wnt inhibitor Dkk1 in valve interstitial cells of

Fbn1
C1039G/+

; Periostin-Cre; tetO-Dkk1; R26-rtTA mice. Dietary doxycycline was administered for 1 month beginning with MVD initiation (1-month-old) or MVD progression (2-month-old). Histological evaluation and immunofluorescence for immune cells were performed.

Results:
Wnt signaling pathway gene expression is activated early in mitral valve disease progression, prior to immune cell infiltration in

Fbn1
C1039G/+

mice. Single cell transcriptomics revealed similar mitral valve cell heterogeneity between WT and

Fbn1
C1039G/+

mice at 1 month-of-age. Wnt ligands and responsive genes were predominantly increased in valve interstitial cells and valve endothelial cells of

Fbn1
C1039G/+

mice. Inhibition of Wnt signaling by Dkk1 induction at 1 month-of-age prevented the initiation of MVD as indicated by reduced valve leaflet thickness with decreased CD45+ leukocytes and CCR2+ immune cells in

Fbn1
C1039G/+

mice. However, later Wnt inhibition starting at 2 months when inflammation and myxomatous changes are occurring did not prevent the progression of MVD.

Conclusions:
Wnt signaling is involved in the initiation of mitral valve abnormalities and inflammation, but is not responsible for valve disease progression once it has been initiated. Thus, Wnt signaling inhibition prevents initiation of congenital MVD, which provides a promising therapeutic target for the early treatment of congenital MVD.
Abstract 15535: SGK1 is a Key Mediator of Pathological Cardiac Fibrosis
Authors: Murray Victoria , Bagchi Sukriti , Hahn Scott , Glembotski Chris C , Blackwood Erik
Published: December 2023

Background:
Cardiac fibroblasts initially respond to injury adaptively, proliferating and differentiating into myofibroblasts to maintain cardiac structure and function. However, prolonged cardiac stress leads to pathological cardiac fibrosis, ultimately resulting in heart failure (HF). Thus, there is a major interest in developing therapeutic strategies to constrain fibroblast differentiation and sustained activation. We recently identified the cytosolic protein kinase, serum/glucocorticoid regulated kinase 1 (SGK1), as being largely involved with pathological remodeling in the cardiac myocyte. While there have been reports that SGK1 may also play a role in fibrosis, the mechanistic role for SGK1 in cardiac fibroblasts in response to injury remains unknown.

Hypothesis:
SGK1 promotes pathological cardiac fibrosis and exacerbates progression to HF.

Methods:
Transforming growth factor beta, (TGFβ) was used in primary cardiac fibroblasts (CFBs),
in vitro
, and transverse aortic constriction (TAC) was used as a HF model in mice,
in vivo
. CFBs were transfected with siRNA to knockdown SGK1,
in vitro
, and SGK1 floxed mice were injected with a novel AAV9 utilizing a myofibroblast-specific promoter to knockout SGK1 specifically in myofibroblasts (SGK1 mfbKO),
in vivo
.

Results:
SGK1 signaling was elevated in cardiac explants obtained from ischemic human HF patients which led us to further evaluate SGK1 activity in CFBs. SGK1 knockdown in CFBs attenuated TGFβ-mediated differentiation and fibrotic signaling. SGK1 mfbKO mice subjected to TAC showed preserved systolic and diastolic cardiac function, measured by echocardiography. At the biochemical level, pathological remodeling and gene markers of fibrosis were attenuated in SGK1 mfbKO mice as determined by qRT-PCR of cardiac extracts. Finally, treatment of CFBs with a small molecule SGK1 inhibitor attenuated differentiation and fibrotic signaling in response to TGFβ treatment.

Conclusion:
SGK1 knockdown is protective against cardiac fibrosis, attenuating differentiation and fibrotic signaling in CFBs. Further, SGK1 mfbKO protected against pathological cardiac remodeling and functional decline in a mouse model of HF, highlighting the specific pathophysiological contributions of CFBs.
Abstract 15544: Manipulating Oxygen-Releasing Levels and Oxidative Stress to Enhance Viability and Functionality of Human Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Infarction Therapy
Authors: He Xingyu , Liang Jialiang , Huang Wei , Paul Christian , Dutta Suchandrima , Wang Yi-gang
Published: December 2023

Introduction:
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold great promise for myocardial infarction (MI) treatment. Although O
2
-releasing engineering approaches have been developed to enhance stem cell engraftment, a significant gap persists in knowledge regarding the oxidative stress controlling viability and functionality of hPSC-CMs.

Hypothesis:
Preconditioning hPSC-CMs with appropriate oxidative levels will enhance their adaptation and engraftment in the infarcted heart.

Aims:
To develop a novel system that produces a controlled release of O
2
to supply engineered heart tissue for regenerative therapies.

Methods:
An O
2
-releasing hydrogel system (ORHS) was engineered using peroxides (sodium percarbonate) and antioxidants (β-carotene) encapsulated in PLGA-based particles. The effect of ORHS on hPSC-CMs was evaluated through oxidative stress assays, cell viability assessments, and contractility measurements. RNA-seq profiling was performed to analyze the gene expression of hPSC-CMs in response to ORHS. After implantation of ORHS-hPSC-CMs in infarcted hearts of immunodeficient mice, heart functions were monitored with echocardiography. Implanted cell engraftment was assessed using in vivo imaging systems and immunostaining.

Results:
The dissolved O
2
levels were increased in ORHS for 7 days, while the oxidative stress was minimized by β-carotene. The optimal ORHS significantly enhanced the viability and mitigated cell death of hPSC-CMs under hypoxic stress conditions. ORHS also enhanced cell contractility and improved calcium signaling in hPSC-CMs. Genes related to maturation and functionality (such as TNNT2, TNNI3, GJA1, and RYR2) were upregulated by ORHS in hPSC-CMs. Implantation of ORHS-hPSC-CMs for 4 weeks resulted in improved ejection fraction, reduced ventricular remodeling, alleviated infarct size, and scar formation. Furthermore, the engraftment and survival of hPSC-CMs were significantly increased by ORHS compared to control hydrogels, as demonstrated by luciferase reporter assays and troponin immunostaining with TUNEL.

Conclusion:
The development of ORHS offers a promising approach for inducing oxidative preconditioning and achieving enhanced regenerative outcomes of hPSC-CMs.
Abstract 15555: Decreased Severity of Underlying CAD in Patients With Acute MI and COVID: Are the Findings Unique to COVID Infection?
Authors: Turi Zoltan G , Landers David B , Hollenberg Steven , Rockett George , Glotzer Taya , Klinkhammer Brent , Tancredi Jana , Parrillo Joseph E
Published: December 2023

Introduction:
Approximately 20% of COVID hospitalizations during the first wave of the pandemic were associated with myocardial injury. The etiology of injury was mixed but preliminary findings from several databases have suggested diminished underlying CAD in patients with MI and COVID.

Hypothesis:
Patients with MI and COVID have less CAD than patients with MI alone or MI in the setting of other acute infections.

Methods:
We quantified CAD by rigorously calculating SYNTAX scores in 3 groups, all undergoing coronary angiography during acute MI: (1) a randomly selected control group with MI alone from 2010 to 2019, (2) patients with MI and COVID during the first COVID wave (2020), and (3) patients with pneumonia and MI from the pre-pandemic era. To improve specificity, the study was limited to patients with clinical features of STEMI and troponin-I > 1.0; pneumonia with or without COVID occurred predominantly
<
48 hours before STEMI.

Results:
From 2010-2019, 9,758 patients presented with STEMI of whom 33 were randomly assigned to Group 1, 13 cases of COVID and STEMI were identified during the first COVID wave (Group 2), and 12 pre-pandemic patients were identified with acute pneumonia and STEMI (Group 3). Median peak troponin-I value for the 3 groups was 39 (range 1.3-440) with no significant difference between groups. Median SYNTAX scores (Figure) were highest (16.5, IQR 11.5-25.3) in Group 1, and were significantly lower in Group 2 (10, IQR 5.5-19.3, p<0.03) and in Group 3 (10, IQR 4.4-13, p<0.001). No difference was seen between Groups 2 and 3.

Conclusions:
Patients with COVID and STEMI had less underlying CAD than patients who had STEMI prior to the pandemic; this finding was not unique to COVID but was also seen in patients presenting with acute non-COVID pneumonia and MI. Our findings are consistent with COVID and non-COVID pneumonia triggering STEMI in the presence of less severe underlying CAD.
Abstract 15559: Mortality Risk Stratification Using Artificial Intelligence Augmented Prediction of Serum Potassium in Cardiac Intensive Care Unit Patients
Authors: Heinrich Christopher , Harmon David , Dillon John J , Kashani Kianoush , Attia Zachi , Friedman Paul , Jentzer Jacob C
Published: December 2023

Introduction:
Hyperkalemia has been associated with increased mortality in cardiac intensive care unit (CICU) patients. An artificial intelligence (AI) augmented electrocardiogram (ECG) can predict hyperkalemia, and other AI-ECG algorithms have predicted mortality in CICU patients.

Hypothesis:
We hypothesized that the AI-ECG hyperkalemia algorithm could stratify mortality risk beyond the serum potassium measurement.

Methods:
We included 11 234 unique Mayo Clinic CICU patients admitted from 2007 to 2018 who had both a 12 lead ECG and blood potassium (K) level obtained at admission with K>=5 mEq/L defining hyperkalemia. ECGs underwent AI evaluation for probability of hyperkalemia (probability >=0.5 defined as positive). Hospital mortality was analyzed using logistic regression and survival to one year was estimated using Kaplan-Meier and Cox analysis.

Results:
The mean age was 70 years, 37.8% were females, and 92.4% were white. Chronic kidney disease was present in 20%. The mean K value was 4.2 mEq/L, and 13% (n=1460) had hyperkalemia. AI-ECG predicted hyperkalemia in 34% (n=3820). In-hospital mortality was higher in patients with laboratory and/or AI-ECG hyperkalemia, and these patients had lower survival out to 1 year. Mortality was lowest in patients with normal K and negative AI-ECG and highest in patients with both laboratory-confirmed hyperkalemia and AI-ECG predicted hyperkalemia. Patients with isolated laboratory hyperkalemia (false-negative AI-ECG) had higher mortality than those with isolated AI-ECG hyperkalemia (false-positive AI-ECG).

Conclusions:
AI-ECG probability of hyperkalemia, even with a normal laboratory K, was associated with higher short-term and long-term mortality in CICU patients. The laboratory K value and AI-ECG probability of hyperkalemia are complementary risk factors. The AI algorithm can detect prognostically important ECG abnormalities which may reflect the effects of K levels on the myocardium.
Abstract 15564: Iron Deficiency Treatment Among Hospitalized Heart Failure Patients
Authors: Nordberg Megan , Foust Rick , May Jori , Morton Kara , Joly Joanna M , Tankersley Anna , Clarkson Stephen
Published: December 2023

Introduction:
Iron deficiency (ID) is prevalent among patients with heart failure (HF). ID is associated with impaired quality of life and increased heart failure hospitalizations and is often missed or untreated. We examined clinical data spanning 10 years, comparing males and females overall and stratifying by admission date to further elucidate undertreatment of ID.

Methods:
We assessed patients who were admitted to UAB with a primary diagnosis of HF and were tested for ID from January 1, 2012, to July 7, 2021. We included patients during their index admission, who were iron deficient based on ferritin levels and/or transferrin saturation, dividing patients into two time periods based on changes in iron treatment patterns. We then compared males and females during each of the time periods. We used logistic regression to explore the association between sex and iron treatment modality, adjusting for relevant covariates.

Results:
In total, 1855 patients were iron deficient and treated with iron. Females were more likely to have a ferritin value less than 50
μ
g/L (48% M vs 55% F, p=0.0006). Despite lower ferritin values, females had lower odds of receiving IV iron than males, both unadjusted (0.66, CI 0.55-0.79, p<0.0001) and adjusted for covariates (0.72, CI 0.59-0.87, p<0.0001).

Conclusions:
When comparing the two time periods, there is an increase in patients with more severe ID, indicated by ferritin values less than 50
μ
g/L, and an increase in utilization of IV iron. Despite being disproportionately affected by severe, iron-deficiency anemia, women received IV iron therapy significantly less often than men across the 10 years studied. Even with improvement in the use of IV iron, treatment disparities remain, and more effort is needed to identify and reduce these disparities.
Abstract 15567: Associations Between Social Determinants of Health and Cardiovascular Health of Adult Cancer Survivors in the United States
Authors: Satti Danish Iltaf , Chan Jeffrey Shi Kai , Dee Edward Christopher , Lee Yan Hiu Athena , Wai Abraham Ka Chung , Dani Sourbha S. , Virani Salim S. , Shapiro Michael D. , Sharma Garima , Liu Tong , Tse Gary
Published: December 2023

Background:
Relationships between social determinants of health (SDOH) and cardiovascular health (CVH) of cancer survivors are underexplored.

Aims:
To investigate associations between SDOH and CVH of adult cancer survivors in the United States (US).

Methods:
Data from the US National Health Interview Survey (2013-2017) were used. Participants reporting a history of cancer were included, excluding those with only non-melanoma skin cancer, or with missing data for any domain of SDOH or CVH. SDOH was quantified with a six-domain, 38-item score consistent with the Centers for Disease Control and Prevention recommendations (higher score indicated worse deprivation). CVH was quantified based on the American Heart Association’s
Life’s Essential 8.
As detailed dietary data were unavailable, a seven-item CVH score was used (higher score indicated worse CVH). Survey-specific multivariable Poisson regression was used to test associations between SDOH quartiles and CVH.

Results:
Altogether, 8254 participants were analyzed, representing a weighted population of 10,887,989 persons. Worse SDOH was associated with worse CVH (highest vs. lowest quartile: risk ratio 1.30 [95% confidence interval 1.25, 1.35], p<0.001), with a grossly linear relationship between SDOH and CVH scores (
Figure 1A)
. Subgroup analysis found significantly stronger associations in younger participants (p
interaction
=0.026) and females (p
interaction
=0.001), but without statistically significant interactions with race (p
interaction
=0.051) (
Figure 1B)
. Higher scores in all domains of SDOH were independently associated with worse CVH (all p<0.001). Higher SDOH scores were also independently associated with the presence of all items of the CVH score (all p<0.05 for highest SDOH quartile).

Conclusions:
An unfavorable SDOH profile was independently associated with worse CVH among adult cancer survivors, with notably stronger associations in females and younger individuals.
Abstract 15572: Assessing the Impact of Renal Denervation on Heart Failure: Results From the Pooled Analysis of Randomized Controlled Trials
Authors: Elfaituri Muhammed K , Alzubi Alhasan Saleh , Khaled Ala , BenGhatnsh Ahmed , Elfaituri Ahmed , Faraj Hazem Abdelkarem A , Msherghi Ahmed
Published: December 2023

Introduction:
Renal denervation (RDN), first developed for hypertension management, is currently being investigated as a potential treatment for heart failure (HF). However, its efficacy and safety for these patients necessitate further investigation.

Hypothesis:
This study aimed to assess the impact of renal denervation on various clinical and hemodynamic parameters in heart failure patients.

Methods:
A comprehensive search of PubMed, Cochrane Library, and Embase databases was performed for randomized controlled trials (RCTs) comparing RDN with standard care or placebo in HF patients, published until January 2023. Data were pooled using a random-effects model, and results were reported as Mean Differences (MD) with a 95% confidence interval (CI). All statistical analyses were performed using R software (version 4.0.3) with the metafor and meta packages.

Results:
The search identified five RCTs involving 208 patients (103 in the RDN group and 105 in the control group). RDN was associated with significant improvements in left ventricular ejection fraction (MD: 4.48%, 95% CI: 0.57-8.4%, P=0.02, I2=77%), 6-minute walk distance (MD: 78.71 meters, 95% CI: 47.01-110.41 meters, P<0.01, I2=0%), left ventricular end-systolic diameter (MD: -3.18 mm, 95% CI: -5.64 to -0.72 mm, P=0.01, I2=24%), and left ventricular end-diastolic diameter (MD: -4.16 mm, 95% CI: -6.04 to -2.29 mm, P<0.01, I2=0%). However, no significant changes were noted in left atrial diameter (MD: -4.49 mm, 95% CI: -9.19 to 0.20 mm, P=0.06, I2=79%), New York Heart Association class (MD: -0.71, 95% CI: -1.65 to 0.24, P=0.14, I2=96%), heart rate (MD: -3.71 beats per minute, 95% CI: -8.45 to 1.03 beats per minute, P=0.12, I2=62%), systolic blood pressure (MD: -0.35 mmHg, 95% CI: -11.51 to 10.79 mmHg, P=0.95, I2=88%), and diastolic blood pressure (MD: -1.46 mmHg, 95% CI: -7.12 to 4.19 mmHg, P=0.61, I2=79%).

Conclusions:
RDN has shown the potential to improve left ventricular function and exercise capacity in managing heart failure. The results, marked by high heterogeneity in some outcomes and constrained by the limited number of trials and patients, necessitate larger multicenter trials for validation and further exploration of renal denervation's role in heart failure management.
Abstract 15586: Efficacy and Safety of Cerebral Embolic Protection Devices in Transcatheter Aortic-Valve Replacement: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Elfaituri Muhammed K , Khaled Taha , BenGhatnsh Ahmed , Faraj Hazem Abdelkarem A , Msherghi Ahmed
Published: December 2023

Introduction:
Transcatheter aortic-valve replacement (TAVR) has emerged as a viable alternative to surgical aortic-valve replacement for high-risk patients. However, the procedure carries a significant risk of cerebral embolism. Cerebral embolic protection (CEP) devices have been proposed to mitigate this risk, yet current evidence of their efficacy remains inconsistent.

Hypothesis:
This study aims to comprehensively evaluate the effectiveness and safety of CEP devices during TAVR.

Methods:
A systematic literature search was conducted in MEDLINE, EMBASE, and Scopus up to April 2023. Randomized controlled trials (RCTs) comparing TAVR with and without CEP were included. The study assessed total lesion volume using mean difference (MD), while stroke, mortality, bleeding and vascular complications, and new magnetic resonance imaging (MRI) detected lesions were evaluated with relative risk (RR); both were analyzed via random-effects models using R software (version 4.0.3) with the metafor and meta packages.

Results:
The meta-analysis incorporated five RCTs involving 3,845 patients (2,070 received CEP devices, and 1,775 served as a control). The pooled analysis showed a non-significant mean difference in total lesion volume of -14.43 (95% CI: -104.97 to 76.09, P=0.75, I2=90%), indicating that CEP devices did not significantly alter the total lesion volume. In terms of other outcomes, the use of CEP devices did not significantly reduce the risk of stroke (RR 0.86, 95% CI: 0.62 to 1.22, P=0.41, I2=0%), disabling stroke (RR 0.50, 95% CI: 0.24 to 1.04, P=0.06, I2=0%), overall mortality (RR 1.35, 95% CI: 0.59 to 3.12, P=0.48, I2=0%), life-threatening or major bleeding (RR 1.09, 95% CI: 0.37 to 3.22, P=0.88, I2=19%), vascular complications (RR 1.83, 95% CI: 0.80 to 4.19, P=0.15, I2=29%), or the occurrence of new lesions seen on MRI (RR 0.99, 95% CI: 0.93 to 1.06, P=0.78, I2=17%).

Conclusions:
The results indicate that CEP devices during TAVR did not significantly alter important clinical outcomes, challenging the presumed benefits of these devices. Owing to the limited number of studies and short follow-up periods, further large-scale RCTs with more sophisticated designs and longer follow-ups are needed to validate these results and inform future guidelines.
Abstract 15595: In-Hospital Outcomes in Patients With Psoriasis Who Undergo Transcatheter Aortic Valve Replacement
Authors: Severdija Ryan M , Dangl Michael , Akbar Fatemah , Colombo Rosario
Published: December 2023

Background
Psoriasis is a chronic inflammatory condition associated with an increased prevalence of aortic stenosis (AS). There is paucity of evidence regarding transcatheter aortic valve replacement (TAVR) outcomes in patients with psoriasis.

Methods:
The National Inpatient Sample Database was queried from 2016-2019 for relevant ICD-10 diagnostic and procedural codes. Beeline characteristics and in-hospital TAVR outcomes were compared in patients with and without psoriasis. Multivariate logistic regression was performed for select outcomes to adjust for differences in baseline characteristics. A p value <0.05 was considered significant.

Results:
227,920 hospitalizations for TAVR were identified of which 1,510 (0.6%) were patients with psoriasis. See Table 1 for baseline characteristics. Patients with psoriasis were more likely to be white, and have concurrent diagnoses of hypertension, diabetes mellitus, hyperlipidemia, coronary artery disease, obesity, tobacco use disorder, COPD, and thrombocytopenia. Adjusting for baseline characteristics, those with psoriasis were found to have higher rates of in-hospital all-cause mortality OR 2.20 [1.57-3.09], and major bleeding events OR 1.38 [1.13-1.69].

Conclusions:
Psoriasis is associated with worse outcomes and higher in-hospital mortality in TAVR. Further studies are warranted to optimize outcomes in this higher risk cohort.

Table 1.
Patient Characteristics. Values are reported as mean ± standard deviation or median [interquartile range] for continuous variables. Categorical variables are represented as n (%). Between-group comparisons were performed for continuous data using T-test for parametric and Mann-Whitney U test for nonparametric variables, respectively. Categorical variables were compared using Chi squared test. A p-value <0.05 was considered significant (bold).
Abstract 15632: Warfarin Dose Management Using Offline Deep Reinforcement Learning
Authors: Ji Hannah , Gill Matthew F , Draper Evan W , Liedl David A , Hodge David O , Houghton Damon E , Casanegra Ana I
Published: December 2023

Introduction:
Warfarin is a commonly prescribed anticoagulant for treating atrial fibrillation, mechanical valves, and venous thromboembolism. Warfarin dose management remains challenging due to dosing variability between patients and warfarin’s narrow therapeutic window. Time in therapeutic range (TTR) is critical to warfarin’s safety and efficacy, but TTR typically remains low (40-50%) in community practices. Specialized anticoagulation clinics and protocolized approaches can increase TTR but have great administrative burdens and health care costs.

Aim:
To develop standardized optimal warfarin dose decision support using a machine learning model based on time series anticoagulation data and patient demographic characteristics

Methods:
The dataset included 12,497 warfarin patients monitored in the anticoagulation tracker of electronic medical records across the Mayo Clinic Enterprise. The dataset contained time series anticoagulation data (warfarin dose, INR, INR target range) and patient demographic characteristics. We implemented an offline deep reinforcement learning model (DRL) to predict the cumulative warfarin dose for the days until the next INR test based on a patient’s historical anticoagulation data. Prior approaches utilized traditional supervised learning methods such as regression or Long Short Term Memory (LSTM) neural networks to approximate a function mimicking the behavior of the training data. On the other hand, DRL learned an optimal dosing policy through continuous interaction and feedback from the training data. The key advantage of DRL is the model can learn to behave differently (and potentially better) for suboptimal clinical states in the data such as overdosing or underdosing. To evaluate the DRL model we compared the predicted warfarin doses with the physician-prescribed doses

Results:
DRL model’s prediction accuracy was 96.96%, outperforming our implementation of a baseline LSTM model with a prediction accuracy of 70.58%. Further evaluation of the DRL model indicated that the model correctly adjusted the warfarin dose at time steps when patients had out-of-range INRs.

Conclusions:
Offline deep reinforcement learning demonstrates potential in supporting warfarin dose management to maximize TTR.
Abstract 15636: NFATC1 Modulates Atrial Excitability and Arrhythmogenesis
Authors: Torres Natalia S , Kauffman Christopher , YANG YUEQIN , Acuna Alexandra , Shah Karishma , Cho Scott , Tristani-Firouzi Martin
Published: December 2023

Transcription factors have emerged as important loci for atrial fibrillation (AF) susceptibility. We identified a novel mutation (M527L) in a conserved site of the transcription factor NFATC1 in a multigenerational family with an autosomal dominant young onset AF (<40 years old) phenotype. M527L reduces NFATC1 nuclear translocation (nuclear/total cellular ratio: M527L 0.50±0.02; WT 0.64±0.04, p<1E-5; n=10/each), DNA binding (M527L 0.69±0.02; WT 0.83±0.01, p=0.02; n=3/ each), and transcriptional activity (M527L 0.0003±0.00005; WT 0.0009±0.0002, p=0.01; n=5/each) in expression systems, underscoring the functional consequences of this mutation. To study the broader role of NFATC1 in atrial excitability we employed a CRISPR/Cas9 strategy to create an nfatc1 null (KO) zebrafish. KO fish exhibited reduced survival, with ~80% of juvenile fish succumbing to sudden death (log rank test p=0.0001), with no observable change in body or heart gross morphology. Explanted juvenile atria displayed spontaneous tachyarrhythmias or irregular rhythm (29 /40 KO atria vs 11/28 WT atria; Chi-Squared, p=0.0013) accompanied by irregular Ca
2+
handling (10/11 KO atria vs 5/16 WT atria). Furthermore, we found an abbreviated action potential duration in KO atrium (80±1 ms in KO (n=607) vs 91±1 ms in WT (n=441), p=0.0001), but not ventricle (186±3 ms in KO (n=109) vs 191±2 ms in WT (n=160), p=0.8). Taken together, our data suggests that NFATC1 is a modulator of atrial excitability and plays a role in AF susceptibility. Experiments are ongoing to further define the mechanisms underlying arrhythmia susceptibility and to identify the gene networks downstream of NFATC1 in the atria.
Abstract 15668: The Incidence and Predictors of Delayed and Late Response to Cardiac Re-Synchronization Therapy
Authors: Pollevick Matias E , Bruce Samuel L , Lavelle Michael , Guber Kenneth , Majure David , Biviano Angelo B , Wan Elaine Y , Garan Hasan , Kosmidou Ioanna , Yarmohammadi Hirad
Published: December 2023

Background:
The incidence and predictors of delayed response to cardiac resynchronization therapy (CRT) have not been well established. Our study aimed to investigate the incidence and predictors of delayed and late response in CRT patients.

Research Question:
What patient-specific characteristics are associated with delayed or late response to CRT?
Goal/Aim:
To investigate the incidence and predictors of delayed and late response in CRT patients.

Methods:
We conducted a retrospective analysis of 201 patients who underwent CRT implantation with placement of a CS lead. Patients meeting the enrollment criteria were categorized into three groups: Group A comprised conventional responders with a response observed at the 6-month follow-up, Group B consisted of delayed responders with a response seen between 6 months and 1-year follow-up, and Group C included late responders with a response observed after 1 year of follow-up. CRT response was defined as an absolute increase of ≥ 5% in left ventricular ejection fraction. All echocardiograms were performed at the same institution. Only patients who were defined as responders to CRT were included in the analysis.

Results:
Among the patients analyzed, 59 patients (67.2 ± 12.3 years, 39 male) achieved a conventional response to CRT, while 40 patients (69.6 ± 9.5 years, 30 male) experienced a delayed response, and 29 patients exhibited a late response (66.1 ± 11.4 years, 18 male). The mean follow-up time was 267 days (± 341 days). The incidence of delayed and late responses was 19.9% and 14.43%, respectively. In univariable logistic regression analysis, a history of coronary artery disease (p = 0.047) was associated with delayed and late CRT responses.

Conclusions:
Our findings demonstrate a significant proportion of patients experiencing delayed and late responses to CRT. This study suggests the need for reconsidering the waiting time for CRT response, particularly in patients with a history of coronary artery disease.
Keywords:
cardiac resynchronization therapy, delayed response, heart failure
Abstract 15674: Association of Diastolic Blood Pressure and Coronary Artery Calcium Score in South Asian Adults: The MASALA Study
Authors: Moorthy Meena , Kandula Namratha , Lancki Nicola , Siddique Juned , Thangada Neela , Shimbo Daichi , Pedamallu Havisha , Kanaya Alka M , Shah Nilay S
Published: December 2023

Background:
Diastolic blood pressure (DBP) is associated with coronary artery calcium (CAC). Prior evaluation of this relationship has not included South Asian populations, who experience a disproportionate burden of cardiovascular disease.

Hypothesis:
High DBP is associated with CAC independent of systolic BP in South Asian adults.

Methods:
In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we evaluated the cross-sectional association of sex-specific DBP quartiles and CAC≥100 with robust Poisson regression adjusted for age, sex, systolic BP, body mass index, smoking, low- and high-density lipoprotein cholesterol, triglycerides, diabetes, lipid-lowering and hypertension (HTN) medication use. Restricted cubic splines examined the continuous association of DBP with CAC probability. Secondary analysis examined the association between baseline DBP quartile and incident CAC over median 4.7 years of follow-up.

Results:
Among 1164 participants (48% female, mean age 57 years), mean (standard deviation) DBP was 74 (10) mmHg, 67% were not on HTN medications, 22% had CAC ≥100. The probability of CAC≥100 across levels of DBP is modeled in the Figure. DBP in quartiles 3 and 4 was significantly associated with CAC≥100 with adjusted prevalence ratio (PR, versus quartile 1) of 1.57 [95% CI, 1.20-2.06] and 1.50 [1.08-2.07], respectively. Among those not on HTN medication, the PR for CAC≥100 for DBP quartiles 3 and 4 was 1.98 [1.29-3.04] and 1.80 [1.00-3.24], respectively. Baseline DBP quartile was not associated with incident CAC, but those in quartile 4 had greater risk of CAC≥100 over follow-up compared to quartile 1 (RR 2.47, 1.17-5.23).

Conclusion:
Among South Asian adults in MASALA, having DBP in quartiles 3 or 4 was associated with a higher probability of CAC≥100. DBP may be an important clinical risk factor when assessing cardiovascular risk among South Asian adults.
Abstract 15689: Ablation for Atrial Fibrillation in Patients With Rare Pathogenic Variants in Cardiomyopathy and Arrhythmia Genes
Authors: El-Harasis Majd A , Yoneda Zachary , Anderson Katherine , Ye Fei , Quintana Joseph , Martinez-Parachini Jose R , Jackson Gregory , Varghese Bibin , Crawford Diane , Sun Lili , Williams Hollie L , O'Neill Matthew , Davogustto Giovanni E , Laws James L , Murphy Brittany , Tomasek Kelsey , Su Yan Ru , Solem Emily , Metz Emma , Smith Carly , Stubbs Douglas , Grauherr Dakota , Wells Quinn , Michaud Gregory , saavedra pablo , Estrada Juan C , Richardson Travis , Shen Sharon , Kanagasundram Arvindh , Montgomery Jay A , Tandri Harikrishna , Ellis Christopher R , Crossley George H , Kannankeril Prince , Stevenson Lynne W , Stevenson William G , Lubitz Steven A , Ellinor Patrick T , Roden Dan M , Shoemaker Ben B
Published: December 2023

Introduction:
Patients with rare, pathogenic cardiomyopathy (CM) and arrhythmia variants can present with atrial fibrillation (AF), with or without overt ventricular involvement. The efficacy of AF ablation in these patients is unknown.

Research Questions/Hypothesis:
To test the hypotheses that: 1) patients with a pathogenic variant in any CM or arrhythmia gene have a higher risk of recurrence following AF ablation, and 2) patients with a pathogenic variant associated with a specific gene group (arrhythmogenic left ventricular CM [ALVC], arrhythmogenic right ventricular CM [ARVC], dilated CM [DCM], hypertrophic CM [HCM], or a channelopathy) have a higher risk of recurrence.

Methods:
We performed a prospective observational cohort study in participants referred for AF catheter ablation who underwent whole exome sequencing. Our primary outcome was AF recurrence, defined as >30 seconds of AF, atrial flutter, or atrial tachycardia that occurred at least 90 days after AF ablation.

Results:
Among 1,366 participants, 109 (8.0%) had a pathogenic or likely-pathogenic (P/LP) variant in a CM or arrhythmia gene. In multivariable analysis, presence of a P/LP variant in any gene was not significantly associated with recurrence (HR 1.15 (0.84-1.60), p=0.53,
Figure 1A
). When analyzed according to gene group, P/LP variants in the ALVC gene group, predominantly
LMNA
, were associated with increased recurrence (N=10; HR 3.75 (1.84-7.63), p<0.001), compared to those in the ARVC gene group (N=6; HR 1.97 (0.62-6.27), p=0.25), DCM gene group (N=50; HR 0.98 (0.59-1.63), p=0.94), HCM gene group (N=33; HR 1.28 (0.76-2.17), p=0.35), and channelopathy gene group (N=17; HR 0.58 (0.21-1.56), p=0.28), as shown in
Figure 1B, 1C
.

Conclusions:
Our results support the continued use of AF ablation for most patients with rare pathogenic CM or arrhythmia variants, including
TTN
. However, patients with ALVC variants, such as in
LMNA
, may be at a significantly higher risk for arrhythmia recurrence.
Abstract 15690: The Impact of Frailty on 6-12 Months Adverse Outcomes Following Left Atrial Appendage Closure
Authors: Liu Simon , Zayyad Zaid , Sreepathy Pranati , Bhayani Siddharth , Ambalavanan Manoj , Dickens Helena , Tiu David , Tiu Daniel , Hammad Bayan , Khan Azmer , Kansal Mayank M , Ibrahim Khalil , Shroff Adhir R
Published: December 2023

Introduction:
Frailty is a syndrome of functional decline characterized by an increased risk for adverse health outcomes. The association between frailty and left atrial appendage closure (LAAC) outcomes has not been extensively studied yet. This study aims to analyze the impact of frailty on adverse health outcomes following LAAC.

Method:
Retrospective review of electronic medical records from June 2016 to December 2021 at the University of Illinois, Chicago identified LAAC patients, who were included if they were followed-up within 6 and 12 months of the procedure. Patients were stratified into frail and non-frail groups based on the Johns Hopkins Claims-based Frailty Indicator, an externally validated index. Outcomes included 6- and 12-months major bleeding event defined by VARC, death, and hospitalization indexes. Two-sample t-tests and chi-squared tests were used to compare continuous and categorical variables, respectively.

Results:
Our cohort included 101 patients (age 72 ± 9 years, 75% male, 24% white): frail (N=34) and non-frail (N=67) groups. There were no statistically significant differences in baseline demographics, comorbidities, and medication except for older age in frail patients (79.6 vs 68.3 years, p=0.000). Although frail patients had higher mortality rate at 6 months (8.82% vs 0%, p=0.014), no differences were seen for nonhome discharges (6.67% vs 1.54%, p=0.184), 6-months major bleeding events (2.94% vs 2.99%, p=0.990), 6-month emergency department visits (38.2% vs 28.4%, p=0.313), and 6-month hospital admission (20.6% vs 25.4%, p=0.593). There were also no differences seen for mortality rate at 12 months (11.8% vs 5.97%, p=0.308), length of hospital stays (1.35 vs 1.37 days, p=0.966), 12-months major bleeding event (2.94% vs 4.48%, p=0.708), and 12-months hospital admission (29.4% vs 31.3%, p=0.842).

Conclusion:
Our results suggest that frail patients are at a higher risk for death within 6 months following LAAC despite no observable differences in comorbidities, medications, other adverse events, and hospitalization indexes, including nonhome discharges. Additional analysis is needed to determine factors that may preclude frail patients from hospital admissions or precipitate earlier death.
Abstract 15699: A Wolf in Sheep’s Clothing- CD13 Activation Mediates Pericyte to Smooth Muscle Cell Switch in Pulmonary Hypertension
Authors: James Joel , Dekan Aleksandr , Valuparampil Varghes Mathews , Niihori Maki , Lawal Odunayo , BHARTI DINESH , Rafikova Olga , Rafikov Ruslan
Published: December 2023

Introduction:
Pulmonary hypertension (PH) is a fatal disease lacking effective treatment strategies to prevent its progression or reverse its effects. PH is characterized by vascular remodeling caused by excessive cell proliferation in the vascular layers. Often, pulmonary artery smooth muscle cells (PASMC) are implicated in the proliferative remodeling of the artery. We recently discovered that in PH, PASMC’s highly expressed a pericyte marker, CD13. Previous studies have shown CD13 pathology in cancer. We hypothesized that increased CD13 expression and activation could mediate a phenotype switch from pericytes to proliferative “PASMC like” cells.

Methods:
In this study, we used rats with a mutation in NFU1G206C, which spontaneously develop PH with severe vascular remodeling. We also used isolated PASMC from PH patients. We used whole lung single cell transcriptomics to uncover the phenotypes of various lung cells.

Results:
Pericytes of NFU1 rats showed a significant increase in CD13. Additionally, we found a 40-fold increase of CD13 in NFU1 PASMC. scRNA transcriptomics revealed a high similarity of PASMCs with pericytes in the NFU1 rats. Conversely, we also observed that pericytes of NFU1 rats highly expressed canonical SMC markers like SMMHC and CNN3. CellChat analysis revealed pericyte dysfunction with decreased interaction strength and interaction numbers with endothelial cells (ECs). Correspondingly, confocal imaging revealed a severe decrease in pericyte-EC association and a greater coverage area by pericytes in the NFU1 lungs. Treatment of NFU1 rats with a peptide blocking CD13 signaling (B-CD13) significantly attenuated right ventricular systolic pressure, Fulton index and vascular remodeling. Excitingly, treating isolated PASMC from PH patients and NFU1 rats with B-CD13 reverted the high proliferation rates back to control, indicating the pathological role of CD13 in cell proliferation. scRNA analysis of rat lungs treated with B-CD13 showed improvement in pericyte- EC interaction numbers and interaction strength, indicating that CD13 could play an important role in the migratory and proliferative switch of pericytes.

Conclusion:
Targeting CD13 signaling is a novel strategy to potentially reverse vascular remodeling in PH.
Abstract 15705: Perceived Control Over Own Health Buffers the Negative Impact of Patient Symptom Burden on Quality of Life in Patient-Caregiver Dyads: A Dyadic Mediation Analysis
Authors: Chung Misook L , Lin Chin-Yen , Miller Jennifer L , Moser Debra K
Published: December 2023

Introduction:
Patients with heart failure (HF) experience multiple physical and psychological symptoms that are associated with poor quality of life (QoL) for patients and family caregivers. Perceived control is known to buffer the adverse consequences of symptom burden on QoL among patients and caregivers at the individual level. However, there is limited knowledge about these associations within dyad members. Our aim was to determine whether perceived control over one’s personal health mediated the association of patient symptom burden and QoL in each member of the dyad.

Methods:
In this cross-sectional study, patients with HF (N= 154, 65% male, 50% NYHA III/V) reported physical and psychological symptom burden (Memorial Symptom Assessment Scale-HF). Informal caregivers (N = 154, 76% female) and patients completed surveys of perceived control (Control Attitudes Scale-Revised) and physical and mental well-being (MOS Health Survey-36v2). Dyadic data were analyzed using four multilevel Actor Partner Independence Mediation Models.

Results:
Symptom burden was associated with perceived control of each dyad member (P <.05). Physical symptom burden was directly associated with physical well-being for patients, not caregivers. Physical and psychological symptom burden was directly associated with mental well-being for each dyad member. Perceived control significantly mediated the association of physical symptom burden with physical and mental well-being in each dyad member (Figures A & C). Similarly, perceived control mediated the association of psychological symptom burden with physical and mental well-being in each dyad member (Figures B & D). Perceived control did not influence QoL in partners.

Conclusions:
Physical and psychological symptoms in HF patients were linked with each dyad member's QoL through perceived control over their health. Fostering perceived control may minimize the negative impact of symptom burden on the QoL of dyad members.
Abstract 15726: Large-Scale Plasma Proteomics and Mendelian Randomization of Cardiovascular Performance and Peak Arterio-Venous Oxygen Difference Identify Novel Biology Related to VO
2
max
Authors: Rao Prashant , Barber Jacob L , Mi Michael Y , Tahir Usman A , Deng Shuliang , Farrell Laurie A , Dev Prasun K , Bouchard Claude , Clish Clary B , Sarzynski Mark A , Robbins Jeremy M , Gerszten Robert E
Published: December 2023

Introduction:
VO
2
max is the product of maximal cardiac output (Q) (maximal stroke volume (SVmax) x heart rate) and peak arterio-venous oxygen content difference (a-vO
2
diff). SVmax and peak a-vO
2
diff have important implications across the spectrum of human health and performance. However, the molecular mechanisms underlying SVmax and peak a-vO
2
diff remain largely unknown. We characterize SVmax and peak a-vO
2
diff using large-scale plasma proteomics and genotyping to identify circulating proteins and putative mediators of these traits.

Methods:
763 physically inactive adults without overt cardiovascular disease underwent cardiopulmonary exercise testing with rigorous measurements of Q. High-throughput plasma proteomic profiling was performed to identify proteins associated with SVmax, a-vO
2
diff, and VO
2
max. cis-Mendelian Randomization (MR) analysis was conducted to assess causal relationships between protein markers and cardiovascular performance traits.

Results:
Proteomic profiling revealed associations between SVmax and several adiposity-related proteins, as well as secretory muscle factors (cathepsin B, α-actinin 2, and troponin I) (Figure). Proteins associated with peak a-vO2diff reflected oxygen-carrying capacity, muscle biology, and glucose metabolism (erythropoietin, myoglobin, fructose-1,6-bisphosphatase). Significant overlap was observed between proteins associated with SVmax, a-vO
2
diff, and VO
2
max. Cis-MR identified myocilin (MYOC) and caspase recruitment domain family member 9 (CARD9) as potential mediators of cardiovascular performance and VO
2
max.

Conclusions:
This study provides novel insights into the molecular influences of cardiovascular performance and VO
2
max. The identified protein markers associated with SVmax and a-vO
2
diff, along with the possible mediators MYOC and CARD9, merit further investigation into their role in endurance exercise capacity and cardiometabolic health.