bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12359: Thioridazine Suppresses Endothelial Inflammation and Atherogenesis Through Inhibition of Yap-jnk Signaling Axis
Authors: Jiang Minchun , Ding Huanyu , Wang Li , Huang Yu
Published: June 2023

Introduction:
Atherosclerosis is a critical public health issue as cardiovascular disease has been on the rise globally for decades. Our previous study found that YAP plays a critical role in endothelial inflammation and atherosclerosis, indicating that YAP is a promising therapeutic target against atherosclerotic vascular diseases. Therefore, we established the drug screening platform, aiming to seek new YAP inhibitors through repurposing FDA-approved drugs.

Methods and Results:
Drug screening was initially performed by luciferase reporter gene assay. We found that the anti-psychotic drug thioridazine can significantly inhibit the YAP/TAZ activity in human endothelial cells. Thioridazine downregulated the mRNA levels of YAP/TAZ target genes (ANKRD1, CTGF, CYR61) in endothelial cells. Thioridazine also increased the phosphorylation of YAP and inhibited the nuclear translocation of YAP in endothelial cells. Thioridazine suppressed endothelial inflammation, as demonstrated by downregulation of JNK phosphorylation, activity of JNK effector AP-1 as well as mRNA expression of pro-inflammatory markers including JNK target genes. Moreover, we observed that oral administration of thioridazine alleviated the formation of atherosclerotic plaques in

ApoE
-/-

mice on a western diet.

Conclusion:
Overall, the FDA-approved clinical drug, thioridazine suppresses endothelial inflammation and atherogenesis through inhibition of YAP-JNK signaling pathway. As a novel YAP inhibitor, thioridazine might need further investigation and development for potential use of treating atherosclerotic vascular disease.
Abstract 12364: Exogenous Sphingosine-1-Phosphate Restores Nitric Oxide-Mediated Flow-Induced Dilation During Acute Inhibition of Ceramide Formation
Authors: Senthilkumar Gopika , Katunaric Boran , Bordas-Murphy Henry , Freed Julie K
Published: June 2023

Our previous work has shown that chronic exposure to ceramide, a sphingolipid that when elevated in plasma is an independent risk factor major adverse cardiac events, causes microvascular endothelial dysfunction in arterioles collected from healthy adult patients. This presents as a change in the mediator of flow-induced dilation (FID) from the vasoprotective nitric oxide (NO) to the pro-atherosclerotic hydrogen peroxide (H
2
O
2
). Despite the known detrimental effects of ceramide, its metabolite sphingosine-1-phosphate (S1P) can promote NO formation. However, shear-induced ceramide formation is also necessary for maintaining NO-mediated FID, as arterioles from healthy individuals transition to H
2
O
2
-mediated FID during inhibition of the ceramide-forming enzyme neutral sphingomyelinase (NSmase). We hypothesize that the transition in mediator is due to the loss of acute S1P production, and thus addition of exogenous S1P can prevent microvascular endothelial dysfunction during inhibition of NSmase. Human arterioles (100-250μm) were dissected from otherwise discarded adipose tissue from healthy patients undergoing surgery. Videomicroscopy was used to assess vascular function
in vitro
. Microvessels were pre-constricted with endothelin-1, and changes in internal diameter were measured following exposure to increased levels of flow. Dilation to flow was significantly impaired in the presence of the NO-synthase inhibitor L-NAME (100μM, 30 min) when healthy human arterioles were treated acutely with S1P (1μM, 30 min) in the presence of the NSmase inhibitor, GW4869 (10μM, 30 min), compared to GW4859 alone (% maximal diameter±SEM, 5.1±8.7, n=4 vs 70.1±5.3, n=4; p=0.001, 2-way ANOVA). Whereas, the presence of PEG-catalase, an enzyme that breaks down H
2
O
2
, had no effect (85.0±4.3; n=3). These data highlight the importance of S1P in maintaining NO signaling during exposure to shear and strengthens the concept that the conversion of ceramide to S1P is critical in promoting a quiescent endothelium.
Abstract 12372: In-Situ Constructive Myocardial Regeneration With A 3-D Tissue-Engineered Cardiac Patch Combined Myocardial Cells and Extracellular Matrix
Authors: Watanabe Tatsuya , Koda Yojiro , Kawaji Keigo , Staneviciute Austeja , Beaser Andrew , Vaicik Marcella K , Ota Takeyoshi
Published: June 2023

Objective:
We developed a tissue-engineered cardiac patch derived from a myocardial cell block reinforced with extracellular matrix (ECM) to enhance in-situ myocardial regeneration. We sought to assess constructive and functional regeneration of the patch in a porcine preparation.

Methods:
A scaffold-free myocardial cell block was created with cardiomyocytes and embryonic fibroblast cells using a 3D Net Mold system(
Fig.A
). The myocardial cell block incorporated with ECM sheets(cbECM) was surgically implanted into a right ventricular (RV) of a healthy porcine model (n=4), or Dacron patches (n=4) which served as control (
Fig.B,C
). After 60 days, the implanted patches were assessed with cardiac magnetic resonance imaging including the rest perfusion(RP) analysis, Extracellular volume fraction(ECV) analysis, and electroanatomical mapping(EAM) studies as well as post euthanasia analyses including histological analysis and Quantitative reverse transcription-polymerase chain reaction(RT-PCR).

Results:
RP analysis showed improved regional tissue perfusion in the cbECM patch area(
Fig.D
). ECV values were much less in the cbECM patch compared to Dacron patch(36.1±3.6 vs. 72.0±13.6, p=0.012)(
Fig.E
), which implied the cbECM patch had less fibrosis and edema. EAM revealed regenerated electrical conductivity in the patch as evidenced by relatively preserved voltage regions (1.11±0.8 mV) compared with the normal RV control 4.7±2.8 mV(
Fig.F
). RT-PCR showed increased expression of growth factors in cbECM group(
Fig.G
). Repopulation of site-specific host cells including premature cardiomyocyte and active vasculogenesis were confirmed with histology/tissue analysis(
Fig.H
).

Conclusions:
The tissue-engineered cardiac patch facilitated in-situ constructive functional myocardial regeneration with increased regional tissue perfusion, and positive electrical activity in the porcine RV model.
Abstract 12373: Process Evaluation of a Vanguard Phase of a Trial for a Smartphone- App Based Model Of Care
Authors: Redwood Eleanor , Indraratna Praveen , Yu Jennifer , Delbaere Kim , Lovell Nigel H , Ooi Sze Yuan M , Liu Hueiming
Published: June 2023

Background:
Home-based monitoring and timely intervention of patients with acute coronary syndrome (ACS) and heart failure (HF) can improve patient outcomes. TeleClinical Care (TCC-Cardiac) is a smartphone app-based model of care designed to improve community-based care. We conducted a process evaluation within a multi-centre RCT to elucidate barriers and facilitators to implementation.

Methods
Patients were enrolled during their hospital stay and provided with an app and Bluetooth observation monitors. Patients were encouraged to engage with the app regularly (i.e. exercise program, record their observations). Data were monitored by a dedicated Remote Monitoring Solution team (RMS), and information was made available to the care team. Interviews were conducted with patients at 6 months, and with 3 RMS members, 2 HF nurses and 1 cardiologist.

Results
Of the 35 enrolled patients, 27 (77%) had a diagnosis of ACS and 8 (23%) of HF. Patient engagement with the app was good overall, with adherence tailing off over time, demonstrated by median (IQI) patient self-BP recordings of 93.3% (90-100%) at 1-month compared to 70% (43-90%) at 6-months. Older patients had higher levels of adoption (>50%), with a median age amongst high adopters of 67-years (IQI 40-82) compared to 63-years (IQI 50-87) for medium adopters (50-70%) and 44-years (IQI 33-53) amongst low adopters (<50%) (p=0.0184) (Fig 1). Interviews revealed good acceptance of Telehealth and remote monitoring. Higher motivation and health and tech literacy facilitated adherence. 21% of participants meeting inclusion criteria but not enrolled did not possess a smartphone. GPs did not engage. Other health professionals identified the time requirements of supporting less tech-literate patients and responding to alerts as potential barriers to adoption. However, most valued the potential for early detection and prevention of deterioration of this cohort of patients.

Conclusion
TCC-cardiac was generally considered an acceptable and viable model of care by patients and health professionals. Adherence was best amongst older patients with the highest potential to benefit. Designing strategies to overcome barriers to adherence in younger patients and GPs, combined with adequate tech support is recommended.
Abstract 12390: Accelerometer-Based Digital Measurement of Functional Capacity in Heart Failure Patients
Authors: Dwiyasa Felis , Vaishnava Prashant , McLeod Christopher J , Wibowo Sandi , Velarde Jackie , Sim David K , Soon Dinna Kar Nee , Wong Raymond C , Lee Shao Guang Sheldon , Loh Seet Yoong , Chen Hao , Majmudar Maulik
Published: June 2023

Introduction:
Repeated 6MWT in clinic are inconvenient for patients and disruptive to usual clinic throughput. Digital measures may be a means to overcome these challenges and reliably measure functional capacity.

Methods:
As part of an observational clinical trial (NCT04191356), during an 8-week observation period, patients with heart failure (HF) utilize arm-band biosensors (Biofourmis Everion®) for at least 15 hours daily while carrying out daily activities and complete an in-clinic investigator-guided 6MWT on the first and last days of participation. Interim data (N=30, age 56.17 ± 11.26; 24 males; 3 NYHA I, 25 NYHA II, 2 NYHA III) are used for validation, where the distance of baseline 6MWT is used as reference standard.

Results:
Passive 6MWT, which is the maximum 6-minute step count derived from daily accelerometer data (Fig 1), is strongly correlated with the reference standard (R=0.7501, P<0.0001, N=30) (Fig 2). Further analysis (Fig 2) reveals that regardless of the duration of the step count, the digital measures consistently have strong correlations with the reference standard, with the highest correlation obtained by Passive 10MWT (R=0.7746, P<0.0001, N=30).

Conclusions:
Early data highlights that accelerometer data collected during daily activities appears to indicate functional capacity of HF patients. Continued data will validate digital measures against various patient outcomes.

Fig 1
Aggregation of Passive 6MWT from step count recorded during daily activities

Fig 2
Correlation between accelerometer-derived passive step count digital measures and distance manually measured during baseline investigator-guided 6MWT as reference standard (N=30)
Abstract 12398: CD151 Expression Reflects Different Features in Cardiac Subtype Specification From Human Pluripotent Stem Cells
Authors: Koakutsu Misato , Miki Kenji , Naka Yuki , Sasaki Masako , Okubo Chikako , Narita Megumi , Imahashi Kenichi , Yoshida Yoshinori
Published: June 2023

Introduction:
In conventional cardiac differentiation methods, a heterogeneous cardiac population is generated from human induced pluripotent stem cells (hiPSCs). Purifying ventricular- or atrial cardiomyocytes (VCMs or ACMs, respectably) is valuable for drug discovery for region-specific heart diseases. Previously, we have identified a novel marker, CD151, which can separate advanced specified subtypes; CD151
high
VCMs in ventricular inducing condition (VIC) and CD151
low
ACMs in atrial inducing condition (AIC). Although CD151 is known as a cell adhesion molecule, the function in cardiac subtype specification is unclear. In this study, we addressed the mechanisms of how CD151 distinguishes cardiomyocyte subtypes in cardiac differentiation from hiPSCs.

Methods:
We performed RNA sequencing in VIC- and AIC- CD151
high/low
CMs. Pathway analysis using differential expression genes between CD151
high/low
CMs was conducted to identify prominent pathways in subtype specification.

Results:
In VIC, mitosis-related genes were enriched in CD151
high
VCMs. To clarify whether those genes affect cell proliferation or multi-nucleation, we performed the flow cytometric analysis of CD151
high/low
VCMs with KI-67 proliferation marker and Hoechst staining. Although the percentage of KI67-positive cells was almost the same, binucleated cells were significantly more in CD151
high
VCMs than in CD151
low
VCMs. In AIC, transcriptome analysis suggested that Notch signaling was activated in CD151
high
ACMs. To reveal that Notch signaling inhibits atrial specification, we analyzed ACMs treated with LY411575, a Notch signaling inhibitor. LY411575 induced atrial marker gene expression and increased the number of cells showing action potentials of ACMs. CD151
low
ACMs after LY411575 treatment contained ACMs with the highest efficiency.

Conclusion:
Our results demonstrate that the CD151 expression indicates mitotic activity in VCMs. CD151
high
VCMs are more advanced specified VCMs with binucleation without cell proliferation. On the other hand, in ACMs, CD151 works as an indicator of Notch signaling, which suppresses atrial specification. Our study provides a novel approach to generating and purifying hiPSCs-ACMs by Notch inhibition and CD151 separation.
Abstract 12399: Impact of Heart Failure and Chronic Kidney Disease on Clinical Outcome in Relation to Presence of Type-2 Diabetes Mellitus - Results From the Population-Based Gutenberg Health Study
Authors: Troebs Sven , Prochaska Juergen H , Stuermlinger Anna , Velmeden David , Ley Ludwin , Mueller Felix , Heidorn Marc , Schuch Alexander , Koeck Thomas , Schulz Andreas , Schmidtmann Irene , Michal Matthias , Schuster Andreas , Tuescher Oliver , Weimann-Menke Julia , Schattenberg Joern M , Lackner Karl J , Muenzel Thomas , Wild Philipp S
Published: June 2023

Background:
Type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD) are pathophysiologically linked and impact clinical outcome. The aim of this study was to determine the co-prevalence of T2DM, CKD and HF and to evaluate their additive prognostic significancefor all-cause mortality.

Methods:
Data from the population-based, prospective Gutenberg Health Study were analyzed (n=15,010). Clinical parameters were assessed during a highly standardized comprehensive 5-hour investigation at a dedicated study center. HF, T2DM and CKD were defined according to international guidelines. All-cause mortality was determined by regular checks of vital status via standardized follow-up examinations and regular alignment with registration offices.

Results:
In total 14,872 individuals were eligible for analysis (prevalence of T2DM: 8.6%; CKD: 29.1%; HF: 3.3%). During a median follow-up of 11.8 [interquartile range 10.3-13.2] years, 1,281 individuals died. In Cox regression analysis adjusted for age and sex, CKD and HF independently denoted an increased risk for all-cause mortality in diabetics (hazard ratio (HR)
CKD
1.67 [95% confidence interval 1.33-2.09], P<0.0001; HR
HF
2.44 [1.86-3.20], P<0.0001) and non-diabetics (HR
CKD
1.22 [1.07-1.41], P=0.0042; HR
HF
2.55 [2.07-3.14], P<0.0001). Further adjustment for traditional cardiovascular risk factors (CVRF) marginally reduced effect estimates. When considering the interaction of CKD and HF in Cox regression analysis, adjusted for age, sex, and CVRF, CKD without HF indicated a higher risk for all-cause mortality in diabetics (HR 1.66 [1.28-2.14], P=0.00011) compared with non-diabetics (HR 1.17 [1.01-1.36], P=0.04). A similar pattern, but with higher estimates was detected for HF without CKD (HR
T2DM
2.56 [1.63-4.00], P<0.0001 vs. HR
non-diabetics
2.13 [1.60-2.83], P<0.0001), and the highest were found for the co-prevalence of CKD and HF (HR
T2DM
3.69 [2.59-5.27], P<0.0001 vs. HR
non-diabetics
3.44 [2.54 - 4.65], P<0.0001).

Conclusion:
CKD and HF each show an independent but different risk for all-cause mortality that is modified by the prevalence of T2DM. The co-prevalence of these diseases increases mortality, underscoring the need for a holistic treatment approach.
Abstract 12400: The LDL-C / ApoB Ratio Predicts Future Cardiovascular Events in Cardiovascular Disease Patients With Nonalcoholic Fatty Liver Disease as Well as in Those Without Nonalcoholic Fatty Liver Disease
Authors: Maechler Maximilian , Sprenger Lukas , Mader Arthur , Larcher Barbara , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: June 2023

Introduction:
A low LDL-C / apoB ratio reflects small LDL particle size and is associated with insulin resistance. Non-alcoholic fatty liver disease (NALFD) is an important feature of the insulin resistance syndrome and confers an increased cardiovascular risk. The impact of the LDL-C / apoB ratio on the risk of cardiovascular events in patients with NAFLD is unclear.

Hypothesis:
We hypothesize that the LDL-C/apoB ratio predicts cardiovascular events in patients with NAFLD.

Methods:
We enrolled a large high risk cohort of 1515 patients with established cardiovascular disease (1272 patients with angiographically proven stable CAD and 243 patients with sonographically proven peripheral artery disease). NAFLD was diagnosed using the validated fatty liver index. Prospectively, cardiovascular events were recorded over a mean follow-up period of 7.6±4.9 years.

Results:
At baseline, the LDL-C / apoB ratio was significantly lower in patients with NAFLD (n=709) than in subjects who did not have NAFLD (1.34±0.29 vs. 1.39±0.26 mg/dl; p=0.001). During follow-up, 755 patients suffered cardiovascular events. The event rate was higher in patients with than in those without NAFLD (53.6 vs. 47.6%; p=0.020). The LDL-C/ApoB ratio significantly predicted cardiovascular events in the total study cohort, with a standardized adjusted hazard ratio (HR) of 0.86 [0.80-0.94]; p<0.001 and both in patients with NAFLD (HR 0.87 [0.78-0.97]; p=0.013) and in subjects who did not have NAFLD (HR 0.87 [0.77-0.97]; p=0.013, respectively).

Conclusions:
We conclude that in subjects with established cardiovascular disease the LDL-C / apoB ratio predicts cardiovascular events both among patients with NAFLD and in those who do not have NAFLD.
Abstract 12429: Grade Of CRS is Associated With Cardiac Dysfunction in the Acute Phase, but Do Not Predict the Prognosis of Diffuse Large B Cell Lymphoma Patients Who Underwent CAR-T Therapy
Authors: Sunayama Isamu , Min Kyung-Duk , Orihara Yoshiyuki , Yoshihara Satoshi , Yoshihara Kyoko , Teramoto Masahiro , Matsumoto Yuki , Oboshi Makiko , Nishimura Koichi , Naito Yoshiro , Tamaki Hiroya , Higasa Satoshi , Asakura Masanori , Ishihara Masaharu
Published: June 2023

Introduction:
As Chimeric Antigen Receptor T cell (CAR-T) therapy gains advantage in the management of diffuse large B cell lymphoma (DLBCL), accumulating evidence shows that it frequently accompanies cardiac dysfunction. Previous retrospective studies indicated the potential involvement of cytokine release syndrome (CRS) in cardiac dysfunction after CAR-T therapy, but no prospective study has reported the time course of cardiac dysfunction and its association with prognosis. Purpose: To prospectively examine the sequential changes in cardiac markers over time after CAR-T therapy and to clarify their association between the grade of CRS, cardiac markers, and prognosis.  

Methods:
In this prospective study, 30 DLBCL patients who underwent CAR-T therapy were enrolled. Before and after the treatment, the level of cardiac biomarkers and echocardiographic index were sequentially collected. We classified all patients into two groups according to the severity of CRS after CAR-T therapy, namely Low-CRS group (CRS<2) and High-CRS group (CRS≧2). Cardiac biomarkers, echocardiographic index, and long-term survival prognosis were further analyzed in both groups.  

Results:
The average age of participants was 59.6 years, and 9 (30%) were female. The number of patients in Low- and High-CRS group was 13 and 17, respectively. At the baseline before CAR-T therapy, there were no significant differences in cardiac parameters between two groups. In High-CRS group, NT-proBNP levels were significantly increased on day 3 and 7 compared to the baseline and were significantly higher than Low-CRS group at both timepoints, whereas troponin T level did not show any differences. Likewise, in High-CRS group, GLS was significantly decreased on day 7 and 14 compared to the baseline and recovered toward baseline on day 28. GLS and EF did not show significant differences between Low- and High-CRS groups throughout the follow-up. The Kaplan-Meier analysis demonstrated that there was no significant difference in long-term survival prognosis according to the severity of CRS.

Conclusion:   
This study revealed that CAR-T therapy induced transient changes in NT-proBNP level and GLS especially in High-CRS group in the first 2 weeks, but they did not predict the long-term prognosis.
Abstract 12434: ECG-Only Deep Learning Algorithm Predicts Risk of Arrhythmia in Phospholamban Cardiomyopathy
Authors: Van De Leur Rutger , de Brouwer Remco , Bleijendaal Hidde , Verstraelen Tom , Mahmoud Belend , Cox Moniek , van Tintelen Peter , van den Berg Maarten , Wilde Arthur , Doevendans Pieter , De Boer Rudolf A , van Es Rene
Published: June 2023

Introduction
Phospholamban (PLN) p.Arg14del mutation carriers are at risk of developing arrhythmogenic cardiomyopathy, but phenotypic penetrance is incomplete and much interpatient variability exists in the risk of malignant ventricular arrhythmias (MVA). Accurate risk stratification allows for timely device implantation which may prevent sudden cardiac death (SCD). The current prediction model is multimodal and uses data from ECG, echocardiography, MRI and 24-hour Holter monitoring.

Hypothesis
We hypothesized that a deep learning-based approach may allow for accurate risk prediction using only 12-lead ECG data.

Methods
A total of 679 PLN p.Arg14del mutation carriers without MVA at baseline were identified. MVA was defined as sustained VA, appropriate ICD intervention or (aborted) SCD. Prediction models were developed using Cox regression and validated using a bootstrap-based optimism corrected area under the receiver operating curve (AUC). A deep learning-based variational auto-encoder, trained on 1.1 million ECGs, was used to convert the median beat baseline ECG into its FactorECG. The FactorECG is a compressed version of the ECG which summarizes it into 21 explainable factors. Seven ECG factors that were previously shown to be associated with reduced ejection fraction were included in the model. A comparison to conventional ECG parameters and the current prediction model was performed.

Results
The deep learning-based ECG-only approach was able to predict MVA in PLN mutation carriers with an AUC of 0.82 [95% CI 0.78 - 0.86], comparable to the current multimodal prediction model (AUC 0.84 [95% CI 0.80 - 0.88]) and outperforming a model based on conventional ECG parameters (low voltage ECG and negative T waves; AUC 0.66 [95% CI 0.59 - 0.73]).

Conclusions
In conclusion, our deep learning-based algorithm uses only ECG data to accurately predict the occurrence of MVA in PLN mutation carriers, which could allow for easier stratification of patients at risk.
Abstract 12452: Relation of T-Wave Morphology And P-Wave Morphology Parameters With Left Ventricular Fibrosis in Sudden Cardiac Death Victims
Authors: Hekkanen Jenni J , Kentta Tuomas , Tulppo Mikko , Ukkola Olavi , Pakanen Lasse , Junttila Juhani , Huikuri Heikki , Perkiomaki Juha
Published: June 2023

Introduction:
T-wave morphology and P-wave morphology have been observed to have prognostic significance. However, data about their relation with arrhythmic substrate represented by left ventricular fibrosis are limited.

Methods:
We evaluated associations of T- and P-wave morphology parameters analyzed from the standard 12-lead ECGs with left ventricular fibrosis in 379 victims of unexpected sudden cardiac death who underwent medico-legal autopsy.

Results:
T-wave and P-wave area dispersion (TWAd, PWAd) (low values abnormal), non-dipolar components of T-wave and P-wave morphology (T_NonDipolarABS, P_NonDipolarABS) (high values abnormal) all had a significant association with left ventricular fibrosis (p=0.008, p=0.011, p=0.027, p=0.005 between the groups with different stages of left ventricular fibrosis, respectively, post hoc Bonferroni p-values are shown in Figures).

Conclusions:
Abnormal values of T- and P-wave morphology are associated with arrhythmic substrate represented by ventricular fibrosis partly explaining the mechanism behind their prognostic significance.
Abstract 12462: Percutaneous Repair of Chronic Aortic Pseudoaneurysm: A Single Center Experience
Authors: Lewis Bruce , Bufalino Dominick , Allen Sorcha , Burke Lucas , Hussein Mohammed H , Belin Rashad , Schwartz Jeffrey
Published: June 2023

Introduction:
Aortic pseudoaneurysm (AP) is a late complication of aortic repair. Without intervention, it carries a mortality rate up to 61%. Surgical repair has significant in-hospital mortality (6.9-12.6%) and high healthcare costs. Endovascular stent grafting has 15.2% all-cause mortality and 9.3% re-intervention rates. Percutaneous vascular plug/occluder technology emerged as a potentially safer and cheaper alternative to surgical AP closure. We will share our experience with this technology to enhance its success rate, safety, and cost-effectiveness.

Methods:
We retrospectively reviewed percutaneous AP closure cases with vascular plug/occluder technology published (2005 - 2016) and analyzed them alongside those performed at our institution (2017 - 2019).

Results:
We identified 40 cases of percutaneous AP closure with vascular plug/occluder technology in the literature and 10 performed at our institution. Our patients had a 1.9-day average length of stay with 100% successful targeted AP closure compared to 92% in the literature group. Over a 12-month median follow-up period (range 3-47 months), AP demonstrated stable or reduced sac size in 6 (60%) of our cases but increased in 4 (40%), necessitating surgical intervention. Literature cases had a 2-month median follow-up period with a 65% success rate. Death occurred in 40% of our patients from non-AP-related causes and in 8% of the literature group from AP closure-related complications. The cost per procedure was $49,580, which is hypothetically less than open surgical repair.

Conclusion:
Our experience shows a viable option for vascular plug/occluder technology in percutaneous AP repair, given its initial safety and cost-effectiveness. Our results highlight the critical role of follow-up imaging in identifying AP expansion and the need for further intervention. The high non-aorta-related mortality seen in follow-up emphasizes the high-risk nature of the population due to co-morbidities. .
Abstract 12482: Practical Adherence to AHA/ACC 2018 Guidelines Among Secondary Prevention Patients
Authors: Kainat Aleesha , Alish Yousef , Ateya Mohammad , Becich Michael J , Bradley Alison , Demicco David A , Fernandez Soledad , Ford Dan , Hegeman-Dingle Rozelle , Hwang Wenke , Jeong Jong , Jurczak Martha O , Kirchner H Lester , McLeod Euan , McTigue Kathleen M , Morgan Richard S , Paranjape Anuradha , Saccone Phillip , Thomas Neena , Townsend Kevin A , Williams David A , Arnold Jonathan
Published: June 2023

Introduction:
Patients with ASCVD are at increased risk for CV events. The 2018 AHA/ACC lipid guidelines recommend treating these patients with high intensity or maximally tolerated statin therapy. The objective of this study was to describe lipid lowering treatment (LLT) patterns and lipid values across 7 regional health systems.

Methods:
We conducted a cross-sectional analysis of electronic health records transformed into the PCORnet common data model (CDM) from 7 sites in the PaTH Clinical Research Network. Adults were eligible for inclusion if an LDL-C value was measured within the past year and > 6 months of pre-index data were available prior to the first LDL-C value in the study period. We defined computable phenotypes for adults meeting AHA/ACC criteria for ASCVD at very high risk (VHR) and not at very high risk (NVHR). Medication use was assessed during the study period using the CDM prescribing table. Descriptive statistics were used to summarize LLT and lipid values within these groups and across sites.

Results:
NVHR patients (n=69,854) had mean (SD) LDL-C, TG and non-HDL-C of 92.1 (37), 138 (104) and 114.4 (43) mg/dl, respectively; 71% had LDL-C > 70 mg/dL, 30% had TGs 150-500 mg/dL, and 61% had non-HDL-C ≥ 100 mg/dL. VHR patients (n=117, 689) had mean (SD) LDL-C, TG and non-HDL-C of 82.9 (43), 138.5 (99), and 106 (43) mg/dl, respectively; 58.6% had LDL-C > 70 mg/dL, 30.5% had TGs 150-500 mg/dL, and 49.8% had non-HDL-C ≥ 100 mg/dL. Documented LLT in NVHR and VHR patients was 58% and 69% for statin therapy, 25% and 36% for high intensity statin therapy, 12% and 16% for statin therapy + another LLT, while 37% and 27% had no documented LLT.

Conclusions:
In this cross-sectional study of NVHR and VHR ASCVD patients, although most had documented statin therapy, only 25% and 36%, respectively were on high intensity statins while more than a quarter of patients had no documented LLT. Recorded LDL, TG and non-HDL-C lab values suggest there may be unaddressed risk in these populations.
Abstract 12498: Incidence Of Non-Sustained Ventricular Tachycardia and Arrhythmic Disease Progression During Follow-Up in Hypertrophic Cardiomyopathy Patients
Authors: Bjerregaard Louise , Nielsen Christoffer H , Poulsen Steen H , Jensen Morten S
Published: June 2023

Introduction:
One of the most well-established risk markers for sudden cardiac death is non-sustained ventricular tachycardia (NSVT; 3 ventricular beats with a rate of ≥120 bpm, lasting for <30 seconds). Forty-eight-hours Holter monitoring is recommended to identify NSVT in patients with hypertrophic cardiomyopathy (HCM) .
Purpose:
The study aims to estimate the 48 hour-incidence of NSVT in HCM patients and to analyze arrhythmic disease progression during follow up.

Methods:
The study retrospectively evaluated HCM patients enrolled in the Registry for Hereditary Cardiovascular Diseases from 2011 to 2020. A total of 145 patients met the inclusions criteria to be a proband with HCM or a relative with left ventricular hypertrophy ≥13mm. A cross sectional analysis was done in 131 patients with at least one available Holter monitoring. A follow-up Holter monitoring was available in 97 patients.

Results:
Of 145 patients, the mean age was 54±15 years and 98 (68%) were male. The proportion of patients free of NSVT were 66% after 48 hours of Holter monitoring (n=131) (Kaplan-Meier estimates). Fifteen percent of NSVTs occurred from 36 to 48 hours into the Holter monitoring. The mean follow-up time between first and latest Holter (n=97) was 4.3 (±2.5) years and the median Holter monitoring time was both 48 (IQR, 48-48) hours at the first and 48 (IQR, 47-48) hours at the latest Holter. The proportion of patients free of NSVT in the first 48 hour Holter monitoring was 69% compared to 63% in the latest 48 hour Holter monitoring (p=0.17). Wilcoxon signed rank test showed no difference in number of ventricular cycles or the calculated frequency analyzing the first episode of NSVT in each Holter. Cox regressions analysis showed no significant difference in event rates between first and latest Holter (HR 0.84, 95% CI 0.26-2.70, p=0.77) and no association between age and NSVT (HR 1.03, 95% CI 0.83-1.28, p=0.80).

Conclusions:
NSVT occurred with an incidence rate of 34% per 48-hours Holter monitoring. An important part of NSVTs was identified in the last 12 hours of monitoring. The was no significant progression in the incidence rate of NSVT nor the characteristics of NSVT during follow up. Age had no effect on the incidence of NSVT.
Abstract 12505: Patients With Heart Failure Living in Socioeconomically Deprived Neighborhoods Have Unique Metabolomic Profiles
Authors: Morris Alanna A , Liu Chang , Udeshi Eisha , Steinberg Rebecca , Wang Jeffrey , Okoh Alexis K , Butler Javed , Jones Dean P , Quyyumi Arshed A
Published: June 2023

Introduction:
Patients living in neighborhoods with lower socioeconomic status have a greater risk for incident heart failure (HF), more severe symptoms, and increased risk of adverse clinical outcomes. We used high resolution metabolomics profiling to identify novel biomarkers associated with neighborhood socioeconomic status (nSES) in patients with HFrEF.

Methods:
The Area Deprivation Index (ADI) was used to characterize nSES in a discovery (n=170) and a validation (n=166) cohort of patients with HFrEF. Targeted and untargeted high-resolution plasma metabolomics profiling coupled with partial least-squares discriminant analysis (PLS-DA) was used to identify metabolites and metabolic pathways uniquely perturbed in patients in the highest tertile of the ADI (indicating lower nSES). Metabolites with a variable importance in projection (VIP)
>
1 entered pathway enrichment analysis.

Results:
Compared to patients in the lower and middle ADI tertiles, patients with HFrEF living in the highest ADI tertile were more likely to be Black, and had higher body mass index and lower ejection fraction (all P
<
0.01). PLS-DA confirmed metabolites that may be associated with worse diet quality in patients in both the discovery and validation cohorts who lived in neighborhoods in the highest ADI tertile, including amino acids and their metabolic products (carnitine, methionine, tryptophan, phenylalanine, valine, phenethylamine, indole), and urate. Moreover, metabolites associated with the human exposome (5-valerolactone, 1-naphthylamine) were also identified. Pathway enrichment analysis revealed branched-chain amino acid metabolism, fatty acid metabolism, and purine metabolism as part of this distinct metabolic signature (
Figure
).

Conclusions:
Patients with HFrEF living in neighborhoods with lower SES have a distinct metabolic signature that may, in part, be related to worse diet quality and more severe HF.
Abstract 12525: Synergistic Effects of Pitavastatin and Pemafibrate on Hepatic Steatosis and Inflammation in
Ldlr
+/-
Mice Fed Fat Diet
Authors: Tanaka Katsunao , Koseki Masahiro , Okada Takeshi , Inui Hiroyasu , Jiuyang Chang , Omatsu Takashi , Saga Ayami , Ohama Tohru , Nishida Makoto , Sakata Yasushi
Published: June 2023

Introduction:
The combination therapy of statin, ezetimibe and PCSK9 inhibitors enables us to reduce serum LDL-C and risk of atherosclerotic diseases. However, there remain patients who cause cardiovascular diseases. Recently, it has been reported that nonalcoholic fatty liver disease (NAFLD) might be a background for cardiovascular diseases. However, there are few reports on the combination therapy of statin and pemafibrate on hepatic steatosis and inflammation.

Hypothesis:
The aim of this study is to examine the impact of statin and/or pemafibrate on hepatic lipid contents and inflammatory gene expression in
Ldlr
+/-
mice.

Methods:
Eight to ten weeks old male
Ldlr
+/-
mice were used. Mice were fed high fat diet (HFD) ± 0.01% pitavastatin ± 0.00003% pemafibrate for four weeks. Serum lipids and liver histology/ lipid contents/ mRNA expression in four groups were examined.

Results:
Pemafibrate reduced serum triglycerides, particularly chylomicron and VLDL fractions, and increased HDL-C as previously reported. Hepatic triglyceride was unchanged, and very importantly, hepatic cholesterol and free-cholesterol were decreased with pitavastatin + pemafibrate compared to pitavastatin (pitavastatin vs pitavastatin + pemafibrate: cholesterol; 13.5±4.7 vs 9.4±1.9 mg/g of liver, P<0.01, free-cholesterol; 10.4±4.8 vs 6.9±1.4 mg/g of liver, P<0.01). The addition of pemafibrate resulted in a 46% increase in Cyp7a1 mRNA expression, suggesting that cholesterol in liver was reduced due to enhanced cholesterol excretion. Tnfa mRNA in liver was reduced by 62% and F4/80 staining of the liver showed decreased macrophage infiltration.

Conclusions:
Adding pemafibrate to pitavastatin did not alter hepatic triglyceride, however decreased cholesterol and free-cholesterol and improved inflammatory gene responses in liver, suggesting that the synergistic effect of pitavastatin and pemafibrate may be beneficial in NAFLD related atherosclerotic patients.
Abstract 12534: Comparative Performance of Distinct Frailty Measures Among Patients Undergoing Percutaneous Left Atrial Appendage Closure
Authors: Wang Allen , Ferro Enrico G , Xu Jiaman , Song Yang , Sun Tianyu , Yeh Robert W , Kim Dae H , Strom Jordan B , Ko Darae , Kramer Daniel B
Published: June 2023

Introduction:
Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). We compared the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC.

Methods:
We identified patients 65 years and older who underwent LAAC between October 1, 2016 and December 31, 2019 in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25.

Results:
Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson’s correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and short time at home (p<0.01 for all) regardless of the frailty instrument used. Model discrimination was similar between the HFRS and the CFI with fair discrimination of all outcomes (C-statistic 0.686 - 0.759). The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and short time at home (Delong p-value <0.001).

Conclusions:
Despite significant variation in frailty detection and only modest agreement between the two frailty measures, frailty status was highly predictive of mortality, readmission, long hospital stay, and days at home. Future studies should focus on prospective evaluation of frailty in patients eligible for LAAC, which may further refine the relationship between frailty and adverse outcomes, and help inform shared decision-making in this population.
Abstract 12549: What is the Efficacy of New Therapies in Black Patients With Heart Failure and a Reduced Ejection Fraction? A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Pandey Arjun K , Dhingra Nitish K , Pandey Avinash K , Puar Pankaj , Ahmed Shamon , Verma Raj , Mazer David , Butler Javed , Badiwala Mitesh V , Yau Terrence , Yanagawa bobby , Bhatt Deepak L , Verma Subodh
Published: June 2023

Introduction:
Evaluating the efficacy of newer medical therapies in black patients with heart failure with reduced ejection fraction (HFrEF) remains an important and unanswered question. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) in HFrEF to compare outcomes in black versus non-black patients with a specific focus on new therapies, namely ARNIs and SGLT2 inhibitors.

Methods:
Medline, Embase and Cochrane CENTRAL were searched from inception until May 2022. Pairs of reviewers independently identified RCTs that 1) compared either an SGLT2 inhibitor or an ARNI to placebo/standard of care in HFrEF patients and 2) reported outcomes stratified by race. Outcomes were pooled using the Generic Inverse Variance or Mantel-Haenszel models, and risk of bias was assessed using the Cochrane tool.

Results:
Four RCTs (n=17,797; 6.6% black) were identified, all of which were published in the past decade. In the placebo/control arm, black patients had a higher rate of heart failure hospitalization or cardiovascular death compared to non-black/white patients (OR: 1.52, 95% CI: 1.26, 1.84; absolute difference: 81, [95% CI: 43, 124] more events per 1,000 patients). In two RCTs, there was a trend towards a greater reduction in the composite of cardiovascular death or heart failure hospitalization with SGLT2 inhibitors in black patients (n=483; RR: 0.61, 95% CI: 0.45, 0.83) compared to white patients (n=6,445; RR: 0.84, 95% CI: 0.75, 0.95; p-interaction=0.06). In two RCTs, treatment with an ARNI was associated with reductions in the composite of cardiovascular death or heart failure hospitalization in both black patients (n=744; HR: 0.67, 95% CI: 0.40, 1.11) and non-black/white patients (n=6,109; HR: 0.80, 95% CI: 0.72, 0.89; p-interaction= p=0.49).

Conclusions:
Black patients are poorly represented in contemporary heart failure trials, and have worse outcomes compared with non-black patients. Newer therapies such as ARNIs and SGLT2 inhibitors are efficacious in black patients. SGLT2 inhibitors may afford greater risk reduction in black compared to non-black patients.
Abstract 12551: Self-Monitoring of Blood Pressure and Feedback Using App in Treatment of Uncontrolled Hypertension: SMART-BP Study
Authors: YOON MINJAE , Choi Dong
Published: June 2023

Introduction:
Self-monitoring of blood pressure (SMBP) is a reliable method used to assess blood pressure (BP) accurately. However, patients do not often know how to respond to the measured BP value. We developed a mobile application-based feedback for tailored recommendations and aimed to evaluate whether this feedback is superior to SMBP alone in terms of BP reduction and drug compliance improvement in patients with hypertension.

Methods:
Self-Monitoring of and Feed-back using APP in TReatment of UnconTrolled Blood Pressure (SMART-BP) is a prospective, randomized, open-label, multicenter trial to evaluate the efficacy of SMBP-App compared with SMBP alone. In the SMBP alone group, the patients performed home BP measurement and receive the standard care, whereas in the SMBP-App group, the patients received additional recommendations from the application using feedback algorithm in response to the obtained BP value. The primary endpoints were mean home BP and adherence of antihypertensive medication. Follow-up visits were scheduled at 12 and 24 weeks after randomization.

Results:
Among total 173 patients (88 for SBMP-App and 85 for SMBP alone) with full-analysis set, 53% were men, and mean age was 59.8 years. Baseline characteristics including BP were not significantly different between the two groups. At 24 weeks, mean reduction in home systolic BP was significantly higher in SMBP-App group than SBMP alone group (-22.4±13.5 vs. -17.2±13.3, P=0.019). Also, SMBP-App group showed higher drug adherence value and proportion of ≥95% adherence than in SMBP alone group (100% [97.2%-100.0%] vs. 97.6% [94.0%-100.0%], P=0.025; 86.1% vs. 68.0%, P=0.013). Reduction in home systolic BP at 12 weeks and office systolic BP at 12 or 24 weeks were also higher in SBMP-App, similar with primary end point.

Conclusions:
SMBP-App is superior to SMBP alone in terms of blood pressure reduction and improved drug adherence in patients with hypertension.
Abstract 12552: Causal Effect of Exposure to Elevated Lipoprotein(a) Levels on the Blood Transcriptome : A Mendelian Randomization Study
Authors: Bourgault Jerome , Arsenault Benoit
Published: June 2023

INTRODUCTION:
Lipoprotein(a) [Lp(a)] is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases (ASCVD). Several ex vivo studies have revealed a pro-inflammatory and pro-atherogenic role of Lp(a) in the etiology of ASCVD, mainly through induction of inflammation, metabolic processes, and apoptosis. However, whether Lp(a) causally influences the human transcriptome is unknown. Here, we aimed at identifying whether genetically-predicted Lp(a) levels could also affect the whole blood expression of genes involved in metabolic- and inflammatory-related pathways.

Methods:
We performed a series of inverse-variance weighted mendelian randomization analyses using single-nucleotide polymorphisms located in the
LPA
locus (±500kb; p<5x10
-8
) from the UK Biobank GWAS on Lipoprotein(a) quantiles as exposure (n=377,590 and whole blood expression levels of 14,288 coding gene from eQTLGen as outcomes (n=31,684 from 37 studies). We then used the Functional Mapping and Annotation of Genome-Wide Association Studies tool (FUMA) to identify gene sets for cardiometabolic- and inflammatory-related pathways from gene ontology biological processes.

Results:
The MR analyses identified 1363 genes that may be causally influenced by exposure to high Lp(a) levels (with p<0.05). The 10 most strongly associated genes with genetically-predicted Lp(a) levels are
FSTL3
,
PRKC1
,
PDE6C
,
PLXNB3
,
SESN1
,
SASH1
,
CD1D
,
CCDC102A
,
SS18L1
and
TCF12
. These genes are also differentially expressed in the heart. We identified 16 cardiometabolic-related pathways, mostly related to immune response, signaling, apoptosis, cardiovascular and vasculature development, cell proliferation, metabolic process, and catalytic activity. The 5 most significant pathways are regulation of cell population proliferation, regulation of intracellular signal transduction, positive regulation of cell population proliferation, cardiovascular system development and TOR signaling.

Conclusions:
Results of this study highlight a potentially causal effect of exposure to elevated Lp(a) levels on several key genes involved in metabolic processes and inflammation and provide mechanistic insight on the pathobiological role of Lp(a) in the etiology of ASCVD.
Abstract 12553: Adverse Cardiovascular Outcomes in Heart Failure (HF) With Preserved Systolic Function Associated With Atrial Fibrillation Are Due to Loss of Rhythm Control Impacting HF Status : A Propensity Score Matched Analysis of the TOPCAT Americas Study
Authors: Saksena Sanjeev , Slee April
Published: June 2023

Background:
Atrial fibrillation (AF) is associated with excess mortality and cardiovascular (CV) hospitalizations in HF patients (pts) with preserved systolic function (pEF), Whether this is due to advanced co-morbidities or loss of atrioventricular (AV) synchrony & rate control in AF is unclear.

Hypothesis:
To analyze the independent impact of AF on clinical outcomes of HFpEF pts in the TOPCAT AMERICAS study using propensity score matched (PSM) cohorts to account for confounding by other comorbidities.

Methods:
Study cohorts were matched for 20 clinical, demographic & ECG variables. 3 matched cohorts based on baseline rhythm status at study entry were compared viz. subjects in sinus rhythm (SR), subjects in AF on baseline ECG & subjects with Any AF event by history or ECG. We analyzed CV mortality, adjudicated modes of death & morbidity during a mean follow up period of 2.9 yrs.

Results:
418 subjects in SR (SR cohort) were PSM with 418 subjects in AF on baseline ECG (AF on ECG cohort) & 418 pts with any AF event by history or ECG (Any AF cohort) at study entry. Any AF increased risk of CV death(D), pump failure death (PFD), CV and HF hospitalization(H) and HF progression. AF on ECG increased risk of CVD, CVH, HFH and PFD (Tables). Neither AF cohort increased risk of sudden death (SD) {Figure}.

Conclusion:
1. AF is an independent risk factor for worsening CV outcomes in HFpEF. 2. This increased risk is due to a selective increase in HF worsening, HFH and PFD rather than SD. 3. Loss of AV synchrony & rate control in AF can independently impact HF progression in HFpEF with consequent HFH and PFD. Restoration of SR may offer benefits for CV outcomes in HFpEF & warrants evaluation.