bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14019: Comparing the Effect Profile of CETP in Individuals of East Asian and European Ancestries
Authors: Dunca Diana , Choapde Sandesh , Gordillo-Marañón Maria , Hingorani Aaron , Kuchenbaecker Karoline , Finan Chris , Schmidt Amand Floriaan
Published: December 2023

Introduction:
Cholesteryl ester transfer protein (CETP) is a lipid drug target under development for CHD in both European and East Asian populations.Previous drug target Mendelian randomization (MR) studies conducted in East Asians failed to show a CHD effect, which has been interpreted as lack of effectiveness of CETP inhibition for CHD prevention in this population.

Hypothesis:
In this study, we inferred the effect of CETP inhibition in individuals of European and East Asian ancestries using drug target Mendelian randomization.

Methods:
We leveraged genetic associations of CETP variants with major blood lipid fractions for individuals of European (n=1,320,016) and East Asian (n=146,492) ancestries. Colocalization was employed to identify potential cross-ancestry signals of CETP variants for plasma concentrations of LDL-C or HDL-C. Drug target MR was used to estimate ancestry-specific effects of on-target CETP inhibition. Differences between ancestries were evaluated using interaction tests, applying a multiplicity corrected alpha of 1.9х10
-3
based on the 26 considered traits.

Results:
There was strong support (posterior probability=1.00) of a shared causal CETP variant affecting HDL-C in both populations, which was not observed for LDL-C. Employing drug target MR scaled to a standard deviation increase in HDL-C, we found that lower CETP was associated with lower LDL-C, Lp[a], systolic blood pressure and pulse pressure in both groups, but the effects were more pronounced in European individuals (interaction p-values < 1.9х10-3). Lower CETP was protective against CHD, angina, intracerebral haemorrhage and heart failure in both ancestries, for example for CHD in East Asians (OR 0.89, 95%CI 0.84;0.94) compared to Europeans (OR 0.95, 95%CI 0.92;0.99, interaction p-value=0.05).

Conclusions:
In conclusion, on-target inhibition of CETP is anticipated to decrease cardiovascular disease in individuals of both European and East Asian ancestries.
Abstract 14035: Clinical Outcomes Following Hospitalization for COVID-19 in Patients With Cardiac Sarcoidosis in the United States
Authors: Farhan Muzammil , Ramphul Kamleshun , Ahmed Raheel , Hassan Azeem , Hasan Ali , Ahmad Hasan , Okafor Joseph , Carver Caleb , Jadoon Ayesha , Amanullah Khadija , Jamil Yumna , Bilal Maham , Ahmed Sajeel , Memon Rahat A , Sakthivel Hemamalini
Published: December 2023

Background:
Chronic immunosuppressive therapy and concomitant pulmonary involvement are two possible factors that could contribute towards adverse outcomes for patients with a history of Cardiac Sarcoidosis (CS) who are hospitalised with Covid-19. In this study, we aimed to identify co-morbidities and clinical outcomes for patients with CS post hospitalization for Covid-19.

Methods:
Patients aged ≥18 years, with a positive diagnosis of COVID-19 (via ICD-10 code “U071”) between 1st April 2020 to 31st December 2020, were identified from National Inpatient Sample Database. Patients with CS were compared for patient characteristics, demographics and hospital-related outcomes against patients without CS using multivariable regression analysis.

Results:
We identified a total of 1,608,285 cases of COVID-19 infection admitted to the hospital out of whom 60 patients were confirmed to have CS. CS patients were younger (mean 57.8 vs. 63.3 years, p<0.01), had a higher mean Charlson comorbidity index (CCI: 5.17 vs. 2.72, p<0.01) with greater prevalence of previous myocardial infarction (25.0% vs. 4.2%, p<0.01), atrial fibrillation (58.3% vs. 15.6%, p<0.01), smoking (50% vs. 26.1%, p<0.01), chronic kidney disease (66.7% vs. 20.6%, p<0.01) and diabetes (75.0% vs. 40.0%, p<0.01) as compared to patients without CS. Moreover, clinical outcomes of patients with CS were more adverse following hospitalization for COVID-19 including use of mechanical ventilation (25.0% vs. 11.2%, p<0.01, adjusted OR 1.39 95% CI: 1.37-1.41), acute kidney injury (50.0% vs. 28.2%, p<0.01, adjusted OR 1.86, 95% CI: 1.84-1.88) and death (25.0% vs. 13.1%, p<0.01, adjusted OR 3.15, 95% CI: 3.10- 3.20) (Table 1).

Conclusion:
CS patients hospitalized for COVID- 19 infection had greater CCI and worse clinical outcomes such as mechanical ventilation use, acute kidney injury and death when compared to patients without cardiac sarcoidosis.
Keywords:
Cardiac sarcoidosis, COVID- 19, outcomes.
Abstract 14050: Association of Health Literacy With Hospital Readmission and Mortality After Heart Transplantation
Authors: Dixon Debra D , Xu Meng , Lowery Brandon D , Buttafuoco Kayla A , Shaffer Lauren Lee , Wells Quinn S , Kripalani Sunil , Gupta Deepak K , Schlendorf Kelly H
Published: December 2023

Background:
Higher health literacy is associated with lower risk of hospitalization and mortality in patients with heart failure (HF). Health literacy assessment is recommended in patients undergoing heart transplant evaluation, yet few data report health literacy status or its associations with post-heart transplant outcomes.

Objective:
To characterize health literacy among heart transplant recipients and investigate its associations with post-transplant hospital readmissions and mortality.

Methods:
We retrospectively analyzed 513 patients (median age 57 years, 28% female, 27% Black) who underwent heart transplantation at Vanderbilt University Medical Center between 2015-2021. Health literacy was assessed using the validated 3-item Brief Health Literacy Screen (BHLS). Each item is on a 5-point Likert scale yielding a total score range of 3-15, with 15 indicating optimal health literacy. All cause readmissions post-transplant were ascertained from the electronic medical record (EMR). Vital status was determined through linkage with the Social Security death index or the EMR through March 2023. Ordinal logistic and Cox models adjusted for age at transplant, sex, race, body mass index, hypertension, dialysis at time of transplant, length of stay post-transplant, and wait list status at transplant were used to quantify associations between health literacy and readmissions or mortality, respectively.

Results:
The median BHLS score was 14 and 42% of patients had a score of 15. In the year following transplantation, 288 (56%) patients had 661 rehospitalizations. In the multivariable adjusted model, BHLS of 15 compared to any lower score associated with 29% lower odds of readmission (OR 0.71, 95% CI: 0.51, 0.99). Over a median 2.8 years (IQR 1.7, 4.9) follow-up, 90 individuals died. Health literacy was not associated with mortality (HR 1.10, 95% CI: 0.69, 1.73).

Conclusions:
At a high-volume heart transplant center, optimal health literacy was present in the minority of patients and associated with lower risk of post-transplant hospital readmissions, but neutral association with mortality. Screening for health literacy and providing transplant education that is clear and accessible at all literacy levels may improve post-transplant outcomes.
Abstract 14080: Broadening Indications for Neonatal Balloon Atrial Septostomy in Dextro-Transposition of the Great Arteries Reduce Predictive Value of Fetal Echocardiography
Authors: Chandrasekar Hamsika , Maskatia Shiraz A , Beattie Meaghan J , Kaplinski Michelle A , Punn Rajesh , Reddy Charitha D , Tacy Theresa A
Published: December 2023

Introduction:
Neonates with dextro-transposition of the great arteries (d-TGA) require adequate mixing at the atrial level. If not present, these infants experience severe cyanosis, necessitating an urgent balloon atrial septostomy (BAS). Multiple studies have identified various fetal echocardiography (FE) findings as risk factors for postnatal BAS. Anecdotally, the predictive value of these findings remains poor in clinical use.

Hypothesis:
We aimed to determine the relationship between inter-rater reliability (IRR) of FE BAS predictors and need for postnatal BAS, hypothesizing that IRR would be poor and perhaps contributing to limited predictive value of FE findings.

Methods:
We identified d-TGA pregnancies followed at our institution between 2012 and 2022, excluding fetuses with large ventricular septal defects and pregnancies that were either terminated or lost to follow up. Three independent readers blinded to BAS outcome assessed 7 FE predictors: pulmonary vein Doppler velocity > 41 cm/sec, reverse flow in patent ductus arteriosus (PDA), restrictive PDA, restrictive patent foramen ovale (PFO), bidirectional PFO flow, flat septum primum, and hypermobile septum primum. IRR was determined with the S metric. Clinical information immediately before BAS was collected to evaluate postnatal physiology. A multivariable logistic regression was used to determine significant associations between FE findings and postnatal BAS.

Results:
Fifty-six fetuses were included in this study, of whom 25 (45%) underwent BAS. IRR was lowest for PFO flow direction and highest for restrictive PDA, likely due to its rarity. The remainder of FE predictors had either a moderate or substantial level of IRR. The last pre-BAS range of PaO
2
(24-49 mmHg), O
2
saturation (56-86%) and pH (7.18-7.52) reflected variable physiology. Of the 5 FE characteristics that could be included in the regression analysis, none were found to be significantly associated with odds of a BAS.

Conclusions:
Our results demonstrate substantial but not excellent IRR for current FE BAS predictors, but no significant association between these predictors and postnatal BAS in d-TGA patients. Poor predictive value of FE for postnatal BAS could be impacted by broadening indications for BAS.
Abstract 14105: Impact of Aortic Atheromatous Plaques Identified by Aortic Angioscopy on Five-Year Clinical Events: Novel Evaluation by Non-Obstructive General Angioscopy Registry
Authors: Kojima Keisuke , Komatsu Sei , Kakuta Tsunekazu , Yoshida Junichi , Fukamachi Daisuke , HIKITA Hiroyuki , Fujii Hiroyuki , Kimura Shigeki , Matsuura Masayoshi , Kawakami Hideo , Dai Kazuoki , Higuchi Yoshiharu , Ueda Yasunori , Abe Shichiro , Takamisawa Itaru , Sato Akira , Watabe Hiroaki , Takahashi Satoru , Usui Eisuke , Asakura Masanori , Yutani Chikao , Okumura Yasuo , Hirayama Atsushi , Kodama Kazuhisa
Published: December 2023

Introduction:
Non-obstructive general angioscopy (NOGA) has become a novel method of evaluating atheromatous plaques of the aortic intimal wall. Aortic atheromatous plaques are potentially related to future cardiovascular events, but these associations remain undetermined regarding long-term follow-up.

Methods:
We conducted a multicenter, observational, prospective registry of consecutive 577 patients with confirmed or suspected coronary artery disease underwent NOGA at 13 centers in Japan and counted atheromatous plaques from aortic cusp to terminal aorta with intra-aortic scan of NOGA. All patients were divided into three groups based on the tertile of the number of aortic atheromatous plaques. The relationships between aortic atheromatous plaques and clinical events after five-year follow-up were evaluated.

Results:
The median number of aortic atheromatous plaques was 6 [IQR: 3-12]. The mean follow-up duration was 1860 ± 860 days. At five-year follow-up, the incidence of major adverse cardiovascular events (MACE) (cardiovascular death, non-fatal myocardial infarction, cerebral infarction, or peripheral artery disease) was significantly higher in the higher tertile group (lower tertile 7.4% vs. middle 13.2% vs. higher 20.7%, p<0.001, respectively). Kaplan-Meier analysis demonstrated a significantly higher probability of MACE in higher tertile group of all (log-rank test: p < 0.001).

Conclusions:
Aortic atheromatous plaques identified by NOGA could be vulnerable, and thus were strongly associated with clinical events during five-year follow-up.
Abstract 14120: Characteristics, Outcomes and Treatment Response With Dapagliflozin Across the Range of Ejection Fraction in People With HF and a History of CABG Surgery: A Pooled Analysis From DAPA-HF and DELIVER
Authors: Verma Subodh , Butt Jawad , de Boer Rudolf A , Desai Akshay S , Docherty Kieran , Hernandez Adrian F , Jhund Pardeep S , Kober Lars , Kosiborod Mikhail N , Lam Carolyn S , Langkilde Anna Maria , Martinez Felipe , Ponikowski Piotr , Sabatine Marc S , Shah Sanjiv J , Vaduganathan Muthiah , Solomon Scott , McMurray John J
Published: December 2023

Introduction:
There is a paucity of data on contemporary outcomes of patients with a history of CABG who have heart failure (HF) with either reduced or preserved left ventricular ejection fraction (LVEF). We aimed to compare the baseline characteristics and outcomes by history of CABG, as well the efficacy and safety of the SGLT2 inhibitor, dapagliflozin, across the full range of LVEF in patients with heart failure.

Methods:
We conducted a patient-level pooled analysis of two trials testing dapagliflozin in 11,007 participants with HF and LVEF ≤40% (DAPA-HF trial) and >40% (DELIVER trial). The primary outcome was the composite of a worsening HF event or death from CV causes; other outcomes examined included total hospital admissions for HF, MACE, all-cause mortality and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. Outcomes were compared by history of CABG.

Results:
Among 11,007 patients, 1576 had a prior history of CABG (~14%). Patients with CABG were characterised by a higher proportion of men, lower eGFR and LVEF, and higher rates of prior MI, PCTA, type 2 diabetes, antiplatelet and statin therapy. CABG patients were more likely to experience primary outcome (adjusted hazard ratio [aHR] 1.21, 95% CI 1.08-1.36), CV death (aHR 1.22, 95% CI 1.04-1.42), all-cause death (aHR 1.22, 95% CI 1.07-1.38), HF hospitalization (aHR 1.31, 95% CI 1.14-1.51), total HF events (adjusted rate ratio 1.38, 95% CI 1.20-1.59), and MACE (aHR 1.34 (1.17-1.52). Dapagliflozin consistently reduced the primary and key secondary endpoints in both people with and without a history of CABG across the entire spectrum of LVEF (P-interaction for all > 0.48) (Table). Adverse events and tolerability were similar between groups.

Conclusions:
In patients with HF, a prior history of CABG is associated with higher rates of CV outcomes and mortality compared to those without a history of CABG. The efficacy and safety of dapagliflozin was similar in patients with and without a history of CABG.
Abstract 14125: Tricuspid Mass- Solving a Curious Case of Li-Fraumeni Syndrome
Authors: Huffaker Tyler , Asif Anum , Hui Dawn , Otchere Prince
Published: December 2023

Background:
Primary cardiac tumors are extremely rare (0.001-0.03%), but can have significant embolic, obstructive, and arrhythmic consequences. Li-Fraumeni syndrome (LFS) is an autosomal dominant genetic syndrome characterized by multiple malignancies, including osteosarcomas, CNS tumors, and adrenocortical, breast, and soft tissue sarcomas. We report diagnostic challenges of a patient with Li-Fraumeni syndrome found to have tricuspid valve mass and atrial septal defects.

Case:
30-year-old female with Li-Fraumeni syndrome (ovarian cancer at 6 years,osteosarcoma and soft tissue sarcoma at 16 years, bilateral breast cancer at 26 years) found to have a tricuspid valve leaflet mass, as well as two atrial septal defects on surveillance echocardiography. There was concern for a primary cardiac tumor such as sarcoma or rhabdomyoma. She underwent surgical resection with biopsy showing organized mural thrombus. Decision making: Li-Fraumeni syndrome is a rare autosomal dominant cancer-predisposing syndrome, which can present with various tumor types. Cardiac tumors are extremely rare and have been limited to case reports. Although multimodality imaging is now more readily available, some cases remain diagnostic challenges if imaging is non-conclusive, histopathological studies remain the gold standard. In our case, the mass demonstrated mild enhancement in the post-gadolinium images suggestive for primary cardiac tumor versus a secondary metastatic cancer (Figure). A histopathological analysis by surgical resection demonstrated an organized thrombus.

Conclusion:
Diagnosis of cardiac masses in the setting of hereditary cancer syndromes such as LFS are rare and remain a challenge given the increased likelihood of primary or metastatic lesions. When imaging is inconclusive, further invasive investigations are warranted since it can alter the clinical management.
Abstract 14168: A Randomised Open-Label Controlled Trial of a Remote Cardiac Rehabilitation System With Wearable Medical Devices - An Interim Report of the TELE-REHA Trial
Authors: Nakayama Atsuko , ISHII NORIKO , Hori Kentaro , Yoshida Azusa , Isobe Mitsuaki
Published: December 2023

Introduction:
Outpatient cardiac rehabilitation (CR) prevents recurrence after cardiac surgery or cardiac catheterisation, but participation rate of outpatient CR is low. Although attempts at remote CR have been investigated with advances in equipment, they have not yet reached the stage of social implementation, and it is not clear whether remote CR can be an alternative to outpatient CR.

Objective:
The aim of this study was to confirm the safety and efficacy of remote CR management using wearable devices feasible in Japan, and to implement the device early in society.

Primary outcome:
All-cause death, cardiovascular events, EFs, e/e', BNPs, CRPs, PeakVO2, VE-VCO2 slop, muscle mass; secondary outcome: EQ5D.

Subjects:
Patients discharged home after hospitalization for cardiovascular diseases.

Study design:
A single-centre, randomised, open-label, parallel-group study was conducted to evaluate the efficacy and safety of wearable device (Apple Watch)-based Remote-CR versus Outpatient-CR. In Remote-CR group, ECG and SpO2 are measured by Apple Watch before and after exercise. Biweekly health information, weight, blood pressure, heart rate, electrocardiogram (ECG) and EQ5D are automatically transmitted by the app. Tele-nursing was provided by trained nurses on a bi-weekly basis, based on the health information provided by the app. For both groups, the intervention period was 90 days, and blood sampling, ECG, cardiopulmonary exercise testing (CPX), and body composition testing were performed at the end of the study.

Results:
A total of 110 cardiovascular patients were randomly divided into Remote-CR group and Outpatient-CR group. The background of the two groups was similar. Though the PeakVO2 and EQ5D scores after the CR program were not significantly improved in Outpatient-CR group, those were significantly improved in Remote-CR group (P=0.02). The dropout rate from CR program was lower in Remote-CR group than Outpatient-CR group. No significant incident occurred in both group.

Conclusions:
Remote-CR is expected to be as effective as Outpatient-CR and safe for patients after cardiac treatment, and can provide a relapse prevention programme for those who are difficult to attend.
Abstract 14169: Deletion of P21 Activated Kinase-1 Modulates Energy Homeostasis and Affects Cardiac Function
Authors: Rosas Paola C , Munoz Marcos , McCann Maximilian , Rafael-Clyke Koreena , Park Jooman , Chowdhury Shamim , Jiang Yuwei
Published: December 2023

Introduction:
We investigated the consequences of P21-activated kinase-1 (PAK1) deletion on cardiac function, body weight, body composition, and energy balance using a mouse model of global PAK1 knock out. PAK1 is a protein kinase that plays a role in multiple aspects of cardiac health. We hypothesize that PAK1 plays a role in cardiometabolic health including cardiac function and adipose tissue homeostasis.

Methods:
We used PAK1
-/-
in the FVB/N background. We included 10-12-week-old male and female mice. Age and sex-matched FVB/N mice were used as wild-type (WT) controls. Most results included both male and female mice together, as no differences were found between sexes. Ca
2+
kinetics was measured in neonatal cardiomyocytes.

Results:
Deletion of PAK1 was found to have a significant impact on cardiac function. Specifically, slower Ca
2+
release and reuptake kinetics accompanied with decreased phospholamban phosphorylation was observed in PAK1
-/-
mice. These changes affected cardiac systolic (EF, s’) and lusitropy parameters (E/e’, IVRT). Moreover, our findings revealed body weight differences between PAK1
-/-
and WT at 12 weeks, accompanied with increased % fat mass and decreased % lean mass in PAK1
-/-
, indicating a shift towards adiposity. Further analysis revealed that PAK1
-/-
mice had increased weights of white adipose tissue (WAT), and brown adipose tissue (BAT). Moreover, we found increased food intake, increased number of feeding bouts and decreased energy expenditure accompanied with decreased thermogenic markers in subcutaneous WAT and BAT in PAK1
-/-
, further contributing to the obesogenic phenotype (see table for results).

Conclusions:
Deletion of PAK1 affected systolic and diastolic functions, and resulted in increased energy intake, decreased energy expenditure, and increased adiposity. Therefore, targeting PAK1 signaling pathways may represent a promising therapeutic strategy for improving cardiometabolic diseases.
Abstract 14173: Generation and Characterization of Clinically Relevant Disease Models for Port Wine Birthmark Using Induced Pluripotent Stem Cells
Authors: Nguyen Vi , Gao Chao , Hochman Marcelo L , Friedman Harold I , Chen Elliot H , Wang Yunguan , Jegga Anil , Nelson John S , Tan Wenbin
Published: December 2023

Introduction:
Port Wine Birthmark (PWB) is a congenital vascular malformation with a progressive development. The current treatments for PWB are Pulse Dye Laser and Photodynamic Laser Treatment. However, the efficacy of blanching the birthmark is inadequate, and the reoccurrence after treatment is a major clinical barrier. Developing clinically relevant disease models that can be used for mechanistic and therapeutic development studies is the critical unmet need. Induced pluripotent stem cell (iPSC) is a powerful tool in different disease models and drug discovery. Besides, iPSC-derived cells can retain and exhibit the disease phenotypes from donors. Therefore, iPSCs and their-derived vascular cells could be potential models for PWB study.

Hypothesis:
It was hypothesized that PWB iPSC-derived endothelial cell (EC) could retain the disease phenotypes, thus serving as clinically relevant disease models.

Methods:
PWB lesions and normal skin biopsies were cultured for outgrowths of fibroblasts, followed by reprogramming using CytoTune-iPS Kit. The induction of PWB and normal iPSC into EC was performed using reported protocols with tailored modifications. Bulk RNA and ATAC-seq were performed on both iPSC and iPSC-derived EC. The functional phenotypes of iPSC-derived ECs were characterized using in vitro capillary formation and in vivo Matrigel plug-in assays.

Results:
PWB EC showed impaired tube formation in vitro with larger perimeters (p=6.22x10
-24
) and thicker branches (p=1.07x10
-77
) comparing with normal EC. In plug-in assay, the perfused human vasculatures were characterized by using UEA1 and anti-human CD31 antibodies. Perfused vasculature formed by PWB EC showed larger perimeters (p=8.45x10
-6
) and greater densities (p=7.34x10
-8
) than those formed by normal EC. Additionally, 16.6% of perfused vessels formed by PWB EC showed perimeters over 300 μm. KEGG analysis of RNA-seq DEGs showed significantly dysregulated pathways related to cell differentiation, organ development, and lipid metabolism in PWB iPSCs and ECs as compared with normal ones.

Conclusions:
PWB-derived EC retained critical disease related phenotypes including forming enlarged vessels and thick branches in vitro and in vivo, which can be utilized as valuable PWB models.
Abstract 14175: Risk of Cardiovascular Disease in Women Who Underwent Salpingo-Oophorectomy to Prevent Hereditary Breast Ovarian Cancer: A Systematic Review and Meta-Analysis
Authors: A de Moraes Francisco Cezar , Cavalcanti Souza Maria Eduarda , Dal moro Lucca , Rodrigues Anna , Batista Donadon Isabelle , Ferraz Barbosa Barbara , Pasqualotto Eric , Moraes de Souza Dilma do Socorro , Feio Danielle , Stecca Carlos
Published: December 2023

Introduction:
Hereditary breast and ovarian cancer (HBOC) syndrome is defined by family history and identification of germline pathogenic variants (PVs). In particular, the mutations in BRCA1/2 (BRCAm) increased approximately 44% and 17% risk of ovarian cancer or fallopian tube cancer and 72% and 69% risk of breast cancer. Risk-reducing salpingo-oophorectomy (RRSO), the physiologic removal of the ovaries and fallopian tubes, effectively reduces the risk of ovarian cancer by 80-95% in women with HBOC.

Hypothesis:
Is performing a RRSO in women with HBOC or BRCAm associated with the development of cardiac and metabolic diseases?

Aims:
To assess the risk of myocardial infarction (MI)/coronary artery disease (CAD), hypertension, diabetes mellitus (DM), and hypercholesterolemia/dyslipidemia among women with HBOC or BRCA1/2 mutation after performing RRSO.

Methods:
We searched in PubMed, Scopus, and Web of Science databases for studies that assessed cardiovascular and metabolic events following RRSO in women with HBOC or BRCAm. Statistical analysis was performed using RStudio v4.4.2 using the DerSimonian and Laird random-effects model. Heterogeneity was examined using the Cochran Q test and I
2
statistics. Significance for heterogeneity was set at a p-value<0.01.

Results:
Five studies were included with a total of 1320 patients. Among them, 956/1320 (72.4%) had BRCAm: 469 (35.5%) had BRCA1 and 400 (30.3%) had BRCA2. The majority of patients (928;69.3%) had RRSO<50 years, and the mean age of the study sample was 54.3 years (41.45-57, 2.35). The incidence of MI events was reported in 18/1126 patients (1.4%, 95% Cl, 5-2.3%; I
2
=40.15%). Most common metabolic comorbidities were hypercholesterolemia. Observed in 170/994 women (19.6%, 95% Cl, 4.6-34.6%; I
2
=97.88%), hypertension, in 125/994 women (12.9%, 95% Cl, 4-21.8%; I
2
=96.93%), and DM, reported in 46/1320 patients (3%, 95% Cl, 1.2-4.7%; I
2
=75.41%).

Conclusions:
This meta-analysis provides evidence to support that patients with HBOC or BRCAm who undergo RRSO have an increased risk of developing heart and metabolic diseases. Larger studies with longer follow-up are required to further explore these associations.
Abstract 14190: Simultaneous Analysis of Myocardial Flow Reserve and Intra-Ventricular 4D Flow Using Hybrid
13
N-ammonia Positron Emission Tomography/Magnetic Resonance Imaging in Patients With Coronary Artery Disease
Authors: Endo Keiichiro , Katahira Masataka , Kiko Takatoyo , Yamakuni Ryo , Ukon Naoyuki , Shimizu Takeshi , Ishii Shiro , Yamaki Takayoshi , Nakazato Kazuhiko , Fukushima Kenji , Ito Hiroshi , Takeishi Yasuchika
Published: December 2023

Introduction:
Intra-left ventricular (LV) blood flow dynamics is closely related to wall kinetics and myocardial perfusion. 4D flow magnetic resonance imaging (MR) has been developed to simulate and quantify intra-LV blood flow. We aimed to evaluate the usefulness of simultaneous analysis of myocardial flow reserve (MFR) and intra-LV 4D flow measured by hybrid
13
N-ammonia positron emission tomography (PET)/MR in patients with coronary artery disease (CAD).

Methods:
Forty patients (mean 65±18 years, male 32) with CAD who underwent pharmacological stress PET/MR were enrolled. MFR was calculated from a series of dynamic rest-stress PET scans. Simultaneously, 4D flow MR acquisition was performed during the stress PET scan. The intra-LV 4D flow was visually assessed, where the smooth flow was defined as normal pattern, and random, or reverse flow was defined as abnormal (Figure A). The velocity of LV inflow and outflow were measured.

Results:
A normal flow pattern was found in 22 patients, while abnormal pattern was found in 18. MFR showed a significant correlation with the velocity of LV inflow and outflow (inflow: R = 0.552, P < 0.001; outflow: R = 0.563, P < 0.001). MFR was significantly lower in the abnormal flow compared to the normal flow (1.484 ± 0.559 vs. 1.931 ± 0.775, P = 0.041, Figure B). Additionally, when analyzing MFR in coronary artery territories, MFR in the left anterior descending artery was significantly lower in the abnormal flow compared to the normal flow (1.405 ± 0.526 vs. 1.881 ± 0.791, P = 0.029, Figure C).

Conclusion:
Simultaneous analysis of MFR and intra-LV 4D flow has a potential to serve as a novel indicator for assessing the severity of ischemia in patients with CAD.
Abstract 14198: Therapy for Myocardial Ischemia-Reperfusion Injury Using Novel Allogenic Mitochondria and Associated Organelle Complex
Authors: Shimizu Yuuki , Hayashi Takumi , Che Yiyang , Pu Zhongyue , Ota Hisashi , Tsai Rick , Suganuma Masashi , Murohara Toyoaki
Published: December 2023

Background:
Ischemia and reperfusion (I/R) injury induces intracellular calcium overload and generation of reactive oxygen species, which trigger intracellular mitochondrial damage, resulting in cardiomyocyte apoptosis. Freshly prepared autologous mitochondria improved damaged cardiac function, however, little is known whether allogenic mitochondrial organelle complex -Q (MRC-Q) can be replenished in the heart to achieve cardioprotective effects against I/R injury.

Purpose:
The aim of this study was to investigate whether the exogenous administration of allergenically isolated mitochondria leads to a protective effect on the myocardium after I/R injury using a well-established murine model.

Methods and Results:
The MRC-Q used in the current experiments were isolated by a proprietary technology (
WO2021132735A2)
. All MRC-Q was frozen and stored at -80 °C before use. First, purified GFP-labeled HUVEC-derived MRC-Q were added to a rat cardiomyocyte cell line, and observed to be uptaken in cardiomyocytes in a time-dependent manner, which was also confirmed by quantitative polymerase chain reaction detecting human mitochondria DNA in rat cardiomyocytes. In addition, we demonstrated that cell viability was improved in the MRC-Q-treated group 96 hours after hypoxia/reoxygenation (H/R). Further examinations suggested the one of mechanism on cardioprotection by incorporating MRC-Q into the cardiomyocyte to be mediated by the secretion of mitochondria-derived peptides (MDP), which could inhibit apoptosis-promoting signals in addition to anti-ROS activity of MRC-Q. Next, we examined potential cardioprotective effect of MRC-Q administration on I/R injury in a murine model. Simultaneously at reperfusion, MRC-Q were administered intramyocardially in the damaged myocardium area. Compared to the vehicle group, MRC-Q-treated group showed a reduction in infarct size with fewer apoptotic cells, a decrease in circulating cardiac enzymes, and an improvement in cardiac function 24 hours after reperfusion. Finally, a preclinical pig model also confirmed the cardioprotective effects of MRC-Q.

Conclusion:
Our data demonstrated that MRC-Q have a protective effect on the heart by modulating cardiac apoptosis after ischemia/reperfusion injury.
Abstract 14207: Mobile ECG Atrial Fibrillation Prediction Enhancement Powered by Standard ECG Algorithm With Artificial Intelligence
Authors: Lee Kihong
Published: December 2023

Introduction:
Artificial intelligence (AI) using electrocardiogram (ECG) enabled to predict atrial fibrillation (AF) in patients without documented AF. It needs 12-lead ECG with tremendous data learning. Mobile 1-lead ECG is more convenient to surveil cardiac rhythm with simple measurement. However, AI-enabled arrhythmia predictability by mobile ECG is limited due to single channel utilization and longer duration for arrhythmia diagnosis.

Hypothesis:
We aimed to enhance mobile ECG AF prediction AI algorithm integrated with 12-lead ECG deep learning model.

Methods:
Based on 552,372 12-lead ECG data of 318,321 patients, a statistical AF prediction model employing a deep-learning approach was constituted. The raw data of 6,792 1-lead mobile ECGs were acquired from 6,792 patients for about 1 minute at 250Hz. A statistical AF prediction model with mobile ECG employing a deep-learning approach was constituted. Resnet structure was utilized to distinguish subtle changes of the vicinity of P-wave. Both 12-lead ECG and mobile ECG were allocated to training, validation, testing datasets in a 6:2:2 ratio. Then, we conducted transfer learning using the standard 12-lead ECG’s deep learning model to improve performance of 1-lead mobile ECG deep learning model.

Results:
AF was annotated in 26,541 (4.8%) with 12-lead ECG whereas 1,443 (21.2%) with 1-lead mobile ECG. The area under the curve (AUC) value for predicting AF was 0.910 with 12-lead ECG, and 0.721 with mobile ECG . The predictive performance of mobile ECG was 79.7% in accuracy, 47.5% in sensitivity and 50.3% in F1-score. The AUC value of mobile ECG after applying transfer learning based on 12-lead ECG for AF prediction was increased to 0.905 with accuracy of 89.1%, sensitivity of 71.3% and F1-score of 57.7%.

Conclusions:
Integration with deep learning algorithm of standard 12-lead ECG significantly improved the model performance of mobile ECG AF prediction model compared to 1-lead mobile ECG only based model. Easy application of mobile ECG with enhanced AF predictability might serve a more convenient method as a pre-emptive assistive tool to provide probabilistic prediction for PAF screening rather than 12-lead ECG.
Abstract 14241: Alcohol Exposure Among Patients With Dilated Cardiomyopathy: A Report From the DCM Precision Medicine Study
Authors: Jimenez Javier , Ni Hanyu , Cao Jinwen , Kinnamon Daniel , Jordan Elizabeth , Rubens Muni , Chaparro Sandra , Saxena Anshul , Hershberger Ray E
Published: December 2023

Introduction:
Alcohol-related cardiomyopathy is characterized by cardiac dysfunction and dilatation due to prolonged and excessive alcohol (ETOH) consumption. This study aims to determine the prevalence, use patterns and genetic associations of ETOH exposure in patient with dilated cardiomyopathy (DCM) and their first-degree relatives (FDR).

Hypothesis:
1. There is increased prevalence of EOTH use among patients who develop DCM. 2. Non-genetic co-morbidities are more common in patients who use ETOH and developed DCM. 3. Probands and FDR who use ETOH and develop DCM are more likely to have genetic variants.

Methods:
We analyzed clinical and genetic data on individuals aged 18 and older enrolled in the US DCM Precision Medicine Study. Partial and full DCM phenotypic expression were included in the analysis. The AUDIT-C score was used to evaluate the intensity of ETOH use. ETOH use and presence of DCM-related rare genetic variants were examined in FDRs using GEE type logistic mixed models adjusted for intra-family correlation and site heterogeneity.

Results:
A total of 2,595 subjects (1,188 probands and 1,407 FDRs) were included. Prior and current ETOH users were 270 (23%) and 546 (46%) for probands, and 30 (10%) and 168 (54%) for FDRs with DCM/partial DCM. Avg. years of drinking were 25.2 for probands and 24.0 for FDRs with DCM/partial DCM; the percent with AUDIT-C positive scores were 31.5 for probands and 32.7 for FDRs with DCM/partial DCM. In probands, moderate or high/severe ETOH use was more likely to be in men, white, Hispanic and those with </=12 yrs. of education (p<0.001). Patients drinking heavily were more likely to have hypertension, diabetes, hypercholesterolemia, and history of arrhythmia/conduction disease. Among FDRs, DCM/partial DCM was associated with the presence of DCM-related variants but not with moderate-severe drinking years in quartile after controlling for demographics and comorbidities. ETOH use did not modify the genetic effect on DCM/partial DCM.

Conclusions:
There is a high prevalence of prior or current ETOH use among probands and FDRs with DCM/partial DCM with an average ETOH use between 24-25 yrs. ETOH use was not found to associate with DCM or to modify the association between the presence of genetic variants and development of DCM.
Abstract 14254: Myocarditis in Athletes and Non-Athletes: Evaluating the Persistence and Degree of Myocardial Fibrosis at Follow Up
Authors: Abela Mark , Demanuele Joseph , Buttigieg Lisa , Farrugia Mark , Borg Bernard , Yamagata Lara , YAMAGATA KENTARO , Borg Alexander
Published: December 2023

Introduction:
Myocarditis is a common acquired cardiac disorder that may lead to persistent scar. Current guidelines recommend follow up cardiac MRI (CMR) in 3-6 months for athletes. Data supporting this recommendation is unfortunately very limited.

Aim:
The aim of this study was to evaluate the demographic and clinical variables of patients diagnosed with myocarditis. Clinical data for those who had a follow up CMR was also evaluated separately.

Methodology:
Patients who had a cardiac MRI (CMR) organised between July 2019 till December 2022 because of a MINOCA/Myocarditis hospital admission were retrospectively reviewed. Those with a myocarditis diagnosis were included. An athlete was defined as an individual who engaged in >4 hours of physical activity weekly or underwent organized sport.

Results:
105 patients were included (mean age 35.4±15.6 years, 83.8% male). 34.3% were athletes. 12.4% had possible acute myocarditis, 10.5% had likely myocarditis and 77.1% had confirmed myocarditis on cardiac MRI (median 4 days from presentation). ECG was abnormal in 60.0%. 8.6% had arrhythmias. Echocardiography was abnormal in 26.7%. CMR revealed 15.2% reduced LV EF, 57.1% regional wall motion abnormalities, 5.7% reduced RV EF, 25.7% pericardial effusion, 84.5% myocardial oedema. Most (88.5%) had late gadolinium enhancement (LGE). 56.2% were started on anti-heart failure medical therapy.

29.5% had a CMR repeated (interval between scans 14.7±14.2 months). 77.4% showed persistent LGE, less pronounced in most (71.0%). Diffuse LGE at baseline was the only predictor for persistent scar (p=0.004). Scar persisted equally in athletes and non-athletes (p=0.666). Clinical variables were similar in both.

At follow-up (24.6±15.3 months), 8.6% had adverse outcomes. The event rate was similar in athletes and non-athletes. A low LV EF on CMR (p=0.011) and abnormal ECHO (p=0.027) were the only variables that could predict outcome.

Conclusion:
LGE after myocarditis persists in 77.4% of cases, albeit better. No variable could predict the persistence of LGE in this cohort. Athletes and non-athletes had a similar clinical course, suggesting that repeat CMR in non-athletes is reasonable. The diagnostic utility of repeat CMR after myocarditis remains questionable.
Abstract 14275: Allosteric Inhibition Restricts Motion of the SMURF1 Glycine Hinge and Reverses Experimental Pulmonary Arterial Hypertension
Authors: Rothman Alex M , Florentin Amir , Quigley Catherine , Zink Florence , Bonneau Olivier , Hemming Rene , Hachey Amanda , Rejtar Tomas , Thaker Maulik , Jain Rishi , Zhang Ji-Hu , Cotesta Simona , Ottl Johannes , Kordinsky Alina , Avishid Reut , Troxler Thomas , Binmahfooz Sarah K , Morrell Nicholas W , Humbert Marc , Cobb Jennifer , Osterman Nils , Tallerico John , Shaw Duncan , Guth-Gundel Sabine , Prag Gali , Rowlands David J
Published: December 2023

Background:
Reduced expression of bone morphogenetic protein receptor 2 (BMPR2) predisposes to pulmonary vascular remodelling and the development of pulmonary arterial hypertension (PAH). The HECT E3 ligase SMURF1 is a key negative regulator of this pathway that is overexpressed in the pulmonary vasculature of patients with PAH. However, the absence of an active-site pocket renders E3s undruggable.

Hypothesis:
We hypothesized that a large, unbiased screen would be needed to identify SMURF1 inhibitors and that a SMURF1 inhibition would augment BMP signaling and treat experimental PAH.

Aims:
We aimed to: identify SMURF1 inhibitors through a large, unbiased screen; determine mechanism of action; examine the effects on BMP signalling, cell phenotype and experimental models of PAH.

Methods:
We constructed a time-resolved fluorescence resonance energy transfer-based assay reporting SMURF1 self-ubiquitylation and undertook a 1.1 million compound screen. Primary hits were rationalised based on biochemical selectivity and cell-based assays designed to prioritize and optimize molecules for specific inhibition of SMURF1. Crystal structure of SMURF1 and SMURF2 were determined in the bound and unbound state at 2.05-2.75 Å. Target interaction was examined in a split-CAT based system. The effect on signaling and phenotype was examined in primary pulmonary artery endothelial and smooth muscle cells, and in rats with PAH induced by monocrotaline and sugen hypoxia.

Results:
Screening identified lead compounds that selectively inhibited SMURF1. Structures reveal that inhibitor binding induces an α-helix elongation over an invariant glycine-containing hinge, limiting a motion mandatory for catalytic activity. We affirmed this structure-based model with mutants engineered to resist inhibition and demonstrated that inhibition prevents direct BMPR2 ubiquitylation, normalized BMP signaling and restored homeostasis in pulmonary vascular cells from patients with PAH. Finally, we demonstrated that SMURF1 inhibition reverses established, experimental PAH.

Conclusions:
Our structural understanding enables design of HECT and other glycine-hinge protein inhibitors opening a new druggable space.
Abstract 14285: Sodium Glucose Co-Transporter 2 Inhibition Eliminates Senescent Cells Through Downregulation of PD-L1 and Improves Pathological Aging
Authors: Katsuumi Goro , Suda Masayoshi , Shimizu Ippei , Yoshida Yohko , Furihata Takaaki , Joki Yusuke , Hsiao Chieh Lun L , Minamino Tohru
Published: December 2023

Introduction:
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been developed as a new class of anti-diabetic drug, and shown cardio- and renal-protective effects in patients with diabetes, heart failure, and chronic kidney diseases. SGLT2 inhibitor also has effect to expand lifespan in aged mice, suggesting anti-aging effect. But the detailed machinery of these protective effects is still to be clarified. Here we demonstrate that canagliflozin has a effect to eliminate senescent cells from pathological tissues, so-called "senolysis" in murine aging or age-related disease models.

Methods:
Canagliflozin mixed in food at 0.03% (w/w) was administered for up to 4 weeks to high-fat-fed diabetic mice, for 2 weeks to ApoE-knockout atherosclerotic mice model, for 20 weeks for chronological aged mice, and for lifetime to Zmpste-knockout progeroid mice. Burden of senescent cell accumilation as well as pathological or aged phenotype were measured in each mice model.

Results:
Canagliflozin reduced senescent cells in visceral adipose tissue within 1 week. Also, we found that senolytic effect of canagliflozin was provided through enhancing endogenous senolytic function by immune cells such as CD8+T cells. This machinery was mediated by enhanced AMPK signaling through incrase of endogenous AICAR production, which leads to the downregulation of PD-L1 expression on senescent cells. Oppositely, inhibition of AMPK signaling with Compound C administration (10mg/kg ip daily) resulted in abolishing senolytic effect of canagliflozin. Furthermore, canagliflozin reduced their senescent cell burden and alleviated atherosclerosis in ApoE-knockout mice, extended lifespan in progeroid mice, and altered physical function in aged mice.

Conclusions:
Our results showed new aspect of protective efficacy of SGLT2 inhibitors and would be promising evidence that SGLT2 inhibitors can be used as not only cardio- or renal-protective drugs but also anti-aging drugs.
Abstract 14289: Anti-Inflammatory Therapies to Prevent Cardiovascular Events: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials
Authors: Boczar Kevin E , Shin Sheojung , Pearson Alexander , Shahab Saba , Geejo Aishwarya , Visintini Sarah , Fehlmann Christophe , Bezzina Kathryn , Beanlands Rob S , Wells George
Published: December 2023

Introduction:
Anti-inflammatory therapies have been increasingly investigated for the reduction of cardiovascular (CV) events. The goal of this study was to summarize and compare the relative effectiveness of anti-inflammatory medications for the reduction of CV events in a systematic review and network-meta-analysis.

Methods:
In our systematic review, we included studies from Medline, Embase, the Cochrane Central Register of Controlled Trials, as well as clinical trial registry websites, Europe PMC, and conference abstract hand-searching. Randomized controlled trials were selected for inclusion if they included at least one anti-inflammatory treatment and involved patients with CAD. Bayesian network meta-analyses was performed to calculate risk estimates using random effects analyses in patients with ACS as well as stable CAD for the reduction of MACE.

Results:
A total of 14,699 studies were screened; sixty-one articles, all randomized control trials, met eligibility criteria for inclusion. A total of 41,647 patients were included in the stable CAD network analysis and 29,388 patients were included in the ACS network analysis. In the ACS analysis, both non-steroidal anti-inflammatory (NSAID) use (OR: 0.30, 95% Credible Limits [CrI]: 0.11-0.74) and colchicine use were associated with a significant reduction in MACE compared to control (OR: 0.71, 95% Credible Limits [CrI]: 0.58-0.88). In the stable CAD analysis, both corticosteroids (OR: 0.44, 95% CrI: 0.26-0.73) and colchicine (OR: 0.65, 95% Credible Limits [CrI]: 0.54-0.77) were associated with a significant reduction in MACE compared to control.

Conclusions:
In patients with acute coronary syndromes, NSAIDs and colchicine were associated with a reduction in the risk of major adverse cardiac events. In patients with stable coronary artery disease, both colchicine and steroids were associated with a reduction in the risk of major adverse cardiac events. For a comprehensive analysis of benefits and harms of anti-inflammatory therapies, large comparative studies or network meta-regression analyses of patient-level data will be required. Systematic review registration number: PROSPERO registry—CRD4202230328
Abstract 14290: Prospective Clinical Validation of the STOPSHOCK Smartphone Application - Artificial Intelligence Model for Prediction of Cardiogenic Shock in Patients With Acute Coronary Syndrome
Authors: Bohm Allan , Jajcay Nikola , Spartalis Michael , Gubareva Ekaterina , Jankova Jana , Segev Amitai , Krychtiuk Konstantin , Tavazzi Guido , Rathod Krishnaraj , Maurizi Kevin , Jarakovic Milana , Guerra Federico , Matetzky Shlomi , Skurk Carsten , Thevathasan Tharusan , Huber Kurt , Dragunova Patricia , Brucknerova Jana , Kollarova Marta , Berta Imrich , Petrikova Katarina , Bezak Branislav
Published: December 2023

Background:
Cardiogenic shock (CS) complicating acute coronary syndrome (ACS) is a life-threatening condition with mortality reaching 50% despite the use of mechanical circulatory support devices (MCS). It is hypothesized that early implantation of MCS before hemodynamic deterioration could prevent CS. For this purpose, we have developed and externally validated an AI model for CS prediction available as a smartphone application (STOPSHOCK app).

Research question:
Could the STOPSHOCK app identify ACS patients at high risk of CS development in contemporary clinical practice?

Methods:
The STOPSHOCK model was derived on a population of 3232 and validated on an external cohort of 5123 patients with high discrimination (c-statistics: 0.84 in external validation). The model was based on variables that were available at first medical contact. A dedicated app was developed to test the performance of the model in the clinical setting. 103 consecutive ACS patients were enrolled in intensive cardiac care units in 8 centers from USA, Europe, and Asia.

Results:
Heart rate, respiration rate, SpO2, blood glucose level, systolic BP, age, sex, shock index, heart rhythm, type of ACS, history of hypertension, congestive heart failure and hypercholesterolemia were used as input variables. Clinical outcome (presence of CS) was reported at hospital discharge. STOPSHOCK model had a c-statistics of 0.97.

Conclusions:
Our machine learning model for CS prediction in patients with ACS available at first medical contact showed high discrimination and feasibility in clinical settings as a smartphone app.