bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13808: Investigating Autophagy in Experimental Autoimmune Myocarditis Using Single Cell RNA Sequencing and Spatial Transcriptomics
Authors: Stefanska Monika , Bielawska Magdalena , Tkacz Karolina , Sarad Katarzyna , Krzysztofik Daria , Weglarczyk Kazimierz , Siedlar Maciej , Kania Gabriela , Blyszczuk Przemyslaw
Published: November 2023

Background:
Autophagy has emerged as an important process in the context of heart failure. Experimental autoimmune myocarditis (EAM) represents an animal model of acute myocarditis (d19) and post-inflammatory dilated cardiomyopathy (d35).

Aim:
To explore autophagy dynamics in a mouse model of EAM at the single cell level.

Methods:
6-8-week-old BALB/c mice were immunized with αMyHC peptide and complete Freund’s adjuvant. Single-cell RNA (scRNA) libraries were prepared using 10x Genomics technology and sequenced, targeting 50’000 reads/cell. For spatial transcriptomics, snap-frozen hearts embedded in OTC were sectioned into 10 μm-thick fragments and placed on 10x Genomics Visium Gene Expression Slide and processed using 10x Genomics Visium protocols. The data were analyzed using RStudio software. LC3B and Beclin-1 proteins were detected by IHC.

Results:
After quality control check, we included in the RNAseq analysis 25’058 cells clustering in 11 distinct cell populations (Fig. 1A). Expression of autophagic genes
Atg7
and
Becn1
was relatively consistent across all cell populations, whereas
Atg3
and
Map1lc3b
(encoding LC3B) showed high expression specifically in monocytes. Analysis of monocytes indicated up-regulation of
Atg3,
Atg7
and
Becn1
during the progression of EAM. Spatial transcriptomics analysis identified 5911 spots under the tissue and results showed an up-regulation of
Atg3,
Atg7, Becn1
and
Map1lc3b
in the hearts during the inflammatory phase of EAM. This increased expression was found throughout the entire heart section (Fig. 1B). Moreover, we detected the presence of LC3B and Beclin-1 proteins specifically localized within the inflammatory compartment of inflamed hearts (d19).

Conclusions:
In the EAM model, acute inflammation in the heart is associated with activated autophagy. Targeting this autophagic response could potentially improve disease outcomes.

Financed by the National Science Centre (Poland), grant 2019/35/B/NZ5/00551
Abstract 13814: Combined Omental and Bilateral Pectoralis Major Flaps for Treatment of Thoracic Aortic Graft Infections
Authors: Kuonqui Kevin , Janhofer David E , LaValley Myles N , Diaddigo Sarah E , Takayama Hiroo , Ascherman Jeffrey A
Published: November 2023

Introduction:
Aortic graft infections have historically been managed through graft removal and replacement. However, coverage with vascularized tissue flaps may provide an effective alternative, particularly in patients who are not able to undergo extended extra-anatomic bypass procedures.

Hypothesis:
Here we describe our experience treating thoracic aortic graft infections with combined omental and bilateral pectoralis major myocutaneous (PMM) advancement flaps.

Methods:
All patients undergoing sternal wound treatment with PMM flaps by the senior author (JAA) at a high-volume cardiac surgery center from 1996-2023 were reviewed. Patients with evidence of aortic graft infection were included.

Results:
Complete data were available for 598 patients, 11 of whom had combined PMM and omental flaps mobilized for aortic graft infections. ASA score was >4 in 9/11 (81.9%). At the index cardiac surgery, 11/11 (100%) underwent aortic root repair/replacement, and 9/11 (81.9%) also underwent aortic valve repair/replacement. Indications in this group for flap surgery included culture-positive infection (8/11; 72.7%), dehiscence (5/11; 45.5%), drainage (7/11; 63.6%), and inability to close the sternotomy incision due to hemodynamic instability (5/11; 45.5%). During chest exploration, 7/11 (63.6%) underwent complete removal of the infected graft, compared to 4/11 (36.4%) who underwent graft-preserving washout and debridement. Immediate flap closure was performed in 4/11 (36.4%). Intraoperative mediastinal cultures were positive in 3/11 (27.3%). Post-operative complications included dehiscence (1/11; 9.1%), seroma (2/11; 18.2%), hematoma (1/11, 9.1%), abdominal hernia (1/11; 9.1%), and recurrent infection (1/11; 9.1%). One (9.1%) patient died within 30 days of sternal reconstruction from mitral valve failure and a tachyarrhythmia. None have undergone reoperation for flap-related complications, while one patient underwent elective resection due to aesthetic complaints.

Conclusions:
Low postoperative morbidity and mortality indicate that combined omental and pectoralis major flaps are a safe and effective treatment for aortic graft infections.
Abstract 13820: Association of Cardiothoracic Ratio With Heart Failure Events in Atrial Fibrillation Without Heart Failure: The Fushimi AF Registry
Authors: Ikeda Syuhei , Hamatani Yasuhiro , Okamoto Keita , Nakanishi Yumiko , Minami Kimihito , Ishigami Kenjiro , DOI KOSUKE , Yoshizawa Takashi , Ide Yuya , Fujino Akiko , Ishii Mitsuru , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Abe Mitsuru , Akao Masaharu
Published: November 2023

Background:
The cardiothoracic ratio (CTR) is a readily available and non-invasive tool with which to assess cardiac volume status. We previously reported that N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was associated with higher incidence of clinical events in patients with atrial fibrillation (AF) without pre-existing heart failure (HF). However, it remains unknown whether CTR on chest radiography is associated with the incidence of HF events in AF patients without HF.

Methods:
The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto, Japan. After excluding patients with pre-existing HF (defined as having one of the following; prior HF hospitalization, New York Heart Association class ≥2, or left ventricular ejection fraction <40%), we divided 1,049 patients into four groups according to their CTR and NT-proBNP level (median value: 495 ng/L) at baseline, and compared the incidence of HF events (composite of cardiac death or HF hospitalization) among the groups; G1 (Lower CTR<50% and Lower NT-proBNP<495, n=256), G2 (Higher CTR≥50% and Lower NT-proBNP<495, n=268), G3 (Lower CTR<50% and Higher NT-proBNP≥495, n=117) and G4 (Higher CTR≥50% and Higher NT-proBNP≥495, n=408).

Results:
During the median follow-up of 5.4 years, the incidence rates of HF events in the groups either having higher NT-pro BNP group or higher CTR group were higher, as compared with patients with lower CTR and lower NT-proBNP (G1: 0.5% per person-year, G2: 1.3%, G3: 1.6% and G4: 2.5%; p<0.01) (Figure). Multivariate Cox regression analysis revealed that higher CTR (≥50%) was independently associated with the incidence of HF events in AF patients without prior HF hospitalization (hazard ratio: 1.47,

95% confidence interval: 1.09-2.00).

Conclusion:
In Japanese AF patients without pre-existing HF, higher CTR was associated with higher incidence of HF events irrespective of NT-proBNP level.
Abstract 13821: Induction of Immune Tolerance to Intramyocardial Transplantation of Cardiac Progenitor Cells by Regulatory T Lymphocytes
Authors: Derisio de Lima Aline , Garibotti Hernán G , Assal Myriam , Haddouche Aness , BELLAMY VALERIE , Wang Qing Dong , Graneli Cecilia , Miyara Makoto , Silvestre Jean-Sebastien , Jennbacken Karin , Menasche Philippe
Published: November 2023

Introduction:
The clinical use of human embryonic stem cell (hESCs)-derived cardiac cells is still hampered by rejection which is managed by immunosuppressive drugs and exposes to their side-effects.

Hypothesis:
We evaluated an alternate strategy based on the induction of immune tolerance by adoptive regulatory T lymphocytes (Treg) transfer.

Methods:
Human hTreg were isolated from peripheral blood mononuclear cells, expanded for 9 days and phenotyped. Immune-competent mice were then subjected to a myocardial infarction. Three weeks later (baseline), mice with an echocardiographically-measured ejection fraction (EF) ≤50% underwent trans-cutaneous echo-guided peri-infarct injections of 1.4x10
6
hESC-cardiovascular progenitor cells (CPC; n=11) or an equivalent volume of PBS (controls, n=4). Among the CPC-transplanted mice, 6 were intravenously injected with 2x10
6
hTreg at the time of transplantation and 3 days later and 5 only received the vehicle (PBS). Functional and histological end points were assessed 3 weeks after treatments (final) and spleen tissue was processed by flow cytometry for the evaluation of immune cell populations.

Results:
Three weeks after treatments, all CPC-transplanted hearts had a significantly better preservation of EF [m±SEM], compared with their respective baseline values, than PBS-injected hearts (35.4% ± 5.4% in CPC and 37.5% ± 6.8% in CPC+hTreg
vs.
-1.3 ± 7.3% in PBS, p=0.004) which was mainly driven by a reduction in LV end-systolic volumes (p=0.004) but only in the hTreg group global longitudinal strain improved by 15.7% ± 13.3% from baseline while it worsened by 36.5% ± 18.8% in their non-hTreg counterparts (p=0.037). Infarct size did not differ among the 3 groups but Treg reduced interstitial fibrosis in remote non infarcted myocardium (0.6% ± 0.1%, p=0.007
vs.
CPC-non hTreg and PBS, respectively) and, in spleen tissue, induced significant decreases in CD80+ M1 macrophages (p=0.010) and NKG2D+ NK cells (p=0.013) and an increase in CD206+ M2 macrophages (p=0.004) compared with the other 2 groups.

Conclusions:
Systemic hTreg administration mitigates adverse heart remodeling by modulating the immune response, potentially facilitating transplantation of hESC-CPC with reduced immunosuppression requirements.
Abstract 13822: Guideline Directed Medical Treatment in Patients With Heart Failure in China
Authors: Cui Xiaotong , Yang Aiwen , Lu Long , Zhou Jingmin , Chen Hungta , Miao Feng , Zhao Tianyu , Xie Mengyu , Zhao Xuwen , Hunt Phillip R , yang jiefu , Ge Junbo
Published: November 2023

Introduction:
Patients with Heart Failure (HF) are often treated at less than target dose or lack Guideline Directed Medical Treatments (GDMT), this has also been reported for patients with HF with reduced ejection fraction (HFrEF) in China. However, data on treatment patterns in different subgroups by disease onset and ejection fraction phenotypes is scarce.

Research Question:
What are the patient characteristics and treatment for HF in China in relation to concurrent guidelines?

Aim:
To describe characteristics of incident and prevalent patients with HF and treatment with GDMT (RAASi, BB and MRAs) for HFrEF patients in China prior to SGLT2i approval for HF.

Methods:
Data from the Heart Failure Registry at the Chinese Cardiovascular Association Heart Failure Center from Jan. 1, 2018 to July 31, 2021 was used. Data on the first 10 new HF inpatients each month is recorded on a case report form at discharge and 1-, 3- and 12-months follow-up. GDMT at discharge and 12 months was described for HFrEF patients.

Results:
We identified 32047 patients with HF: 21698 incident and 10349 prevalent cases, 13117 (40.9%) HFrEF, 6,368 (19.9%) HFmrEF, 10826 (33.8%) HFpEF and 1736 (5.4%) had no EF measurement. Mean age was 64.8 years in incident and 66.1 years in prevalent patients. A larger proportion of HFpEF patients were women than in other EF phenotypes. At discharge, 71.2% of incident and 75.7% of prevalent patients were treated with RAASi, 77.9% and 81.2% were treated with BB and 65.7% and 75.8% with MRA. Treatment was consistently lower at 12 months. In HFrEF 65.6% and 69.2% of incident and prevalent patients had three GDMTs at discharge; 37.3% and 39.9% at 12 months. Patient target/maximum tolerated dose for incident HFrEF patients was reached for17.6% (RAASi), 28.3% (BB) and 48.7% (MRA); for prevalent this was 24.8%, 38.4% and 50.8%.

Conclusions:
In this study on HF patients in Chinese clinical practice, 40% had HFrEF whereas the majority had preserved or mildly reduced EF. In the HFrEF patients, less than half of patients had three concurrent GDMTs at 12 months. Moreover, few patients received the target dose at 12 months and many discontinued treatment. These results show an urgent need for improved treatment strategies and effective implementation of new guidelines in China.
Abstract 13825: Post-PCI Outcomes in Patients on SGLT2 Inhibitor Therapy
Authors: Dhulipala Vishal R , Siano Matthew , Vogel Birgit , Farhan Serdar , Vinayak Manish , Koshy Anoop N , Arora Ayush , Smith Kenneth , Tanner Richard , Sartori Samantha , Sharma Samin K , Kini Annapoorna , Mehran Roxana
Published: November 2023

Introduction:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve cardiorenal outcomes among patients with and without diabetes mellitus.

Hypothesis:
We aimed to investigate their impact on the risk of acute kidney injury (AKI) and major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI).

Methods:
Consecutive patients undergoing PCI at a high-volume PCI center between 2015 and 2022 were analyzed. Patients on SGLT2 inhibitors prior to PCI were compared to those not on SGLT2 inhibitors. The primary outcome was AKI, as defined as serum creatinine increase of ≥0.5 mg/dL or ≥25% from baseline within 30 days of PCI. MACE was defined as death or myocardial infarction (MI) and was assessed at 1 year post PCI.

Results:
There were significant differences in baseline clinical characteristics between patients on (n = 347) vs. not on (n = 16,594) SGLT2 inhibitors. Patients on SGLT2 inhibitors had higher prevalence of diabetes (90.5% vs. 45.5%), hypertension (96.8% vs. 92.1%), hyperlipidemia (95.7% vs. 90.5%), and prior CABG (21.0% vs 15.8%). SGLT2 inhibitor use was associated with a decreased rate of post-PCI AKI (3.3% vs. 6.6%; adjusted odds ratio [OR] 0.33; 95% confidence interval [CI] 0.08-0.89, P=0.025). At one year after PCI, patients on SGLT2 inhibitors had increased rates of MACE (8.2% vs. 3.9%; adjusted hazard ratio [HR] 1.74, 95% CI 0.99-3.06, P=0.052), driven by an increased risk of MI (6.9% vs. 2.1%; HR 2.63, 95% CI 1.42-4.90, P=0.002).

Conclusions:
SGLT2 inhibitor use was associated with lower post-PCI AKI, but was associated with an increased risk of MACE. The latter finding was driven by increased risk of MI, which may be explained by unmeasured confounders in these heterogeneous groups of patients.
Abstract 13831: Engineered Development: Directed Morphogenesis of an Embryonic Heart Tissue Model
Authors: Gershlak Joshua R , Ott Harald
Published: November 2023

Introduction:
The embryonic heart undergoes a complex looping morphogenesis, transforming a tube into the four-chambered organ. This phenomenon creates proper alignment leading to specification in the developing heart. Disruptions in the looping process are indicative for the onset of CHDs. Directed morphogenesis of an engineered tissue could be useful as a model of cardiogenesis. We created such a model system through the directed morphogenesis of an engineered tissue mimic of the embryonic heart.

Methods:
Embryonic heart tubes (EHT) were engineered to have an inner acellular layer surrounded by a thin iPS derived cardiomyocyte layer (A), mimicking the
in vivo
anatomy. In the embryo, cardiac looping is driven through both internal and external forces (B), leading to elongation of the tube resulting in a rightward rotation at the cranial end of the embryo and a dorsal deflection at the caudal end. We created a novel bioreactor (C) that mimics the external forces that are exhibited upon the heart within the embryo to direct morphogenesis. Our bioreactor allows for rotation on the cranial end, dorsal deflection on the caudal end, and tissue shortening on the entire tube.

Results:
EHTs were looped using the bioreactor system and found to recapitulate specific anatomical shapes (D). Looped EHTs were maintained for seven days via perfusion culture (E). After the culture period, ends of the looped EHTs were found to have fused together. Histological investigation discovered the generation of different complex anatomical structures (F). Namely, the generation of an intraventricular septum, cellular orientations that match measured angles within mammalian hearts, and ventricular shapes that closely resemble native heart.

Conclusions:
In conclusion, through directed morphogenesis, we created a model of the embryonic heart that matches native anatomical structures. This model could be further expanded to further study cardiogenesis or modified to study the onset of CHDs.
Abstract 13850: Cost-Effectiveness Analysis of Universal Screening for Atrial Fibrillation Using Electrocardiographic Artificial Intelligence in a Rural Community in Taiwan
Authors: Liu Wei-Ting , Lin Chin-Sheng , LIN CHIN , Hsieh Ping-Hsuan
Published: November 2023

Introduction:
Atrial fibrillation (AF) substantially contributes to strokes, and screening for AF is generally recommended. However, implementing universal screening for AF is challenging in rural areas with limited medical resources. This study assessed the cost-effectiveness of using artificial intelligence-enabled 12-lead electrocardiography (AI-ECG) for AF screening in a rural community.

Methods:
The cost-effectiveness analysis focused on screening individuals aged 65 or older and utilized a lifelong decision analytic Markov model. The AI-ECG for AF was trained at a medical center in Taiwan, achieving a sensitivity of 0.944 (standard error [SE]: 0.015) and specificity of 0.941 (SE: 0.008). Costs and efficacy of anticoagulant treatments, utility of health status, and clinical variables such as stroke and major bleeding risks were estimated based on literature and epidemiological data from Taiwan. Results were presented as US dollars per quality-adjusted life year (QALY). The base-case analysis compared technicians using AI-ECG for AF detection and referral, and physicians' evaluation with standard 12-lead ECGs to no screening. Uncertainty in the model was addressed through probabilistic sensitivity analysis.

Results:
Both AI-ECG screening and screening by a physician were found to be more costly yet more effective when compared to no screening. While both strategies exhibited similar effectiveness, the cost was lower with AI-ECG than by a physician ($453 versus $490). Based on 10,000 Monte Carlo simulations, if the willingness to pay (WTP) for a QALY exceeds $9,514, screening by a physician is a cost-effective strategy. However, if the WTP per QALY falls between $2,289 and $9,514, AI-ECG screening is more cost-effective than physician-based screening.

Conclusion:
This economic evaluation demonstrates the cost-effectiveness of AI-ECG screening for AF, making it a practical alternative for AF screening in areas with limited medical resources.
Abstract 13852: Sex Differences in Blood Pressure Reduction and Cardiovascular Outcomes in Patients With Resistant Hypertension Undergoing Radiofrequency Renal Denervation: Global SYMPLICITY Registry DEFINE
Authors: Mihailidou Anastasia S , Mahfoud Felix , Schlaich Markus P , Schmieder Roland E , Narkiewicz Krzysztof , Ruilope Luis M , Williams Bryan , Fahy Martin , Boehm Michael , Mancia Giuseppe , Hettrick Doug , Weil Joachim
Published: November 2023

Introduction:
Hypertension (HTN) prevalence and outcomes differ by sex. Radiofrequency renal denervation (RF RDN) safely reduces blood pressure (BP) in patients with resistant HTN.

Hypothesis:
After RF RDN, there are no sex-based differences in BP changes and cardiovascular (CV) outcomes.

Methods:
The Global SYMPLICITY Registry (GSR) DEFINE is an all-comer registry of patients with uncontrolled BP undergoing RF RDN. BP changes (analysis of covariance [ANCOVA] adjusted for baseline BP and age), CV death, stroke, myocardial infarction (MI) rates at 3yrs were compared between sexes with office systolic BP (OSBP) ≥140mmHg, prescribed ≥3 anti-HTN drugs.

Results:
Patients enrolled up to March 2023 were included (N=2502, female=1062). Females were older (62 vs 59 y; p<0.0001), less likely to have a history of sleep apnea (12.5 vs 25.0% p<0.0001), cardiac disease (45.2 vs 50.3%; p<0.0012) and smoking (19.1 vs 41.3%; p<0.0001). Body mass index, rates of diabetes and chronic kidney disease, number of anti-HTN drugs (5.1±1.5 in both sexes; p=0.88) and 24-hr SBP were similar by sex. Baseline OSBP was higher in females (174±23 vs 169±19mmHg; p<0.0001).

After 3yrs, OSBP significantly decreased in both sexes from baseline (female: -21.5mmHg vs male: -20.4mmHg; ANCOVA adjusted difference: 3.2mmHg [95% CI: 0.5 to 6.0; p=0.021]). There was no difference in 24-hr SBP change (Figure 1A) or number of anti-HTN drugs by sex. CV death rate was significantly higher in females (4.1% vs 2.1% vs p=0.024), but MI rate was significantly lower in females (1.3% vs 3.5%; p=0.007). Stroke rate was similar by sex (Figure 1).

Conclusion:
Females with resistant hypertension referred for RF RDN were older, had higher OSBP with fewer comorbidities compared to males. Despite similar BP reductions up to 3yrs after RF RDN, CV death rate in females was greater than males. These results suggest the need for sex specific analyses and control of HTN in females.
Abstract 13861: Risk Prediction in Adults Late After Tetralogy of Fallot Repair: Does Machine Learning Provide Incremental Value Above Expert Clinical Judgement?
Authors: Ishikita Ayako , McIntosh Chris , Roche Susan L , Barron David , Oechslin Erwin , Benson Lee N , Nair Krishnakumar , Lee Myunghyun M , Hanneman Kate A , Rani Karur Gauri , Wald Rachel M
Published: November 2023

Introduction and Aim:
Machine learning (ML) can be used to predict major adverse cardiovascular events (MACE) in adults with repaired tetralogy of Fallot (rTOF). We sought to determine the incremental value of ML above expert clinical judgement for rTOF risk prediction.

Methods:
Adult congenital heart disease (ACHD) experts (≥10 years of clinical experience) participated (1 congenital heart surgeon and 4 cardiologists [2 with pediatric and 2 with adult cardiology training] with expertise in heart failure [HF], electrophysiology, imaging and intervention). Clinicians were individually asked to identify 10 high-yield clinical variables for 5-year MACE prediction (composite of mortality, resuscitated sudden death, sustained ventricular tachycardia and/or HF). Clinicians were blinded to outcomes and were asked to assign 5-year MACE risk (low, moderate, high) using 10 pre-specified variables for 25 adults with rTOF identified from an institutional database (prevalence of 5-year MACE 12%). A validated ML model was also used to predict outcomes in the same rTOF population using 10 variables.

Results:
Variables selected for risk prediction are shown (Figure A). As compared with the individual expert, the aggregate of 5 experts resulted in enhanced predictive capacity (Figure B). Predictive capacity of the ML model was similar to the aggregate of experts (Figures C,D). Experts with ≥20 years experience had better discriminative capacity for MACE prediction compared with <20 years (AUC 0.98 [95%CI 0.86-0.99] versus 0.80 [95%CI 0.56-0.93], p=0.03). In those with <20 years experience, ML provided incremental value such that the combined AUC approached ≥20 years (AUC 0.85 [95%CI 0.61-0.95], p=0.06).

Conclusions:
Prediction of 5-year MACE in rTOF using ML was similar to a multi-disciplinary team of ACHD experts. Risk prediction of less experienced clinicians was enhanced by incorporation of ML suggesting that there may be incremental value in select clinical settings.
Abstract 13867: Sustained Improvement in Door-to-Balloon Time Over 15 Years: The Aurora St. Luke’s 24x7 STEMI Program With Redefinition of Contemporary Door-to-Balloon Time Less Than 60 Minutes: 60 is the New 90
Authors: Ashraf Muddasir , Allaqaband Suhail Q , Bajwa Tanvir , Walczak Sara , Tunink Kirsten , Peterson Michael , Koblosky Christopher , Jan M F
Published: November 2023

Background:
In April 2004, Aurora St. Luke’s Medical Center implemented an in-house 24x7 interventional cardiology program to improve door-to-balloon time (D2BT) in ST-segment elevation myocardial infarction (STEMI). Previously published data showed a significant reduction in median D2BT, from 98 minutes (January 1, 2002-March 31, 2004) to 55 minutes (April 1, 2004-June 30, 2008), along with a reduction in major adverse cardiovascular events (MACE) and mortality after implementation of the program.

Hypothesis:
We hypothesized that the continued experience with the 24x7 program would demonstrate further gain in STEMI outcomes in regard to D2BT.

Aims:
The primary objective was to evaluate the overall median D2BT over a 15-year period. The secondary objectives were to evaluate median D2BT stratified by weekdays and weekends, on- and off-hours, the proportion of D2BT <90 minutes, and the proportion of D2BT <60 minutes over time.

Methods:
We collected data on all non-transfer adult patients with STEMI from April 1, 2004, to March 31, 2019, at our center. On-hours were from 7:30 a.m. to 5 p.m. and off-hours from 5 p.m. to 7:30 a.m.

Results:
A total of 1889 patients with STEMI (median age [IQR] 61 [54-71] years, 31% female) were evaluated. Over 15 years, median D2BT decreased from 69 minutes to 46 minutes (P < .001; Fig 1A). The decreasing trend was seen on weekdays and weekends (Fig 1B) and on-hours and off-hours. The percentage of cases with a median D2BT <90 minutes increased from 77% to 97% over 15 years, and those with a median D2BT <60 minutes increased from 36% to 76% (Fig 1B).

Conclusion:
We show sustained improvement in our median D2BT and remarkable improvement in the proportion of D2BT <60 minutes. This paves the way for redefining the contemporary D2BT from <90 to <60 minutes.
Abstract 13871: Portrayal of Acute Myocardial Infarction in Popular Film
Authors: Shaw Kirsten E , Diedrich Amy , Holbrook Amy , Carlson Michelle D , Harris Kevin M , Saxena Retu
Published: November 2023

Introduction:
The representation of cardiovascular disease (CVD) in popular media plays a pivotal role in shaping public conceptions about CV health. CVD is the leading cause of death among women and disproportionately affects racial/ethnic minority populations in the United States, yet recent national surveys indicate a significant decline in public awareness. Our study sought to investigate the portrayal of acute myocardial infarction (AMI) in popular film.

Hypothesis:
Portrayal of AMI in film will predominantly show white men exhibiting symptoms of chest pain. Women, racial/ethnic minority populations, and subtle symptoms of AMI will be underrepresented.
Aims:
To examine 100 full length feature film scenes depicting AMI and evaluate the representation of gender, race/ethnicity, and symptoms.

Methods:
The 100 most popular films with scenes depicting AMI were identified using the Internet Movie Database (IMDb). Scenes and AMI symptoms were analyzed by cardiologists/cardiology fellows. Gender and race/ethnicity were acquired via movie plots/scripts or via actor self-identification if the former was unavailable.

Results:
Of the 100 scenes analyzed, 10% depicted women. The representation of people of color was only 6% in contrast to the 94% of scenes featuring non-Hispanic whites. Of the 10 women portrayed, 1 was non-white. The distribution of gender and race/ethnicity for all scenes is shown in
Figure 1.
The most prevalent presenting symptom observed in 65% of scenes was chest pain accompanied by loss of consciousness.

Conclusions:
Popular film depictions of AMI appear to be under representative of women and racial/ethnic minority populations. This may be a contributing factor to the inaccurate public perception that CVD does not affect these populations. Film depictions of AMI, which predominantly portray dramatic symptoms of chest pain and loss of consciousness may also perpetuate false beliefs on typical (or even atypical) symptoms of AMI.
Abstract 13874: N Terminal Pro-Brain Natriuretic Peptide Levels and Benefits of Chronic Total Occlusion Revascularization
Authors: Gold Daniel A , Sandesara Pratik B , Jain Vardhmaan , Gold Matthew E , Vatsa Nishant , Desai Shivang , Elhage Hassan Malika , Yuan Chenyang , Ko Yi-An , Liu Chang , Ejaz Kiran , Alvi Zain N , Alkhoder Ayman , Rahbar Alireza , Murtagh Gillian , Varounis Christos , Jaber Wissam , Nicholson William , Quyyumi Arshed A
Published: November 2023

Background:
The management of chronic total occlusion (CTO) remains a subject of debate, as the mortality benefit from revascularization remains controversial. Whether specific populations gain a survival benefit from CTO revascularization remains unknown.

Purpose:
In this prospective study of patients with stable coronary artery disease (CAD), we investigated whether patients with CTO have higher adverse event rates and higher N terminal pro-brain natriuretic peptide (NT pro-BNP) levels than patients without CTO. We also investigated whether a higher NT pro-BNP level predicts adverse events in patients with CTO and whether those with elevated NT pro-BNP levels have a survival benefit from revascularization.

Methods:
In 2,253 patients with significant CAD (
>
50% coronary luminal stenosis) undergoing cardiac catheterization, all-cause mortality, cardiovascular mortality and the composite of cardiovascular death, myocardial infarction and heart failure hospitalization rates were evaluated. Unadjusted and adjusted Cox proportional and Fine and Gray sub-distribution hazard models were performed to determine the association between NT pro-BNP level and event rates.

Results:
Patients with CTO had higher incident event rates by > 20% and had higher NT pro-BNP levels than those without CTO (median 230.0 vs. 177.7 pg/mL, p=<0.001). In patients with CTO, every doubling of NT pro-BNP level was associated with > 25% greater risk of adverse events. In patients with elevated NT pro-BNP level (> 125 pg/mL), CTO revascularization was associated with >50% lower adverse event rates than those without CTO revascularization (adjusted cardiovascular death hazard ratio 0.24, 95% confidence interval 0.07 - 0.81). Among patients with low NT pro-BNP level (< 125 pg/mL), event rates were similar in those with and without CTO revascularization.

Conclusion:
Patients with CTO have higher adverse event rates than those with significant CAD without CTO. NT pro-BNP levels are higher in patients with CTO and higher levels portend a worse prognosis. Moreover, NT pro-BNP levels can help identify individuals who may benefit from CTO revascularization.
Abstract 13876: Women Face Unique Obstacles During Pediatric Cardiology Fellowship Training
Authors: West Caroline L , Yu Sunkyung , Lowery Ray , Goldberg Caren S , Balasubramanian Sowmya
Published: November 2023

Background:
There are persistent disparities in career advancement for women physicians in pediatric cardiology. We sought to explore differences by gender in fellowship experience, as these may set the foundation for long-term gender inequity.

Aims:
To describe and compare fellowship experiences, career aspirations and family obligations of men and women in pediatric cardiology training.

Methods:
We performed a national survey of pediatric cardiology fellows examining mentorship, scholarly and DEI work, clinical experiences, career intentions and family commitments. Descriptive analyses were performed.

Results:
A total of 176 responses were included in the analysis (men=74, women=102). Most fellows were white (69%) and aged 30-34 years old (68%).

Men and women reported similar mentorship, scholarly and clinical experiences, and influential factors in their decision to pursue subspecialty training. More women plan to pursue advanced imaging training (42% vs. 24%, p=0.04), to have administrative responsibilities (27% vs. 14%, p=0.06), and to work part time during their career (28% vs. 5.6%, p=0.001). Men reported greater interest in teaching (93% vs. 83%, p=0.04).

While similar proportions of men and women were married, the spouses of women were more likely to be employed (91% vs. 71%, p=0.002). Among fellows with children, more women than men planned for additional children (75% vs. 25%, p=0.0004). Among fellows without children, more men than women planned for additional children (93% vs. 74%, p=0.01). Women were more likely to report delay in childbearing due to training (71% vs. 40%, p=0.0002), that childbearing decisions were influenced by the risk of radiation exposure (22% vs. 0%, p<.0001), and the use of assistive reproductive technologies (11% vs. 1%, p=0.01).

Conclusion(s):
Women and men in pediatric cardiology fellowship have similar training experiences and career aspirations yet differ in their plans to raise families. Women face unique obstacles to childbearing and child raising during training. Motherhood in pediatric cardiology may be a vulnerable period during career development and advancement.
Abstract 13877: Podoplanin Positive Cell-Derived Extracellulatr Vesicles as Novel Mediators of Cardiac Amyloidosis After Myocardial Infarction
Authors: Cimini Maria , Tukel Cagla , Hansmann Ulrich H.E. , Gonzalez Carolina , Chesney Andrew , Truongcao May , Wang Chunlin , Gao Erhe , Wang Tao , Roy Rajika , Lucchese Anna Maria , Mallaredy Vandana , Gurrala Charan T , Magadum Ajit , Joladarashi Darukeshwara , Benedict Cindy , Koch Walter J , Kishore Raj
Published: November 2023

Amyloidosis represent a major long-term complication of myocardial infarction (MI);however, the exact mechanisms of post-MI cardiac amyloidosis are yet to be fullyunderstood. Onset of amyloid fibers deposition alongside with extra-cellular-matrix (ECM)proteins in the ischemic tissue exacerbates rigidity and stiffness of the scar hindering thecontractility of viable myocardium in the left ventricle. Amyloid proteins, at the site of injury, are released after inflammation mostly by activated immune cells and mesenchymalstomal cells. We have reported earlier that two days after MI, a cohort of mesenchymalstromal cells begin to de novo express Podoplanin (PDPN), a platelet aggregation-inducing type I transmembrane glycoprotein, as a sign of activation. PDPN acquisitionallows mesenchymal stromal cells to communicate with macrophages bearing PDPNreceptor, a C-type lectin-like receptor 2 (CLEC-2). Here we show that in addition to cell-to-cell contact, Podoplanin positive cells (PDPN+ cells) further activate macrophagesthrough their extracellular vesicles or exosomes. Specifically, PDPN+ cells derivedexosomes deliver Serum Amyloid A 3 (SAA3) protein that, after binding to Toll-likereceptor 2 (TRL2) on macrophages, triggers an overproduction of SAA3 in macrophages,with consequent impaired clearance of SAA3. Saturated lysosomes release SAA3protofilaments that are prone to misfold and aggregate as extracellular, insoluble, andrigid amyloid deposits leading to cardiac amyloidosis. We show that injection of exosomesfrom PDPN+ mesenchymal stromal cells induce infiltrating fibrosis, SAA3 deposition anddepressed cardiac function in healthy mouse hearts. Using SAA3 and TLR loss-of-function mouse models we show that SAA3 delivered by PDPN+ cell exosomes have alocal function in promoting post-MI amyloidosis. In vivo administration of newly developedD-peptide inhibits the aggregation of misfolded SAA3 with consequent scar stiffnessreduction and positive modulation of the ischemic heart function. In addition to providingnew mechanistic insights into post-MI amyloidosis, our findings suggest that SAA3 maybe an attractive target for effective scar reversal after ischemic injury.
Abstract 13881: Coronary Artery Calcium as a Risk Marker in Patients With Myocardial Infarction but Without Standard Modifiable Risk Factors (SMuRF-Less)
Authors: Anderson Jeffrey L , Knight Stacey , Dong Li , May Heidi T , Le Viet T , Bair Tami L , Knowlton Kirk U
Published: November 2023

Introduction:
Recent publications have reported that myocardial infarction (MI) patients (pts) without standard modifiable risk factors (SMuRF-less) are surprisingly common (14-27%) and have a notable risk of adverse outcomes. These reports raise the question of how these pts can be identified in advance and provided with effective preventive therapies (e.g., statins, aspirin).

Methods:
Pts presenting between 2001-2021 to Intermountain Healthcare catheterization laboratories with a diagnosis of MI were included if they also had a coronary artery calcium scan (CACS) by computed tomography within 2 years. SMuRF included a clinical diagnosis of, or treatment for, hypertension, hyperlipidemia, diabetes, and/or smoking. The co-primary endpoints for this study were the proportion of patients with an elevated (>50%ile) CACS score (MESA criteria) and the presence of an indication for statin therapy with or without aspirin (i.e., >=75%ile score or CAC>=100 AU). Major adverse cardiovascular event (MACE) outcomes at 60-days and long-term were evaluated and compared to MI pts with SMuRF.

Results:
We identified 429 MI pts with a concurrent CACS, of which 60 were SMuRF-less and 369 had SMuRF. The 2 groups were similar in age, sex, most risk factors, and interventions, but fewer SMuRF-less pts had a history of heart failure or a family history (Table 1). SMuRF-less pts had a high prevalence and an increased percentile of CAC (82% >=50%ile; median, 80%ile;), and 77% met criteria for preventive therapy. Pts with SMuRF, as expected, had high CAC scores and percentiles (Table 1). Outcomes were more favorable for SMuRF-less status (Table 2A) and for lower CAC scores (Table 2B).

Conclusions:
Despite absence of SMuRF, SMuRF-less pts presenting with an MI have a high prevalence and percentile of CAC. Wider application of CACS, to include those without SMuRF, appears promising as a method to identify an additional at-risk population for consideration of preventive therapy.
Abstract 13886: Impaired Locomotor Muscle Blood Flow During Cycling Exercise in Heart Failure With Preserved Ejection Fraction
Authors: Cifci Gizem , Hammer Shane , Bruhn Eric , Bissen Thomas , Borlaug Barry A , Olson Thomas P , Smith Joshua R
Published: November 2023

Introduction:
Obesity and hypertension (HTN) are highly prevalent comorbid risk factors for heart failure with preserved ejection fraction (HFpEF). Obesity and HTN independently increase sympathetic nervous activity and impair muscle blood flow during exercise. Previous work has reported attenuated limb blood flow in patients with HFpEF; however, these findings were compared to controls with dissimilar comorbidities and during small muscle mass exercise. It is unclear if HFpEF alters muscle blood flow responses independent of the obesity- and HTN-mediated alterations.

Hypothesis:
We hypothesized the muscle blood flow response during cycling would be lower in HFpEF patients than age, sex, BMI, and HTN matched controls (CTL).

Methods:
HFpEF patients (n=14, 9M/5W, 71±7yrs, 32±4 kg/m
2
) and CTL (n=12, 8M/4W, 69±7yrs, 31±4 kg/m
2
) performed an incremental cycling test. Blood pressure was measured by manual sphygmomanometry, cardiac output (Q) by open-circuit acetylene wash-in technique, and systemic vascular resistance (SVR) was calculated. Vastus lateralis blood flow index (BFI) was measured by near-infrared spectroscopy and indocyanine green dye injections and venous norepinephrine concentration was measured. Changes from rest to 40 W of the incremental test are reported.

Results:
Resting Q, mean arterial pressure, SVR, and venous norepinephrine concentration were not statistically different between groups (p>0.18). From rest to 40 W, the increases in Q (CTL: 3.9±0.8 vs. HFpEF: 3.6±0.7 L/min), mean arterial pressure (CTL: 5.7±2.7 vs. HFpEF: 6.6±6.1 mmHg), and SVR (CTL: -7.3±2.1 vs. HFpEF: -6.0±2.0 mmHg/L/min) were not statistically different between groups (all, p>0.13). The HFpEF group had smaller increases in vastus lateralis BFI at 40 W compared to CTL (CTL: 7.2±3.6 vs. HFpEF: 4.2±2.6 fold-increase from rest) (p=0.02). The HFpEF group had greater increases in venous norepinephrine concentration from rest to 40 W than CTL (CTL: 164±216 vs. HFpEF: 377±247 pg/mL) (p=0.05).

Conclusions:
Our findings suggest that, compared to age, sex, BMI, and HTN matched controls, patients with HFpEF have an impaired locomotor muscle blood flow response during submaximal cycling exercise likely due to higher locomotor muscle vascular resistance.
Abstract 13892: Enhancing Guideline-Directed Medical Therapy in Post-Discharge Heart Failure Patients Through Comprehensive Medication Management Visits With Virtual Clinical Pharmacists
Authors: Plotke Melanie , Thai Tram , Jafri Farrukh
Published: November 2023

Introduction:
According to national registries, the adoption and effective titration of GDMT for patients with HFrEF remains notably inadequate. Utilizing virtual clinical pharmacists (VCPs) to identify deficiencies in medication therapy presents a flexible and efficient approach for thorough and immediate interventions following discharge.

Methods:
A single-center retrospective analysis from May 2022-April 2023 examined post-discharge HF patients who participated in a comprehensive medication management (CMM) visit conducted by a VCP within 72 hours of their discharge.

Results:
Of 116 participants, 108 (93%) had a discharge diagnosis of HFrEF, and 8 (6.8%) with HFimpEF. During the VCP visit, 27 (23.3%) presented with active HF exacerbation symptoms including SOB (33%), fatigue (22%), weakness (19%), lower extremity swelling (11%), weight gain (11%), and tachycardia (4%). The percentages of the total population currently prescribed GDMT for HRrEF and HFimpEF classes are as follows: Beta Blocker (89.7%), ARNI (47.4%), MRA (33.6%), SGLT2i (25.9%), and ACEI/ARB (22.4%). Up-titrating of dosage was recommended for 75% of patients currently prescribed ARNI, 64% for Beta Blockers, and 51% for MRAs. Additionally, VCPs recommended adding the following drug classes to those not prescribed, despite being indicated: SGLT2i (45%), ARNI (30%), MRA (29%), Beta Blocker (25%), and ACEI/ARB (24%). Comprehensive counseling on HF self-care practices was delivered to the entire cohort (100%). Furthermore, support was extended to facilitate the management of comorbid conditions for 105 patients (91%), and social assistance was provided to 7 patients (6%).

Conclusions:
The utilization of VCPs played a crucial role in identifying care gaps, including but not limited to patient symptoms, suboptimal medication therapy, insufficient disease education, social assistance, and comorbidity management, which collectively contributed to initiating and up-titrating GDMT.
Abstract 15628: Digital Health Interventions for the Optimization of Postpartum Cardiovascular Health: A Systematic Review
Authors: Hausvater Anais , Pleasure Mitchell , Vieira Dorice , Banco Darcy , Halpern Dan , Dodson John A
Published: November 2023

Introduction:
Insufficient maternal care in the postpartum period (PP) has resulted in significant maternal morbidity and mortality in the U.S., most commonly due to cardiovascular (CV) disease. Digital health technologies have been proposed as a potential solution to eliminate barriers to maternal CV care. In this context we performed a systematic review to determine the benefit of digital health interventions designed to improve postpartum CV health.

Methods:
We conducted a systematic review of PubMed/MEDLINE, EMBASE, CINAHL, Web of Science and the Cochrane Library. We included studies if the study population included PP women, and an intervention that involved digital or mobile health (including wearable devices, telemedicine, or remote monitoring). We only included studies that measured an outcome related to CV health. Two independent reviewers screened all studies and a third independent reviewer resolved any conflicts.

Results:
Our initial search identified 1448 studies. After removal of 143 duplicates, 1305 abstracts were screened of which 51 full studies were assessed for eligibility. Of these, 17 met inclusion/exclusion criteria. Studies were categorized into 3 broad CV outcomes: blood pressure (BP), physical activity (PA), and diet/weight loss. The majority of remote BP monitoring programs paired with telemonitoring (N=5 studies) were successful in optimizing BP, and increasing likelihood of BP measurement within 10 days PP. Interventions aimed at increasing PP physical activity included mobile applications, text-based coaching, and wearable devices such as pedometer and FitBit (N=9 studies). Just over half of these studies showed no change in PA, while the other half showed modest benefit at increasing daily or weekly PA. Weight loss interventions included smartphone applications, interactive websites, or text-based coaching (N=6 studies). Most of these studies showed a modest benefit in terms of lowered caloric intake and/or weight loss up to 1 year PP.

Conclusions:
The majority of studies we reviewed found that digital health interventions such as mobile health, telemonitoring and wearable devices were effective at improving postpartum CV health in the postpartum period.
Abstract 16081: Cardiovascular Outcomes of Individuals With Sleep Deprivation; a Retrospective Population-Based Analysis
Authors: Evbayekha Endurance O , Gaibor Carlos , Jelwan Yara , Desai Purav , Kuttab Rani , Bastidas Leonela , Abbas Amer , Dixon Brittany , LaRue Shane
Published: November 2023

Introduction:
Inadequate sleep quality and duration have been linked to adverse cardiovascular effects. Examining the cardiovascular outcome profile of the inpatient population with sleep deprivation (SD) has been relatively scarce. We aimed to study the outcomes in this setting.

Hypothesis:
We hypothesize that SD is associated with adverse cardiovascular outcomes, and studying the effect will help inform clinical care and prevention strategies.

Methods:
We used the ICD-10 code to identify all hospitalizations aged 18-85 with a primary or secondary SD diagnosis from the Nationwide Inpatient Database (NIS) 2016-2020. We excluded individuals with sleep apnea and those with established SD due to medical or psychiatric illnesses. A multivariate logistic regression model was used to account for confounders (including demography, smoking history, hospital setting, and insurance type) and estimate the probability of outcomes. Our outcomes of interest were hypertension (HTN), dyslipidemia (DysL), and obesity.

Results:
There were 27,294,891 hospitalizations aged 18-85 during the study period, and 2.6% (718,083) had a sleep deprivation diagnosis, mean age of 57.7 years ± 17. Of these, 74.8% (519497) were Caucasians, 12.1% (84463) were Blacks, and 8.1% (56316) were Hispanics. Individuals with SD had a higher likelihood of HTN, adjusted odds ratio (aOR) =1.28 (1.27-1.30, p<0.0001), DysL 1.3 (1.2-1.3, p<0.0001), and obesity 1.02 (1.01-1.02, p<0.0001).

Conclusions:
Our analysis showed that sleep deprivation was associated with a higher likelihood of hypertension, dyslipidemia, and obesity. Encouraging lifestyle modification, including adequate sleep hygiene, cannot be overstated.