bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143125: Definition of cardiomyocyte generation in infants with heart disease
Authors: Bargaje Anita , AMMANAMANCHI NIYATIE , Yester Jessie , Zhou Hairu , Mich-Basso Jocelyn , Guillermier Christelle , Steinhauser Matthew , Guan Yunbin , Little Kathryn , Thomas Dawn , Janzef Shannon , Weinberg Jacqueline , Johnson Jennifer , Seery Thomas Joseph , Funari Bryan , Harris Tyler , Arora Gaurav , Rose-Felker Kirsten , Zinn Matthew , MILLER SUSAN , West Shawn , Feingold Brian , Morell Victor , VIEGAS MELITA , da Silva Luciana , Castro Medina Mario , Sullivan Mara , Moulik Mousumi , Reyes-Mugica Miguel , Liu Honghai , Kuhn Bernhard
Published: November 2024

Introduction:
Cell cycle entry and division of differentiated heart muscle cells (cardiomyocytes, CMs) is the evolutionarily conserved mechanism of heart development and regeneration. Quantification of CM proliferation in humans is a critical step towards developing new regenerative therapies for heart failure. To provide definitive evidence for CM proliferation and to characterize the generated phenotypes in humans, we implemented a new research approach using
15
N-thymidine administration to mark cells in S-phase.

Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease and heart failure is the most common indication for heart transplantation. We selected these patient populations because they undergo heart surgery or transplantation, which provide myocardial samples for research.

Research Goal:
To define CM generation in human infants.

Methods:
We administered
15
N-thymidine on five consecutive days in infants who subsequently underwent heart surgery or heart transplantation. The retention of
15
N was visualized by analyzing heart muscle sections with Multi-isotope Imaging Mass Spectrometry (MIMS). Tissue sections adjacent to the MIMS sections were stained with the DNA-dye, Hoechst, to identify and quantify formation of post-mitotic phenotypes, i.e., CMs with polyploid nuclei and multinucleated CMs. Quantitative results presented as mean ± SEM.

Results:
Infants of 2 months of age and younger at label administration generated 3.9 ± 1.3% new cardiomyocytes (n = 5) and infants between the ages of >2 to 4 months at label administration generated 2.9 ± 1.0% new cardiomyocytes (n = 6). Infants 4 months of age and older generated 0.1 ± 0.1% new cardiomyocytes (n = 3). In ToF (n = 9 infants), 36.0 ± 10.5% of generated cardiomyocytes were mononucleated with polyploid nuclei. Available results from four infants showed formation of binucleated CMs, with the majority having polyploid nuclei.

Conclusions:
Infants with ToF or heart failure showed a decrease in CM generation with increasing postnatal age. Infants with heart disease generated a high proportion of multinucleated CMs and CMs with polyploid nuclei, indicating increased formation of postmitotic CMs. In conclusion, this study provides definitive evidence for the generation of CMs in infants with heart disease, identifies formation of postmitotic CMs as targetable cellular mechanism, and defines the age window in which therapies to direct CM generation could be effective.
Abstract 4143128: Understanding the Circumflex Aortic Arch Anatomy is Critical in Transcatheter Aortic Valve Replacement and Critical Bicuspid Aortic Valve Stenosis.
Authors: Lan Merrina , Boudoulas Konstantinos , Henn Matthew , Marshall William
Published: November 2024

Case description:
A 64-year-old male was referred for transcatheter aortic valve replacement (TAVR) due to critical bicuspid aortic valve stenosis (Figure 1A/B) with multiple episodes of unexplained syncope. A multidisciplinary discussion determined that he was at high surgical risk due to multiple comorbidities, including developmental delay, and prior renal transplantation with baseline serum creatinine of 1.8 mg/dL.

Transfemoral and trans-subclavian arterial approaches for valvular replacement were not anatomically feasible due to the circumflex aortic arch (Figure 2A/B). Left transcarotid approach was considered due to the location of the vessel as the first branch of the ascending aorta (Figure 2B, 3A) but was unsuitable due to significant left carotid artery calcification. Thus, the decision was to perform a transaortic approach under general anesthesia.

A right femoral artery sheath was inserted, and a wire was advanced to the aortic root (Figure 2B) for pigtail placement used to guide positioning during TAVR. A mini upper hemi-sternotomy was performed and J-ed into the right second intercostal space. The pericardium was suspended, and two concentric purse string sutures were placed in the aorta at the site of sheath placement. The valve was crossed and following valvuloplasty, the 29-mm Edwards SAPIEN 3 valve was delivered across the aortic valve annulus and deployed following balloon inflation with rapid ventricular pacing (Figure 3A). Postoperative echocardiography showed no prosthetic stenosis (Figure 3B) and no valvular or paravalvular regurgitation.

Discussion:
To our knowledge, this is the first report of a transaortic TAVR performed on a patient with a circumflex aortic arch. Circumflex aortic arch is a rare congenital anomaly and poses challenges to transcatheter aortic valve interventions from the extremities. This case illustrates the potential of transaortic TAVR as treatment for symptomatic aortic stenosis when there are no other options for access. Multidisciplinary collaboration and comprehensive imaging are critical in tailoring individualized cardiovascular intervention in patients with congenital anatomical variations.
Abstract 4143137: Lets talk about sex: update on sexual health and information need of persons with a cardiac illness.
Authors: Jaarsma Tiny , Klompstra Leonie , Persson Tommy , Klingvall Elin , Skoglund Anna , Saren Frida
Published: November 2024

Background:
Sexual health is an important aspect of quality of life, regardless of cardiac disease. However, there is a significant gap between patients' information needs and the ability of the healthcare system to meet these. Most studies focus on clinical populations in specialized clinics, but data on sexual health and information needs among community based cardiac patients is scarce.

Method:
We conducted an online national survey in Sweden in 2024. The survey was developed based on literature and previous international surveys on sexual health in cardiac patients. Recruitment took place via patient organizations, clinical outpatient departments and via social media. All data was collected anonymously.

Results:
In total 135 persons (59% male, mean age 65, range 30-89) answered the survey, 47% had hypertension, 36% had a myocardial infarction, 30% atrial fibrillation, 24% heart failure.

In total 76% stated that their sexual health was impacted by their disease and affects their mood and well-being (n=102). Men more often than women thought their disease impacted their sexual health (65% vs. 35%, p=0.02) and more often that sexual health affected their mood and well-being (64% vs. 36%, p<0.01).

Only 5% received sexual health information, but 78% wanted it. Men more often expressed a desire for information compared to women (87% vs. 64%, p=0.02).

The most desired topics include medication side effects (60%, n=81), erectile dysfunction (50%. n=68), impact on relationships (47%, n=63) and anxiety before sex (35%, n=47). Men wanted information on erectile dysfunction (80% vs. 7%), and women wanted more often information on pain during sex (13% vs. 1%, p<0.01).

Patients prefer to receive information during annual check-ups (57%, n=77), and/or during diagnosis (51%, n=69), and/or during medication follow-ups (40%), n=54. Patients most favor conversations with healthcare professionals (79%) and/or getting information at various times from different sources (43%).

Conclusion:
This study highlights a significant gap between patients’ needs for sexual health information and the actual support provided by the healthcare system. Despite 76% of patients reporting that sexual health affects their mood and well-being, only 5% received relevant information or counseling. The study underscores the importance of structual policy changes addressing sexual health concerns in cardiac patients.
Abstract 4143185: Association between Secondary Mitral Regurgitation and Left Atrial Structural Abnormalities in Atrial Fibrillation
Authors: Kassar Ahmad , Chamoun Nadia , Chahine Yaacoub , Akoum Nazem
Published: November 2024

Background:
Atrial fibrillation (AF) is increasingly recognized as a cause of secondary mitral regurgitation (SMR), exacerbating heart failure symptoms and complicating the management of AF.

Hypothesis:
SMR quantified using cardiac magnetic resonance (CMR) 4D flow is associated with left atrial (LA) structural derangements in patients with AF.

Goals:
To demonstrate an association between the atrial volume and fibrosis with mitral regurgitation severity

Methods:
Patients were recruited from the University of Washington Medical Center AF clinics. CMR was used to quantify LA fibrosis through late gadolinium enhancement, LA emptying fraction (LAEF), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF) (Panel A). Total mitral valve flow, regurgitant fraction, and peak velocity were quantified using CMR-derived 4D flow and cine images (Panel B). Patients with valvular disease (rheumatic valvular disease and prosthetic valves) were excluded from the analysis.

Results:
A total of 44 patients were included (71 years (64-76), 39% with persistent AF, BMI 28.8 kg/m
2
± 6.2, 45% females, 43% hypertensive, and 20% with a history of heart failure). 4D flow quantified MR was at 14% (3.7-45) which represented the median percentage of mitral regurgitant flow (MR flow/Total Mitral Flow), total mitral flow 29.2 mL (14.2-60.8), and peak velocity 194.5 cm/s ± 72.6. Using CMR cine images, median LVEF was 62.4% (56.4-66), heart rate was 65 bpm (49.5-75), left atrial volume was 97.3±39.3 mL, LAEF was 42.4±18.5%, and LVEDV was 146±44.6 mL. Left atrial fibrosis was 14.0% ± 7.9. Using multivariable linear regression, there was a significant association between LA volume and MR fraction (β = 0.35, p=0.04) after adjusting for peak velocity, LAEF, fibrosis, LVEDV, LVEF, and HR. Moreover, there was an association between HR and MR fraction (β = -0.3; p=0.04) and between total mitral flow and MR fraction (β = -0.78; p<0.001).

Conclusion:
In a cohort of AF patients without primary valvular abnormalities, secondary mitral regurgitation quantified using 4D flow CMR was associated with advanced atrial remodeling manifesting through LA volume increase.
Abstract 4143206: Gender Disparities in Heart Transplant Outcomes for Heart Failure Patients: Insights from the National Inpatient Sample Dataset
Authors: Odo Chinenye , Tolu-Akinnawo Oluwaremilekun , Awoyemi Toluwalase , Ogunniyi Kayode , Anuforo Anderson , Barriga Guzman Rocio
Published: November 2024

Background:
Heart failure is a leading cause of morbidity and mortality globally, and heart transplantation remains a definitive treatment for end-stage heart failure. Previous studies have suggested potential gender disparities in access to and outcomes of heart transplantation, but comprehensive analyses using large datasets are limited.

Objective:
This study aims to investigate gender disparities in heart transplant outcomes among heart failure patients using the National Inpatient Sample (NIS) dataset.

Methods:
Using the National Inpatient Sample NIS dataset (2017-2020), we analyzed data from 11,025 heart failure patients who underwent heart transplantation, with 7,920 males and 3,105 females. Demographic characteristics, comorbidities, and clinical outcomes were compared between genders. Multivariate analyses were conducted to adjust for potential confounders.

Results:
In this study, females undergoing heart transplant were significantly younger than males (51.6 ± 29.8 vs. 55.0 ± 26.4 years, p < 0.001). Males exhibited higher incidences of comorbid conditions including hypertension (80.7% vs. 69.7%), diabetes (37.3% vs. 24.8%), and ischemic heart disease (43.4% vs. 26.3%) (all p < 0.001). Both genders had comparable odds of in-hospital mortality (OR 0.98, 95% CI 0.80-1.19, p = 0.842) and mechanical ventilation requirements (OR 1.04, 95% CI 0.93-1.17, p = 0.509). Additionally, the length of hospital stay (difference -2.09 days, 95% CI -3.81 to -0.37, p = 0.223) and hospital charges (difference $31,645, 95% CI -$15,309 to $78,599, p = 0.044) were similar between genders. However, females had significantly higher odds of post-transplant complications such as vasopressor requirements (OR 1.14, 95% CI 1.03-1.26, p = 0.014), stroke (OR 1.22, 95% CI 1.01-1.47, p = 0.044), and vascular complications (OR 1.35, 95% CI 1.17-1.57, p < 0.001).

Conclusion:
These findings suggest that while age and pre-existing conditions vary by gender, in-hospital outcomes are largely similar, though females may face higher risks of specific post-transplant complications.
Abstract 4143309: Fluorescence-Labeled Very Low-Density Lipoproteins (VLDLs) Clearance Method for the Assessment of Dynamic VLDLs Function in Mice
Authors: Zu Yujiao , Pahlavani Mandana , Walker Tatum , Scoggin Shane , Moustaid-Moussa Naima
Published: November 2024

Introduction:
Very Low-Density Lipoproteins (VLDLs) serve as crucial transporters of triglycerides (TG) and cholesterol (C) from the liver to peripheral tissues, thereby contributing significantly to metabolic disorders such as atherosclerosis. Assessing the dynamic of VLDLs function involves evaluating its clearance from the bloodstream and distribution across various organs. Although VLDLs clearance has been extensively studied using dual radioactive isotopes
3
H and
14
C to label TG and C, this method requires large amounts of expensive tracers, compliance, and technical complexities. Our objective is to design and test a fluorescence-based approach to simultaneously assess and visualize VLDLs kinetics in a mouse model. Through this approach, we aim to unravel the intricate interplay between thermogenesis and VLDLs metabolism and provide insights into their collective influence on the progression of atherosclerosis in vivo.

Method:
Fluorescence-labeled VLDLs-like TG-rich nanoparticles (F-VLDLs) were prepared at various intensity by incorporating lissamine rhodamine-TG (Rhoda-TG, 1-5% of total TG) and TopFluor®-C (TopF-C, 20-80% of total C) to a mixture containing glycerol trioleate (7mg), egg yolk phosphatidylcholine (2.3mg), lysophosphatidylcholine (0.23mg), cholesteryl oleate (0.3mg), cholesterol (0.2mg) and kolliphor HS15 (2mg). B6 mice were fasted for 4 hours and injected via the tail vein with various intensities of F-VLDLs (2 mg TG/mouse). Blood samples were collected at 5-, 10- and 15-min post-injection to determine the plasma clearance of Rhoda-TG and TopF-C, after which mice were euthanized, and tissues harvested and imaged using an IVIS® spectrum in vivo imaging system.

Results:
The mean particle size of F-VLDLs was 80nm, with polydispersity index values of about 0.2. The Zeta potential of freshly made F-VLDLs was about −20 mV. In B6 mice, both Rhoda-TG and TopF-C signal intensities peaked at 5 minutes post-injection and subsequently declined in an intensity-dependent manner. In the collected tissues, Rhoda-TG and TopF-C intensity was as follows: liver>brown fat>subcutaneous white fat >visceral white fat.

Conclusion:
We have designed novel fluorescence-labeled VLDVs-like particles as a viable approach for quantifying and visualizing dynamic VLDLs-TG and C flux in vivo. This approach will facilitate the assessment of how various metabolic interventions impact VLDLs metabolism and atherosclerosis.
Abstract 4143332: Cross-Platform Variations in Transthoracic Echocardiography: Implications for Clinical Decision-Making
Authors: Hashemi Mohammad , Farsiani Yasaman , Pressman Gregg , Amini MohammadReza , Kheradvar Arash
Published: November 2024

Background:
Precise measurement of cardiac chamber size and function is crucial for clinical decision making, and these measurements should be consistent across different echocardiography systems. Despite the assumption that modern echocardiography machines have negligible cross-platform variations, few studies have rigorously compared them. This study evaluates the cross-platform variations between Philips EPIQ CVx (release 9.0.3) and Canon Aplio i900 (release 7.0) in assessing cardiac volumes, ventricular function, and valve structures.

Hypothesis:
Data acquired across various echocardiography platforms exhibit statistical equivalence.

Aims:
To study cross-platform variations in transthoracic echocardiography and their implications for clinical decision-making

Methods:
In this gender-balanced prospective study, 40 volunteers aged 40 and older were scanned sequentially by both systems. Each subject was scanned by the same sonographer using identical settings for both 2D and 4D acquisitions. Ventricular volumes were compared using Simpson’s biplane method. Data were analyzed by two board-certified cardiologists with respect to diagnostics.

Results:
Left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) showed no significant differences (p>0.05) between platforms across both 2D and 4D methods. However, left ventricular end-diastolic volume (LVEDV) significantly differed (p<0.03) between platforms. Right ventricular volumes and ejection fraction (RVESV, RVEDV, RVEF) from 4D imaging were consistent across platforms (p>0.05), but 2D versus 4D volume measurements showed significant differences (p<0.01) within each platform. Notable differences between platforms were observed in LV Systolic Dyssynchrony Index (p=0.03), LV Longitudinal Strain (p=0.04), LV Twist (p=0.004), and LV Torsion (p=0.005). cardiologists' assessments of aortic and mitral valve’s structure varied between platforms, with a notable increase in frequency of reported valvular abnormalities when using the Philips platform (Fig.1).

Conclusions:
While LV and RV volumetric measurements are largely consistent across platforms, LV strain metrics show significant variation. Differences in valve structure assessment between platforms suggest that interpretation may vary depending on the echocardiography system used. The study results suggest that patients should undergo follow-up examinations using the same echocardiography platform to ensure diagnostic consistency.
Abstract 4143356: Validation of a High Bleeding Risk Definition in Cancer Patients Undergoing Percutaneous Coronary Intervention
Authors: Gitto Mauro , Gilhooley Sean , Smith Kenneth , Vogel Birgit , Bay Benjamin , Krishnan Prakash , Sweeny Joseph , OLIVA ANGELO , Moreno Pedro , Leone Pier Pasquale , Di Muro Francesca , Krishnamoorthy Parasuram , Sartori Samantha , Kini Annapoorna , Dangas George , Mehran Roxana , Sharma Samin
Published: November 2024

Background:
Currently, there are no validated tools to stratify bleeding risk in cancer patients undergoing percutaneous coronary intervention (PCI). The presence of cancer itself is considered a major high bleeding risk (HBR) feature according to the Academic Research Consortium (ARC) definition. However, cancer creates a hypercoagulable state and predisposes patients to thrombotic complications as well as bleeding.

Hypothesis:
A dedicated HBR definition for cancer patients undergoing PCI could be useful to identify subjects at higher risk of adverse events.

Aims:
To validate an adapted version of the ARC-HBR criteria in patients with cancer undergoing PCI.

Methods:
Consecutive patients with a history of cancer undergoing PCI between 2012 and 2022 at a tertiary care center (Mount Sinai Hospital, New York, US) were included. According to our adapted definition, patients were considered at HBR if they met at least one of the major ARC-HBR criteria (other than cancer) or two minor criteria.

The primary endpoint was a composite of periprocedural in-hospital or post-discharge bleeding at 1 year. The key secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE) consisting of death, myocardial infarction, or stroke.

Results:
Of the 2,007 cancer patients included in this study, 1,142 (56.9%) were classified as HBR. Moderate to severe anemia was the most prevalent major HBR criterion (
Figure 1
).

At 1 year, the incidence of bleeding was significantly higher in HBR compared to non-HBR patients (10.9% vs. 3.9%, adj. HR: 2.10, 95% CI: 1.39-3.18, p<0.001), mainly driven by a higher risk of periprocedural bleeding (7.4% vs. 2.4%, p<0.001). Similarly, HBR patients were at higher risk of MACCE (11.0% vs. 3.2%, adj. HR: 2.33, 95% CI: 1.44-3.78, p<0.001) and death (8.8% vs. 2.2%, adj. HR: 2.59, 95% CI: 1.45-4.61, p=0.001) than non-HBR ones.

Conclusions:
An adapted version of the ARC-HBR definition, in which cancer is not a major criterion, effectively delineates cancer patients undergoing PCI who are at HBR. Cancer patients at HBR, according to this definition, also exhibit a higher risk of thrombotic events and mortality.
Abstract 4143377: Higher Intraoperative Blood Pressure Targets Are Associated with Reduced Delirium After Cardiac Surgery
Authors: Abbas Mostafa , Morland Thomas , SHARMA ROHIT , Kirchner H Lester , LeMaire Scott , El-Manzalawy Yasser
Published: November 2024

Background:
Intraoperative hypotension has been associated with several adverse outcomes including postoperative delirium (POD). While current guidelines recommend an intraoperative mean arterial pressure (MAP) above 65 mmHg during non-cardiac operations, there is no clear consensus regarding the optimal MAP threshold for cardiac surgery patients. We aim to determine an intraoperative MAP threshold that is associated with a reduced risk of delirium following cardiac surgery.

Methods:
We established a retrospective observational cohort of adult patients who underwent cardiac surgery within our healthcare system between 2014 and 2021. After excluding patients with preoperative delirium or with no documented Confusion Assessment Method for the ICU (CAM-ICU) result, the final cohort included 4,060 patients. Delirium was defined as a positive CAM-ICU test in a patient with a Richmond Agitation-Sedation Scale (RASS) >= -3. Intraoperative hypotension was defined as the number of MAP measurements below a threshold,
k
, normalized by the total number of MAP measurements. We experimented with
k
= 55, 60, 65, …, and 85 mmHg. Separate multivariable logistic regression analyses were conducted for each threshold,
k
, to investigate its association with POD.

Results:
POD was documented in 369 patients (9.1%). Patients with POD had higher median age (70 vs 66 years, p<0.001), CHA2DS2VASC score (4 vs 3, p<0.001), and surgery duration time (4.4 vs 3.8 hours, p<0.001). Multivariable regression analysis, summarized in Table 1, showed that intraoperative MAP values below 75 mmHg were consistently associated with increased risk for POD. The number of drops in intraoperative MAP measurements below 75 mmHg was associated with higher risk of POD (adjusted OR=2.17, p=0.010), while the number of drops in intraoperative MAP measurements below 80 mmHg was not significantly associated with higher risk of POD (adjusted OR=1.65, p=0.147).

Conclusions:
Our results suggest that using a threshold of 75 mmHg for intraoperative MAP during cardiac operations may reduce the incidence of POD. Further research, including prospective clinical studies, is needed to validate and ensure the generalizability of our findings across diverse patient populations.
Abstract 4143525: Real-World Data On Cardiovascular Outcomes In Colchicine Use After Acute Myocardial Infarction
Authors: Thangjui Sittinun , Abdelsayed Kerollos , Fouad Michele , Amer Basma , Abdelazeem Basel , Ellabban Mohamed , Elfert Khaled , balla sudarshan
Published: November 2024

Background:
After acute myocardial infarction (AMI), physicians typically address traditional coronary artery disease risk factors such as LDL-C, smoking, hypertension, and diabetes. However, residual inflammatory risk may be overlooked. Low-dose colchicine has been shown to reduce stroke and recurrent angina requiring revascularization in clinical trials, but real-world data is limited. This study aims to evaluate the use of colchicine post-AMI and its impact on cardiovascular outcomes.

Methods:
We utilized the TriNetX database (January 2006 to January 2023) to include all new AMI patients aged ≥18 years who underwent revascularization, comparing those started on colchicine post-AMI to those who were not. Baseline characteristics were assessed. At a 5-year follow-up, outcomes such as death, cardiac arrest, recurrent AMI or revascularization, heart failure (HF), stroke, new-onset atrial fibrillation (AF), and diarrhea were evaluated.

Results:
Out of 151,182 patients, 3,099 (2%) were started on colchicine after the index AMI. The mean ages were 64.7±12.1 years for the non-colchicine group and 65.6±11.8 years for the colchicine group. At 5 years, the colchicine group had a lower incidence of composite cardiovascular outcomes (56.3% vs. 82.6%, p < 0.01). Specifically, recurrent AMI/revascularization (12.4% vs. 71.2%, p <0.01), cardiac arrest (2.7% vs. 5.3%, p<0.01), and stroke (5.8% vs. 7.3%, p<0.01) were lower in the colchicine group. However, new-onset AF was higher in the colchicine group (26.8% vs. 21.8%, p<0.01). No significant differences were observed in death (14.3% vs. 15.1%, p=0.25), HF (38.1% vs. 37.7%, p=0.62), and diarrhea (8.5% vs. 8.2%, p=0.62). Propensity matching showed better cardiovascular outcomes for the colchicine group across all subgroups.

Conclusion:
Colchicine use post-AMI is associated with improved cardiovascular outcomes in a real-world setting, although its utilization remains low.
Abstract 4143552: Prognostic Value of Peak Circulatory Power Versus Peak Oxygen Uptake in Patients with Repaired Tetralogy of Fallot
Authors: Niu Evan , Sareli Rachel , Das Bibhuti , Sareli Candice , Niu Jianli
Published: November 2024

Background:
Cardiopulmonary exercise testing (CPET) is an essential tool for identifying early signs of clinical deterioration in patients with congenital heart disease (CHD), primarily through the measurement of peak oxygen uptake (VO
2
). Circulatory power (CircP), a less commonly evaluated variable derived from CPET, has been proposed as a surrogate for cardiac power. However, there is limited direct comparative data on CircP to inform prognostic assessment in these patients.

Objective:
This study aimed to investigate the prognostic value of peak CircP in individuals with repaired Tetralogy of Fallot (rToF) compared to peak VO
2
.

Methods:
Forty-seven rToF patients underwent CPET between August 2014 and April 2018 at Memorial Healthcare System, Hollywood, Florida. The Cox proportional hazards model assessed CPET variables associated with major adverse cardiac events (MACEs), adjusting for covariates. Optimal cut-off values for CircP and peak VO
2
were derived from the receiver operating curve (ROC). Kaplan-Meier survival plots illustrated the prognostic significance of CircP and peak VO
2
.

Results:
Among the 47 patients, 9 experienced MACEs during the follow-up period. Multivariable Cox regression identified that both CircP and peak VO
2
independently predicted MACEs (
p
= 0.029 and
p
= 0.041, respectively). The optimal prognostic threshold value for CircP was 3225 mm Hg mL/kg/min, with an area under the ROC curve (AUC) of 0.93 (95% confidence interval [CI]: 0.84-1.0,
p
< 0.001), sensitivity of 88.9%, and specificity of 92.1% (Figure 1A). The optimal prognostic threshold value for peak VO
2
was 21.2 mL/kg/min (AUC = 0.91, 95% CI: 0.82-1.0,
p
< 0.001; sensitivity = 77.8%, specificity = 89.5%) (Figure 1B). AUC values were comparable between CircP and peak VO
2
in predicting MACEs (0.93 vs 0.91,
p
= 0.777) (Figure 1C). Individuals with CircP < 3225 mm Hg mL/kg/min or peak VO
2
< 21.2 ml/kg/min had a significantly higher MACE risk than those with CircP ≥ 3225 mmHg.ml/kg/min or peak VO
2
≥ 21.2 ml/kg/min (Figure 2, A and B).

Conclusions:
The prognostic significance of peak CircP was comparable to peak VO
2
in predicting MACEs in rToF patients. Peak CircP may serve as an independent marker for risk stratification in rTOF patients.
Abstract 4143581: Dipeptidyl Peptidase 4 Inhibitor Linagliptin Improves Cardiac Function, Fibrosis and Apoptosis in a Swine Model of Chronic Myocardial Ischemia
Authors: Harris Dwight , Stone Christopher , Broadwin Mark , Kanuparthy Meghamsh , Sabe Sharif , Nho Ju-Woo , Hamze Jad , Abid Ruhul , Sellke Frank
Published: November 2024

Introduction:
Interest is increasing in using novel diabetic medications, such as GLP-1 receptor agonists, to manage coronary artery disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors enhance GLP-1 activity through the same pathway as GLP-1 agonists; however, DPP-4 inhibitors have not been fully evaluated in the setting of ischemic heart disease. We chose to study the DPP-4 inhibitor linagliptin (LIN) in a swine model of chronic myocardial ischemia (CMI).

Goals:
Study the effect of DPP-4 inhibitor LIN in a clinically relevant swine model of CMI to gain insight into potential therapies for patients with myocardial ischemia.

Methods:
Seventeen Yorkshire swine underwent left thoracotomy and ameroid constrictor placement on the left coronary circumflex (LCx) at age 11 weeks. Two weeks later, swine received either vehicle without drug (CON, n=9, F=4, M=5) or LIN 2.5 mg (n=8, F=5, M=3). After 5 weeks of treatment, swine underwent terminal harvest.

Results:
LIN significantly increased cardiac output, stroke volume, ischemic myocardial perfusion at rest, ischemic myocardial perfusion while pacing at 150 beats per minute, and ejection fraction, while decreasing tau (all p<0.05). Trichrome staining showed a marked reduction in ischemic myocardial interstitial and perivascular fibrosis, accompanied by decreased levels of transforming growth factor beta (all p<0.05). Apoptosis, measured by TUNEL, was significantly reduced, along with decreases in apoptosis-inducing factor, Caspase-9, BAD, and cleaved Caspase-9 (all p<0.05). Additionally, there were significant increases in PI3K, phospho-AKT, AMPK, phospho-AMPK, and ENOS, and a significant reduction in collagen 18 and angiostatin (all p<0.05). There were no significant changes in heart rate, arteriolar density, capillary density, or total oxidative stress.

Conclusion:
LIN significantly improved myocardial function and perfusion, likely due to reduced fibrosis and apoptosis. The increased perfusion, independent of vascular density, suggests enhanced vascular reactivity. These benefits in a high-fidelity large animal model of CMI warrant further investigation of LIN to fully understand its potential as a therapy for ischemic heart disease.
Abstract 4143634: Macrophage MST4 Exacerbates Cardiac Microvascular Ischemia/reperfusion Injury by Phosphorylating ACLY
Authors: Chen Ao , Xia Yan , Che Xinyu , Chen Zhangwei , Qian Juying , Ge Junbo
Published: November 2024

Background:
Cardiac microvascular dysfunction is a contributing factor to cardiac ischemia/reperfusion (I/R) injury. The impact of mammalian Ste20-like kinase 4 (MST4) on cardiac microvascular I/R injury remains unknown.

Aims:
To decipher the role of MST4 in cardiac microvascular I/R injury and the underlying mechanisms.

Methods:
Single-cell RNA sequencing was performed to explore the expression changes of MST4 in different cardiac cell types. Myeloid-specific MST4 knockout mice (MST4 CKO) and bone marrow transplantation were used to testify to the role of myeloid-derived MST4 in cardiac microvascular I/R injury. Bone-marrow-derived macrophage (BMDM) and cardiac microvascular endothelial cells (CMEC) were used to dissect molecular mechanisms. Adeno-associated virus and adenovirus were constructed to overexpress ATP Citrate Lyase (ACLY) with mutation of serine 455 (S455A) in vivo and in vitro, respectively.

Results:
MST4 was dominantly upregulated in CCR2+ monocyte-derived macrophages. Myeloid-specific deficiency of MST4 or wild type mice that were transplanted with BMDM from MST4 CKO mice improves cardiac performance in the I/R mouse model. Metabolomics showed that the primary bile acid biosynthesis pathway was upregulated in BMDM overexpressing MST4. The level of 7α-hydroxyl3-oxo-4-cholestenoic acid (7-HOCA), an intermediate of bile acid, was dramatically increased in I/R mice or BMDM overexpressing MST4, which can be reversed by knocking down MST4. Phosphoproteomics and LC-MS/MS analysis discovered that ACLY was one of the most important substrates of MST4 in the process of I/R injury. ACLY was directly phosphorylated by MST4 at serine 455, which increased ACLY enzyme activity. Mechanistically, ACLY promoted cholesterol catabolism through the bile acid synthesis pathway, leading to the accumulation of 7-HOCA in the macrophage-endothelial cell microenvironment. A high level of 7-HOCA was able to promote endothelial cell mtDNA release, leading to endothelial cell pyroptosis through the inflammasome pathway. However, mutation of serine 455 of ACLY blocked the role of MST4.

Conclusions:
Our data defined a previously unrecognized role of the MST4/ACLY pathway in cardiac microvascular I/R injury. MST4 led to the accumulation of 7-HOCA by phosphorylating ACLY, furthermore, 7-HOCA promoted endothelial cell injury. Targeting the MST4/ACLY pathway ameliorated cardiac microvascular I/R injury, which may provide a novel therapeutic strategy for I/R injury.
Abstract 4143662: Reverse J-shaped Associations of Serum Hypoxia-inducible Factor 1α Levels With All-cause Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
Authors: Iguchi Moritake , Suzuki Masahiro , Matsuda Morihiro , Ajiro Yoichi , Shinozaki Tsuyoshi , Sakagami Satoru , Yonezawa Kazuya , shimizu masatoshi , Funada Junichi , Takenaka Takashi , Morita Yukiko , Nakamura Toshihiro , Fujimoto Kazuteru , Matsubara Hiromi , Kato Toru , Unoki Takashi , Takagi Daisuke , Wada Kyohma , Wada Miyaka , Nakayama Takumi , Maeda Yuka , Masunaga Nobutoyo , Ishii Mitsuru , Kotani Kazuhiko , Abe Mitsuru , Akao Masaharu , Hasegawa Koji , Wada Hiromichi
Published: November 2024

Background:
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of a constitutively expressed β subunit (HIF-1β) and an oxygen-dependent α subunit (HIF-1α). HIF-1α has an important protective effect on the pathophysiology underlying coronary artery disease (CAD). However, the association between serum HIF-1α levels and mortality in patients with suspected or known CAD is unknown.

Methods and Results:
Serum levels of HIF-1α were measured in 2,418 patients with suspected or known CAD using a commercially available enzyme-linked immunosorbent assay kit (sensitivity, 30 pg/mL). The outcomes were all-cause death, cardiovascular (CV) death, and non-CV death. Patients were divided into 5 groups according to HIF-1α levels; below the sensitivity (Q0, <30 pg/mL) and quartiles of measurable HIF-1α levels (Q1, 31-127; Q2, 128-303; Q3, 307-765; Q4, 774-4131 pg/mL). Patients were followed up over a 6-year period. During the follow-up, 536 (22.2%) deaths occurred, including 166 (6.9%) CV deaths, 326 (13.5%) non-CV deaths, and 44 (1.8%) undetermined deaths. At baseline, HIF-1α levels were significantly and inversely associated with the rate of current smoker (P<0.001), and showed significant U-shaped associations with age (P=0.016) and high-sensitivity C-reactive protein levels (P<0.001). Interestingly, HIF-1α levels exhibited U-shaped associations with incidence of all-cause, CV death, and non-CV death (Figure 1). Since the rates of incident outcomes were similar among Q1-Q3, we combined these 3 groups into the reference group for Cox proportional hazard analyses thereafter. After adjustment for potential clinical confounders and established CV biomarkers, the low HIF-1α level (Q0) was significantly associated with all-cause death (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.02–1.91), but not with CV death (aHR, 1.12; 95% CI, 0.68–1.97) or non-CV death (aHR, 1.45; 95% CI, 0.98–2.23), while the high HIF-1α level (Q4) was not significantly associated with all-cause death (aHR, 1.12; 95% CI, 0.66–1.86), CV death (aHR, 0.76; 95% CI, 0.28–1.86), or non-CV death (aHR, 1.17; 95% CI, 0.58–2.25).

Conclusions:
We first demonstrated that serum HIF-1α levels exhibited a reverse J-shaped association with the risk of all-cause mortality in patients with suspected or known CAD.
Abstract 4143663: Quantifying the Coronary Artery Slow Flow Phenomenon: Insight from Dynamic Angiography and Deep Learning
Authors: Vu Loc , Mai Minh , Huynh Thuan , Nguyen Duc Chinh , Pham Thanh Tam , Pham Huan , Nguyen Hien , TRUYEN THIEN TAN TRI TAI , Ngo Khiem , Le Pham Thao Vy , Nguyen Hieu , Lam Vinh Sieu , Ho Dung , Nguyen Thach
Published: November 2024

Background:
The coronary slow-flow phenomenon is frequently seen in patients with coronary stenosis, coronary endothelium dysfunction, microvascular dysfunction, etc. It is diagnosed as TIMI-2 flow grade (requiring ≥ 3 cardiac cycles to opacify the vessel) or a corrected TIMI frame count (TFC) greater than 27 frames. However, the TFC has variability due to its dependence on injection force.

In cases without autonomic injection, how could to quantify frame count with minimal bias?

Methods:
All patients underwent the angiogram included, and the exclusive criteria were patients with heart failure, cardiomyopathy, congenital heart disease, valvular disease, and multivessel disease. The angiographic recording began with the injection of contrast into the coronary artery and continued with the white-colored blood moving until all the contrast had been washed out from the arteries. The review of coronary was 15 frames per second and focused on the white-colored blood flow against a black contrast background. The arterial phase (AP) calculation started when the blood began moving and ended when all the contrast was washed out of the distal arterial vasculature. The artificial intelligence program was built based on U-net and Densenet-121. At first, a segmentation model and a Convolutional neural network (CNN) model are responsible for detecting the starting frame of AP with a full index of contrast. In the end, the CNN model will detect the ending frame of AP.

Results:
151 patients met the inclusion criteria, and 76.8% were males. Subgroup analysis of patients with patent coronary arteries showed that the AP of the group with slow flow at the distal segment was 32.3 ± 4.4 frames. There was a statistically significant difference compared to the no-slow-flow group (p<0.001). The AP of patients with patent coronary artery was 25.8 ± 4.4 frames, compared with the AP of the group with a significant lesion, which was 32.2 ± 4.0 frames (p<0.001). The cut-off value of the AP frame count in diagnosing coronary slow flow was 27.5 frames, with a sensitivity of 91% and a specificity of 67%. Moreover, the Deep Learning model for calculating AP frames was successfully trained, achieving a root mean square error of 5.1 frames.

Conclusion:
In addition to TIMI frame count, AP frame count analysis is feasible for cath labs without autonomic injection. The preliminary results suggest AP is a potential marker for diagnosing the slow flow phenomenon.
Abstract 4143677: Derivation and internal validation of a nomogram for bleeding risk prediction in patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention
Authors: Lyu Si-qi , Jun Zhu , YANG YANMIN
Published: November 2024

Background:
Standard scoring system for bleeding risk assessment has not been developed in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). This study aims to develop a practical nomogram for bleeding risk evaluation in patients with AF and ACS or undergoing PCI who received both oral anticoagulant (OAC) and antiplatelet therapy (APT).

Methods:
A total of 930 patients with AF and ACS/PCI receiving both OAC and APT were consecutively recruited and followed up for 1 year. The primary endpoint was defined according to the bleeding academic research consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5). Potential prognostic variables of the primary endpoint were selected by the LASSO method and incorporated in a multivariable logistic regression model. A nomogram visualizing the logistic regression model was then generated. Discrimination was evaluated and compared by the receiver operating characteristic (ROC) curves and c-indexes. Calibration was assessed by the Hosmer-Lemeshow tests, Brier scores and calibration plots.

Results:
During 1-year follow-up, BARC type 3 or 5 bleeding occurred in 36 patients (3.9%). Four key predictors of the primary endpoint (previous bleeding history, hemoglobin, N-terminal pro-B type natriuretic peptide, and left atrial diameter) were selected by the LASSO method and integrated to construct a nomogram for bleeding risk prediction. This nomogram displayed good discrimination with a c-index of 0.740 (95% CI: 0.639-0.841). Bootstrap resampling was undertaken for internal validation and the bias-corrected c-index was 0.726. Compared to the HAS-BLED score, the nomogram displayed a significant improvement in bleeding risk prediction (c-statistics: 0.740 vs. 0.575, p<0.001). According to the Hosmer-Lemeshow test and the Brier score, the calibration of this nomogram was good.

Conclusion:
In patients with AF and ACS or undergoing PCI who received both OAC and APT, a simple 4-variable nomogram provide a practical tool for 1-year BARC type 3 or 5 bleeding prediction.
Abstract 4143731: Point of Care Ambulatory Blood Pressure Monitoring for Diagnosing Hypertension is Accepted by Youth, Parents, and Primary Providers
Authors: Baker-Smith Carissa , Zadokar Varsha , Hindt Bridgette , Gilces Jorge , Keeth Megan , Byck Hal , Sood Erica
Published: November 2024

Introduction:
Residence within a high deprivation community is associated with a greater odds of hypertension diagnosis in youth. Providers cite uncertainty about the etiology of an abnormal blood pressure (BP) measurement (white coat vs HTN) as a potential barrier to diagnosis. Placement of a 24-hour ambulatory BP monitoring (ABPM) device in the pediatric primary care (PPC) setting – “point of care” ABPM – represents a novel approach to diagnosing HTN in youth.

Hypothesis:
“Point of care” ABPM is (1) accepted by youth, parents, and PPC providers and (2) reduces PPC provider uncertainty regarding a diagnosis of HTN in youth.

Aims:
Qualitative assessment of factors associated with acceptance of “point of care” ABPM and acceptance of subsequent HTN diagnosis.

Methods:
“Point of care” ABPM was made available within a single, high deprivation PPC practice in Wilmington, DE. It was offered when manual BP measured
>
95th (age 10-12 years) or
>
130/80mmHg (13-17 years). Individual qualitative interviews of youth, their parents, and their providers were conducted by trained study team members. Qualitative data were coded and analyzed using an inductive thematic approach.

Results:
Twenty-five youth, 25 parents, and 8 PPC providers completed interviews. ABPM decision-making was influenced by perceptions of 1) importance of early HTN detection, 2) benefits/convenience of ABPM, 3) concerns regarding activity restrictions/discomfort, and 4) trust in the PPC provider (Table 1). Most parents and all providers reported high confidence in ABPM results, which they attributed to multiple BP readings in a comfortable environment, diagnosis consistent with family history, and trust in the PPC provider. Many youth/parents reported comfort with HTN management recommendations (e.g., lifestyle intervention, referral to subspecialist).

Conclusions:
“Point of care” ABPM is accepted by youth and their parents due to perceived high importance of early HTN detection. Youth, parent, and PPC provider confidence in the diagnosis of HTN was aided by the multiple BP readings captured by the ABPM device and measurements that were obtained in a comfortable environment. Trust in the PPC provider was also an important factor impacting both decision making and confidence in “point of care” ABPM results.
Abstract 4143735: Cardiac MRI quantitative susceptibility oxygen mapping predicts prognostic risk among patients with pulmonary hypertension
Authors: Tawde Prianca , Axman Rachel , Li Jiahao , Villar Calle Pablo , Chiu Caitlin , Jin Lily , Tsay Annie , Reza Mahniz , Sahai Aditya , Spincemaille Pascal , Weinsaft Jonathan , Kim Jiwon
Published: November 2024

Background:
Newly developed cardiac magnetic resonance (CMR) derived cardiac quantitative susceptibility mapping (QSM) is a non-invasive technique to quantify venous oxygen saturation (SVO2).

Objective:
In this study, we test whether impaired non-invasive SVO2 (IΔO2) predicts prognosis independent of conventional imaging-based risk stratification.

Methods:
The population comprised of prospectively enrolled patients undergoing CMR for known or suspected pulmonary hypertension. Dedicated QSM imaging was performed to calculate non-invasive SVO2. In accordance with prior validation study of health volunteers, impaired SVO2 (IΔO2) was defined as greater than 23.7%. Echo was performed as a secondary measure of chamber remodeling and right ventricular (RV) afterload. Clinical data including heart failure hospitalization and all-cause mortality were acquired blinded to imaging indices.

Results:
In total, 227 patients underwent CMR (age 55.1 ± 15.2 years, 45.4% men); 41 patients (18.1%) had IΔO2. IΔO2 was associated with greater left ventricular (LV) and RV dysfunction on CMR (p<0.05 for all) which was paralleled by more advanced heart failure symptoms (p<0.001). IΔO2 was also closely linked to RV afterload; pulmonary pressure was significantly higher among patients with IΔO2 versus those without (29.6 ± 11.8 vs. 45.6± 22.8mmHg, p<0.001). During a median follow up of 1.2 years, there were 36 composite outcomes (mortality and heart failure admission). IΔO2 was independently associated with heart failure hospitalization and death even after controlling for LV and RV function (HR: 2.52; CI 1.20-5.30; p=0.02). Figure 1 provides Kaplan Meier survival curve demonstrating increased mortality and heart failure hospitalization among patients with IΔO2 (p=0.004).

Conclusion:
CMR quantified IΔO2 improves prognostic stratification of pulmonary hypertension beyond conventional imaging indices.