bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4138417: A Novel Echocardiography Risk Score Predicted Mortality In Patients With Heart Failure With Preserved Ejection Fraction.
Authors: Iwakura Katsuomi , Tanaka Nobuaki , Okada Masato , OKAMURA ATSUNORI , Heitaro Watanabe , Seo Masahiro , Hayashi Takaharu , Yano Masamichi , Yamada Takahisa , Yoshio Yasumura , Hikoso Shungo , Okada Katsuki , Nakatani Daisaku , Sotomi Yohei , Sakata Yasushi
Published: November 2024

Introduction:
Patients with heart failure with preserved ejection fraction (HFpEF) exhibit several echocardiographic abnormalities, including diastolic dysfunction, left ventricular (LV) hypertrophy, left atrial enlargement or pulmonary hypertrophy. It is not fully understood how these abnormalities are related with prognosis in HFpEF patients.

Hypothesis:
A combination of echocardiography parameters can predict clinical outcome in patients with HFpEF.

Aims:
This study aimed to develop a model to predict all-cause mortality in patients with HFpEF using echocardiography parameters.

Methods:
We analyzed data from 952 patients (81±9 years, 43% male) registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, a multicenter registry of patients hospitalized for acute decompensated HFpEF. Comprehensive echocardiography was performed before discharge. Patients were randomly assigned to the derivation and validation cohorts (2:1 ratio). Stepwise model selection was performed on age, sex and 26 echocardiography parameters to identify independent predictors of mortality. These predictors were used to construct a risk model for mortality. The accuracy of the risk score was validated using time-dependent ROC curves in both the derivation cohort (n=629) and in the validation cohort (n=323).

Results:
During the follow-up period (720 days, IQR: 376, 1100 days), all-cause death was observed in 248 patients (26.1%). Age, sex, diastolic (DWS), E/e’ ratio, LV mass index, LV posterior wall thickness (PWth), relative wall thickness (RWT), tricuspid regurgitant pressure gradient (TRPG) were selected as independent predictors of all-cause death. The score shown in the Table was applied to each factor, and the sum of the scores was calculated as the risk score. The AUC of the risk score for predicting 1-year mortality in the derivation cohort was 0.71 and the optimal cut-off value of 4.5 provided a sensitivity and specificity of 62.8% and 69.1%, respectively. The AUC for 1-year mortality in the validation cohort was 0.67.

Conclusions:
The novel echocardiography score effectively predicted mortality in HFpEF. This model could be a valuable tool for risk stratification.
Abstract 4138420: Impact of the American Heart Association Get-With-The-Guidelines Heart Failure A.S.I.A. Program in Taiwanese hospitals
Authors: Hsu Chien-Yi , Liao Chia-Te , Wu Yen-Wen , Huang Chi-Cheng , Chang Tao-Wei , Chang Hung-Yu
Published: November 2024

Introduction:
The American Heart Association (AHA) Get With the Guidelines – Heart Failure program has been implemented for years in the United States with extensive literature supporting its benefits. In 2022, the AHA Heart Failure Adherence to Science Implementation in Asia (HF A.S.I.A.) powered by Get With The Guidelines program was first introduced in five Asian countries.

Research Question:
This study aims to explore the impact of this program's implementation in Taiwanese hospitals.

Methods:
Data were sourced from the Taiwan Society of Cardiology-HF-Registry 2020, a prospective registry that tracks HF cases from 27 hospitals in Taiwan between 2020 and 2024. Among these, four hospitals began participating in the HF A.S.I.A. program in January 2022. This study compared patients from hospitals that participated and did not participate in the HF A.S.I.A. program.

Results:
A total of 1,933 HF patients with a left ventricular ejection fraction ≤ 40% were included, comprising 460 participants from the HF A.S.I.A. program and 1,473 non-participants. The HF A.S.I.A. group was younger, had significantly lower systolic blood pressure, larger left ventricular diameter, and experienced more frequent prior hospitalizations for HF. However, there were no significant differences between the two groups in terms of baseline heart rate, estimated glomerular filtration rate, blood potassium levels, and most comorbidities. During the study period, due to changes in payment policies, the use of angiotensin receptor neprilysin inhibitor (ARNI) decreased in the non-participant group, while the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) increased. Conversely, the use of ARNI in the HF A.S.I.A. group continued to rise in line with guideline recommendations and the usage of SGLT2i was higher than in the non-participant group. After adjustment, one-year lost to follow-up rate was significantly lower (3.0% vs. 5.6%,
p
=0.032) and all-cause mortality rate trended non-significantly lower (7.6% vs. 11.4%,
p
=0.096) among the HF A.S.I.A. group.

Conclusion:
Despite enrolling sicker patients, participation in HF A.S.I.A. program was associated with higher quality of HF care.
Abstract 4138446: Ceramides Surpass LDL-Cholesterol in Predicting Cardiovascular Mortality in Diabetic and Non-Diabetic Patients
Authors: Leiherer Andreas , Muendlein Axel , Saely Christoph H , Plattner Thomas , Larcher Barbara , Mader Arthur , Vonbank Alexander , Laaksonen Reijo , Fraunberger Peter , Drexel Heinz
Published: November 2024

The power of cardiovascular risk prediction is biased by comorbidities (including T2DM), medical treatment, and age, which impact cholesterol levels. Consequently, when applying LDL-C, the true cardiovascular risk of such confounded patients is often underestimated. However, it is not clear whether this constraint for risk prediction may likewise apply to other lipid risk markers in particular ceramides.

In this observational cohort study, we recorded cardiovascular mortality for 16 years in 1195 patients. Their median age was 67 years, all of them had a high preexisting cardiovascular risk, 51% were taking statins, and 30% had T2DM.

We found a U-shaped association between cardiovascular mortality and LDL-C. We thus stratified the population according to the vertex into high (≥150mg/dL) and lower LDL-C (<150mg/dL) and also according to the T2DM status. A Cox regression analysis revealed that LDL-C failed to predict cardiovascular mortality in any subgroup. In contrast, no U-shaped but a linear association was found for ceramide-based markers. They were able to significantly predict cardiovascular mortality after stratification and even after multivariate adjustment.

We thus propose that ceramide-based predictors rather than LDL-C should be applied for a more accurate cardiovascular risk prediction in diabetic and other high-risk patients.
Abstract 4138483: Outcomes of Hypoplastic Left Heart Syndrome by Subtype and Presence of Ventriculocoronary Connections: A Fetal Heart Society Multi-Center Retrospective study
Authors: Barris David , Freud Lindsay , Day Patrick , MORRIS Shaine , Lopez Keila , Kavanaugh-Mchugh Ann , Killen Stacy , Peyvandi Shabnam , Nunez Gallegos Flora , Moon-Grady Anita , Michelfelder Erik , Mcbrien Angela , Hornberger Lisa , Lee Caroline , Hogan Whitnee , Chelliah Anjali , Howley Lisa , Arya Bhawna , Keller Sam , Krishnan Anita , Donofrio Mary , taylor carolyn , Husain Nazia , Lemley Bethan , Ronai Christina , Tworetzky Wayne , Ikemba Catherine , Gonsalves Clarelle , Geiger Miwa , Duong Son , Cohen Jennifer
Published: November 2024

Background:
Hypoplastic left heart syndrome (HLHS) is classified by subtype: mitral atresia and aortic atresia (MA-AA), mitral stenosis and aortic atresia (MS-AA), and mitral stenosis and aortic stenosis (MS-AS). It is controversial whether specific HLHS subtypes and presence of ventriculocoronary connections (VCC) are associated with transplant-free survival. We aimed to determine whether there is an increased risk of mortality associated with specific HLHS subtypes, whether this risk is stratified by the presence of VCC, and if a specific type of stage I palliation in patients with VCC improves survival. We also aimed to determine practice variation in the evaluation of HLHS patients with VCC.

Methods:
We performed a multicenter retrospective cohort study of fetuses and infants < 2 months of age with HLHS admitted between 1/2012-12/2016 to participating Fetal Heart Society institutions. Patients with HLHS variants were excluded. We collected patient specific data and surveyed participating centers for practice variation. Kaplan-Meier curves with log-rank test were used to assess transplant-free survival and cox proportional hazard analysis was performed with adjustment for center as a random intercept.

Results:
341 patients from nine centers were included. MA-AA was the most common subtype (177, 52%), followed by MS-AA (102, 30%), and MS-AS (62, 18%). VCC were diagnosed or suspected in 65 patients (19%). A total of 287 patients were live born with intention to treat. HLHS subtype was not associated with transplant-free survival (Figure 1A). Presence of VCC was associated with a lower transplant-free survival (p=0.026, Figure 1B). In the subset of patients diagnosed with VCC, there was not a significant difference in survival based on type of stage I palliation (Figure 1C). Cox proportional hazard modeling adjusted for center demonstrates that presence of VCC has a hazard ratio of 1.74 (CI 1.02-2.98), p =0.04. Survey data regarding practice variation for patients with VCC (Figure 2) demonstrates 33% of centers modify the type of stage I palliation based on presence of VCC.

Conclusions:
In a multicenter cohort of HLHS patients, patients with VCC had lower transplant-free survival compared to those without VCC, while subtype and type of stage I palliation did not have a statistical difference. There is considerable practice variation in the management of HLHS patients with VCC that may warrant further investigation.
Abstract 4138546: From Nature’s Remedy to Cardiac Emergency: A Case of Takotsubo Cardiomyopathy Induced by High-Dose Berberine Supplementation
Authors: Jain Aakriti , Almeidinha Lara , Teibel Zachary , Takla Andrew , Ukrani Hina , Nand Nikita , Anderson Nevin , Rao Mohan , Balmer-Swain Mallory
Published: November 2024

Introduction:
Takotsubo cardiomyopathy (TCM) is a reversible cardiac condition often precipitated by emotional or physical stress. Certain medications have also been implicated. While prognosis is generally favorable, associated QTc prolongation and ventricular arrhythmias can be life threatening, necessitating identification of potential triggers. This report highlights TCM in a patient using high-dose berberine, a plant alkaloid known for its hypoglycemic properties.

Case description:
A 69-year-old female with a history of type 2 diabetes mellitus, and hyperlipidemia presented after a syncopal event. It was preceded by sudden onset of dizziness, nausea, and vomiting. She had been using berberine for a year to lower her blood sugar and had recently switched to a higher dose of a more potent formulation. Vitals were unremarkable. Initial evaluation revealed a prolonged QTc interval of 659 ms (Figure 1A) and elevated troponin-I levels. She was treated with intravenous magnesium, which improved her QTc to 540 ms and revealed new T-wave inversions in the precordial leads. Echocardiogram showed an ejection fraction (EF) of 35%, with LV apical akinesia and hypercontractile basal segments. Cardiac catheterization ruled out significant coronary artery disease, leading to a diagnosis of TCM. Berberine was discontinued, and guideline-directed medical therapy was initiated. Given the presentation with syncope and high suspicion of aborted sudden cardiac death (SCD), she was discharged with a wearable cardioverter-defibrillator (WCD) as a precaution due to the risk of ventricular arrhythmias during recovery. At her 8-week follow-up, QTc and EF had normalized (Figure 1B), prompting WCD removal.

Conclusion:
The pathophysiology of berberine-induced cardiomyopathy remains uncertain and requires further research. This case underscores the importance of recognizing the potential cardiotoxic effects of berberine, particularly when used in high doses. A thorough medication and supplement history is crucial in patients presenting with unexplained cardiac symptoms. The reversible nature of TCM, when promptly recognized and treated, highlights the need for comprehensive follow-up to ensure recovery of cardiac function.
Abstract 4138553: Sodium-Glucose Cotransporter-2 Inhibitors After Acute Myocardial Infarction: A Meta-analysis of Randomized Controlled Trials
Authors: Ibrahim Sammudeen , Chinnatambi Christopher , Osman Abdul-Fatawu , Addo Basilio , Allihien Saint-Martin , Ozaeta Jan Camille , Kesiena Onoriode , Singireddy Shreyas , Amoateng Richard , Ahmed Ibrahim
Published: November 2024

Background:
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were initially developed to treat type 2 diabetes mellitus, but they have also shown benefits in mitigating cardiovascular risk. Given the increasing evidence of their efficacy in diverse disease states and their proposed mechanisms of action, it is plausible that SGLT2i could improve outcomes in patients with acute myocardial infarction (AMI) if administered early after presentation. However, the efficacy and safety of these therapies when used early in the course of acute coronary heart disease remain largely unexplored.

Objective:
The aim of this current study was to assess the benefit of early initiation of SGLT2i after AMI.

Methods:
We searched the Cochrane Central Registry of Controlled Trials, PubMed, Embase, Web of Science, and clinicalTrials.gov databases for all randomized controlled trials (RCTs) published up to May 2024 comparing SGLT2 inhibitors to placebo. The primary clinical endpoints included overall mortality, cardiovascular (CV) death, heart failure (HF) hospitalization, and adverse effects. Data were analyzed using a random-effects model to account for potential heterogeneity among the included studies. Significant heterogeneity was defined as an I-squared statistic ≥ 50%; a fixed-effects model was employed if heterogeneity was not significant. The odds ratio (OR) with a 95% confidence interval (CI) was calculated for each endpoint.

Results:
Four RCTs were included in the analysis, comprising 11,108 patients (SGLT2i, n = 5,561; placebo, n = 5,547) who enrolled with a mean age of 63±9 years and 77% males. SGLT2i were associated with a 28% reduction in risk of HF hospitalization (OR: 0.72 [95% CI, 0.59-0.88]; p = 0.001; I
2
= 0%). However, there was no significant reduction in overall mortality (OR: 1.01 [95% CI, 0.83-1.23]; p = 0.93; I
2
= 27%), CV mortality (OR: 1.04 [95% CI, 0.83-1.30]; p = 0.74; I
2
= 0%), and serious adverse effects (OR: 1.06 [95% CI, 0.87-1.28]; p = 0.59; I
2
= 62%).

Conclusion:
In patients with AMI, early initiation of SGLT2i was associated with a lower risk of HF hospitalization without increasing the incidence of serious adverse effects when compared to placebo. However, no significant difference was observed in overall mortality and CV deaths.
Abstract 4138559: Cystatin C Predicts Cardiovascular Events in Patients With Coronary Artery Disease Both Among Patients With and Among Those Without Type 2 Diabetes
Authors: Plattner Thomas , Larcher Barbara , Mader Arthur , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: November 2024

Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD).

We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM.

During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p<0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p<0.001).

We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.
Abstract 4138570: The Hidden Killer in Patients with Sepsis Spectra Disorders: Systolic Heart Failure
Authors: Jaafar Nadim , Sharma Rahul , Rahima Kenan , Guru Siddartha , Strobos Nisha
Published: November 2024

Introduction:
Sepsis and systolic heart failure (sHF) often prompt hospitalization and require near diametrically opposite treatment strategies. We, therefore, studied whether sHF would impact outcomes in patients with sepsis spectra.

Methods:
We examined the National Inpatient Sample 2021 for adults admitted with sepsis spectra (sepsis, severe sepsis, and septic shock). We compared patients with sHF vs those without. STATA 18
th
edition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges.

Results:
In 2021, nationwide, 3,030,351 adults were admitted for sepsis spectra, and 209,134 (6.9%) had concomitant sHF. Patients with sHF and sepsis spectra (as compared to those without sHF) were less likely female (35.5% vs. 48%), had a substantially higher likelihood of a prior MI, and nearly 50% were diabetic and hyperlipidemic with a higher comorbidity index. Baseline characteristics are in the Table.

Sepsis and sHF resulted in substantially higher mortality (22.7%) as compared to patients with sepsis alone (14.9%) adjusted odds ratio (aOR) of 1.11 (CI 1.08-1.14; p-value < 0.001). Patients with sepsis and sHF were more likely to require intubation 22.2% vs. 14.0% aOR 1.21 (CI 1.18-1.25; p-value < 0.001), had more cardiac arrest 7.7% vs. 4.0% aOR 1.38 (CI 1.32-1.44; p-value < 0.001), and a longer LOS (11.9 vs 9.4 days adjusted incidence rate ratio (aIRR) 1.06; CI 1.05 – 1.08; p-value < 0.001). Consequently, total hospital charges were also higher, $189,415 vs $133,720, aIRR 1.15 (CI 1.13-1.18; p-value < 0.001).

Conclusion:
In 2021, nationwide, sepsis spectra remain a major cause of in-patient mortality. We demonstrate that the coexistence of systolic heart failure and sepsis dramatically worsens complications, mortality, and total hospital costs. This study is a call to action for the in-depth analyses of this very high-risk group of patients.
Abstract 4138603: Adult-onset Kawasaki Disease: An Updated Review of the English-Language Literature from 1980 Through 2023
Authors: Adusei Poku Frank , Biney Bernice , Mensah Samuel , Ampadu Joshua Oppong , Aghasili Chukwuemeka , Oppong-Twum Sandra , Baygani Shawyon , Okafor Henry
Published: November 2024

Introduction:
Kawasaki disease (KD) is a pan-vasculitis that primarily affects children and rarely adults. Available data on adult-onset KD are based on case reports and case series, both of which are limited by small sizes. We aimed to characterize the epidemiology, presentation, hospital course, and outcomes of adult-onset KD published in the English literature from 1980 through 2023.

Methods:
We retrospectively reviewed and included published articles with a diagnosis of KD in patients age ≥18 years. We searched PubMed and Google scholar for case reports/series published in English using the keywords “adult”, “Kawasaki disease”, and “mucocutaneous lymph node syndrome”. We extracted data from individual articles onto an Excel spreadsheet for analysis. Outcomes of interest were the demographic characteristics of patients, clinical presentation and hospital course, management, and complications. Descriptive statistics were used to analyze the data.

Results:
A total of 137 patients from 29 countries were included in this study. The majority were male (90/137, 64.9%; M:F ratio 1.8) and the median age was 25 years (range, 18-68). The median time to clinical presentation was 5 days (range, 4-60). The main signs and symptoms were fever (95.7%), skin rash (92.9%), conjunctivitis (89.3%), extremity changes (84.3%), oral changes (85.7%), and cervical lymphadenopathy (73.7%). The majority of the patients had no co-morbidities (125/137, 91.2%). EKG changes were not reported in 48 patients (35%). In the remaining 89, 26 (29.2%) had normal EKG or sinus tachycardia, 9 (10.1%) had ST segment elevation, and 9 (10.1%) had arrythmias or abnormal EKGs. Pharmacotherapy included IVIG (80/137, 58.4%), Aspirin (105/137, 76.6%), steroids (31/137, 22.6%) and antibiotics (68/137, 49.6%). For complications, 18.2% (25/137) had aneurysms, 8% (11/137) had myocardial infarction, 10.9% (15/137) had myocarditis, 10% had pericarditis/pericardial effusion, and 10.9% (15/137) had KD shock syndrome. The median length of stay was 14 days (range, 1-60 days). Three patients (2%) died from KD.

Conclusion:
Adult-onset KD is rare and is associated with significant cardiovascular complications. Clinicians should have high index of suspicion for prompt diagnoses and initiate appropriate treatment to improve outcomes.
Abstract 4138617: Temporal and Regional Trends in Cardiovascular Mortality Associated with Parkinson's Disease from 1999 to 2020: A Retrospective Study in the United States
Authors: Nadeem Zain , Rehman Obaid Ur , Sardar Muhammad Bilal , Ahmad Eeman , Nadeem Aimen , Ochani Rohan Kumar
Published: November 2024

Introduction:
Parkinson’s disease (PD) is a common neurodegenerative disorder, and existing evidence links it to cardiovascular (CVD) mortality.

Research Question:
Is the CVD-related mortality higher in PD patients compared to that in the general population?

Goals:
We aim to identify CVD-related mortality trends in patients with PD in the US stratified by age, sex, race, and region, and compare them to CVD-related mortality trends in the general population.

Methods:
Death certificates from the CDC-WONDER database were examined for adults aged ≥65 years. Crude rates (CR) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and change in AAMR was estimated via annual percent change (APC) and the average annual percent change (AAPC) using Joinpoint regression.

Results:
From 1999 to 2020, a total of 138,151 CVD-related deaths occurred in individuals with PD. The AAMRs decreased moderately till 2002 (APC: -3.25), then sharply till 2014 (APC: -5.43), but increased thereafter till 2020 (APC: 1.77). Males had higher AAMR than females, and the AAPC for CVD-related deaths in PD differed significantly from those in the general population. NH Whites displayed the highest AAMR (16.14) while NH Blacks or African Americans displayed the lowest (9.65). Hispanics or Latinos showed an AAMR of 11.22, followed by NH Asians or Pacific Islanders (10.24) and NH American Indians or Alaska Natives (9.70). AAMRs also varied substantially by region (West: 16.64; Midwest: 16.40; Northeast: 15.59; South: 13.12). States with the highest AAMRs were Nebraska, California, and Oklahoma. Rural regions exhibited a higher AAMR (16.34) than Urban regions (14.88). The AAPC for CVD-related deaths in PD differed significantly from those in the West and in urban regions. Most deaths occurred at nursing homes or long-term care (43.85%). The adults aged ≥85 years exhibited an alarmingly high CR (53.04), and the AAPC differed significantly from the general population due to CVD.

Conclusions:
We observed overall decreasing trends in CVD-related deaths in adults with PD from 1999 to 2014, which increased thereafter till 2020. Highest mortality was exhibited by males and NH Whites, residents of the West and the Midwest, and adults ≥85 years.
Abstract 4138620: Assessment of the Accuracy of the Perioperative Mortality Risk in Adults with Congenital Heart Disease (PEACH) Score
Authors: Taylor-Fishwick Jon , Duarte Vivian , Olson Kaitlin , Khanna Amber , SooHoo Megan
Published: November 2024

INTRODUCTION:
Previous mortality risk scores for adult cardiac surgery patients did not include adult congenital heart disease (ACHD) patients. Development of ACHD specific mortality risk scores include the procedure-specific ACHS score and recently derived PEACH score. While validated in Europe, further evaluation of the PEACH score in additional settings is necessary.

RESEARCH QUESTION:
We assessed the efficacy of the PEACH score to predict mortality in ACHD patients undergoing congenital cardiac surgery at our institution. We compared the PEACH score to the ACHS and STS scores and assessed for additional risk factors which may further augment the PEACH score.

Methods:
A retrospective cohort study was conducted of patients who underwent congenital cardiac surgery at the University of Colorado Hospital and Children’s Hospital Colorado between 2010-2022. Patients were identified by the institutional STS congenital cardiac surgery database and were eligible if 18 years or older and underwent congenital cardiac surgery. Components of the PEACH score and additional postulated risk factors were evaluated by univariate analysis. A receiver operating characteristic (ROC) curve was used to compare the PEACH score to existing risk models. Logistic regression analysis determined additional risk factors to augment the PEACH score.

Results:
A total of 516 patients were included with a median age of 30 (IQR 23-42) and 51% were male. There were nine deaths overall. The PEACH score was predictive of mortality (OR: 2.09, p<0.001) with a score of 0: 0 deaths/240 patients (0%); 1-2: 6 deaths/229 patients (2.6%); 3+: 3 deaths/41 patients (7.3%). Of additional risk factors tested, platelets less than 184,000 per mcL (OR: 8.36, p=0.01) was significantly associated with mortality. Comparison of the models revealed PEACH score AUC 0.832 (95% CI: 0.740,0.924), ACHS score AUC 0.869 (95% CI: 0.806, 0.932), and STAT AUC 0.769 (95% CI: 0.616, 0.922, Figure 1). The addition of platelet level improved the predictive ability of the PEACH score (AUC 0.881).

Conclusion:
In this single-center analysis, the PEACH score provided strong predictive ability for peri-operative mortality. The addition of platelet levels may further augment this score.
Abstract 4138633: Infusion of human apolipoprotein A-I (CSL112) promotes several aspects of reverse cholesterol transport
Authors: Mathias Rommel , Velkoska Elena , Diditchenko Svetlana , Greene Brandon , Tan Xiahui , Navdaev Alexey , Collins Heidi , Adelman Steven , Young Kyal , Gille Andreas , Duffy Danielle , Gibson C. Michael , Pelzing Matthias , Kingwell Bronwyn
Published: November 2024

Background:
High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent apolipoprotein A-I (apoA-I), to increase reverse cholesterol transport.

Objective:
To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI).

Methods:
A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in
ex vivo
cell-based assays.

Results:
CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC strongly correlated with cholesterol uptake by hepatic cells (r=0.95 p<0.001).

Conclusion:
CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway.
Abstract 4138661: Targeting Arginase I Alleviates Cardiomyopathy
Authors: Di Lin , Hong Natalie , Switala Lauren , Maiseyeu Andrei
Published: November 2024

Introduction:
Emerging data have shown that pathological cardiac fibrosis and heart failure is driven by recruitment of CD4
+
T cells to injured heart tissue. Systemic deletion of CD4
+
T cells or splenectomy has been shown to attenuate CD4
+
T cell heart infiltration and inflammation. We engineered cargo-less nanoparticles using a biocompatible and biodegradable polymer that target splenic macrophages to overexpress arginase I, leading to local depletion of L-arginine, an amino acid crucial for CD4
+
T cell activation and expansion.

Hypothesis:
Cargo-less nanoparticles attenuate CD4
+
T cell activation, expansion, and heart infiltration in experimental models of cardiomyopathy by regulating cross talk between macrophages and CD4
+
T cells via L-arginine depletion in the spleen.

Methods:
Spleen-targeting, cargo-less nanoparticles were synthesized from poly(L-lactide-co-glycolide) (PLLGA) and administered to murine and human macrophages in vitro. Arginase I expression and activity were assessed via Western blotting and arginase activity assay. Epigenetic modulation was analyzed using Western blotting and CHIP-seq. Conditioned media was collected to culture CFSE-labeled T cells to assess proliferation. The nanoparticles were administered to mouse heart failure models induced by isoproterenol or angiotensin II and phenylephrine. Immune cell composition in mouse spleens and hearts was investigated by flow cytometry. Cardiac function was assessed by echocardiography and heart fibrosis was examined via immunohistochemistry and Western blotting.

Results:
Primary murine macrophages treated with our nanoparticles exhibited a dose-dependent T cell suppression in vitro. This effect was abrogated when an arginase inhibitor was administered together with the nanoparticles. The nanoparticles upregulated arginase I protein expression and arginase activity by increasing histone lactylation. In vivo testing with mouse heart injury models showed that the nanoparticles restored levels of effector and regulatory T cells in injured mice to non-injured levels. Additionally, the nanoparticles reduced cardiac fibrosis and restored ejection fraction. Furthermore, Western blotting of heart tissue lysate revealed that the nanoparticles downregulated the TGFb and p-SMAD signaling pathway.

Conclusion:
Collectively, these findings highlight a novel therapeutic strategy for heart failure, addressing the gap of fibrosis treatment by targeting upstream immunological pathways.
Abstract 4138674: Long-acting CRF2 receptor agonist, COR-1389, improves cardiopulmonary function in the rat model of Sugen plus hypoxia-induced pulmonary hypertension and right heart failure
Authors: Kowala Mark , Guignabert Christophe , Ozoux Marie-Laure , Lawson Francesca , Janiak Philip
Published: November 2024

Introduction:
Urocortin-2 (UCN-2), a peptide which is part of the corticotropin-releasing factor (CRF) family, functions as an autocrine and paracrine factor, exerting its effects on cardiac and pulmonary function through agonism of CRF2 receptors. Although acute administration of UCN-2 has shown promise by improving heart and lung function in conditions like heart failure (HF) and pulmonary hypertension (PH), its limited stability impedes its chronic therapeutic use.

Hypothesis:
In this study, we explored the efficacy of COR-1389, a potent, selective and long-acting CRF2 agonist peptide, in the Sugen 5416 (VEGFR2 inhibitor, Su) combined with hypoxia (Hx) rat model of PH and right heart failure (RHF).

Methods:
To this aim, male adult Sprague Dawley rats were divided into three groups: Control rats (normoxia) were compared with rats injected subcutaneously with 20 mg/kg Sugen 5416 and exposed to chronic hypoxia for 3 weeks, followed by 2 weeks of normoxia. At 5 weeks, control rats and one SuHx group received subcutaneously vehicle (control and SuHx), while the third group received COR-1389 at a dose of 100 μg/kg every 4 days subcutaneously for 3 weeks (SuHx + COR-1389). At 8 weeks, cardiac and pulmonary hemodynamic functions of the three groups were evaluated using echocardiography and right heart catheterization, and heart and lung tissue were evaluated by histology and immunohistochemistry.

Results:
Compared to controls (n=10), SuHx exhibited increased mean pulmonary arterial pressure (mPAP), right ventricle (RV) hypertrophy (Fulton Index/body weight), muscularization of distal pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy, alongside reduced RV systolic function (Tricuspid Annular Plane Systolic Excursion, TAPSE) and cardiac output (CO). Conversely, compared to the SuHx + vehicle group (n=11), curative treatment with COR-1389 for 3 weeks in SuHx rats (n=13) led to enhanced RV systolic function (TAPSE) and CO, together with reductions in mPAP, RV hypertrophy, muscularization of pulmonary arteries, RV fibrosis and cardiomyocyte hypertrophy. Systolic blood pressure remained unchanged across all groups.

Conclusion:
These findings indicate that COR-1389 ameliorates the deteriorating cardiopulmonary parameters observed in the SuHx model and represents a promising approach for the treatment of PH and RHF.
Abstract 4138704: Safety and Efficacy of Generic Atorvastatin in Korean Dyslipidemia Patients: A Non-Interventional Observational Study
Authors: kim sun mi , Kim Hee Seok , MIN SOUNG JUN , Hong Bum Kee
Published: November 2024

Background:
Statins are widely used for controlling dyslipidemia. However, most evidences for dyslipidemia prevention and treatment with statins are based on studies involving Caucasian populations, resulting in limited data on Korean patients. This study was conducted to evaluate the efficacy lipid profile and safety of generic atorvastatin in a real-world clinical setting among Korean dyslipidemia patients.

Methods:
This study was conducted as a non-interventional, multi-center observational study. It was carried out across 264 institutions and clinics from October 2017 to July 2021. Total 16,992 participants were enrolled. The safety and efficacy evaluation cohorts consisted of 16,803 and 11,035 subjects, respectively. The liver function evaluation cohort included 13,889 subjects. The main eligibility criteria were dyslipidemia patients prescribed generic atorvastatin according to approved indications. Adverse event rates were collected for safety evaluation, and lipid profiles, including LDL-C, were collected for efficacy evaluation.

Results:
In the safety endpoint evaluation, 1,612 adverse events were reported in 1,027 subjects (6.11%). Common adverse events such as dizziness, headache, and constipation, which were frequently observed in this study, were within the approved labels. Muscle pain occurred in 0.14% of subjects, and myopathy, myositis, rhabdomyolysis, and CK abnormalities or increases were reported in 0.01% of subjects, respectively. Most of the adverse events were confirmed to be mild or resolved, and the study was completed without changing the dose. All abnormal liver function test results were reported in less than 1% of subjects (AST increase: 0.14%, ALT increase: 0.1%, ALP increase: 0.01%, γ-GT increase: 0.01%).

The mean LDL-C decreased from 117.31 mg/dL to 89.97 mg/dL, showing a statistically significant improvement in LDL-C levels (p < 0.0001).

Conclusions:
Generic atorvastatin demonstrated tolerable safety as well as significant efficacy on lipid profile. Generic atorvastatin might be safe and effective for Korean patients with dyslipidemia.
Abstract 4138738: Clinical Evidence of Immune Response to Transplanted Allogeneic iPS Cell-Derived Cardiomyocytes
Authors: Kawamura Takuji , ito Emiko , Takeda Maki , Yoshioka Daisuke , Kawamura Ai , Misumi Yusuke , Saito Shunsuke , Yamauchi Takashi , Miyagawa Shigeru
Published: November 2024

Background&Purpose:
The clinical application of cell transplantation therapy utilizing induced pluripotent stem cells (iPS cells) for heart failure is progressing, with the primary strategy being the use of pre-prepared allogeneic iPS cells. The immune response to these transplanted cells is crucial and may affect therapeutic efficacy, necessitating the use of immunosuppressive drugs. However, detailed clinical reports on immune responses are sparse. This study aims to analyze the immune response to transplanted cells in clinical iPS cell-derived cardiomyocyte (iPSC-CM) transplants and examine the correlation between immune response and therapeutic efficacy.

Methods:
In the "Phase 1 multicenter clinical trial of transplantation of iPSC-CMs for ischemic cardiomyopathy" (https://jrct.niph.go.jp/en-latest-detail/jRCT2053190081), conducted as the First-in-Human trial, the immune response to transplanted cells was analyzed in four cases at our hospital. Comprehensive analysis of anti-human leukocyte antigen (HLA) antibodies in serum and single-cell RNA sequencing in peripheral blood mononuclear cells was performed to investigate their relationship with therapeutic effects on cardiac function.

Results:
Patients received immunosuppressive drugs (tacrolimus, mycophenolate mofetil, and steroids) for 3 months post-transplantation, followed by a 1-year follow-up. In all cases, an increase in transplant cell HLA-specific antibodies was observed after discontinuing immunosuppressive drugs (Figure 1 and 2). Single-cell analysis revealed a decrease in immunocompetent cells in peripheral blood during immunosuppressive therapy. Cardiac function analysis showed improvements in all cases except Case 2 (Figure 3), where pre-existing anti-HLA-DQ antibodies were present before transplantation.

Conclusions:
No immune response to the transplanted cells was observed during immunosuppressive therapy. In a case with limited therapeutic response, pre-existing antibodies to transplanted cells were detected, potentially impacting the therapeutic outcome.
Abstract 4138745: Blockade of Mineralocorticoid Receptor by Esaxerenone Improves Insulin Sensitivity in Obese Mice
Authors: Bavuu Oyunbileg , Sata Masataka , Fukuda Daiju
Published: November 2024

Background:
Aldosterone regulates blood pressure and electrolyte balance. However, overactivation of the mineralocorticoid receptor (MR) and elevated aldosterone levels are implicated in the pathogenesis of cardiometabolic disorders, though the underlying mechanisms are not fully understood. In this study, we investigated whether a novel, non-steroidal selective MR blocker, esaxerenone, ameliorates the development of metabolic disorders in obese mice models and examined the underlying mechanism.

Methods:
Esaxerenone (3 mg/kg/day) was orally administered to high-fat diet (HFD)-fed C57BL/6J or normal chow-fed db/db mice. Metabolic parameters, tissue morphology, and effects of esaxerenone on insulin sensitivity were assessed. Gene expression and insulin signaling, determined by Akt phosphorylation, were examined using quantitative RT-PCR and western blotting, respectively. In in-vitro experiments, insulin targets cell lines such as 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes were used. Insulin-responsive cells were treated with 10 nM or 100 nM esaxerenone or eplerenone for 30 minutes before 4-hour 1000 nM aldosterone stimulation. Insulin signaling was assessed 15 minutes after stimulation with 17 nM insulin.

Results:
Esaxerenone improved insulin sensitivity (P<0.05) without altering metabolic parameters in HFD-induced obese and db/db mice. Esaxerenone suppressed fat accumulation, adipocyte size, and liver lipid droplets compared with the vehicle-treated group (P<0.01). In adipose tissue, esaxerenone reduced macrophage infiltration (P<0.01) and the expression of inflammatory molecules (P<0.05). In in-vitro experiments, aldosterone significantly decreased the expression levels of PPARγ and adiponectin in 3T3-L1 adipocytes. Moreover, aldosterone attenuated insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes in a dose-dependent manner (P<0.01). Pretreatment with esaxerenone reversed the effect of aldosterone, whereas eplerenone, an MR antagonist, did not show a similar effect at the same dose.

Conclusion:
Inhibition of MR by esaxerenone improved insulin sensitivity in HFD-induced obese and genetically diabetic mice. The reduction of inflammation and fat accumulation and enhancement of insulin signaling were suggested to be underlying mechanisms. Esaxerenone might be a beneficial therapeutic approach for managing metabolic disorders.
Abstract 4141805: High Frequency of Ejection Fraction Decline in Patients with Heart Failure with Improved Ejection Fraction
Authors: Pensa Anthony , Davis Lucia , Wu Tingqing , Zheng Veronica , Harap Rebecca , Wilcox Jane
Published: November 2024

Background:
Heart failure with improved ejection fraction (HFimpEF) is defined by prior HF with reduced EF (HFrEF) and evidence of systolic improvement and is associated with improved outcomes. Despite this, HFimpEF patients remain at risk of future adverse events, including EF decline. However, little is known about factors associated with EF trajectory in this population.

Question:
Are baseline clinical characteristics associated with future EF decline in HFimpEF?

Goals:
To describe the EF trajectory in HFimpEF and to identify if clinical characteristics are predictive of eventual EF decline.

Methods:
This was a retrospective observational study of 115 patients in our HFimpEF registry. Inclusion criteria were a history of HFimpEF (prior HFrEF [EF ≤40%] with subsequent EF improvement ≥10% and resulting EF >40%) and at least one follow-up echocardiogram after improvement. The primary outcome was EF decline (EF drop ≥10% from peak improvement EF). Cox proportional hazard models were built using baseline factors at time of HFrEF diagnosis to identify predictors of EF decline.

Results:
The median time from initial HFrEF diagnosis to development of HFimpEF was 0.61 years (IQR 0.26-1.17). Most patients (77%) continued to have EF improvement after HFimpEF diagnosis, and the peak EF was 60% (IQR 54-65%). Over a mean follow-up of 4.7±3.2 years, 35 (30%) HFimpEF patients developed EF decline. Baseline characteristics were similar between those with sustained EF and EF decline (
Table 1
), as was peak EF (60.0% vs 60.3%, p=0.571). Indexed end-systolic dimension (1.78 vs 1.93 cm/m
2
, p=0.014) was smaller at time of HFimpEF diagnosis in those with sustained EF. In multivariate analysis, current/former tobacco use was associated with EF decline (HR 2.60, 95% CI 1.02-6.63, p=0.045;
Table 2
).

Conclusions:
Many HFimpEF patients develop EF decline, highlighting the need for continual clinical follow up in this high-risk patient population.
Abstract 4141807: Exposure to PM2.5 and 1-year postoperative risk of death among patients with congenital heart surgery: a report from the Pediatric Cardiac Care Consortium
Authors: Yang Yanxu , Xu Ke , Hao Hua , Huang Eugene , Liu Yang , Kochilas Lazaros
Published: November 2024

Background:
Congenital heart disease (CHD) is the leading cause of birth defect-related deaths among infants in the US. While ambient particulate matter (PM) PM2.5 is a known cardiovascular risk factor, its effect on CHD patients remains unclear. This study examines the link between county-level PM2.5 and 1-year mortality risk following pediatric congenital heart surgery (CHS).

Methods:
We conducted a retrospective cohort study using data from the Pediatric Cardiac Care Consortium (PCCC), a large US-based multi-institutional registry of interventions for CHD. We included patients with available identifiers, initial CHS, county information and birth between 1989 and 2003. We obtained sex, birth year, CHD severity, chromosomal abnormality and neighborhood socioeconomic status (nSES). PM2.5 concentrations at 1-km resolution across the US were derived using spatiotemporal ensemble models integrating machine learning algorithms. The data were assigned to county-level scale by geo-information provided by the US Census Bureau. We used Cox proportional hazards regression with shared frailty models to estimate the hazard of death considering state as a random effect.

Results:
We included a total of 27,327 patients who were enrolled in PCCC after an initial CHS (47.3% females). Patients exposed to higher PM2.5 quintile were more likely to be born in early birth era (1990-1993) (p<0.01) and at low nSES (p<0.01). After adjusting for sex, birth era, CHD severity, chromosomal abnormality and nSES, the hazard of death in patients exposed to the highest vs lowest PM2.5 quintile was 1.33 (95%CI: 1.02-1.72, p=0.03). In addition, there was a linear dose-response relationship between PM2.5 exposure and 1-year mortality risk (P
non-linearity
=0.90) with each 1 μg/m
3
increase in monthly PM2.5 exposure associated with 2% increase in the 1-year post-discharge hazard of death (aHR: 1.02, 95%CI: 1.00-1.04, p=0.05) (Figure).

Conclusion:
Higher PM2.5 levels were independently associated with increased risk of death after pediatric CHS. Improving environmental conditions may mitigate the adverse health effects of particulate matter exposure for patients with CHD.