bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140333: Maximizing the yield of human genetics-based target discovery from circulating proteins for cardiometabolic diseases
Authors: Zhang Wenmin , Yoshiji Satoshi , Sladek Robert , Dupuis Josee , Lu Tianyuan
Published: November 2024

Background:
Circulating proteins are attractive candidate drug targets for cardiometabolic diseases. Identifying promising circulating proteins that have a causal role in disease pathogenesis is challenging and expensive. Mendelian randomization (MR) has emerged as an important tool for testing potential causal effects while mitigating biases from confounding and reverse causation. MR findings require validation by colocalization analysis to guard against bias due to correlation between genetic variants (linkage disequilibrium, LD). However, existing colocalization methods often fail to validate MR findings because of highly complex LD structures in the genome, rendering a low yield of human genetics-based target discovery.

Methods:
In this study, we developed a new computational method, called SharePro, to effectively assess colocalization evidence for MR-identified circulating proteins as targets for cardiometabolic diseases. Based on large-scale genome-wide association studies, we performed MR analyses to assess the associations between 1,535 circulating proteins and key cardiometabolic traits, including diastolic blood pressure, systolic blood pressure, serum hemoglobin A1c, serum low-density lipoprotein cholesterol, and serum triglycerides. We then benchmarked SharePro against state-of-the-art colocalization methods, including coloc, coloc+SuSiE, and PWCoCo, and evaluated the power and robustness of these methods in supporting MR findings. We further examined whether colocalization evidence-supported associations implicated known drug targets for cardiometabolic diseases.

Results:
SharePro demonstrated the highest power and robustness in supporting 160 (79.6%) of the 201 Bonferroni-significant protein-trait associations identified by MR, while existing methods supported up to 46.8% of these associations. Protein-trait associations identified by MR and supported by SharePro were more likely to implicate known drug targets for cardiometabolic diseases (Figure 1). Furthermore, eight protein-trait associations were exclusively supported by SharePro, suggesting novel targets, such as HSF1 and HAVCR2.

Conclusions:
SharePro most effectively supports promising protein-trait associations identified through MR for cardiometabolic diseases. Combining multiple lines of evidence using different methods may substantially increase the yield of human genetics-based drug target discovery by nearly twofold.
Abstract 4140336: Reclassification of Congenital Heart Disease Severity via Cardiac Magnetic Resonance in a Tertiary Care Center in Latin-America
Authors: Manzur Barbur Maria Carolina , Torres Gomez Daniela , Amado Sergio , Urbina Thomas , Valderrama Daniela , Perez-Fernandez Oscar , Medina Hector M , Jaimes Claudia , Forero Julian , Acosta-Izquierdo Laura , Guerrero Carlos
Published: November 2024

Introduction/Background:
Cardiovascular magnetic resonance (CMR) has emerged as an invaluable non-invasive modality for accurate diagnosis and treatment in patients with congenital heart disease (CHD).

Goals/Aims:
Prevalence and reclassification of CHD severity by CMR referred to a tertiary-care center in Latin America (LATAM).

Methods/Approach:
Single-center retrospective study analyzing our institutional CMR database. The initial CMR requisition and final diagnoses were classified according to the 2018 American Heart Association (AHA) guidelines for CHD to establish a standardized diagnosis. We evaluated the change in severity between the pre-CMR and final CMR diagnoses and its relationship to mortality after reclassification. Descriptive statistics were used to present categorical variables as frequencies and percentages. A Sankey diagram illustrated changes in severity and mortality, and the association between reclassification and mortality using chi-square tests.

Results/Data:
Of 10,135 CMR performed between January 2016 and December 2023, 6.4% (656) were CHD, which increased over time (6.1% of all CMR referrals in 2016 up to 8.2% in 2023). 65.2% were adults with a mean age of 29.3 years (IQR 14-43), 55.8% female sex. Based on the pre-CMR diagnosis AHA classification, 30% were classified as simple, 43% as moderate, and 12.5% as complex. Reclassification of severity occurred in 33.2% of patients after the final CMR diagnosis, with the final CMR diagnoses reclassified into simple 16.5%, moderate 67.6%, and complex 15.9%. 14.5% of the cohort were initially undiagnosed with CHD and were diagnosed through CMR. Reclassification occurred most frequently in the simple group, with 56.1% reclassified to a more severe form and 7.7% becoming severe. The moderate group had the most significant increase in the severity of the final CMR diagnosis. Despite an observed increase in mortality among patients reclassified to moderate complexity, this did not reach statistical significance (p=0.68).

Conclusion(s):
Our study demonstrates that CMR is feasible in LATAM for diagnosing and reclassifying severity in CHD patients. Improved diagnostic yield of CMR may aid in properly diagnosing and directing CHD patients' care in our region.
Abstract 4140345: 3D Statistical Shape Analysis Predicts Type A Aortic Dissection Better Than Aortic Diameters
Authors: Marway Prabhvir , Campello Jorge Carlos Alberto , Wagner Catherine , Baker Timothy , Burris Nicholas
Published: November 2024

Introduction/Background:
The vast majority of type A aortic dissection (TAAD) patients do not meet diameter thresholds for ascending aortic repair before their dissection. Increased ascending aortic length has been suggested to improve risk predictions, but this metric simplifies the aortic shape to a single dimension and doesn’t capture 3D features like tortuosity/torsion.

Research Questions/Hypothesis:
Are there distinct shape features of the ascending aorta that differentiate patients with TAAD better than aortic diameter?

Methods/Approach:
We retrospectively identified patients with good quality, pre-dissection CT imaging of the chest at our center prior to surgical repair of acute TAAD, excluding those with pre-existing dissection or prior aortic intervention. This pre-TAAD group was compared to a reference cohort of ‘normal’ patients (no aortic disease), patients with borderline ascending aortic dilation (35-44 mm) and ascending aneurysm (≥45 mm; aTAA). A shape score, based on statical shape modeling (SSM) and cosine similarity was computed (tubular ascending and arch) to quantify the similarity between an individual aortic shape compared to the mean ‘normal’ shape (defined as -1) and mean pre-TAAD shape (defined as +1).

Results/Data (descriptive and inferential statistics):
We identified 30 spontaneous TAAD patients with CTs at a median of 1.5 (IQR: 0.7-3.8) years pre-dissection. We compared against pre-existing cohorts with normal aortas (n=165), borderline dilation (n=119) and aTAA aneurysm (n=42). Age, sex and hypertension did not significantly differ between TAAD and aTAA groups. Max diameter (47.7 ± 2.0 vs. 40.6 ± 6.0 mm, p<0.01), centerline length (130 ± 11.5 vs. 120 ± 16.7 mm, p<0.01) and tortuosity (1.33 ± 0.08 vs. 1.27 ± 0.07, p<0.01) were higher in aTAA versus TAAD. Median SSM scores were higher in the (TAAD group 1.25, IQR: 0.76-1.46) compared to the aTAA group (-1.25, IQR: -1.60, -0.95; p<0.01) and the borderline dilation group (-1.03, IQR: -1.25, -0.84; p<0.01),
Figure 1
. SSM scores for normal, borderline dilated and aTAA did not significantly differ.

Conclusion:
A novel SSM-based scoring method of assessing ascending aorta and arch geometry reveals clear shape differences among patients prior to TAAD.
Abstract 4140366: Diagnostic Stewardship to Improve Appropriate Use of Inpatient Echocardiography
Authors: Welch Megan , Paras Molly , Moore Amber , Wing Jonathan , Letourneau Alyssa , Tucker Tyler , Solemina Kristen , Hung Judy , Weiner Rory
Published: November 2024

Background:
Overuse of cardiovascular imaging, including echocardiography, is a form of low-value care contributing to waste in the US healthcare system. Historically, appropriate use criteria (AUC)-based educational programs and feedback reports have improved transthoracic echocardiography (TTE) ordering practices, but prior efforts have shown only modest and short-lived impact and have focused on the outpatient setting. Contemporary capacity and financial constraints highlight the importance of leveraging AUC to promote more efficient utilization of echocardiography resources.

Methods:
We conducted a prospective controlled cohort study testing an education-based diagnostic stewardship intervention to reduce rarely appropriate TTEs on inpatient medical services. AUC categorize TTE indications into three groups: appropriate (A), may be appropriate (mA), and rarely appropriate (rA). Modeled after successful antimicrobial stewardship programs, the intervention involved screening TTE orders from control and intervention units for appropriateness in real-time. For medical units in the intervention group, the diagnostic steward contacted ordering clinicians of those with mA and rA orders. The steward clarified order indications and made recommendations regarding the utility of the TTE. The ordering clinician chose to continue or discontinue the order. The primary outcome was the odds of rA TTEs in the intervention vs control groups.

Results:
Over 3 months, 150 TTEs were screened in the control group and 160 were screened in the intervention group. After initial screening, 8.8% (13) and 10.6% (17) were rA in the control and intervention groups, respectively. The stewardship intervention was employed for 17 rA TTEs and 13 mA TTEs. After the stewardship intervention, 17 of the rA TTEs remained classified as rA and 1 of the mA TTEs was reclassified as rA. Of the 18 rA orders, 16 were discontinued and 2 were completed (88% reduction). The stewardship intervention was associated with a significant reduction in completed rA TTEs when compared to the control group (OR = 0.15; 95% CI 0.03, 0.67; p = 0.005; Table).

Conclusion:
A stewardship intervention resulted in a significant decrease in completed rA inpatient TTEs among screened orders. In the era of capacity constraints, such a reduction represents a solution to improve clinical operations through targeted resource allocation. Future work to partially automate this initiative is important for scalability.
Abstract 4140406: Common Misdiagnoses During the Workup of Inherited Channelopathies
Authors: Bains Sahej , Neves Raquel , Bos Johan , Giudicessi John , Ackerman Michael
Published: November 2024

Background:
Cardiac channelopathies are a heterogenous group of genetic heart diseases (GHDs) that affect cardiac ion channel function. The most prevalent among these are long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) which predispose patients to potentially life threatening ventricular arrhythmias. Accurate and timely diagnosis is important for the management and risk stratification of the index case and identification of potentially at-risk relatives. Unfortunately, despite rising awareness of these GHDs, critical warning signs are overlooked.

Objective:
To describe the phenotypes of patients who present with a delayed or missed diagnosis of LQTS or CPVT.

Methods:
EMR data was reviewed for all patients evaluated and treated at Mayo Clinic between 2000-2023 who arrived with a mis- or delayed diagnosis of LQTS or CPVT. Data was abstracted for patient demographics, clinical characteristics, family history of SCD, and cardiac and genetic test results.

Results:
Overall, 47/2119 (2%) patients [33 (70%) female, mean age at correct diagnosis 26±18 years] diagnosed with LQTS (30; 2% of LQTS cohort) or CPVT (17; 7% of CPVT cohort) arrived with an outside misdiagnosis (37, 79%) or underdiagnosis (10, 21%). The most common misdiagnosis was epilepsy (20; 43%) or vasovagal syncope (14; 30%) and 3 CPVT patients (6%) were misdiagnosed with LQTS. Of the 10 underdiagnosed patients, 4 (40%) had QT prolongation, 4 (40%) family history of SCD, 3 (30%) bilateral deafness, and 1 (10%) fetal bradycardia and syndactyly. Overall, 40/47 (85%) were symptomatic (syncope: 29 [73%], seizures: 21 [53%], SCA: 10 [25%]) prior to diagnosis. Of note, 34/40 (85%) had symptoms with exertion, 5 (13%) at rest, and trigger was unknown in 1 (2%). Of the 7 asymptomatic patients (15%), 4 (57%) had QT prolongation and 4 (57%) had family history of SCD. In total, 20/47 patients (43%) had positive family history of SCD under 45 years of age. Overall, patients experienced a median delay in diagnosis of 8 years during which a median of 4 events (range: 1-150) occurred. As a result, an additional 29 family members of these patients received a delay in their diagnosis.

Conclusions:
Recognizing the signs and symptoms of patients with GHDs is important to reduce the ongoing burden of misdiagnosis or delayed diagnosis in LQTS and CPVT. The most important factors for suspicion of an inherited channelopathy are symptoms during exertion and family history of SCD.
Abstract 4140419: Targeting Cardiac Fibrosis with Chimeric Antigen Receptor Neutrophils from Human Pluripotent Stem Cells
Authors: Jin Gyuhyung , Bao Xiaoping
Published: November 2024

Cardiac fibrosis is a pathological hallmark of almost all forms of heart disease, characterized by excessive deposition of extracellular matrix (ECM) proteins by activated fibroblasts, leading to cardiomyocyte hypertrophy, arrhythmias, and heart failure. Current treatments, predominantly pharmacological, target signaling pathways involved in fibroblast activation but often come with side effects such as cardiac toxicities. There is a critical need for therapies that specifically target activated cardiac fibroblasts to mitigate these adverse effects.

Recent advances have shown that chimeric antigen receptor (CAR)-T cells targeting fibroblast activation protein (FAP), expressed by activated fibroblasts, can significantly reduce fibrosis and improve cardiac function in mouse models. However, CAR-T cell therapies face challenges such as the requirement for large quantities of healthy primary immune cells, lengthy process, and the high cost of personalized treatments. To address these issues, we propose an innovative strategy using off-the-shelf CAR-neutrophils derived from human pluripotent stem cells (hPSCs).

We hypothesize that hPSC-derived CAR-neutrophils engineered to target FAP will effectively reduce cardiac fibrosis and improve cardiac function post-injury due to their potent cytotoxic effects and ability to infiltrate infarct regions. To test this hypothesis, anti-FAP CAR hPSCs were generated by CRISPR/Cas9 genome editing and differentiated into neutrophils. The differentiated anti-FAP CAR hPSC-neutrophils exhibited molecular characteristics comparable to unmodified hPSC-neutrophils. We also established an in vitro cardiac fibrosis model utilizing a previously reported protocol for the generation of hPSC-derived epicardial fibroblasts. Importantly, our anti-FAP hPSC-neutrophils exhibited significant cytotoxicity against activated epicardial fibroblasts, while unmodified hPSC-neutrophils showed no/minimal killing efficiency.

This study suggests a proof-of-concept therapeutic approach against cardiac fibrosis utilizing FAP-targeting CAR-neutrophils. This strategy can potentially be adapted to treat fibrosis in other organs, thereby having a broad and significant impact on the treatment of various fibrotic diseases, ultimately contributing to longer, healthier human lives.
Abstract 4140451: Loss of Stem Cell Antigen-1 Worsens Aortic Remodeling in Angiotensin II-Induced Hypertension
Authors: Wang Tao , Momen Abdul , Husain Mansoor
Published: November 2024

Background:
Stem cell antigen-1 (Sca-1) marks progenitor cells that contribute to vessel remodeling by differentiating into vascular smooth muscle cells and related myofibroblasts. We previously demonstrated that Sca-1 is required for pro-fibrotic differentiation following arterial injury. Here, in a mouse model of experimental hypertension (HTN), we assessed the requirement for Sca-1 in aortic dysfunction and remodeling.

Methods&Results:
Male and female mice homozygous for GFP knock-in/Sca-1 knockout (Sca1KI
-/-
), heterozygous littermates (Sca1KI
+/-
), and control GFP-labeled Sca-1 reporter mice (Sca1GFP), age 12-14-wk, were subjected to angiotensin II-induced HTN (Ang-II 1000 ng/kg/min) by osmotic mini-pump for 28d, or vehicle (0.9% saline). GFP
+
CD31
-
CD45
-
cells from Sca1KI
-/-
, Sca1KI
+/-,
and Sca1GFP represent progenitor cells with no-, partial-, or normal Sca-1 expression, respectively. Partial- or total loss of Sca-1 expression exacerbated aortic GFP
+
CD31
-
CD45
-
cell expansion, compared to Sca1GFP [Sca1KI
-/-
32±7-fold change of vehicle
vs.
Sca1KI
+/-
39±9
vs.
Sca1GFP 5±1; n=11-13/group; p<0.0001], suggesting disinhibited progenitor responses. Interestingly, Sca1KI
-/-
mice manifest blunted HTN in response to Ang-II [Sca1KI
-/-
130±9 mmHg
vs.
Sca1KI
+/-
159±8
vs.
Sca1GFP 160±10; n=6-7/group; p<0.01]. Partial- or total loss of Sca-1 worsened aortic dilation [Sca1KI
-/-
1.25±0.06 mm
vs.
Sca1KI
+/-
1.21±0.06
vs.
Sca1GFP 1.04±0.05; n=6-7/group; p<0.05], aortic wall thickness [Sca1KI
-/-
105±9 μm
vs.
Sca1KI
+/-
136±16
vs.
Sca1GFP 82±5; n=6-7/group; p<0.01], adventitial area [Sca1KI
-/-
79±13 mm
2
vs.
Sca1KI
+/-
178±46
vs.
Sca1GFP 51±6; n=6-7/group; p<0.01], and aortic aneurysm formation [Sca1KI
-/-
6/17
vs.
Sca1KI
+/-
6/20
vs.
Sca1GFP 2/18]. Underlying these differences, in cultured progenitor cells subjected to TGFβ, pro-fibrotic CD44 expression increased 3.4-fold in Sca-1 deficient progenitors
vs
. wild-type [54±9%
vs.
16±2; n=2-3/group]. Concomitantly, stem cell marker PDGFRα expression on these cultured progenitors was reduced [0.4±0.1%
vs.
11±1; n=2-3/group], suggesting depletion of progenitors skewed towards a pro-fibrotic lineage.

Conclusion:
Partial or complete loss of Sca-1 worsens aortic remodeling in Ang-II HTN by increasing progenitor expansion and pro-fibrotic contributions. These data highlight a critical role for vascular Sca-1 expression, which may inform a novel approach to preventing and treating HTN and associated vascular remodeling.
Abstract 4140480: The Relationship Between Obesity Status and Change in NT-proBNP with Angiotensin-Neprilysin Inhibition in Patients with Mildly Reduced or Preserved Ejection Fraction and Recent Worsening Heart Failure Event: Results from the PARAGLIDE-HF Trial
Authors: Harrington Josephine , Mentz Robert , Adams Kirkwood , Hernandez Adrian , Lala Anuradha , Peikert Alexander , Solomon Scott , Starling Randall , Velazquez Eric , Ward Jonathan , Williamson Kristin , Zieroth Shelley , Sharma Kavita
Published: November 2024

Background:
In PARAGLIDE-HF, patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) and a recent worsening HF event randomized to sacubitril/valsartan (sac/val) vs val had a significantly larger reduction in NT-proBNP and were numerically more likely to derive clinical benefit as assessed by a win ratio. Patients with obesity and HFpEF may represent a unique phenotype, characterized by a high risk for recurrent HF hospitalization and lower levels of NT-proBNP.

Research Question:
Does BMI category modify the relationship between sac/val vs val on NT-proBNP change and/or a win ratio among patients with HFpEF or mildly reduced EF?

Methods:
To assess the interaction between BMI and sac/val vs val on NT-proBNP, the time-averaged proportional change in NT-proBNP from baseline to Weeks 4 and 8 was assessed with an analysis of covariance model including the interaction of treatment-by-BMI group (obese with BMI ≥30 vs normal/overweight, BMI 18.5 to <30 kg/m
2
). A win ratio of cardiovascular death, total HF hospitalizations, urgent HF visits, and change in NT-proBNP was calculated for both BMI groups, including an interaction term with significance set at ≤0.1.

Results:
Overall, 65% (n=298) of patients had obesity and 35% (n=164) of patients had normal/overweight. When the interaction between BMI category and the effect of sac/val vs val on the time-averaged proportional change from baseline NT-proBNP was assessed, patients with obesity had a non-significant but numerically larger decrease in NT-proBNP (
Table
). Patients with obesity were also more likely to derive clinical benefit overall from sac/val vs val as compared to patients with normal/overweight (win ratio 1.38, 95% CI 1.01-1.90 vs 0.90, 95% CI 0.62-1.32, p interaction = 0.09).

Conclusion:
These preliminary data suggest that patients with HF with mildly reduced or preserved EF and obesity may experience a larger clinical benefit from sac/val than patients with normal/overweight BMI.
Abstract 4140484: Socioeconomic Status and Outcomes of Patients with In-Hospital Cardiac Arrest
Authors: Irwin Hannah , abdallah nadhem , Mohamoud Abdilahi
Published: November 2024

Background:
Some studies illustrate an association between adverse outcomes and lower socioeconomic status (SES) in patients with cardiovascular disorders. Limited data exist on in-hospital cardiac arrest outcomes in the context of SES.

Objectives:
Using mean income as a surrogate for SES, we assessed the association of SES on outcomes and resource utilization for patients with in-hospital cardiac arrest.

Methods:
We queried the 2016-2019 Nationwide Inpatient Sample and identified inpatient cardiac arrest as the primary diagnosis. We compared in-hospital outcomes based on zip code mean income quartiles (≦2 (< $59,000) vs. ≧3). The primary outcome was inpatient mortality, while secondary outcomes included Palliative Care involvement, vasopressor use, mechanical ventilation use, targeted temperature control, mean length of stay (LOS), and total hospitalization cost (THC). Multivariable regression models were used to adjust for potential confounders.

Results:
Of 2,122,805 cases of in-hospital cardiac arrest, 1,146,314 (54%) involved patients with a lower income quartile. Lower quartiles were associated with higher odds of in-hospital mortality (adjusted OR [aOR] 1.08, 95% CI 1.05–1.11) and mechanical ventilation use (aOR 1.11, 95% CI 1.08-1.15), while they had lower odds of vasopressor use (aOR 0.62, 95% CI 0.55–0.71, p<0.001), Palliative Care involvement (aOR 0.95, 95% CI 0.92-0.99), and targeted temperature control (aOR 0.76, 95% CI 0.67-0.85), with less THC ($171,639 vs. $183,247, p <0.001) compared to patients in higher quartiles.

Conclusion:
In cases of in-hospital cardiac arrest, patients with lower income quartiles had higher mortality and less healthcare resource utilization compared to patients with higher income.
Abstract 4140486: Cardioprotective Role of Metformin: A Systemic Review and Meta-Analysis on Reducing Reperfusion Injury and Improving Endothelial Function
Authors: Notta Shahnawaz , Magacha Hezborn , Al Akeel Mohannad , notta Nasir , Jagadish Ashwin , jbara manar , Ramu Vijay
Published: November 2024

Introduction:
Reperfusion injury, defined as the injury to tissue upon restoring blood flow after a period of ischemia, remains a concern in many clinical scenarios such as myocardial infarction and coronary artery bypass surgery. Among several mechanisms of action, metformin, a commonly used antidiabetic medication, has received attention recently for its potential protective effects against reperfusion injury.

Hypothesis:
Metformin ameliorates reperfusion injury due to a reduction in myocardial injury markers and improvement in endothelial function across diverse clinical settings.

Methods:
A systematic literature search of PubMed, Embase, and Cochrane Library databases up to January 2022 was performed. Metformin's effects on reperfusion injury were identified by searching myocardial injury and endothelial dysfunction. The study included eight articles on metformin and reperfusion injury. Animal studies, expert opinions, and reviews were excluded.

Results:
Treatment with metformin significantly lowered myocardial injury markers, with reduced troponin levels: pooled SMD -0.61, 95% CI -0.87 to -0.36, and infarct size by a pooled mean difference of -5.25%, 95% CI -8.96 to -1.53. Additionally, metformin had beneficial effects on the endpoints of endothelial function, including flow-mediated dilation (pooled SMD 0.68, 95% CI 0.38 to 0.97) and markers of oxidative stress and inflammation. Subgroup analysis showed a consistent effect of metformin across different patient populations and different clinical settings. The sensitivity analysis did not indicate the presence of a single study that affected the stability of the result.

Conclusion:
This meta-analysis supports the protective effect of metformin against reperfusion injury in various clinical settings. Metformin appears to reduce myocardial injury and promote improvement in endothelial function, which may translate into reducing the risk of adverse cardiovascular events among patient populations at high risk for them. Further research is warranted to investigate the mechanisms for its cardioprotective effect.
Abstract 4140513: Temporal Trends in Cardiovascular Risk Factors and Cardiovascular Disease Among Subgroups of Asian Americans in the United States
Authors: Liu Xiaoyue
Published: November 2024

Aims:
Asian Americans experience disproportionate burdens of cardiovascular risk factors and cardiovascular disease (CVD). However, the trends in cardiovascular risks in adults from different Asian ethnic backgrounds remain understudied. Therefore, we examined the temporal trends in cardiovascular conditions among Chinese, Filipino, and Asian Indian adults living in the U.S.

Methods:
We conducted a cross-sectional analysis using the 2004-2018 National Health Interview Survey. Age-standardized prevalence rates were calculated for eight conditions, including hypertension, type 2 diabetes, alcohol use, smoking, physical inactivity, overweight/obesity, short sleep (< 7 hours), and CVD (defined as having coronary heart disease, heart attack, or stroke). Average annual percent change (AAPC) was employed to summarize and compare the trend of each outcome of interest over 15 years.

Results:
The sample consisted of 14,073 Asian adults, with 13% aged 65 years or older and 53% female. Of the sample, Filipino adults had the highest prevalence rates for most conditions, except for physical inactivity and overweight/obesity. Over 15 years, Chinese adults showed a 2% annual increase in short sleep (
p
= 0.010). Asian Indian adults exhibited uptrends in overweight/obesity (AAPC: 1.1%,
p
< 0.001) and alcohol use (AAPC: 2.3%,
p
< 0.001), but downtrends in smoking (AAPC: -4.8%,
p
= 0.005) and physical inactivity (AAPC: -0.8%,
p
< 0.001). Filipino adults demonstrated similar trends in the prevalence of alcohol use and smoking, with AAPCs at 1.6% (
p
= 0.001) and -3.1% (
p
= 0.001), respectively. No significant trends were found for other cardiovascular conditions in all three groups.

Discussion:
Our study assessed temporal trends in CVD and its risk factors among the three largest Asian ethnic groups in the U.S. The findings showed that Asian Americans from different ethnic backgrounds face varying disparities in cardiovascular health. Public health strategies should be customized to effectively address specific cardiovascular risks for each Asian subgroup.
Abstract 4140514: Virtual Versus Center-Based Cardiac Rehabilitation: A Comparison of Outcomes and Cost
Authors: Shah Neil , Banta Conor , Berger Andrea , Hattenberger Andrea , Zimmerman Alex , Martin Bryan , Wu Edward , Majumdar Usnish , Kirchner H Lester , Matsumura Martin
Published: November 2024

Introduction:
Despite robust evidence supporting improved outcomes in eligible patients, cardiac rehabilitation (CR) remains underutilized. Virtual cardiac rehab (VCR) has been proposed as an alternative to traditional center-based CR (CBCR) to improve utilization rates. However, data supporting VCR efficacy and cost-effectiveness are lacking. In this study, we compared outcomes and cost of VCR vs. traditional CBCR.

Methods:
This retrospective cohort study compared VCR vs CBCR for Geisinger Health System, which primarily serves patients in rural Pennsylvania. CBCR data were collected from January 2018 to September 2023 and VCR data were collected from July 2021 to September 2023. Propensity scores were used to weight the observations and health outcomes were assessed using a weighted time-to-event analysis. Primary health outcomes measured were 1-year mortality rates, recurrent MI, all-cause hospital readmission, and emergency department visits, expressed as the incident rate ratio (IRR) of VCR:CBCR. Primary cost outcomes were analyzed as cost ratios of VCR:CBCR assessing total medical costs allowed, pharmacy costs, and total costs of care over the 12 months post-CR enrollment, while address data were used to compare the two modalities’ geographic footprints.

Results:
There were 3006 CR participants with mean age 67.7 years with 1017 (33.8%) women and 2924 (97.9%) white. A total of 2303 patients were enrolled in CBCR (76.6%) and 703 in VCR (23.4%). The VCR group was significantly older and had a significantly higher percentage of comorbidities including heart failure, diabetes and chronic pulmonary disease.

Compared to CBCR, VCR was associated with a significant reduction in 1-year all-cause hospital readmission (IRR=0.616, p<0.001) and 1-year ED admission (IRR=0.557, p<0.001). The IRR of MI and all-cause mortality did not significantly differ between VCR and CBCR. In addition, VCR was associated with significant reductions in medically related (cost ratio=0.814, p=0.0144) and total costs (cost ratio=0.838, p=0.0176) in the year following initiation of CR.

Conclusions:
To our knowledge, the present study is the first to demonstrate both improvements in clinical efficacy and cost of VCR compared to CBCR. While this study’s retrospective design has limitations, it supports VCR as a viable addition to CBCR with at least comparable efficacy and cost, and as such, represents a key mechanism for improving access to and participation in CR for eligible patients.
Abstract 4140540: Difference of escalation and de-escalation strategies and outcome in cardiogenic shock patients supported with Impella; acute myocardial infarction versus de novo heart failure versus acute on chronic heart failure
Authors: Hattori Hidetoshi , Kikuchi Noriko , Ichihara Yuki , Saito Satoshi , Nunoda Shinichi , Niinami Hiroshi , Yamaguchi Junichi , . J-PVAD investigators
Published: November 2024

Background:
Timely initiation of temporary mechanical circulatory support (tMCS), escalation and de-escalation strategies are key components for treatment of cardiogenic shock (CS). However, little is known about tMCS strategies and outcomes based on etiology of CS and chronicity of heart failure. We evaluated differences of tMCS strategies and outcome in patients supported with Impella in acute myocardial infarction related CS (AMI-CS), de novo heart failure related CS (de novo HF-CS), and acute on chronic heart failure related CS (acute on chronic HF-CS).

Methods and Results:
The Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) is multicenter, observational registry enrolling all consecutive patients treated with Impella in Japan. We conducted a retrospective analysis of patients with Impella in J-PVAD between February 2020 and December 2022. Among 3678 CS patients supported with Impella. 2418 (65.7%) patients were presented with AMI-CS, 758 (20.6%) patients with de novo HF-CS, and 502 (13.7%) patients with acute on chronic HF-CS. The median time from hospital entry to initiation of Impella were 127 min, 339 min, and 1117 min in AMI-CS, de novo HF-CS, and acute on chronic HF-CS, respectively (P < 0.001 for each). 2233 (92.4%) patients with AMI-CS underwent percutaneous coronary intervention during index hospitalization with median door-balloon-time of 108 min. Patients treated with multiple mechanical circulatory supports were 51.4%, 64.2%, and 55.2% in AMI-CS, de novo HF-CS, and acute on chronic HF-CS, respectively. Using de novo CS-HF as a reference, the risk for in-hospital mortality for AMI-CS and acute on chronic HF-CS were: odds ratio (OR) 1.24 [95% confidence interval (CI) 1.04–1.50], P = 0.02 and OR 1.43 (95% CI 1.12–1.81), P = 0.004, respectively.

Conclusions:
In CS patients supported with Impella, time course and utilization of tMCS varied in AMI-CS, de novo HF-CS, and acute on chronic HF-CS. De novo HF-CS had significantly better mortality relative to AMI-CS and acute-on-chronic CS. Further research is required for tMCS strategies based on etiology of CS and chronicity of heart failure.
Abstract 4140549: Association of Liver Stiffness measured by Transient Elastography with All-Cause Mortality in Heart Failure patients: Trinetx Database 2015-2023
Authors: Varadarajan Vinithra , Agrawal Nirav , Karpman Mitchell , Busaileh Ahmad , maxted william
Published: November 2024

Introduction:
Persistently elevated filling pressure leading to central venous congestion is associated with poor prognosis. This central venous congestion stimulates connective tissue hyperplasia causing tissue fibrosis and stiffness of the liver. However, risk stratification involving hepatic fibrosis in heart failure is limited.

Research Question:
Is liver stiffness associated with higher mortality in heart failure?

Aims:
To utilize liver stiffness measured by transient elastography as an imaging phenotype in HF risk stratification and prevention.

Methods:
De-identified data from 285 HF patients without pre-existing liver disease/cirrhosis, with liver stiffness measured (kPa) by transient elastography from 2015-2023 were extracted from TriNetX, a real-time, electronic, federated data network of 34 healthcare organizations. Liver stiffness was further classified as high and low with 8kPa as a cut-off. Comparisons employed the chi-square or Fisher’s exact test for categorical variables and the student’s t-test or Mann-Whitney-Wilcoxon test, as appropriate. Multivariable Cox proportional hazards models were applied to evaluate the association with mortality and readmissions in 30 days.

Results:
The mean age of the cohort is 65±11 years. The majority were women (57.9%). Participants were followed for a median of 3.8 (1.52-6.67) years; 83 out of 285 patients died. Multivariable analysis showed that 1 SD increase in liver stiffness was associated with increased mortality (HR 1.13, 95% CI 1.05-1.21; p<0.01) and 30-day readmissions (HR 1.13, 95% CI 1.06-1.21; p<0.01). The adjusted HR for all-cause mortality for the high liver stiffness (≥8 kPa) group was 2.30 (95% CI 1.21-4.37; p=0.01). The analysis of liver stiffness association with mortality stratified by heart failure preserved ejection fraction (HFpEF) was HR 1.14 (95% CI 1.06-1.24, p<0.01). There were no significant differences in mortality when stratified by heart failure with reduced ejection fraction, gender, and race.

Conclusion:
In a multi-ethnic cohort of heart failure patients with HFpEF and no preexisting cirrhosis, higher liver stiffness was independently associated with excess mortality and 30-day readmissions.
Abstract 4140555: Sleep Quality Mediates the Relationship Between Sleep Hygiene Practices and Psychological Stress Among Adults With Multiple Cardiovascular Risk Factors
Authors: Liu Xiaoyue , Li Junxin , Hu Jinyu , Fletcher Jason , Commodore-Mensah Yvonne , Dennison Himmelfarb Cheryl
Published: November 2024

Background:
Psychological stress and poor sleep quality are interrelated and disproportionately affect adults who have multiple risk factors of cardiovascular disease (CVD). Sleep hygiene practices, such as maintaining an optimal household environment and engaging in healthy bedtime behaviors, are essential to sleep health. These practices may also impact psychological stress; however, their relationships remain under-studied. This study aimed to examine the associations among sleep hygiene practices, sleep quality, and psychological stress in adults with multiple CVD risk factors.

Methods:
Adults diagnosed with hypertension and type 2 diabetes completed an online survey (N = 300). Psychological stress and sleep quality were assessed using the Perceived Stress Scale 4 and the Pittsburgh Sleep Quality Index, respectively. A sleep hygiene instrument was used to examine 8 individual factors focusing on negative household environment (safety, physical comfort, temperature, and light) and poor in-bed behaviors (watching TV, playing video games, using screens, and eating). Multiple regression was employed to examine the association of each sleep hygiene factor with sleep quality and psychological stress. Subsequently, mediation analyses were conducted to examine the mediating role of sleep in the association between the composite sleep hygiene score and psychological stress.

Results:
Of the sample, 78% reported poor sleep quality and 44% reported high psychological stress. Individual sleep hygiene factors (e.g., unsafe household and eating at bedtime), as well as the composite sleep hygiene score, were significantly associated with poorer sleep quality and higher psychological stress. Sleep quality partially mediated the association between the composite sleep hygiene score and psychological stress (Indirect effect: 0.183; 95% bootstrap confidence interval: 0.057-0.339).

Conclusions:
The findings showed strong links between sleep hygiene practices, sleep quality, and psychological stress. Although causality cannot be inferred, current evidence suggests that promoting sleep hygiene education and implementing strategies to enhance sleep quality may alleviate psychological burdens in adults with multiple CVD risk factors.
Abstract 4140558: Circulating plasma proteins in the Fontan circulation predict mitochondrial oxidative stress
Authors: Gan Sushrima , Lecointe Joiliana , Ichimura Shoko , Kushwaha Ankit , Mercer-Rosa Laura , Reddy Sushma
Published: November 2024

Background:
Single ventricle congenital heart disease such as hypoplastic left heart syndrome (HLHS) with a Fontan circulation constitute the largest group of children hospitalized with circulation failure, experiencing an in-hospital mortality rate of 20-50%. We investigated the mechanisms leading to circulation failure so as to identify novel therapeutic targets.

Methods:
Blood was collected from patients with HLHS s/p Fontan and controls with normal cardiac anatomy and function (N=6/group). Plasma microvesicles (MV) were isolated, and proteomics assessed using data independent acquisition mass spectroscopy. Dysregulated proteins with a fold change >1.5 or < -1.5, p<0.05, were evaluated using DAVID and Ingenuity pathway analysis. We assessed the association of most highly dysregulated proteins with NYHA class (clinical indicator of heart failure), right ventricular fractional area change (RV FAC) (echocardiographic indicator of RV systolic function), oxygen saturation and hemoglobin using Pearson correlation.

Results:
Age of Fontan patients vs. controls was 16.14±23 vs. 15.78±2; 40% were male in both groups. 80% of Fontan patients were in NYHA class II/III, 20% in NYHA class IV; 60% had Fontan-associated liver disease. Increasing expression of the following proteins was associated with worsening NYHA class: complement system (C1QA, r=0.91; C7, r=0.53; FCN3, r=0.52), membrane transporters (SLC2A1, r=0.82; SLC4A1, r=0.76), mitochondrial reactive oxygen species (mROS) generation (HSPD1, r=0.81; ATP5F1A, r=0.75) and cytoskeletal proteins (ANK1, r=0.63; ACTN1, r=0.76). Increasing expression of proteins involved in mROS generation were also associated with worsening RV FAC. Decreasing expression of the following proteins was associated with worsening NYHA class and RV FAC: B-cell lymphopoiesis (DOCK10; r=-0.80), adhesion (ADAM10, r=-0.72; CD151, r=-0.69), and coagulation (SERPINF2, r=-0.55). Higher expression of proteins involved in mitochondrial ROS generation and lower expression of proteins involved in lymphopoiesis and adhesion were associated with lower oxygen saturation and higher hemoglobin(Figure).

Conclusion:
Circulating plasma proteins in the Fontan circulation predict complement activation, mROS, cytoskeletal changes and decreased cell-cell adhesion. This circulating proteomic profile is associated with worsening heart failure and cyanosis providing mechanistic insight into heart failure progression and highlights novel therapeutic targets.
Abstract 4140612: Non-canonical CDC20 signaling promotes smooth muscle and adventitial fibroblasts hyper-proliferation and remodeling in pulmonary arterial hypertension
Authors: Dey Tapan , Goncharov Dmitry , Zhyvylo Iryna , Lin Derek , Shah Maanvi , Saiyed Aisha , Neeli Sanjana , Kudryashova Tatiana , Greenland John , Wolters Paul , Jiang Lifeng , Goncharova Elena
Published: November 2024

Background:
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vasoconstriction and remodeling of small pulmonary arteries (PAs) due to hyper-proliferation and apoptosis resistance of resident PA cells, the mechanisms of which are not completely understood. Specifically, the role of cell division cycle protein 20 (CDC20), a key regulator of cell cycle, canonically acting as an APC/C E3 ubiquitin ligase activator and substrate recruiter, is not known.

Goals:
To determine the role of CDC20 in PA remodeling in PAH.

Methods:
RNAseq, immunoblot, immunohistochemistry, proliferation, apoptosis assays; SU5416/Hypoxia (SuHx) mouse model of PH.

Results:
CDC20 was over-expressed in lungs, small PAs, isolated PA smooth muscle cells (PASMCs) and adventitial fibroblasts (PAAFs), but not endothelial cells from PAH patients compared to non-diseased controls. siRNA CDC20 significantly reduced proliferation and induced apoptosis in PAH PASMCs and PAAFs. This effect was re-capitulated by CDC20 inhibitor apcin (blocks binding of CDC20 with substrates); however, pan-APC inhibitor proTAME had no effect. Over-expression of CDC20 in PAH PASMCs and PAAFs was correlated with over-accumulation of its substrate, pro-proliferative protein securin, and deficiency of pro-apoptotic protein Bcl-2 interacting mediator of cell death (BIM). Depletion of CDC20 with specific siRNA, but not treatment with proTAME, dramatically reduced securin and restored BIM protein levels in PAH PASMCs and PAAFs. Apcin restored BIM protein content in human PAH PASMCs, and siRNA BIM protected PAH PASMCs from apcin-induced apoptosis. Pharmacological targeting of CDC20 with specific PROTAC degrader CP5V down-regulated CDC20 and securin, restored BIM, inhibited hyper-proliferation, and induced apoptosis in PAH, but not in control PASMCs, and reversed SuHx-induced pulmonary vascular remodeling, PH, and right ventricular hypertrophy in male and female mice.

Conclusions:
Collectively, our data demonstrate that CDC20 is overexpressed and supports proliferative, apoptosis resistant PASMC/PAAF phenotype in PAH via non-canonical APC/C independent upregulation of pro-proliferative securin and downregulation of pro-apoptotic BIM. Our data also suggest that targeting CDC20 could represent a novel potentially attractive strategy to suppress PA resident cells proliferation and reverse established PAH.
Abstract 4140625: Does the Cord predict the Course? Trend And Outcome of Myocardial Infarction in Patients With Spinal Cord Injury; a Retrospective Population-Based Analysis
Authors: Ukenenye Emmanuel , Evbayekha Endurance , Dilibe Arthur , Akinti Oluwasegun , Perry Jamal , Antia Akanimo , Balaji Adarsh , Stojanovic Nikola , Adeniran Olayemi , Alugba Gabriel
Published: November 2024

Introduction:
Spinal cord injury (SCI) has been shown to increase the risk of cardiovascular diseases such as myocardial infarction (MI), atrial fibrillation, and heart failure. Impaired mobility and dysautonomia have been suggested to play a role. We evaluated MI outcomes in patients with SCI.

Methods:
This retrospective cohort study used the National Inpatient Sample (2016-2020) database. We identified hospitalizations with a diagnosis of MI using their ICD-10 codes and then stratified them based on the presence or absence of SCI. Our outcome of interest was in-hospital mortality. A multivariate logistic regression model was used to account for confounders and estimate the probability of the outcome.

Results:
The number of patients hospitalized with MI and a history of SCI was 560, while 3,190,369 patients had MI with no history of SCI. The mean age of the SCI population was 66.9 years, compared to 62 years in the group without SCI. The SCI group were predominantly male 85%, 72% White, 14% Black, and 7% Hispanic. The SCI population had a higher association with in-patient mortality (adjusted odds ratio: 2.5, p= 0.013, CI 1.21 - 5.03) than the group without SCI.

Conclusions:
Our analysis showed that among the population admitted for MI, those with SCI had a higher association with in-hospital mortality than those without SCI. Also, SCI patients admitted for MI tend to be of male sex. More research is needed to explore our findings further.
Abstract 4140679: Defining the Prevalence and Incidence of Heart Failure Phenotypes Among Transgender Adults
Authors: Everitt Ian , Sisson Emily , Streed Carl , Mukherjee Monica
Published: November 2024

Introduction:
Transgender and gender diverse (TGD) adults have disproportionately greater burden of cardiovascular disease (CVD) risk. However, prevalent and incident heart failure (HF) and its risk factors have not been well-characterized in TGD populations.

Objective:
To determine the prevalence and incidence of HF risk factors and phenotype by gender identity.

Methods:
The study included commercial insurance claims data for 408,457 adults from 2006-2022. Gender identity was classified as cisgender male, cisgender female, transmasculine, transfeminine, or unclassified TGD identity. HF risk factors and phenotype (i.e., HFrEF, HFpEF, other HF) were abstracted using administrative billing codes. Multivariate logistic regression and Cox proportional hazard models examined associations between gender identity and prevalent and incident HF, respectively. Models were stratified by HF phenotype and adjusted for clinical comorbidities and presence of CVD.

Results:
Of 57,471 TGD patients, 9,652 (16.8%) were transfeminine, 17,898 (31.1%) were transmasculine, and 29,921 (52.1%) had unclassified TGD identity. The mean age was 35±16 years, followed for 5.5±4.7 years. The prevalence of HF risk factors differed by gender identity (
Table 1
). Among TGD adults the overall prevalence of HFrEF, HFpEF, and other HF were 0.4% (n=204), 0.4% (n=222), and 1.8% (n=1,015), respectively. Prevalent HF differed by gender identity (p<0.001). In adjusted models compared to cisgender males, transmasculine persons had lower odds of HFrEF (OR 0.38 [95% CI 0.21-0.71], p<0.05), unclassified TGD persons had greater odds of HFpEF (OR 1.44 [95% CI 1.17-1.77], p<0.05) and lower odds of other HF (OR 0.77 [95% CI 0.69-0.85], p<0.05). Compared to cisgender males, transmasculine persons had less incident HFrEF, HFpEF, and other HF; transfeminine persons had less incident HFrEF; and unclassified TGD adults had greater incident HFpEF (
Table 2
).

Conclusions:
Among a nationally representative administrative sample inclusive of TGD people, CVD risk factors, prevalent HF, and incident HF differ by gender identity. Gender identity and concomitant gender-affirming therapies represent underrecognized markers of HF risk and may act as HF risk modifiers in TGD adults.