bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4145802: Association between Glucagon-like peptide-1 receptor agonists and risk of Arrhythmias or Heart Failure among patients with Type 2 Diabetes: A Meta-Analysis of 29 Randomized Controlled Trials.
Authors: Jaiswal Vikash , Jaiswal Akash , Kalra Kriti , Danisha FNU , Mattumpuram Jishanth , Biswas Monodeep
Published: November 2024

Background:
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular events (MACE) among patients with type 2 diabetes mellitus (T2DM). However, their effect on reducing the risk of incidence of arrhythmias and heart failure has not been established, and there is very limited literature to date.

Objective:
We evaluated the effect of GLP-1 RAs on the incidence of arrhythmias and heart failure among patients with T2DM.

Methods:
We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with type 2 diabetes and compared GLP-1 RAs and control groups. PubMed and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model.

Results:
A total of 29 RCTs with 72,868 patients (35,631 in the GLP-1 RA group and 37,237 in the control group) were included in the analysis. Pooled analysis showed that there is no significant association between GLP-1 RAs and incidence of atrial fibrillation (OR, 0.94(95%CI: 0.75-1.18), P=0.60), atrial flutter (OR, 0.87(95%CI: 0.60-1.26), P=0.46), cardiac arrest (OR, 0.79(95%CI: 0.51-1.23), P=0.30), ventricular tachycardia (OR, 1.37(95%CI: 0.90-2.07), P=0.14), and ventricular fibrillation (OR, 0.91 (95%CI: 0.45-1.84), P=0.80) when compared with control group. However, GLP-RAs reduced the incidence of atrioventricular block complete (OR, 0.58 (95%CI: 0.35-0.97), P=0.04), and heart failure (OR, 0.795 (95%CI: 0.634-0.997), P=0.047).

Conclusion:
This study shows that GLP-1 RAs reduced the incidence of atrioventricular block complete and incidence of heart failure. However, no significant association has been observed for arrhythmias.
Abstract 4145826: Atrial Fibrillation Screening During Sinus Rhythm Periods by Interrelated Systems Dynamics Analysis
Authors: Keidar Noam , Elul Yonatan , Schuster Assaf , Bronstein Alex , Yaniv Yael
Published: November 2024

Background:
Previous studies have shown that AF screening in at-risk populations can reduce stroke incidence. However, non-targeted screening approaches often result in high false positive rates, placing an unnecessary burden on the healthcare system. In contrast, artificial intelligence-guided screening has been demonstrated to increase diagnostic yield in large prospective clinical trials. This approach, however, requires recording an ECG and a large-scale dataset for model training. Heart rate variability (HRV) analysis has proven effective in deciphering key heart dynamics. By analyzing HRV as interrelated dynamic systems, it may be possible to facilitate targeted AF screening using wearable devices that measure heart rate.

The Koopman operator, used for data-driven modeling of interrelated dynamic systems, has been shown to accurately predict complex phenomena in chaotic systems such as climate forecasting and drug adverse reaction prediction. This is achieved by utilizing common characteristics of the systems for most model parameters, with only a small fraction of the parameters being specific to a certain system.

Methods:
Long (>10 hour) records from 361 individuals (AFDB, LTAFDB) and healthy individuals' datasets from PhysioNet and THEW were analyzed for inter-beat intervals. The unified dataset was then split into 94 training, 17 validation, and 250 test set patients. Recordings from the training set were used to train both the common and specific parts of the interrelated dynamic systems model for each patient, along with a shared small neural network classifying patients into low and high risk for AF based on the unique (not shared between patients) singular values of the dynamic system model. Patient-specific dynamic system models were then fitted for the validation and test sets to calculate the patient dynamic singular values, which were used to classify patients into low and high risk for AF groups.

Results:
Atrial fibrillation occurred in 48 of 202 (23%) patients classified as low risk and 35 of 48 (72.9%) patients classified as high risk (odds ratio 8.63, 95% CI 4.23-17.64), yielding 72.9% sensitivity with 76.2% specificity.

Conclusion:
In this retrospective analysis, classification of the dynamic system model singular values identified patients at high risk for atrial fibrillation from sinus rhythm period.
Abstract 4145876:
Prognostic significance of somatic mutations in myeloid cells of men with chronic heart failure – interaction between loss of Y chromosome and clonal hematopoiesis
Authors: Cremer Sebastian , von Scheidt Moritz , Kirschbaum Klara , Tombor Lukas , Mas-Peiro Silvia , Rasper Tina , Abplanalp Wesley , Krefting Johannes , Leistner David , Speer Thimoteus , Schunkert Heribert , Dimmeler Stefanie , Zeiher Andreas
Published: November 2024

Introduction:
Age-associated clonal hematopoiesis of indeterminate potential (CHIP) has been associated with increased incidence and worse prognosis of chronic heart failure. CHIP is driven by somatic mutations in hematopoietic stem and progenitor cells (HSPC). Mosaic loss of the Y chromosome (LOY), the most common somatic mutation in blood cells of men, also correlates with clonal expansion of myeloid cells, increases with age and was experimentally shown to lead to diffuse cardiac fibrosis and subsequent heart failure in mice. However, the prognostic significance of LOY as well as its potential interaction with CHIP in patients with chronic heart failure is unknown.

Aims/Methods:
We investigated the prevalence and prognostic significance of the extent of LOY and the two most common CHIP-driver mutations DNMT3A and TET2 in 705 male patients with established chronic heart failure across the entire spectrum of left ventricular ejection fraction.

Results:
Both, LOY and DNMT3A/TET2 mutations, increased with age, and LOY co-occurred with DNMT3A/TET2 mutations in 27.1% of men at age > 70 years. LOY was an independent predictor of death during 3-years of follow-up across the entire spectrum of left ventricular ejection fraction. The co-occurrence of harboring LOY and DNMT3A/TET2 mutations significantly contributed to the observed increased mortality observed in carriers of DNMT3A/TET2 mutations. The detrimental effect of LOY on prognosis was confirmed in a validation cohort of patients with ischemic heart disease.scRNA sequencing of peripheral blood cells in patients with chronic ischemic heart failure showed increased profibrotic signaling in LOY monocytes with elevated markers of monocyte mediated inflammation and profibrotic cardiac remodeling (S100A8, TLR2, CLEC4D) and reduced expression of TGF-b inhibiting genes (SMAD7, TGIF2). The proinflammatory phenotype of LOY monocytes was further amplified in LOY monocytes of patients simultaneously harboring DNMT3A mutations, who displayed heightened expression of alarmins (S100A8, HMGB2) and interferon signaling related genes (IFNGR1, TRIM56, CD84) compared to patients without CHIP mutations.

Conclusion:
The age-associated acquisition of somatic mutations in blood cells of men with chronic heart failure is associated with increased mortality, with loss of Y chromosome emerging as an independent predictor of all-cause death across the entire spectrum of left ventricular function.
Abstract 4145883: Elevated International Normalized Ratio Is Associated with Severity of Intracerebral Hemorrhage for Patients Taking Direct Oral Anticoagulants
Authors: Lusk Jay , sun jie-lena , Mac Grory Brian , Schwamm Lee , Smith Eric , Fonarow Gregg , Bhatt Deepak , Saver Jeffrey , Reeves Mathew , Matsouaka Roland , Xian Ying
Published: November 2024

Introduction/Background:
While the international normalized ratio (INR), a marker of functioning of the extrinsic and final common pathways of the coagulation cascade is associated with increased intracerebral hemorrhage (ICH) mortality for patients taking warfarin, it is not understood how it might be associated with outcomes in patients taking direct oral anticoagulants (DOACs), given the inconsistent and variable effect of DOACs on INR.

Research Questions/Hypothesis:
To determine whether INR is associated with increased ICH severity in patients with recent exposure to a DOAC.

Methods/Approach:
We included patients taking Apixaban or Rivaroxaban prior to acute presentation with ICH to hospitals participating in the Get With the Guidelines - Stroke registry, a nationwide quality improvement registry. The primary exposure was INR, which we modeled as a continuous variable with restricted cubic splines. The primary endpoint was stroke severity on presentation, measured by the National Institutes of Health Stroke Scale (NIHSS). Secondary endpoints included Glasgow Coma Scale (GCS) <=8 on admission, in-hospital mortality, composite of in-hospital mortality and discharge to hospice, and modified Rankin Scale (mRS) at discharge. We adjusted for key confounding factors, specifically age, sex, race/ethnicity, insurance status, and medical history, while taking into account within-hospital clustering.

Results/Data:
In total, 13,251 patients were included of whom 7,545 were exposed to apixaban and 5,706 were exposed to rivaroxaban. As shown in Table 1, for patients taking Apixaban, elevated INR was associated with increased likelihood of NIHSS >=21 (aOR 1.02 [95% CI 1.00-1.04, p=0.03] per 0.1 above 1.1) and in-hospital mortality (aOR 1.11 [95% CI 1.05-1.16, p<.001) per 0.1 above 1.1). For patients taking Rivaroxaban, similar trends were seen (aOR 1.21 [95% CI 1.08-1.35, p<.001] per 0.1 up to 1.2 for NIHSS >=21, aOR 1.13, [95% CI 1.09-1.16, p<.001] per 0.1 up to 1.6, for in-hospital mortality).

Conclusion(s):
Elevated INR at admission is associated with worsened ICH severity for patients taking Apixaban or Rivaroxaban.
Abstract 4145890: P-Wave Parameters on 12-Lead Electrocardiogram after Catheter Ablation: A Comparison between Pulsed Field Ablation and Cryoablation
Authors: Chadha Sakshum , Newman Seth , Maan Abhishek , Mirza Jacqueline , Garikapati Srilakshmi , Musikantow Daniel , Turagam Mohit , Koruth jacob , Whang William , Miller Marc , Lampert Joshua , Dukkipati Srinivas , Reddy Vivek
Published: November 2024

Background:
Catheter ablation (CA) is a well-established treatment for atrial fibrillation (AF). The most popular current methods of CA include radiofrequency ablation (RFA) and cryoablation (CRYO) which are thermal methods of ablation known to affect the autonomic nervous system through ablation of cardiac ganglionated plexi (GP). Pulsed[SC1] -field ablation (PFA) is a newer method of CA with demonstrated efficacy that preferentially affects cardiac cells and spares surrounding structures such as GP through irreversible electroporation which does not lead to chronic fibrosis like RFA or CRYO. Elevations in the marker the marker P terminal force (PTF) have been associated with AF/stroke and have been known to correlate with atrial fibrosis, and higher PTF after cryoablation for patients with paroxysmal AF has been associated with an increased risk of recurrence. The differences in P-wave parameters pre and post PFA have not been studied.

Objective:
To investigate the differences in P-wave parameters after PFA and compare them to CRYO.

Methods:
We identified 40 patients who underwent PFA (20 patients) or CRYO (20 patients) for paroxysmal AF and compared P-wave parameters including duration and amplitude in leads aVF, V1 and the PTF calculated as the duration x amplitude of the terminal negative component of the P-wave in V1. Data were obtained from 12-lead electrocardiograms obtained pre and post ablation.

Results:
The mean age of patients in our study was 61 with 75% male and 33% on antiarrythmics. We noticed a significant reduction in PTF for patients who underwent CRYO (54 mVmS at baseline compared to 36.8 mVmS after CRYO, p = 0.04) and no significant reduction in PTF for patients who underwent PFA (46 mVmS at baseline compared to 38 mVmS after PFA, p = 0.27). There was also a significant increase in HR after CRYO (65 bpm at baseline compared to 78 bpm after CRYO, p=0.01) and no significant change in HR after PFA (61 bpm at baseline compared with 60 bpm after PFA, p=0.8). There was no statistical difference in both groups looking at aVF or total V1 duration or amplitude pre and post ablation.

Conclusions:
CRYO leads to a significant change in PTF after ablation while PFA does not, consistent with the notion that PFA does not lead to fibrosis and PTF is not a useful marker for measuring risk of recurrence of AF post PFA.
Abstract 4146301: Relationship Between Calf Muscle Pump Function and Exercise Stress Testing
Authors: Ghorbanzadeh Atefeh , McBane Robert , Liedl David , Bonikowske Amanda , Guarda Max , Houghton Damon
Published: November 2024

Background:
Exercise stress testing uses metabolic equivalents of tasks (METs) to measure the energy cost of activities, aiding in the assessment of exercise capacity and cardiovascular health. Despite its significance, the correlation between calf muscle pump function (CPF) and exercise stress testing remains unexplored. We aimed to evaluate the relationship between CPF and peak METs as determined by cardiopulmonary treadmill exercise stress testing.

Methods:
The study included adults who underwent exercise cardiopulmonary stress testing and venous plethysmography at Mayo Clinic between April 2017 and March 2020. The protocols other than Bruce, Mayo, Modified Naughton, and Naughton protocols were excluded. The CPF ejection fraction (EF) was calculated per leg based on refill volumes post-exercise as a percentage of passive drain refill. The classification of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) was utilized to better understand chronic venous insufficiency (CVI).

Results:
A total of 155 patients who underwent both exercise stress testing and venous plethysmography were included, with a mean age of 61.31 ± 14.03 years, and 84 (54.2%) were male. The peak measured METs for normal, unilaterally reduced, and bilaterally reduced CPF were 8.5 (2.5), 7.3 (2.1), and 7.1 (2.4), respectively (p=0.004, Figure 1). Multiple linear regression models were developed with METs as the outcome to determine if CPF was an independent predictor of METs on cardiopulmonary exercise stress testing. IIn model 1, the following independent variables were included: resting heart rate, peak heart rate, peak systolic blood pressure, recovery heart rate at minute 1, and worst EF (Table 1). In model 1, with only exercise parameters, lower EF was associated with lower METs (p=0.03). In a second analysis, variables identified as statistically significant with METs in the initial model were included, along with CEAP class (model 2) and CCI (model 3) (Table 2). In model 2, CEAP class 3 or higher was associated with decreased METs on the exercise stress test. This correlation implies that individuals with moderate to severe CVI may influence exercise capacity, demonstrating the interconnectedness of the cardiovascular system. Moreover, in model 3, the CCI, a predictor for mortality, was not significantly associated with METs.

Conclusion:
Our findings revealed that more severe CVI (CEAP class and reduced CPF) was associated with reduced exercise capacity after accounting for other factors.
Abstract 4146302: NETosis Attenuating Nanoprobe Improves Survival after Cardiac Arrest
Authors: Chen Howard , Boukhalfa Asma , Hayashida Kei , Miyazaki Yusuke , Pal Rahul , Yuan Hushan , Kumar Anand , Ichinose Fumito , Sosnovik David
Published: November 2024

NETosis, the process of neutrophil cell death due to the formation and release of neutrophil extracellular traps (NETs) has been implicated in the pathogenesis of heart disease. NETs are composed of immunogenic DNA fragments and citrullinated histones. The role of NETosis in the context of cardiac arrest and resuscitation (CA/R) is however unknown. We previously reported the development of a Dextran-Thiazole Orange (DTO) nanoprobe, with nanomolar affinity for nucleic acids, that exerts acute anti-inflammatory effects and reduces ischemia-reperfusion injury in mice. We aimed here to determine whether the DTO nanoprobe would also bind to the nucleic acid in NETS, whether DTO could attenuate the intensity of NETosis, and whether this would improve outcomes and survival after cardiac arrest.

C57Bl6 mice were arrested for 8 minutes before resuscitation. DTO or unmodified dextran (vehicle control) was injected at the time of resuscitation, and again 4 hours later (n=38 mice). Survival and neurological function were scored daily. Time-domain resolved (lifetime) and conventional fluorescence imaging was performed at 4 hours after resuscitation in 6 additional mice injected with DTO. NETosis was evaluated by protein blot in the hearts of cardiac arrest mice injected with DTO or control.

DTO significantly (p<0.05) improved 10-day survival (Fig. A), mean survival (from 4 to 7 days, Fig. B), and neurological function (Fig. C) following CA/R. Lifetime imaging (Fig. D), but not conventional fluorescence imaging (Fig. E) revealed the presence of DTO in the injured heart, liver and kidneys. In the heart, DTO signal was significantly increased in CA/R compared to sham mice injected with DTO or CA/R mice injected with control dextran (Fig. F). Citrullinated H3 and HMGB-1 (High mobility group box 1, a chromatin protein) were both upregulated in CA/R, and were significantly attenuated by DTO injection (Fig. G-I).

We show for the first time that NETosis plays a key role in cardiac arrest and resuscitation. DTO is capable of detecting NETosis as well as attenuating it, likely via a reduction in HMGB-1 activity. The modulation of NETosis may provide a new avenue to improve survival after cardiac arrest.
Abstract 4146306: Rural Urban Disparities in Inpatient Outcomes of Chronic Limb-Threatening Ischemia in the United States
Authors: Goyal Aman , Quazi Mohammed , Sohail Amir , Sheikh Abu Baker
Published: November 2024

Background:
Chronic limb-threatening ischemia (CLTI) is a severe form of peripheral artery disease characterized by chronic ischemic rest pain, non-healing wounds, or gangrene in one or both legs. With prevalence rates of 1-2% in the United States (increasing with age, with over 20% of adults over 70 diagnosed with CLTI) and 1-year mortality rates approaching 20-25%, CLTI is a critical public health issue due to its significant impact on patient morbidity, mortality, and healthcare resources.

Aims:
To understand if disparities exist between rural and urban inpatient outcomes for patients with CTLI.

Methods:
A retrospective analysis of the National Inpatient Sample database from 2016 to 2021 was conducted to identify patients admitted with CLTI according to ICD-10 codes. Patients were stratified by rural and urban status, followed by propensity-matched analysis to compare inpatient outcomes between these groups.

Results:
A total of 2,667,279 patients with CLTI, with 445255 (16.7%) categorized as rural status and the remaining 83.3% categorized as urban status, were included in this study. Patients belonging to rural status had an increased odds of in-hospital mortality (aOR)=1.35; 95% CI 1.26-1.45; p<0.001), in-patient sudden cardiac arrest (aOR=1.27; 95% CI=1.13-1.43; p<0.001), cerebrovascular accidents (aOR=1.31; 95% CI=1.19-1.45; p<0.001), venous thromboembolism (aOR=1.18; 95% CI=1.09-1.27; p<0.001), surgical site infection (aOR=1.25; 95% CI=1.16-1.35; p<0.001), requirement for vasopressors (aOR=2.02; 95% CI=1.76-2.32; p<0.001), invasive (aOR=1.18; 95% CI=1.10-1.26; p<0.001) and non-invasive (aOR=1.37; 95% CI=1.25-1.50; p<0.001) mechanical ventilation, hemodialysis (aOR=1.11; 95% CI=1.06-1.15; p<0.001), major amputation (aOR=1.38; 95% CI=1.32-1.43; p<0.001), surgical revascularization (aOR=1.53; 95% CI=1.46-1.60; p<0.001), endovascular revascularization (aOR=1.53; 95% CI=1.46-1.60; p<0.001), and blood transfusion (aOR=0.92; 95% CI=0.88-0.97; p=0.001). No difference was observed in the odds of acute myocardial infarction (aOR=1.06; 95% CI=0.99-1.14; p=0.082) and risk of acute kidney injury (aOR=0.99; 95% CI=0.96-1.02; p=0.485).

Conclusions:
Disparities in CLTI outcomes are evident, with patients from rural areas experiencing worse outcomes than their urban counterparts. Future research should focus on understanding the underlying causes of these disparities and developing targeted interventions to bridge the gap between rural and urban health care outcomes.
Abstract 4146319: Racial Disparities and Driving Factors in the AHA's Life's Essential 8 Among American Adults: Insights from NHANES 2011-2020
Authors: Yang Huanhuan , Huang Chenxi , Faridi Kamil , Spatz Erica , Li Zhiui , Krumholz Harlan , Lu Yuan
Published: November 2024

Backgrounds:
The AHA introduced "Life's Essential 8" (LE8) in 2022 as a comprehensive metric to facilitate detailed tracking and management of cardiovascular health (CVH) at the population level. However, the racial/ethnic differences in LE8, how these differences change over time, and the driving factors of LE8 in each subgroup remain unclear.

Methods:
We utilized data from the continuous NHANES from 2011 to 2020 to examine racial disparities and driving factors in the AHA's LE8 among American adults. To ensure national representation, appropriate weights were applied. Survey-weighted and age-standardized trends in LE8 scores by racial and ethnic groups were analyzed using generalized linear models (GLMs). To identify the driving factors—specific metrics influencing the LE8 overall score—we calculated z-scores for all components. Then we used the spider chart to visualize the driving factors.

Results:
A total of 13,915 adult were included, of whom the mean age is 47.9 ± 0.37 years, 6,612 (47.55%) were women, 3,485 (14.63%) were Hispanics, 5,335 (69.74%) were non-Hispanic Whites, 3,464 (10.82%) were non-Hispanic Blacks, and 1,631 (4.81%) were Asians. From 2011-2020, the LE8 scores did not change significantly overall and across all racial groups (all p-trend > 0.10,
Figure 1
). During the study period, racial/ethnic disparity persisted with Asian adults consistently having the highest LE8 scores and Black adults having the lowest scores. Notably, the lower LE8 scores in Black adults were primarily driven by lower scores of diet, blood pressure, and sleep health, whereas the higher LE8 scores in Asian adults primarily driven by higher scores of diet, nicotine exposure, and BMI. The LE8 scores in White adults were primarily driven by blood glucose and physical activity and the LE8 score in Hispanic adults were primarily driven by blood pressure (
Figure 2-A
). In 2017-2020 (
Figure 2-B
), Black adults had the lowest scores for all LE8 components, except for blood lipids. In contrast, Asian adults had the highest scores in diet, physical activity, nicotine exposure, and sleep health. Throughout the study period, the racial/ethnic disparity in LE8 score did not change significantly (all p >0.10).

Conclusion:
We found persistent racial disparities in cardiovascular health among U.S. adults, with Black adults having the lowest LE8 scores in almost all components. The driving factors for LE8 scores varied by racial subgroups, emphasizing the need for targeted interventions.
Abstract 4147616: Targeting Skeletal Muscle Growth Improves Diastolic Dysfunction and Left Ventricular Hypertrophy in Obesity-Related Diabetic Cardiomyopathy
Authors: Baka Tomas , Qin Fuzhong , Zhang Aifeng , Yurista Salva , pimentel david , Kotagiri Varshith , Smith Hunter , Lehar Adam , Stoklasek Thomas , Colucci Wilson , Lee Se-Jin , Luptak Ivan
Published: November 2024

Background and Significance:
Mice fed a high-fat, high-sucrose (HFHS) “Western” diet develop a cardiac phenotype similar to patients with type 2 diabetes mellitus-related heart failure with preserved ejection fraction (HFpEF). This includes obesity, insulin resistance, left ventricular hypertrophy (LVH), and diastolic dysfunction. Skeletal muscle is responsible for up to 80% of whole-body glucose disposal, making the relationship between muscle mass and insulin resistance crucial for identifying new therapeutic targets in HFpEF. Myostatin is an evolutionally conserved skeletal muscle growth-limiting signaling molecule. Although whole-body deletion of myostatin/activin signaling (MAS) promotes skeletal muscle hypertrophy (SH) and provides metabolic benefits, overall benefits are complicated by direct inhibition in the myocardium.

Hypothesis:
Sedentary mice with skeletal muscle-specific deletion of MAS will be protected from the adverse cardiac effects of HFHS diet.

Methods and Results:
BL6 mice with floxed alleles for myostatin Acvr2 and Acvr2b receptors were crossbred with mice expressing Cre recombinase from a myosin light chain promoter, rendering the MAS downregulation skeletal muscle specific. Four months of HFHS feeding resulted in similar increase in body weight between Cre+ and Cre- (34% and 37%, respectively). SH was present in Cre+ mice as the muscle weight/tibia length ratio of m. pectoralis, triceps and quadriceps was elevated by 44, 22 and 25%, respectively. Oral glucose tolerance was improved in Cre+ vs Cre-. Echocardiography showed improved LV hypertrophy and diastolic function (increased E/A ratio and Em by 27 and 21%) in the Cre+ group. Moreover, exercise capacity was improved in Cre+ mice by 59%.

Conclusion:
Our novel study demonstrates that targeting skeletal muscle growth through the inhibition of MAS, without direct cardiac effects, can ameliorate the cardiac dysfunction associated with obesity-related diabetic cardiomyopathy. Increased muscle mass improves glucose tolerance, LVH, and diastolic function, demonstrating skeletal muscle-to-myocardium cross-talk. This highlights the potential for muscle-targeted therapies in managing HFpEF, particularly in insulin-resistant conditions.
Abstract 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program
Authors: Blazoski Cameron , Yao Zhiqi , Blaha Michael
Published: November 2024

Introduction/Background:
Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease.

Research questions/Hypothesis:
Do individuals with depression have an increased incidence of cardiovascular disease?

Goals/Aims:
This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention.

Methods/Approach:
We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF.

Results/Data:
100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27).

Conclusions:
This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.
Abstract 4147627: A Pharmacovigilance Study of Bempedoic Acid: Balancing Risks and Benefits
Authors: Khadka Sulochana , Timilsina Bibek , Matai Pallavi , Sharma Seema , Rajak Kripa , Calderon Barahona Gabriela , Oli Seema
Published: November 2024

Introduction:
Bempedoic acid has been approved by FDA since Feb 2020 as an adjunct to maximally tolerated statin therapy for the reduction of LDL-C, specifically in individuals afflicted by atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). Bempedoic acid is also a viable alternative for patients intolerant to statins. Most recently, it has been approved to use for primary prevention of hyperlipidemia, alone or in combination with a statin. It is important to study its side effect profile as it is anticipated to be used more frequentlynin the future.

Methods:
We explored reported adverse events (AEs) of bempedoic acid using FDA Adverse Event Reporting System (FAERS). A total of 1202 adverse effects were reported until March 31, 2024. 69.97% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (32.53%) vs women (53.24%) and in three age groups of 18-64, 65-85, and >85 years.

Results:
A total of 586 (48.7%) events were serious adverse effects. Most common side effects were myalgia which included muscle pain, extremity pain and muscle spasm (25.04%), arthralgia including back pain and bone pain (18.47%), nausea (6.6%), headache(5.5%), gout (4.4%). Among the patients with adverse effects, 4.75% had cardiac side effects which included atrial fibrillation (12%), palpitation (29%), angina pectoris (18%), Myocardial Infarction (5%).

Discussion: A thorough understanding of bempedoic acid's complex pharmacology empowers healthcare professionals to tailor treatment plans based on individual patient requirements. This enables informed decision-making in prescribing, optimizing dosage regimens, and mitigating potential adverse reactions. Most studies have been relatively short term in order to confirm the long term side effect profile. It would be beneficial to be cautious in using this medication for patients with above mentioned clinical conditions like myalgia, arthralgia, gout, rhabdomyolysis, atrial fibrillation, angina pectoris.

Conclusion:
Long term pharmacovigilance is needed to assess the safety profile of bempedoic acid over extended use. With the current increasing use of bempedoic acid, there is a need for more data on safety profiles. In future, further randomized trials are required to better assess the safety profile.
Abstract 4147640: Genetic Insights in Dilated Cardiomyopathy: SSPN as a Key Player
Authors: Albdour Karam , Abu Alragheb Bayan , Younis Ahmad , Turk Ahmad
Published: November 2024

Background:
Dilated cardiomyopathy (DCM) is a complex condition characterized by the dilation and impaired contraction of the left ventricle, which ultimately leads to heart failure. DCM has a multifactorial background, involving genetic, environmental, and infectious components. The genetic aspect of DCM is particularly significant, with numerous genes implicated in its pathogenesis. This study aims to identify differentially expressed genes (DEGs) involved in DCM, thereby contributing to the existing body of literature and facilitating further investigations into potential biomarkers and therapeutic targets for the disease.

Methods:
Data from the GSE1869, GSE3585, GSE4172, and GSE3586 datasets were obtained from the Gene Expression Omnibus (GEO) database. DEGs were identified using the GEO2R tool with an adjusted p-value cutoff of ≤0.05.

Results:
From the GSE1869 dataset, 3,692 DEGs were identified, alongside 691 DEGs from GSE4172, 889s DEG from GSE3586, and 95 DEGs from GSE3585. Intersection analysis revealed one mutual DEG across all four datasets: SSPN. SSPN, or sarcospan, is a component of the dystrophin-glycoprotein complex involved in stabilizing muscle cell membranes. As only one mutual DEG was identified, the findings suggest significant heterogeneity in gene expression profiles associated with DCM or potential limitations in the datasets.

Conclusions:
The identification of SSPN as a DEG associated with DCM provides valuable insights. Its expression in the heart has the potential to affect cardiac structural integrity and function. This gene holds promise as a potential biomarker that could inform the development of targeted therapies, highlighting its significance in the molecular mechanisms of the disease and warranting further investigation.
Abstract 4148095: The Impact of Body-Mass Index on Ventricular Tachycardia Outcomes Post-Catheter Ablation
Authors: Poddar Aastha , Futela Pragyat , Woelber Tiffany , Prasitlumkum Narut , Amin Hina , Deshmukh Abhishek , Heybati Kiyan , Kowlgi Gurukripa
Published: November 2024

Background:
In recent years, catheter ablation has emerged as a sustainable, first-line therapy for the management of ventricular tachycardia (VT). Given the rise of the “obesity paradox” theory in atrial ablation outcomes, we sought to study the effect of BMI on patients undergoing structural VT ablation.

Purpose:
To assess the outcomes of VT ablation, specifically VT recurrence, in patients with elevated vs. normal BMI.

Methods:
Clinical characteristics and demographic data were collected for VT patients who underwent ablation at Mayo Clinic Rochester from 2012-2022. Patient BMI was classified as non-obese (<30 kg/m2), obese (30-40 kg/m2), and morbidly obese (≥40 kg/m2). The endpoint was a composite of initial monomorphic VT recurrence and repeat ablation after adjusting for age, sex, and comorbidities.

Results:
A total of 399 patients underwent 508 ablations. 51.4% of ablations had a BMI <30, 39.2% were between 30-40, and 9.4% were ≥40. There was a greater prevalence of hypertension and type 2 diabetes mellitus in morbidly obese patients (p <0.01). Morbidly obese individuals also had a significantly increased rate of general anesthesia during ablation and long VT cycle lengths. The Kaplan-Meier curve demonstrates no statistically significant differences in time to VT recurrence among the three BMI groups (p = 0.324). Neither morbid-obesity (aHR= 1.20; CI = 0.94-1.56, p = 0.14) nor nonmorbid-obesity (aHR = 0.92; CI = 0.76-1.10, p = 0.4), compared to non-obesity was a significant independent predictor of VT recurrence or repeat ablation on multivariate regression after adjusting for age, sex and comorbidities.

Conclusion:
There was no significant association between BMI groups and VT recurrence or repeat ablation, and no difference in complications. We did not find the obesity paradox to be relevant for VT ablation in our patient population. Further study would be needed with larger samples to corroborate these findings.
Abstract Sa1103: Utility of early Computed Tomography after out-of-hospital cardiac arrest resuscitation
Authors: Halablab Saleem , Shofer Frances , Kaviyarasu Aarthi , Reis William , McFerran Jared , Ghorbani Anahita , Brothers Taylor , Mitchell Oscar , Abella Benjamin
Published: November 2024

Background:
Initial care after out-of-hospital cardiac arrest (OHCA) poses major challenges to clinical teams due to diverse arrest etiologies and the potential need for time-sensitive interventions. Emergency department-based evaluation of these patients is crucial for identifying treatable causes of arrest. Recent data from one academic hospital highlights the potential importance of initial broad computed tomography (CT) immediately following resuscitation.

Objective:
To assess the ability of early post-arrest CT imaging to diagnose potential etiologies and sequelae of OHCA.

Methods:
We employed a registry of consecutive OHCA cases admitted to 3 hospitals within the University of Pennsylvania Health System between 1/2019-10/2020, collecting demographic, arrest, and post-arrest clinical data. Inclusion criteria included age >18 y, OHCA with return of spontaneous circulation (ROSC). We abstracted CT data including findings, contrast use, and timing, and subsequent clinical notes to assess for interventions performed based on CT findings from the EHR. KDIGO definition was used for acute kidney injury (AKI). SAS software was used for data analysis.

Results:
A total of 161 OHCA patients were included (mean age 60.8±15.6y; 42% female). Initial shockable rhythms were present in 16%, with 70% witnessed and 39% receiving bystander CPR. 154 patients survived to admission, and 41 survived to discharge. 117 patients underwent CT imaging in the ED: 117 underwent head CT, 87 chest CT, and 64 abdomen/pelvis CT. Median time to any first CT was 2.0h (IQR:1.4,2.8). Intracranial hemorrhage was diagnosed in 5/117 patients (4.3%); 3 received conservative therapy. Cerebral edema was found in 30/117 patients (25.6%), 10 received treatment. Pulmonary embolism was diagnosed in 8/87 cases (9.2%), 7 of which were acute and treated pharmacologically and/or mechanically. Aspiration and/or pneumonia, pneumonitis, bronchitis, bronchiolitis was found on 65/84 cases (74.7%), 30 received antibiotics. Deep venous thrombosis was detected in 3/64 patients (4.7%), 2 received anticoagulation. We found no significant differences in AKI rates with the use of contrast compared to patients receiving no contrast (p=0.93).

Conclusion:
These results confirm and extend other reports emphasizing the potential value for routine use of CT imaging post-ROSC. Implementing larger scale prospective studies comparing such protocols and standard-of-care is important to determine impact on OHCA outcomes.
Abstract Sa1104: Head and Pulmonary Artery Chest CT Detect Most but Not All Causes of Sudden Death and Resuscitation Injury Compared to Head to Pelvis CT Angiography in Survivors of Out of Hospital Circulatory Arrest
Authors: Sendaydiego Xavier , Ha Khoi , Kudenchuk Peter , Gunn Martin , Johnson Nicholas , Gatewood Medley , Maynard Charles , Sayre Michael , Counts Catherine , Branch Kelley
Published: November 2024

Introduction:
Head-to-pelvis “sudden death computed tomography” angiography (SDCT) has a high diagnostic yield to identify causes and complications of out-of-hospital cardiac arrest (OHCA). The differences in yields of non-contrast head CT (H-CT) and pulmonary embolism chest CT (CT PE) angiography alone or in combination is not clear.

Methods:
Our prospective observational cohort enrolled patients that survived OHCA resuscitation and had a SDCT (H-CT, ECG-gated chest CT, and non-ECG gated venous phase abdomen/pelvis CT) within 6 hours of arrival (December 2015 – February 2018). For this sub-study, we assessed the same scans for diagnoses obtainable from routine H-CT and CT PE axial coverage alone, excluding any added (SDCT) findings from ECG-gating and abdomen/pelvis assessment. The primary outcome was the difference in diagnostic yield of time-critical and non-time-critical diagnoses by CT PE with or without H-CT compared to SDCT.

Results:
SDCT identified 86 time-critical diagnoses in 104 enrolled patients, including 39 pneumonias (45% of diagnoses), 13 myocardial infarctions [MI] (15%), 8 pulmonary embolisms (9%), 8 pneumothoraces (9%), 8 abdominal catastrophes (9%), 3 intracranial hemorrhages (3%), and 1 vascular access hemorrhage (1%) [
Table
]. CT PE alone identified 61 of the 86 time-critical diagnoses (71%), missing 25 diagnoses (29%) compared to SDCT. Missing diagnoses included MI (13/13), abdominal catastrophe (8/8), and active vascular access hemorrhage (1/1). H-CT diagnosed all 3 intracranial hemorrhages. Of the 208 non-time-critical diagnoses identified by SDCT, CT PE identified 183 non-time critical diagnoses (88%), missing 25 diagnoses (12%). H-CT did not identify any non-time-critical diagnoses.

Conclusions:
CT PE imaging with H-CT identifies a majority—but not all—time-critical and non-time-critical diagnoses in OHCA patients, mainly failing to capture coronary and intra-abdominal pathologies. SDCT, which includes ECG-gated chest CT and abdomen/pelvis CT, improves total diagnostic yield, but its incremental utility requires further study.
Abstract Sa1105: The Effect of a Combination of Neuroprotective Medications on Post-Cardiac Arrest Survival
Authors: Pollard Kenna , Gonzales Anelly , Ren Yulan , Leontovich Natalia , Shellen Samantha , Chen Andy , Goins Imani , Amoroso Nancy , Wise Wendy , Kaufman David , Fridman David , Rivera Pedro , Hagedorn Jacklyn , Brosnahan Shari , Papadopoulos John , Katz Alyson , LaFond Elyse , Andriotis Anthony , bakker jan , Goldenberg Ronald , Lubinsky Anthony , Pradhan Deepak , Horowitz James , Drus Karsten , Parnia Sam
Published: November 2024

Introduction:
Reperfusion injury after cardiac arrest (CA) leads to poor survival and neurological outcomes. We hypothesized that a combination of pharmacologic neuroprotection therapies administered 24-72 hours post-CA [“combination therapy”] that target key steps in reperfusion injury; 1) excitotoxicity (Magnesium, Memantine, Perampanel, Minocycline), 2) mitochondrial dysfunction (Thiamine, Coenzyme Q10), 3) oxidative stress (Vitamin C, Vitamin E), and 4) inflammation (Hydrocortisone), would improve survival.

AIMS:
We compared survival between subjects with combination therapy and those without.

Methods:
A retrospective analysis of post-CA patients (01/01/2019 - 06/01/2023) was conducted as part of a quality improvement project. Inclusion: in-hospital CA, age ≥ 18 years, non-COVID, ≥ 5 min CPR, sustained ROSC (≥ 20 min). Exclusion: out-of-hospital CA. Combination therapy was at the discretion of the provider and given in addition to current post-CA standard critical care: targeted temperature management (TTM) (32-36°C), glucose (target 140 mg/dL), PaO2 (target 100 mmHg), PaCO2 (target 40 mmHg), and MAP (target 80 - 100 mmHg). Survival was assessed at hospital discharge.

Results:
Among 196 subjects, 146 received combination therapy (study group) and 50 did not (control group). Demographic variables (age, race, ethnicity) and intra-cardiac arrest variables (initial rhythm, CPR duration, and hospital site) were not statistically different between groups. Post-CA variables (mean PaCO2, PaO2, and glucose) were not statistically different between groups. MAP was 76 (69, 83) for study group and 65 (46, 72) for control group (
P
= <0.001). Lowest temperature in study group was 34.8°C vs. 35.9°C in control group (
P
= 0.034). Survival at hospital discharge was 33% for study group and 14% for control group (
P
= 0.01). There were no known safety concerns or adverse events.

Conclusions:
The administration of a combination of neuroprotective medications that target key pathways in reperfusion injury appears to be feasible and safe, and may improve survival beyond current post-CA standard critical care. A future randomized controlled trial that includes the assessment of neurological outcomes is warranted.
Abstract Sa1106: Computed Tomography Imaging After In-Hospital Cardiac Arrest: An Observational Cohort Study
Authors: Galfund Jack , Hoang Martin , Cela Alban , Miller Ashley , Eisen Lewis , Gong Michelle , Moskowitz Ari , Andrea Luke
Published: November 2024

Introduction/Background:
Computed tomography (CT) imaging is a promising method for diagnosing patients after return of spontaneous circulation (ROSC) from cardiac arrest. CT information could alter management, improving patient outcomes. There are data supporting use after out-of-hospital arrests, but use and impact of CT imaging after in-hospital-cardiac arrest (IHCA) has not been investigated.

Research Question/Hypothesis:
We hypothesize that CT imaging will identify acute pathology, resulting in a change in management.

Goals/Aims:
Our aim is to describe the rates of use, findings, and consequences of CT imaging after IHCA.

Methods/Approach:
We screened for the first IHCA on admission between 1/26 2023, and 1/302024 at 3 hospitals. Patients 18 years of age or older who achieved ROSC were included. Information was collected on demographics, type of imaging performed, imaging findings, and whether the findings acutely changed management. A change in management was defined as a subsequent change in medications, procedures, or consultations that would not have otherwise occurred and was specifically performed to reverse, mitigate, or treat the imaging finding, based on review of chart documentation by critical care fellows and medicine residents. Results are reported as counts and percentages.

Results:
We screened 638 IHCA at 3 hospitals. Of the 201 patients meeting inclusion criteria, 72 (35.8%) died within 24 hours after ROSC. Of those who survived 24 hours, 58 of 129 (45.0%) received CT imaging in the 48 hours after ROSC, 53 (41.1%) received a head CT, 26 (20.2%) received a chest CT, 19 (14.7%) received an abdomen/pelvis CT, and 4 (3.1%) received a CT that was not head, chest, or abdomen/pelvis. The most common findings were ischemic stroke (15), pulmonary airspace opacities (23), and pleural effusion (15). An acute finding (previously unknown) was identified in 32 of 58 scans (55.2%), and there was an acute change in management because of the acute finding in 21 (65.6%) of those patients. For 8 patients (13.8%), the scan identified an acute finding thought to have contributed to the cardiac arrest. Of the 58 patients who received CT imaging, 2 of them (3.4%) suffered cardiac arrest while receiving the CT scan.

Conclusions:
CT imaging within 48 hours after IHCA frequently identified acute pathology, resulting in a change in management. Complications were seen, although we do not know if these were a result of the CT imaging, related transportation, or other causes.
Abstract Sa1108: The Aberrant Autophagy-Apoptosis regulation Mediates the Severe Neurological Dysfunction after Cardiac Arrest in Diabetic Mice
Authors: Tang Songling , Yao Peng , Gan Lu , Cao Yu
Published: November 2024

Background:
Patients with diabetes have lower survival and worse neurological outcome after cardiopulmonary resuscitation (CPR) compared with non-diabetes. Previous studies have mentioned the aberrant autophagy in diabetic mice. However, whether this abnormal autophagy exacerbates neuronal apoptosis and neurological outcome in diabetic mice remains unclear.

Methods:
Patients were divided into non-diabetic cardiac arrest (CA) patients and diabetic CA patients, and the survival and neurological outcomes at discharge and day 28 after ROSC were compared between these two groups. Diabetic mice were fed with high fat diet (HFD), and CA model was established by inducing ventricular fibrillation electrically. The neurological prognosis was assessed by open field test (OPT), novel object recognition (NOR) and Y-maze. Neuronal apoptosis and autophagy were evaluated by immunofluorescence and western blotting, including TUNEL, cleaved caspase 3, LC3B, p62 and beclin1.

Results:
Compared with non-diabetic patients, the survival at discharge and at day 28 after ROSC are significantly lower in IHCA patients with diabetes. Meanwhile, the neurological deficits at discharge and at day 28 after ROSC are much severer in diabetic-CA patients. In addition, the lower survival and worse neurological function have been discovered, and the cognition impairment is more significant after ROSC in HFD mice. Neuronal apoptosis is severer in HFD mice. In ND mice, the activated autophagy has been revealed after CA-CPR-ROSC, however, autophagy can not be activated after ROSC in HFD mice since the baseline autophagy is at a higher level when compared with ND mice. Neuronal apoptosis is exacerbated after autophagy inhibition by 3-MA in ND mice, while after autophagy activation by rapamycin in HFD mice, apoptosis is attenuated after ROSC.

Conclusion:
Diabetes is the risk factor for neurological outcome in IHCA patients. The aberrant autophagy regulation in cortex neurons contributes to the severe apoptosis and neurological deficits after ROSC in diabetic mice.