bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146046: A Chemical Language Model for the Design of De Novo Molecules Targeting the Inhibition of TLR3
Authors: Velasco Juan
Published: November 2024

Background:
Toll-like receptor 3 plays a role in the development of calcific aortic valve disease (CAVD). However, there are currently no pharmacological treatments for CAVD, and the discovery of de novo molecules targeting a specific protein is a time-intensive and financially demanding process. It is hypothesized that language models, trained on encodings of molecular graphs, can tailor the design of novel molecules with specific molecular and pharmacological properties.

Objective:
This study aims to develop a chemical language model tailored for designing novel molecules that target the inhibition of TLR3.

Methods:
A language model was pre-trained on 25,000 chemical structures sourced from the ChEMBL database. Each chemical structure was represented through Simplified Molecular Input Line Entry System (SMILES) strings, which were subsequently tokenized into discrete atomic and functional group tokens. The model leverages an Average-Stochastic Gradient Descent Weight-Dropped Long Short-Term Memory (AWD-LSTM) architecture. Transfer learning was employed for domain-specific fine-tuning of the pre-trained language model on the target chemical structures.

Results:
The model achieved strong performance by unfreezing the pre-trained language model’s parameters for fine-tuning in all layers. Specifically, it achieved an accuracy of 85.49%, a weighted F1-score of 83.28%, and a perplexity of 1.44. This approach yielded better results compared to partially freezing the model’s parameters, where only the latter layers were fine-tuned. The partial freezing approach resulted in an accuracy of 85.06%, a weighted F1-score of 82.44%, and a perplexity of 1.44.

Conclusion:
A chemical language model was developed for designing novel molecules that target the inhibition of TLR3. This provides an efficient and automated method for developing novel molecules with specific molecular and pharmacological properties.
Abstract 4146081: Hospital Outcomes in Hispanic Children with Long QT Syndrome: A Large National Database Study
Authors: Lodeiro Carlos , Lopez Keila , Stephens Sara , Miyake Christina , Konduri Vimal , Howard Taylor , Pham Tam Dan , Lam Wilson , Bruno Michael , Kim Jeffrey , Valdes Santiago
Published: November 2024

Background:
Long QT Syndrome (LQTS) is an inherited arrhythmia syndrome that predisposes patients to sudden death. Prior studies on racial disparities in LQTS have shown similar number of cardiac events, but longer QTc in Black patients compared to non-Hispanic Whites (NHW). There is limited data on cardiac events in Hispanic children with LQTS. We hypothesized that Hispanic children with LQTS have worse outcomes compared to NHW children.

Methods:
This retrospective cohort study of the Pediatric Health Information System (PHIS) database included children ages 0 - 17 years hospitalized from 2013-2024 with an International Classification of Disease 9
th
or 10
th
edition code for LQTS listed in the first five admission diagnoses. Patients with congenital heart disease and chromosomal abnormalities were excluded. The primary predictor variable was race/ethnicity, with covariables including age, sex, and insurance type. Our primary outcome variable was a documented lethal arrhythmia, and secondary outcomes included pacemaker and/or implantable cardioverter defibrillator (ICD) placement. Chi-square was used to assess patient characteristics. Univariable mixed-effect log-binomial regression was used to assess risk of outcomes by characteristics using hospital as a random effect with multivariable models generated via backward elimination.

Results:
We identified 6,476 children (24% Hispanic, 76% NHW). Compared to NHW children, Hispanic children were more often male and presented earlier (median age 11y vs 13y, 25-75 IQR 6-15; p<0.0001) (Table 1). Hispanics had a higher use of public insurance and a longer length of stay (LOS) than NHW (Table 1). Both groups had similar numbers of cardiac arrest and mortality (Table 1). On multivariable analyses, there was no increased risk of lethal arrhythmias (p= 0.76) or pacemaker/ICD placement (p=0.56) for Hispanics compared to NHW.

Conclusion:
This is the first national descriptive study assessing outcomes in Hispanic children with LQTS. Hispanics with LQTS were hospitalized at an earlier age, had a longer LOS, and higher rates of public insurance. Further studies are warranted to determine knowledge of family history of LQTS, medication adherence, and long-term ability for follow up.
Abstract 4146108: Impact of ECPELLA on Mid-Term Survival and Neurological Outcomes in Patients with Refractory Cardiac Arrest Who Received E-CPR
Authors: Ishida Toshifumi , Unoki Takashi , Inamori Taiji , Toyohuku Takaaki , Sato Tomohide , Konami Yutaka , Suzuyama Hiroto , Inoue Masayuki , Horio Eiji , Kodama Kazuhisa , Sawamura Tadashi , Sakamoto Tomohiro , Nakao Koichi , Okumura Ken , Koyama Jyunjiro
Published: November 2024

Background:
Extracorporeal cardiopulmonary resuscitation (E-CPR) with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used for cardiac arrest patients when conventional CPR is ineffective. While VA-ECMO sustains systemic perfusion, it also increases left ventricular (LV) afterload. The recent introduction of the transcatheter LV assist device, Impella, suggests benefits from its combination with VA-ECMO (ECPELLA), but the effectiveness of ECPELLA in E-CPR is still under investigation.

Objective:
This single-site cohort study aimed to evaluate the impact of ECPELLA versus VA-ECMO combined with intra-aortic balloon pump (IABP) in patients undergoing E-CPR.

Method:
We performed a retrospective review of 212 consecutive patients who underwent E-CPR at our institute from January 2012 to December 2023. After excluding 61 patients who received VA-ECMO alone, 151 patients were included in the study. These patients were divided into two groups: 67 in the ECPELLA group and 84 in the VA-ECMO with IABP group. We assessed the 90-day survival rate and favorable neurological outcomes, defined as a Cerebral Performance Categories (CPC) score of 1 or 2.

Results:
No significant differences were noted between the two groups regarding age, male ratio, coronary risk factors, initial shockable rhythm, acute coronary syndrome (ACS), out-of-hospital cardiac arrest (OHCA), and initial lactate levels. The ECPELLA group exhibited a significantly shorter time from cardiac arrest to VA-ECMO placement, known as low flow time (LFT) (35 min [IQR: 18-56] vs. 48 min [IQR: 24-73]; P=0.01), higher total MCS flow, and reduced catecholamine use during the first 72 hours, compared to the VA-ECMO with IABP group. Survival rates and favorable neurological outcomes at hospital discharge were significantly higher in the ECPELLA group (39% vs. 17%, P=0.002; 27% vs. 12%, P=0.02, respectively). The 90-day all-cause mortality was significantly lower in the ECPELLA group (P=0.003 by log-rank test). Multivariate Cox proportional hazard analysis, including age, shockable rhythm, ACS, OHCA, LFT, and ECPELLA, indicated that age (hazard ratio [HR] 1.02, 95% CI 1.01-1.04, P=0.004), LFT (HR 1.02, 95% CI 1.01-1.03, P<0.001), and ECPELLA (HR 0.67, 95% CI 0.45-0.99, P=0.046) were significantly associated with 90-day all-cause mortality.

Conclusion:
ECPELLA was associated with improved 90-day mortality rates and neurological outcomes in patients who received E-CPR.
Abstract 4146110: Patient Characteristics In The Enhancing Cardiac Rehabilitation Adherence Through Home-Based Rehabilitation And Behavioral Nudges (ERA-Nudge) Study
Authors: Fletcher Dana , Gupta Prerna , Martinez Monica , durfee josh , hajoglou amanda , Rice Marina , Orendain Valencia Juan , Waughtal Joy , Bull Sheana , Peterson Pamela
Published: November 2024

Introduction:
Outpatient cardiac rehabilitation (CR) improves outcomes for patients with cardiac disease but has an historically low participation rate. For socioeconomically disadvantaged patients experiencing challenges with access to care, participation can prove especially difficult. The ERA-Nudge trial aimed to evaluate the effect of choice of hospital or home-based CR and the effect of behavioral nudge messaging on participation and adherence in a diverse population of low socioeconomic status. This is the first report of patient characteristics from ERA-Nudge.

Methods:
ERA-Nudge was a pragmatic, randomized, controlled clinical trial using a 2x2 factorial design conducted at an urban safety net hospital in the US mountain west from 2019 to 2023. Patients were required to be eligible for CR, have a smartphone in order to use a mobile phone app, speak English or Spanish, and provide informed consent to participate in the study. At their baseline visit, patients were randomized to 1) choice of hospital or home-based CR with nudges; 2) choice of hospital or home-based CR alone; 3) hospital-based CR with nudges; 4) hospital-based CR alone. At study-required baseline, 6-week, and 12-week visits, clinical and lifestyle outcomes were assessed. Descriptive analyses were conducted on the characteristics of randomized patients.

Results:
Among 697 screened patients who were eligible for CR, 517 consented to participate. There were 70 patients who were not randomized (22 no showed for baseline visit; 2 died before randomization; 1 withdrew; 45 could not be re-contacted or did not provide a reason), resulting in 447 patients randomized in the study (Table 1) and 316 that completed the three study-required visits.

Conclusions:
ERA-Nudge was completed in a diverse, low-income, urban population, supporting the feasibility of evaluating smartphone and mobile app interventions in these patients. Not only did patients enroll, but most completed required study visits. Further analysis of the ERA-Nudge data will provide insight into how these patients responded to nudge-based mobile messaging, and whether having a choice to participate in CR at home impacted their overall CR adherence.

Registration Number: NCT03834155
Abstract 4146140: An Artificial Intelligence Machine Learning Algorithm Approach Using Segmental ECG Analysis to Distinguish Long QT Syndrome from Acquired QT Prolongation
Authors: Bos Johan , Liu Kan , Attia Zachi , Noseworthy Peter , Friedman Paul , Ackerman Michael
Published: November 2024

Background:
Many medications, electrolyte perturbations, and several diseases can prolong the QTc beyond its 99
th
percentile value resulting in acquired QT prolongation (AQTP). In contrast, approximately 1 in 2,000 people have congenital long QT syndrome (LQTS) hallmarked by pathological QT prolongation. Recently, we developed an AI-ECG model to distinguish these two groups, however this model does not elucidate which ECG segments distinguish LQTS from AQTP.

Methods:
Using the cohort from our previous study, all patients with LQTS evaluated in the Mayo Clinic Genetic Heart Rhythm Clinic and controls were included. Next, every patient/control with ≥1 ECG above age- and sex-specific 99
th
percentile for QTc was selected and matched at 1:100 ratio. Subsequently, 5 ML algorithms (logistic regression, Naïve Bayes, random forest, Gradient boosting and XGBoost) were trained using 52 features representing segments of the 12-lead ECG (e.g. wave peak times, amplitudes, areas under wave, duration; 52x12 features). Training and testing sets were spilt at 80:20 ratio and 5-fold cross validation was performed to prevent overfitting. Following analysis, the top 100 features were re-analyzed to refine results.

Results:
Among >1,600 patients with LQTS, 690 had ≥ 1 ECG with a QTc above the established threshold compared to 28,186 controls. Following age- and sex-matching and splitting, 22,410 (training), and 5,776 (testing) ECGs were used. Of the 5 ML algorithms, XGBoost demonstrated best performance (AUC 0.913, accuracy 0.836, sensitivity 0.857, specificity 0.835) to distinguish LQTS from AQTP. Following filtering for the top 100 features, performance of the algorithm remained high with AUC of 0.912 (accuracy 0.84, sensitivity 0.841, specificity 0.84). The features with the greatest impact on classification output included time from T wave onset to T wave peak (leads V1, V4, V4), QRS interval duration (leads V1, V3, V4, aVR), and amplitude at end of ST segment (aVF).

Conclusions:
Distinguishing monogenetically driven LQTS from multi-factorial AQTP is critical in clinical practice for proper management, mitigation of offending QT-prolonging factors, and treatment. Building on our previously developed AI-ECG-LQTS ‘mutation detector’, this model identifies some of the elements within the ‘black box’ that distinguish an ECG and QTc stemming from a patient with LQTS compared to a similar prolonged QTc value that is arising due to non-genetic, acquired QT-prolonging factors.
Abstract 4146141: The Association of Geriatric Syndromes with Cardiovascular Disease: Insights from ARIC Visit 5 on Cardiovascular Risks in Older Adults
Authors: Tom-Ayegunle Kehinde , Echouffo Tcheugui Justin , Oshozimhede Iyalomhe E , Orkaby Ariela , Kwak Min Ji , Goyal Parag , Kochar Ajar , Nanna Michael , Damluji Abdulla
Published: November 2024

Introduction:
Older adults face a high burden of cardiovascular disease (CVD), exacerbated by geriatric conditions such as multimorbidity and polypharmacy. The collective influence on CVD risk remains unclear. We hypothesize that the coexistence of multiple geriatric syndromes increases the risk of incident CVD events
.

Methods:
We conducted a cross-sectional study among individuals aged 45–64 years using a logistic regression to assess the association between geriatric syndrome(had ≥3factors) and CVD events at the end of Visit 5(period prevalence) in the Atherosclerosis Risk in Communities(ARIC study). We examined the following geriatric conditions: multimorbidity (≥2 chronic conditions), polypharmacy (≥5 medications), cognitive impairment vision impairment, hearing impairment, urinary incontinence, functional decline, frailty, and sarcopenia. Primary outcome was prevalence of 3-point MACE, defined as: death, acute myocardial infarction (AMI), or stroke.

Results:
Among the 5,141 participants, 13% had no geriatric conditions, 18% had one, 17% had two, and 52% had ≥3. Participants with ≥3 geriatric conditions were generally older, female, White, and overweight with hospitalization rates of 3. Overall,18% of the cohort experienced MACE events and 82% didn’t, with death being the most common at 9%. Those with ≥3 geriatric conditions had the highest prevalence of stroke (5%), AMI (11%), and death (13%) as compared to 2,1 and 0 geriatric conditions which were 2%,6%,7% and 1%,3%,6% and 1%,2%,3% respectively. In the adjusted model, having ≥3 geriatric conditions was associated with significantly higher odds of AMI (OR = 6.47; 95% CI: 3.57-13.18), stroke (OR=6.33; 95% CI: 2.83-18.08), death (OR = 3.51; 95% CI: 2.20-5.95), and MACE (OR=4.92; 95% CI: 3.44-7.28) compared with having no condition

Conclusion:
We found a strong association between the number of prevalent geriatric conditions and increased cardiovascular risk in the older adults. This highlights the need for integrated care models to identify geriatric conditions in older adults with cardiovascular disease in order to tailor prevention and treatment.
Abstract 4146155: Comparative outcomes of IABP vs. Impella 5.0 and 5.5 support as a bridge to heart transplantation – a matched cohort study
Authors: Al-Ani Mohammad , Balch Jeremy , Bai Chen , Neal Dan , Bledsoe Maisara , Parker Alex , Ahmed Mustafa , Aranda Juan , Shickel Benjamin , Vilaro Juan , Mardini Mamoun
Published: November 2024

Importance:
Despite the increasing use of intra-aortic balloon pumps (IABP) and Impella bridge to heart transplant (HTx), there is a paucity of comparative data on their use as bridges to heart transplantation.

Objective:
To compare the efficacy of IABP vs Impella (5.5 and 5.0) devices as a bridge to HTx in a cohort transplanted under the current UNOS heart allocation system.

Design, Setting, and Participants:
A retrospective longitudinal study of the United Network for Organ Sharing (UNOS) registry included adult patients listed for HTx between Oct 2018 and April 2022 as status 2, who were supported by IABP or Impella (5.5 and 5.0) and had a complete set of demographics, hemodynamics, medical comorbidities, inotrope requirements, and biochemical variables. The primary endpoint was a successful bridging to HTx as status 2. IABP and Impella groups were propensity-matched at a 3:1 ratio for demographics, UNOS region, baseline hemodynamics, and liver and kidney function.

Results:
Of 32,806 HTx during the study period, 991 patients met the inclusion criteria (Impella n=88, IABP n=903). Post-matching, there were no differences between the IABP and Impella groups in any baseline characteristic. The primary outcome occurred in 89.5% of the pre-matched population (IABP 90.1% vs Impella 83%, P = 0.055). In the matched cohort, the primary outcome occurred in 85.2% (IABP 86%, Impella 83%, P = 0.603); there was no difference in the listing by exception, multiorgan transplantation, waitlist time, waitlist mortality, or delisting. Post-transplant graft survival, infection, and renal failure were not different. Impella was associated with a lower rehospitalization rate (OR 0.54, 95% CI 0.33–0.9, P = 0.02), coronary allograft vasculopathy (OR 0.23, 95% CI 0.05–1, P = 0.05), and rejection requiring hospitalization (OR 0.13, 95% CI 0.02–1, P = 0.05).

Conclusions:
IABP and Impella (5.5 and 5.0) devices are equally effective as bridge-to-transplant platforms with a high transplantation rate as status 2. Additionally, Impella was associated with lower post-HTx events.
Abstract 4146177: Oxygen uptake kinetics are not a specific marker of peripheral limitations to exercise among adults with heart failure with preserved ejection fraction.
Authors: Zuazua Michael , Leahy Michael , Campain Joseph , Wakeham Denis , Brazile Tiffany , Samels Mitchel , Macnamara James , Sarma Satyam , Hearon Christopher , Levine Benjamin
Published: November 2024

Introduction:
Oxygen uptake (VO
2
) and cardiac output (Q
C
) kinetics describe the time required for oxygen delivery and blood flow to match metabolic demand during exercise and reflect the efficiency of peripheral oxygen utilization. Individuals with heart failure with preserved ejection fraction (HFpEF) have slow VO
2
kinetics, potentially due to peripherally limited skeletal muscle or a blunted Q
C
response. We characterized cardiovascular kinetics to determine whether the mechanisms of VO
2
kinetics are differentially regulated in adults with HFpEF with peripheral or non-peripheral limitations to exercise.

Methods:
We studied 44 adults with HFpEF (62% female, age: 70 ± 7 [55-83] years, BMI: 38 ± 7 kg/m
2
[26-50]) during submaximal and maximal exercise. The Q
C
response normalized to metabolic demand (Q
C
/VO
2
slope; Direct Fick) assessed from rest to maximal exercise was used to characterize the cardiac output response to exercise. Participants were classified as either peripherally (slope: >6 or stroke volume reserve >50%) or non-peripherally limited (slope: <6 or stroke volume reserve <50%). Kinetics were measured as the mean response time (MRT) to steady-rate exercise during a 6-minute sub-maximal (20 Watts) effort on a semi-recumbent cycle ergometer. We measured VO
2
(indirect calorimetry), heart rate (HR; electrocardiography) and Q
C
(Modelflow analysis of radial arterial catheter waveforms) and compared groups using unpaired t-tests.

Results:
The Q
C
/VO
2
slope was higher in peripherally (n=28, 6.3 ± 2.0) versus non-peripherally limited participants (n=16, 5.2 ± 0.6; p=0.035). There was no difference in VO
2
MRT in peripherally limited (60 ± 20 sec) and non-peripherally limited participants (55 ± 20 sec; p=0.438, Panel A). There were no differences in Q
C
MRT (peripheral: 48 ± 23 sec; non-peripheral: 41 ± 15 sec, p=0.374) or HR MRT (peripherally: 53 ± 21; non-peripheral: 56 ± 20 sec, p=0.708) (Panels B&C).

Conclusion:
There was no difference in oxygen uptake or cardiovascular kinetics between adults with HFpEF with peripheral or non-peripheral limitations to exercise. Our findings indicate that differences in VO
2
kinetics are not a specific marker of peripheral limitations to exercise in adults with HFpEF.
Abstract 4146198: Myoepithelial cardiac tumor of the right atrium in the setting of metastatic recurrent small cell lung cancer status-post chemotherapy and radiation: A rare case report
Authors: Sarkovich Stefan , Kalyanam Rama Sai , Patel Dveet , Patel Mitul , Akel Rami
Published: November 2024

Introduction:
Lung cancer is divided broadly into two main types: Small cell lung cancer (SCLC) and non-small cell lung cancer-NSCLC. Approximately 70% of SCLC cases have metastasized to other parts of the body including lymph nodes, bone, liver, adrenal glands, and brain [1]. SCLS metastasis to cardiac tissue is rare. Primary cardiac tumors are as rare with a reported prevalence of 0.028% [2]. Here we present a 59-year-old female (59F) with recurrent SCLC metastasis with evidence of a newly diagnosed primary cardiac tumor.

Case Presentation:
59F with a past medical history of SCLC status-post chemotherapy and radiation presented for evaluation of worsening left upper extremity pain, paresthesia, motor weakness, and neck pain. During the hospital admission, an echocardiogram demonstrated extensive thrombus from the Superior Vena Cava (SVC) into the right atrium (RA) and an irregular echogenic 37 mm x 26 mm mass partially attached to the posterior leaflet of the tricuspid valve. The RA mass was successfully removed by mechanical thrombectomy. Pathological results of the RA mass revealed significant malignant epithelioid and spindled neoplasm with myxoid stroma– concerning for myoepithelial disease.

Discussion:
Cardiac tumors, although uncommon, should be included in the list of possible diagnoses when observing any abnormal mass detected through cardiovascular or thoracic imaging techniques. Cardiac tumors are likely due to metastatic origins as metastatic cardiac tumors occur 20 times more frequently than primary cardiac tumors[3].When metastatic cardiac tumors are suspected, malignant melanoma and leukemia are the most frequent origins[4]. Rarely does SCLC metastasize to cardiac tissue. Primary cardiac tumors are typically benign (90%), with primary malignant tumors being very rare[5]. Patients may be asymptomatic, or present with nonspecific symptoms such as exertional dyspnea, fevers, arthralgias, or life-threatening cardiac tamponade[6]. For right atrial tumors, treatment strategies are usually dependent on symptomatology, in which removal via aspiration or surgical resection has demonstrated a favorable prognosis[7].

Conclusion:
Given the rarity of primary cardiac tumors in the setting of metastatic SCLC, there exist no evidence-based guidelines for optimal management of right atrial tumors. In our patient, mechanical aspiration was performed without complications and prevented potential adverse cardiopulmonary events from occurring.
Abstract 4146204: Quantification of Atrioesophageal Fistula Morbidity and Mortality Reports Following Left Atrial Catheter Ablation
Authors: Zagrodzky William , Cooper Julie , Joseph Christopher , Putzel Natalie , Sherman Jacob , Lazarus Catherine , Sharkoski Tiffany , Kulstad Erik , Metzl Mark , Girouard Steven , Daniels James , Nazari Jose
Published: November 2024

Introduction:
Atrioesophageal fistulas (AEF) are severe life-threatening complications that can occur after left atrial ablation for the treatment of atrial fibrillation (AF). Although new ablation modalities promote a non-thermal mechanism of action, uncertainty remains surrounding their ability to reduce AEFs when implemented at scale. The international POTTER-AF survey found that AEFs continue to occur despite traditional preventative efforts, but trends in the U.S. are less clear. However, data from the Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) database can provide insight.

Research Question:
What are the recent trends in AEF reporting following left atrial ablation?

Aim:
To determine the number of AEFs and patient outcomes reported using the FDA’s MAUDE database over the last 5 years.

Methods:
Reports were reviewed from the FDA’s MAUDE database for entries filed from January 1st, 2019 through January 1st, 2024. Product codes LPB, OAE, and OAD, representing cardiac ablation catheters and radiofrequency generators, were reviewed for reports of AEFs. Each report was reviewed to remove duplicate reports and to verify patient outcomes.

Results:
A total of 202 reports of AEF were identified, with 128 non-fatal fistulas, and 74 reported deaths. Of the 202 reports, 110 were reported under the code LPB, 66 under OAE, and 26 under OAD. Reports generally increased over the analysis time frame, with 30 reports in 2019, 28 in 2020, 45 in 2021, 45 in 2022, and 54 in 2023 (Figure 1). Esophageal protective methods were reported to be luminal esophageal temperature (LET) monitoring in 61 cases, esophageal deviation in 3 cases, no protective method in 10 cases, and not mentioned in the remaining 128 cases.

Conclusion:
Despite widespread AEF awareness and adoption of traditional preventive efforts the annual rate of reported AEFs in the United States continues to grow, and fatality rates remain high, suggesting the need for improved preventative efforts.
Abstract 4146289: Electronic device use and cardiovascular disease risk in middle-aged and elderly people: evidence from two prospective cohorts
Authors: Zheng Yidan , Jingyu Xu , Qian Xingyu , Hu Shiyan , Zhou Zihao , Liu Yuqi , Tong Fuqiang , Fan Pengning , chen zhe , Zhu Da , Pan Xiangbin , Dong Nianguo , Xu Li , Li Fei
Published: November 2024

Background:
The usage of electronic device has two-sided effects on the health of middle-aged and elderly people. Its protective effects on cardiovascular disease (CVDs) and specific mechanisms are rarely reported.

Hypothesis:
Moderate electronic device usage can reduce the risk of CVDs, with the possible mechanisms of cognitive function and personal well-being.

Method:
Participants from the UK Biobank and CHARLS cohort who were free of the 11 CVDs at recruitment were included. Restricted cubic spline (RCS) analysis was employed to investigate the association between electronic device usage time (not for work reasons) and the hazard ratios (HRs) of CVDs, determining the optimal protective time for grouping. Propensity score matching (PSM) of 1:1 and robust estimation of Cox proportional hazards regression models were utilized to analyze the association between electronic device usage and the risk of CVD incidence, all-cause mortality, and CVD-specific mortality in the UK Biobank, and to reveal the association between internet usage and the risk of CVD in the CHARLS cohort. Mediation analysis and mediation Mendelian randomization (MR) were utilized to screen for potential mediators.

Results:
Total 479,975 participants from two cohorts were included for final analysis. Among the participants recruited from the UK Biobank, RCS analysis indicated that using electronic devices for exactly 1 hour daily received the lowest HRs of general CVDs (HR: 0.984, P<0.001) and specific subtypes. One hour daily electronic device users exhibited reduced risks of all-cause and CVD-specific mortality. Cox analysis validated that internet usage contributes to the prevention of CVDs after PSM in CHARLS cohort (HR: 0.510, P=0.032). Mediation analysis suggested that protective effect of electronic device usage on CVDs was mediated through promoting health satisfaction, enhancing cognitive function, and reducing depression and anxiety (mediating effect: 12.6%, 19.5%, 7.1%, respectively, all p-values<0.001). The mediating effects were further verified by MR.

Conclusion:
No working electronic devices usage for one hour a day contributed to CVDs prevention, which might be mediated by cognitive function improvement in middle-aged and older adults.
Abstract 4146291: Trends and Disparities in Circulatory Disease Prevalence in U.S. Adults: A National Health Interview Survey Database Analysis (2019-2022)
Authors: Yasmin Farah , Moeed Abdul , Shaharyar Maryam , Alim Ur Rahman Hafsah , Fahim Muhammad Ahmed Ali , Ochani Rohan Kumar , Asghar Muhammad Sohaib
Published: November 2024

Background:
Circulatory diseases represent the primary cause of mortality in the US. Comprehending trends and potential disparities in the prevalence of circulatory conditions, such as angina pectoris (AP), myocardial infarction (MI), hypertension (HTN), and coronary heart disease (CHD), is essential for forming public health strategies.

Aim:
To investigate trends in the prevalence of circulatory conditions, including AP, MI, HTN, and CHD among US adults from 2019 to 2022.

Methods:
Prevalence percentages for all available circulatory diseases from the Centers for Disease Control and Prevention's National Health Interview Survey (NHIS) database were retrieved for patients aged >18 years from 2019 to 2022. Annual Percentage Changes (APCs) along with their respective 95% CIs were calculated using regression analysis with Join point. The data was stratified by year, gender, age, race, nativity, veteran status, social vulnerability, employment status, metropolitan statistical area (MSA) status and census region.

Results:
Between 2019 and 2022, HTN was steadily the most prevalent, staying relatively constant at 27.0% (95% CI: 26.4, 27.7) in 2019 and 27.2% (95% CI: 26.5, 27.8) in 2022. Males consistently had higher prevalence than females with significant increases noted from 2019 to 2022 (APC: 1.0234). Black or African American had the highest prevalence (34.4% in 2022). The South (30.1% in 2022) and the West (22.5% in 2022) had respectively the highest and lowest rates. The second highest prevalence was seen in CHD increasing from 4.6% (95% CI: 4.3, 4.9) in 2019 to 4.9 (95% CI: 4.7, 5.2) in 2020. Males consistently exhibited a higher prevalence than females, with both genders showing significant increases in recent years (Male APC: 3.1448) (Female APC: 2.0165). For MI, a slight decrease was noted from 3.1% (95% CI:2.9, 3.4) in 2019 to 3.0% (95% CI:2.7, 3.2) in 2022. White individuals exhibited the highest prevalence (3.3% in 2022). AP had the lowest overall prevalence staying relatively consistent (1.7% in 2019 and 1.6% in 2022) (Figure 1).

Conclusion:
Significant trends (Figure 2) in most common circulatory diseases have been identified. Targeted interventions are imperative, particularly for high-risk demographics such as males, older adults, veterans, and unemployed individuals.
Abstract 4146340: Outcomes of Transcatheter Aortic Valve Implantation (TAVI) in Patients with and without Iron Deficiency Anemia: An Analysis of the National Inpatient Sample (NIS) Data from 2016-2021
Authors: Agrawal Siddharth , Raval Maharshi , Sanghvi Labdhi , Bhargava Sahil , Siddiq Sajid
Published: November 2024

Background:
Iron deficiency anemia (IDA) is a common comorbidity in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). This study investigates the differences in outcomes between TAVI patients with and without IDA, focusing on mortality, procedural complications, and baseline characteristics.

Methods:
A retrospective analysis was conducted using data from the National Inpatient Sample (NIS) from 2016 to 2021. The outcomes for patients undergoing TAVI with IDA were compared to those without IDA. Multivariate logistic regression was employed to analyze outcomes.

Results:
The study included 367,440 patients without iron deficiency anemia and 16,030 patients with iron deficiency anemia. Baseline characteristics showed a significant difference in gender distribution, with 47.15% of IDA patients being male compared to 56.4% in the non-IDA group (P < 0.0001). Racial distribution varied significantly (P < 0.0001), with a higher % of Black patients in the IDA group (6.16% vs. 3.97%).Patients with IDA had higher odds of heart block (OR: 1.146, 95% CI: 1.061-1.238, P = 0.001), bleeding (OR: 1.229, 95% CI: 1.115-1.355, P < 0.001), transfusion (OR: 2.487, 95% CI: 2.209-2.800, P < 0.001), prosthetic dysfunction (OR: 1.377, 95% CI: 1.053-1.801, P = 0.02), post-procedure shock (OR: 1.450, 95% CI: 1.180-1.782, P < 0.001), intra-procedure shock (OR: 1.562, 95% CI: 1.264-1.931, P < 0.001), dialysis (OR: 1.450, 95% CI: 1.044-2.015, P = 0.027), atrial fibrillation (OR: 1.115, 95% CI: 1.033-1.204, P = 0.005), cardiogenic shock (OR: 1.587, 95% CI: 1.283-1.963, P < 0.001), sepsis (OR: 1.541, 95% CI: 1.122-2.117, P = 0.008), respiratory failure (OR: 1.635, 95% CI: 1.462-1.828, P < 0.001), and myocardial infarction (OR: 1.684, 95% CI: 1.421-1.996, P < 0.001). Patients with IDA had a longer length of stay (Coefficient: 2.067, 95% CI: 1.798-2.337, P < 0.001) and higher total hospital charges (Coefficient: $23,107, 95% CI: $16,471-$29,742, P < 0.001) compared to those without IDA.

Conclusions:
Patients with IDA undergoing TAVI are at higher risk for several complications, including heart block, bleeding, transfusion, prosthetic dysfunction, post-procedure and intra-procedure shock, dialysis, atrial fibrillation, cardiogenic shock, sepsis, respiratory failure, and myocardial infarction compared to those without IDA. These findings underscore the need for targeted management strategies and further research to optimize outcomes for TAVI patients with iron deficiency anemia.
Abstract 4146394: Plasma proteomics reveals the potential causal impact of ECM proteins on abdominal aortic aneurysm
Authors: Khodursky Samuel , Yuan Shuai , Spin Joshua , Tsao Philip , Levin Michael , Damrauer Scott
Published: November 2024

Background:
Abdominal aortic aneurysm (AAA) is a common and life-threatening vascular disease. Genetic studies have identified numerous associated loci, many potentially encoding plasma proteins. However, the causal effects of plasma proteins on AAA have not been thoroughly studied. We used genetic causal inference approaches to identify plasma proteins that have a potential causal impact on AAA.

Methods:
Causal inference was performed using two-sample Mendelian randomization (MR). For AAA, we utilized recently published summary statistics from a multi-population genome-wide association (GWAS) meta-analysis including 39,221 individuals with, and 1,086,107 individuals without, AAA from 14 cohorts. We used protein quantitative trait loci (pQTLs) identified in two large-scale plasma-proteomics studies (deCODE and UKB-PPP) to generate genetic instruments. We tested 2409 plasma proteins for possible causal effects on AAA using two-sample MR with inverse variance weighting and common sensitivity analyses to evaluate the MR assumptions. Bayesian colocalization and gene ontology (GO) enrichment analyses provided additional insights.

Results:
MR identified 77 plasma proteins whose levels were associated with AAA at FDR<0.05. Of these proteins, 21/77 (27%) were supported by colocalization analysis (posterior probability H4>0.7), indicating that the plasma levels and AAA likely shared causal variants. Among those supported by both MR and colocalization were previously experimentally validated proteins such as PCSK9 (OR 1.3; 95%CI 1.2-1.4; P<1e-10), along with proteins such as LTBP4 (OR 3.4; 95%CI 2.6-4.6; P<1e-10) and COL6A3 (OR 0.6; 95%CI 0.5-0.7; P<1e-6). GO analysis revealed an enrichment of proteins found in extracellular matrix (ECM, OR 7.8; P<1e-4). Gene expression data suggested that some of these ECM proteins have maximal mRNA levels in aortic tissue. Reverse MR for these ECM proteins found no association between genetic liability for AAA and changes in circulating levels of the proteins – suggesting that changes in their plasma levels were not caused by the aneurysm itself.

Conclusions:
Our results highlight proteins and pathways with potential causal effects on AAA, providing a foundation for future functional experiments. These findings suggest a possible causal pathway whereby genetic variation affecting ECM proteins expressed in the aortic wall cause their levels to change in blood plasma while simultaneously facilitating the formation of AAA.
Abstract 4146396: Age-Associated CD8+ T Cells Accumulate in the Aging Brain
Authors: ALI MD AKKAS , Vardaman Donald , Bolding Chase , Tidwell Harrison , Tyrrell Daniel
Published: November 2024

Introduction/Background:
By 2050, the U.S. will see a demographic shift where individuals over 65 outnumber those under 65. This change underscores a rising prevalence of neurodegenerative diseases, particularly Alzheimer’s disease and various vascular dementias. Over the past 20 years, dementia cases have increased by 20% and are expected to triple in the next 30 years due to aging. The cerebral vasculature becomes increasingly stiff and blood-brain barrier molecules degenerate during aging, leading to accumulation of T cells in the aged brain. The role of T cells on neuroinflammation and dementia during aging is a key unanswered question.

Research questions/Hypothesis:
How does vascular impairment impact immune cells and inflammation in the brain?

How does aging impact immune cells and inflammation in the brain?

Goals/Aims:
To quantify and characterize T cells within the brain during aging and in a model of vascular contributions to cognitive impairment and dementia (VCID).

To determine interactions between brain-resident immune cells (glia) and T cells in aging and a model of VCID.

Methods/Approach:
We isolated T cells and microglia from 3-month old and 21-month old brains in a model of vascular contributions to cognitive impairment and dementia (VCID). We performed single-cell RNA sequencing to identify and characterize peripheral and resident immune cells in the brain in the setting of typical aging and a model of VCID.

Results:
We identified a substantial increase in
Gzmk
+ expressing effector memory CD8+ T cells in the brains of 21-month-old mice compared to 3-month-old mice. These cells were distinguished by their unique transcriptome, cytokine secretion profiles, and accumulation patterns. We also found a significant shift of microglia from an anti-inflammatory expression pattern toward a pro-inflammatory profile in the VCID group compared to control.

Conclusions:
We found a significant accumulation of age-associated T cells which may promote dementias. This study highlights the importance of using aged animal models to understand the cellular dynamics of chronic inflammatory diseases and dementias, potentially guiding the development of targeted therapeutic strategies.
Abstract 4146402: The efficacy and safety of β-blockers in patients with Chronic Obstructive Pulmonary Disease after Myocardial Infarction: a Systematic review and Meta-analysis.
Authors: Prata Alonzo , Katsuyama Eric , Fukunaga Christian , Scardini Pedro Gabriel , Coan Ana Carolina , Falco Neto Wilson , Fernandes Julia , Petri Santos Pinheiro Rafael , Andrade Naieli , Gioli-Pereira Luciana
Published: November 2024

Background:
Previous clinical trials demonstrated the efficacy of beta-blockers (BB) after myocardial infarction (MI). However, the effects and safety of BB in patients with chronic obstructive pulmonary disease(COPD) after MI remain a mystery. Therefore, we conducted a systematic review and meta-analysis evaluating beta-blocker use after MI in patients with COPD.

Methods:
We performed a systematic review and meta-analysis of observational studies that included patients with COPD who received BB after an episode of MI. We searched through Pubmed, Cochrane, and Embase databases. Our primary efficacy outcome was (1) all-cause mortality, and our safety outcome was (2) COPD-related and respiratory adverse events. In our secondary analysis, we evaluated all-cause mortality in patients with a prior history of heart failure (HF). Statistical analysis was done using R Studio 4.3.2.

Results:
A total of 6 studies were included, encompassing 41840 patients, of whom 16561 (39.5%) were in the beta-blocker group. Most of the participants were male (65%) and the mean follow-up was 5.1 years. In the pooled analysis, all-cause mortality was significantly lower in the BB group (HR 0.81; 95% CI 0.66, 0.98; p = 0.03, Fig 1A). Our secondary analysis in the HF subgroup also showed a significant risk reduction in all-cause mortality(HR 0.80; 95% CI 0.66, 0.97; p = 0.02, Fig 1B.) Regarding COPD-related and respiratory adverse events, the analysis demonstrated a significantly lower incidence in the BB group (HR 0.79; 95% CI 0.74, 0.83; p<0.01; Fig 2 ).

Conclusion:
In this meta-analysis involving COPD patients following recent MI, BB utilization was linked to reduced all-cause mortality and a decreased risk of COPD-related adverse events. Additionally, BB administration was correlated with reduced all-cause mortality within the HF subgroup of this cohort.
Abstract 4146494: Multi-Omic Profiling of Adiposity Distribution Patterns
Authors: Pan Michael , Dron Jacqueline , Schuermans Art , Agrawal Saaket , Fourman Lindsay , Koyama Satoshi , Hornsby Whitney , Peloso Gina , Natarajan Pradeep
Published: November 2024

Background:
Distribution patterns for visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue are strongly associated with cardiovascular disease. Circulating metabolites and proteins are dynamic indicators of biological processes and reflect metabolic health. It is not yet clear how these analytes are associated with adiposity distribution patterns.

Aims:
To determine the multi-omic profiles of adiposity distribution and their associated metabolomic and proteomic measurements.

Methods:
MRI-derived volumes of VAT, ASAT, and GFAT adjusted for BMI were available for 40,032 UK Biobank participants. Circulating metabolites and proteins were measured using the Nightingale Health NMR biomarker platform and Olink platform, respectively. We used linear regression models to assess the association between each analyte and VAT, ASAT, and GFAT. Models were adjusted for sex, age at MRI, MRI batch, and time between enrollment and MRI. Functional protein pathway enrichment was performed using the DAVID annotation tool.

Results:
Among 40,032 UK Biobank participants with adiposity volumes, 22,630 (56.5%) and 5023 (12.5%) had 168 metabolomic and 2910 proteomic measurements, respectively. In the metabolomic subset, the mean (SD) age was 55.7 (7.5) years, 10,992 (48.6%) were male, and all self-reported as white. In the proteomic subset, the mean (SD) age was 54.9 (7.8) years, 2417 (48.1%) were male, and all self-reported as white. Multi-variable linear regression revealed 39, 139, and 146 significant metabolite associations (P <1.7e-5) and 65, 207, and 708 significant protein associations (P <1.7e-5) for ASAT, GFAT, and VAT, respectively. We observed opposite directions of effect for 126 (99.2%) metabolites significantly associated with VAT and GFAT, except for pyruvate. Additionally, while proteins involved in cell adhesion were associated with all fat depots, inflammatory response proteins were only associated with VAT.

Conclusion:
Among the fat depots, VAT had the most associations with circulating proteins and metabolites, while ASAT had the least. Assessment of associations with coronary artery disease may further delineate connections between fat deposition and cardiometabolic health.
Abstract 4146526: Impella in Myocardial Infarction Complicated by Cardiogenic Shock: A Meta-Analysis
Authors: Haider Mobeen , Berry Ryan , Hamza Mohammad , Upreti Prakash , Mir junaid , Naveed Hamza , Naseer Usman , Pandya Krutarth , Harmouch Khaled M. , Ahmed Munis , Karamat Mubashar Karamat , Sattar Yasar , Alraies M Chadi
Published: November 2024

Background:
Despite recent technological advancements, myocardial infarction complicated with cardiogenic shock is associated with high mortality. Impella has been advocated as an adjunct to the standard of care, but conflicting data has hindered greater utilization. We performed an updated meta-analysis with the recent data.

Methods:
We searched PubMed and Embase, screened 787 articles, and identified twelve studies that met eligibility criteria; these randomized controlled trials and cohort studies compared Impella to other mechanical circulatory support systems in patients with myocardial infarction complicated by cardiogenic shock. We evaluated groups with twenty-three metrics related to adverse events and clinical outcomes. A random effects model assessed heterogeneity between studies.

Results:
We did not find a statistically significant difference between groups across all twenty-three included metrics: in-house mortality, 30-day mortality, 6-month mortality, brain death, cardiovascular death, non-cardiac mortality, myocardial infarction, need for repeat percutaneous coronary intervention, need for left ventricular assist device, coronary bypass artery graft, stroke, limb ischemia, hemolysis, major bleeding, thrombosis, and sepsis. Table 1 Our subgroup analyses for intra-aortic balloon pump, extracorporeal membrane oxygenation, and medical management revealed similar results for mortality. In terms of bleeding, IABP was associated with better outcomes whereas ECMO was associated with worse outcomes than Impella. Impella was also associated with an increased risk of thrombosis as compared to IABP. Table 2,3,4

Conclusions:
Our updated meta-analysis did not relate Impella use to better outcomes. Heterogeneity in the timing of device implantation calls for stricter reporting in subsequent larger, randomized controlled trials.
Abstract 4146528: Pre-Heart Transplant Physical Rehabilitation in Patients on Impella Support Improves AMPAC Scores and Functional Status
Authors: Jonna Sadhana , Raavi Lekhya , huespe ivan , Perez Rodriguez Allison , Passi Jatin , Khanijo Aditya , Balasubramaniam Prasanth , Isha Shahin , Mundhra Gunjan , Hanson Abby , Jenkins Anna , Jena Anek , Saleem Faiz , Hannon Rachel , Leoni Juan , Lyle Melissa , Thomas Mathew , Sareyyupoglu Basar , Sura Lydia , Davis Olivia , Birst Jennifer , Pham Si , Worsowicz Greg , Patel Parag , Moreno Franco Pablo , Sanghavi Devang
Published: November 2024

Introduction/Background:
Patients with heart failure and those waiting for a heart transplant often experience a significant decrease in their ability to perform daily activities and exercise, leading to a lower quality of life. Although exercise-based cardiac rehabilitation (EBCR) is a possible treatment option, its effectiveness has not been well measured, resulting in limited adoption.

Research Questions/Hypothesis:
Could physical rehabilitation before receiving a heart transplant improve functional status and better outcomes?

Goals/Aims:
Our objective is to evaluate the effect of pre-transplant physical therapy on the standardized improvement of AM-PAC scores, measured from the earliest pre-transplant assessment to the most recent pre-transplant evaluation. Our second objective is to assess the impact of the latest Pre-Transplant AM-PAC Score on the number of hospital-free days following transplantation.

Methods:
We conducted a retrospective study on 91 heart transplant patients who received Impella support from January 2019 to April 2023, approved by the Mayo Clinic Institutional Review Board. We collected data on demographics, AMPAC scores, and outcomes at three time points. Continuous variables were compared using the T-test or Mann-Whitney test, and categorical variables using the Chi-square or Fisher's exact test. We used a linear regression model to investigate the relationship between rehabilitation duration and AMPAC scores. Quantile regression was preferred due to the non-normal distribution of the outcome, hospital-free days.

Results:
We conducted a linear regression analysis and found a statistically significant association between increased hours spent in PT and greater improvement.

After one hour of physical therapy, there was an average increase of 1.07 (95% CI 0.1, 2; p=0.03) in AMPAC scoore. We also compared the change in the AMPAC score with hospital-free days, and it was statistically significant in quantile regression analysis, indicating an increase of 0.28 (95% CI 0.2, 0.55; P=0.03) points in the AMPAC Score, corresponding to an additional hospital-free day.

Conclusion:
Increased hours spent in physical therapy show a significant positive association with greater improvement in standardized AM-PAC Mobility scores and hospital-free days. These findings encourage increasing uptake and support of cardiac rehabilitation programs.