bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4135352: Neighborhood-level Determinants and Disparities in Incident Type 2 Diabetes in a Population-Based Cohort, 2015–2020
Authors: Varghese Ben , Fischer Karen , Gupta Ruchi , Mielke Michelle , Vella Adrian , Chamberlain Alanna , St Sauver Jennifer , Bailey Kent , Dugani Sagar
Published: November 2024

Introduction:
Living in an area with high Area Deprivation Index (ADI) is linked to worse cardiovascular disease (CVD) outcomes. However, the association of ADI with type 2 diabetes (T2D), a major CVD risk factor, is incompletely described. This knowledge may guide primary CVD prevention.

Method:
Rochester Epidemiology Project is a medical record linkage system of persons in southeast Minnesota and southwest Wisconsin. We identified 253,890 persons (aged 4–98 yrs on July 1, 2015) in 9 counties with >90% population coverage. ADI scores, from 2015 home addresses, were grouped into quartiles of low (Q1) to high (Q4) deprivation. We excluded persons with type 1 diabetes (T1D) or history of T2D and identified new T2D cases (2015-2020) using ICD codes, HbA1c and medications. We examined the association between ADI quartile and risk of incident T2D using Cox regression with persons right censored at death, T2D, T1D or last visit. Models were adjusted for age and gender, and reported adjusted hazard ratios (aHR [95% confidence interval]).

Results:
Age, gender, and race statistically differed across ADI quartiles (Table). Age × ADI interaction was significant (
P
<.001). T2D incidence ranged from 6.3 (Q1) to 9.0 (Q4) per 1000 person-years (
P
<.001). Women vs. men/non-binary persons (combined due to limited non-binary persons) had 30% lower risk of incident T2D (aHR 0.70 [0.67–0.72]). Risk of incident T2D was higher in persons from higher ADI areas. At median age of 48.6 yrs, the risk was 30% higher in Q2 (aHR 1.3 [1.22–1.38]), 38% higher in Q3 (aHR 1.38 [1.30–1.47]) and 53% higher in Q4 (aHR 1.53 [1.43–1.62]) vs. Q1. Higher ADI was associated with higher incident T2D in younger persons, with risk attenuation with increasing age (Figure).

Conclusion:
In this population cohort, persons, particularly of younger age, living in more deprived areas had a higher risk of incident T2D. ADI may help identify areas for targeted T2D screening, with implications for CVD screening and prevention.
Abstract 4135425: Add-on Therapy with Dantrolene, a RyR2 Stabilizer, Terminates Ventricular Tachycardia Storm refractory to Intravenous Amiodarone in Heart Failure.
Authors: Nawata Junya , Kobayashi Shigeki , ISHIKAWA MAHO , Nakata Yuki , Murakawa Kaori , Nakashima Yusuke , Hisaoka Masahiro , Matsuyama Tetsuya , Nakamura Yoshihide , Omuro Ayumi , Fukuda Masakazu , Suetomi Takeshi , Miyazaki Yosuke , Fujimura Tatsuhiro , Mochizuki Mamoru , Sano Motoaki
Published: November 2024

Background:
Aberrant diastolic Ca
2+
leak through the cardiac ryanodine receptor (RyR2) is an important cause of heart failure (HF) and lethal arrhythmia. Dantrolene (DAN) specifically binds to the Leu
601-
Cys
620
of N terminal domain in RyR2 and stabilizes the tetrameric structure of RyR2, preventing the Ca
2+
leak through RyR2. Our previous study as a proof-of-concept showed that intravenous injection (i.v.) of DAN was effective in termination and prevention of refractory ventricular tachycardia (VT) storm in HF.

Research Question:
How much is loading dose of DAN i.v. to terminate VT storm in HF? We hypothesized that the optimal dose was within 3mg/kg from our previous study.

Aim:
This study aimed to verify that 3mg/kg DAN i.v. was optimal for the termination of amiodarone-resistant VT storm in HF.

Methods:
This was an open-label, uncontrolled, single-center study. The detail in the study design and methods is shown in
Fig.1
. We studied patients with episodes of VT storm regardless of medications, such as amiodarone and beta-blockers, recommended by HF guidelines. DAN(3mg/kg) was intravenously added on the above guideline treatment. The acute anti-arrhythmic efficacy of DAN was assessed as follows: 1) proportion of patients whose VT storm was terminated by 3mg/kg DAN i.v., 2) incidence rate of VT storm within 24 hours before and after DAN i.v..

Results:
The consecutive 7 patients with refractory VT storm were enrolled in this study (median age:72 years old, male/female: 4/3, median LVEF29%). Underlying heart disease included 3 ischemic cardiomyopathy, 3 acute myocardial infarction after successful percutaneous coronary intervention and 1 tachycardia-induced cardiomyopathy. 2 of 7 patients underwent mechanical circulatory support before DAN i.v. because of pulseless VT. All patients were classified as NYHA class III/IV. 3 mg/kg of DAN i.v. ceased VT storm within 60 min in 7/7 (100%)
(Fig.2, left).
The number of sustained VT within 24 h after DAN i.v. were significantly lower than those within 24 h prior to DAN administration
(Fig 2, right)
. A representative case is shown in
Fig.3
The VT storms refractory to amiodarone and landiolol (beta-blocker) as well as sedation showed complete response to 3mg/kg DAN i.v..

Conclusions:
DAN, a RyR2 stabilizer, was effective in the termination of VT storm in HF resistant to guideline directed medical treatment. This is the first study to evaluate the optimal dose of DAN i.v. against the refractory VT storm in HF.
Abstract 4135447: Demographics, Clinicopathological Outcomes and Comparative Survival Analysis of Pleural and Pericardial Mesothelioma; A Retrospective Population-Based Study
Authors: Khan Rozi , Wali Agha , Yasinzai Abdul Qahar Khan , Iqbal Asif , Sohail Amir , Goyal Aman , Ullah Kaleem , Tareen Bisma , Khan Marjan , Ullah Hafeez , Ghafouri Sayed Ab Reshad , Elhawi Mary , Mahmood Ahmed , Pooja Sethi , Ullah Asad
Published: November 2024

Background:
Malignant mesothelioma (MM) is an aggressive and rare tumor of mesothelial cells that is strongly correlated with asbestos exposure. Due to its long latency period, MM is characterized by its poor prognosis. In this study, we primarily analyzed data for the clinicopathological analysis of malignant pleural mesothelioma with comparative overall survival (OS) and cancer-specific survival (CSS) with primary pericardial mesothelioma.

Method:
The data was collected from the Epidemiology and End Results (SEER) database, comprising 12,991 mesothelioma patients from 2000 to 2020.

Results:
A total of 12,991 cases of MM were extracted from the database, of which 99.55% were pleural and only 0.177% were pericardial. The median age was 74 years. Regarding gender, 80% of the patients were male. MM was found to be more common in older age (>65, 77%). 52% of the patients had a tumor size greater than 5 cm. The common histologic type was mesothelioma NOS (45%), followed by the epithelioid type (36%). The most common treatment modality was chemotherapy. Multivariate analysis showed better survival outcomes in younger, female patients undergoing combination therapies. Moreover, the histologic subtype, especially epithelioid mesothelioma, showed the overall best prognosis. Regarding comparative OS and CSS between pleural and pericardial mesothelioma, the 3-year OS of pleural mesothelioma was 11.2% (95% CI: 0.107 - 0.118) and for pericardial mesothelioma, the 3-year OS was 4.7% (95% CI: 0.007 - 0.317). Pleural mesothelioma had a 1-year CSS of 37.1% (95% CI: 0.343 - 0.401), and for pericardial mesothelioma, the CSS at 9 months was 28.6% (95% CI: 0.089 - 0.922), and all patients survived < 1 year in the cohort.

Conclusion:
Malignant mesothelioma is a rare and aggressive tumor. Pericardial mesothelioma has lower survival in comparison to pleural mesothelioma. Genomic analysis and including all ethnicities in future clinical trials will help in future personalized therapeutic approaches.
Abstract 4135476: The Cardiomyocyte Hypertrophy Inhibitor RFN-409, Identified by High Throughput Screening Assay, Suppresses Pressure Overload-induced Systolic Dysfunction in Mice by Suppressing p38 Activity
Authors: Irokawa Yudai , Katagiri Takahiro , Maeda Risa , Shimizu Satoshi , Funamoto Masafumi , Hamabe Toshihide , Sunagawa Yoichi , Kawase Yuto , Naruta Ryuya , Katanasaka Yasufumi , Hasegawa Koji , Morimoto Tatsuya
Published: November 2024

Purpose:
When the heart is exposed to stresses such as myocardial infarction or hypertension, it undergoes compensatory hypertrophy in response. However, continuation of the stress causes this compensatory mechanism to fail, and eventually systolic dysfunction or decompensated heart failure occur. As the hypertrophy of individual cardiomyocytes has been observed in this process, controlling cardiomyocyte hypertrophy is a potential target the prevention and treatment of heart failure. In this study, we constructed a high throughput screening (HTS) assay using cardiomyocyte hypertrophy as an index parameter. Compounds that inhibit cardiomyocyte hypertrophy were selected from our low molecular compound library.

Methods and Results:
In the primary screening, cultured rat primary cardiomyocytes were treated with each compound at a final concentration of 1 µM and then stimulated with 30 µM phenylephrine (PE) for 48 hours. These cells were subjected to fluorescent immunostaining with α-actinin, and cardiomyocyte area was measured using an ArrayScan™ system. The hypertrophy inhibition rate (%) of each compound was calculated as [(PE(+) - compound) / (PE(+) - PE(-))] × 100. The compounds with a hypertrophy inhibition rate greater than 50% and less than 150% were selected as hit compounds. In the secondary screening, these hit compounds were evaluated based on the dose-dependency of cardiomyocyte hypertrophy inhibition and the inhibition of the mRNA levels of the cardiac hypertrophy response genes ANF and BNP using real-time PCR. From the 269 low molecular-weight compounds in the original compound library, eight were selected through the primary and secondary screenings. Among them, we focused on Reference Number 409 (RFN-409). Western blotting indicated that RFN-409 inhibited PE-induced p38 activation. Next, we investigated the effect of RFN-409 on heart failure. Eight-week-old male C57 BL/6J mice were subjected to transverse aortic constriction (TAC) surgery and then randomly assigned to intraperitoneal treatment with RFN-409 (3, 10 mg/kg) or vehicle for eight weeks. RFN-409 at 10 mg/kg significantly prevented TAC-induced increase in left ventricular posterior wall thickness and decrease in left ventricular fractional shortening.

Discussion:
RFN-409 suppressed TAC-induced development of heart failure, at least partially by inhibiting p38 activity. These findings suggest that RFN-409 may be an effective agent for heart failure therapy.
Abstract 4135517: Echocardiographic Biomarkers Enhance Mortality Predictions in Cirrhosis Patients
Authors: Meyers Brett , Dimitroglou Yannis , Aggeli Constantina , Vlachos Pavlos
Published: November 2024

Introduction:
Cirrhosis, a late-stage liver disease, is associated with numerous systemic complications, making long-term mortality prediction challenging. Traditional models like Child-Pugh and MELD are primarily designed for short-term (3-month) mortality. This study evaluates the impact of incorporating echocardiographic (echo) variables in predicting long-term mortality in cirrhosis patients.

Methods:
A retrospective cohort study was conducted using data from 60 patients with clinically diagnosed cirrhosis from Hippokration Hospital, Greece, spanning 2018 to 2022. Patients were followed for up to 52 months. Exclusion criteria included pre-existing cardiovascular diseases and significant co-morbidities. Patients were categorized into survived to end of study (n=31) and died during study (n=29) groups. Outcomes were analyzed using multivariate logistic regression and Cox proportional hazards models, and include parameters for age, blood pressure, lab-based biomarkers (potassium, pro-brain natriuretic peptide, hemoglobin, platelet count, aspartate transaminase, gamma-glutamyl transferase, uric acid), and echo/ecg measurements (QT interval, left ventricular (LV) ejection fraction, LV global longitudinal strain (GLS), left atrial GLS, annulus velocities, and E/A ratio).

Results:
The multivariate logistic regression model (MELD+) that included echo variables showed a 10% improvement in area under the curve (AUC: 0.901) compared to the MELD model alone (AUC: 0.817). MELD+ improved risk classification accuracy by nearly 10% with a conservative threshold. The Cox proportional hazards model with MELD+ also demonstrated superior performance (AUC: 0.923; C-index: 0.875; Brier Score: 0.097) compared to the MELD model alone (AUC: 0.892; C-index: 0.831; Brier Score: 0.134). The MELD+ model showed less variation in hazard ratio confidence intervals, indicating more consistent risk estimation.

Conclusion:
Incorporating echocardiographic measurements enhances the accuracy of long-term mortality predictions in cirrhosis patients. These findings suggest that cardiac imaging should be considered in risk assessments for cirrhosis patients, particularly for predicting survival beyond three months.
Abstract 4135582: Sociodemographic Trends in Diabetes Medications after Metformin: the BESTMED (oBservational Evaluation of Second line Therapy MEdications in Diabetes) Study
Authors: Lansang Maria , Petito Lucia , Chelliah Indhumathy , Hegermiller Emma , Carnahan Ryan , McDonnell Marie , Sylwestrzak Gosia , Priest Elisa , Wiley Vincent , Goel Satyender , Kaul Alan , Turchin Alexander
Published: November 2024

Objective:
Though updated American Diabetes Association (ADA) guidelines recommend initiating GLP1 receptor agonists (GLP1) or SGLT2 inhibitors (SGLT2i) for persons with type 2 diabetes mellitus (PWT2DM) with high CV risk, metformin was previously recommended as 1st-line treatment. For PWT2DM at moderate CV risk, it is unknown which 2nd-line drug optimizes CV outcomes. Our multicenter observational study describes US-wide trends in 2nd-line T2DM medication use (DPP4 inhibitors [DPP4i], GLP1s, SGLT2i and sulfonylureas [SU]) overall and in key sociodemographic subgroups between 2014-2023.

Methods:
This is a secondary analysis of the oBservational Evaluation of Second line Therapy Medications in Diabetes (BESTMED) study, which used a new-user design to evaluate associations between 2nd-line medications and CV events in PWT2DM at moderate CV risk. The database comprised EHRs and insurance claims for 75,224 PWT2DM from 10 health systems and 2 insurance plans on metformin who initiated a 2nd medication from 1/2013 to 1/2023. Data were obtained from orders or prescription fills. Prescription class was regressed on calendar time via multinomial logistic regression to model trends in prescribing patterns, adjusted for sociodemographic variables. Subgroup analyses were performed by adjustment factors; CIs and p-values for differences were calculated via nonparametric bootstrap (B=200). Due to large sample size, statistical significance was interpreted at p<0.05 and annual rate of change >0.5%.

Results:
We included 75,224 T2DM adults (median A1c 7.8%), of whom 18%,17%, 18%, and 47% initiated DPP4i, GLP1, SGLT2i, SU respectively. From 2014 - 2023, SGLT2i and GLP1 increased: 5.7 to 28.8%, and 3.5 to 30.3%, and DPP4i and SUs decreased: 25.3 to 11.6%, and 65.6 to 29.3%, respectively. Annual rate of change for SGLT2i was higher in men(3.0% vs 2.1%/year; p<0.001) and in
>
65 y (3.0% vs 2.4%; p<0.001), and for GLP1s was higher in those <65 y (3.6% vs 2.1%; p<0.001), women (3.5% vs 2.5%; p<0.001), Hispanic ethnicity (3.2% vs 2.7%; p=0.005), and with class II/III obesity (4.1% versus 2.6% per year; p<0.001). There was no evidence that these trends differed by race, insurance, or SDI.

Conclusion:
In this nationwide study of prescribing patterns PWT2DM at moderate CV risk, prevalences of 2nd-line T2DM therapies are approaching current ADA guidelines for initial therapy for those at high CV risk. Differences between sociodemographic groups appear aligned with clinical expectations.
Abstract 4135700: Effects of Mitochondrial Dysfunction on Extracellular Vesicle Release and Subsequent Disruption of the Lung Vascular Endothelial Barrier
Authors: Letsiou Eleftheria , AL Matni Mohammed Yaman , Meliton Lucille , Lawrence-Foster Rachel , Kadioglu Aras , Dudek Steven
Published: November 2024

Background:
Lung endothelial cell (EC) barrier disruption is a hallmark of acute lung injury (ALI), which is commonly caused by bacterial pneumonia. Alveolar epithelial cells (AEC) are the first line of defence against invading respiratory pathogens in the lungs and can mediate inflammatory signaling to the adjacent EC contributing to barrier disruption. We have previously demonstrated that pneumolysin (PLY), a major
Streptococcus pneumoniae
virulence factor, induces both mitochondrial dysfunction in lung AEC and release of large extracellular vesicles (EVs). These EVs, which are enriched with mitochondrial cargo, contribute to increased permeability of the lung EC barrier. Here, we investigate strategies to inhibit mitochondrial dysfunction in AEC and examine how these interventions impact EC barrier function.

Methods:
Human alveolar epithelial cells (A549) or immortalized AEC (Cell Biologics) were pre-treated with mitoTEMPO (mtROS scavenger), P110 (excessive fission inhibitor), or ensifentrine [dual phosphodiesterase (PDE) 3/4 inhibitor] prior to PLY treatment (100-300 ng/ml, 4 hrs). Mitochondrial function was assessed by the JC-1 assay. EVs were isolated from cell media and analyzed for their mitochondrial content (Tom20 and Tim23 expression). To assess their functional role, EVs were added to TNF-α treated human lung microvascular EC, and barrier function was then determined using the ECIS assay to measure transendothelial electrical resistance (TER).

Results:
PLY-induced mitochondrial dysfunction was reduced in the presence of mitoTempo or P110. EVs from PLY-treated AEC (EV
PLY
; enriched mitochondrial content) exacerbated TNF-α-induced EC barrier permeability as indicated by the significant decrease in TER. EV
PLY
derived from MitoTEMPO or P110-pretreated AEC contained less mitochondrial cargo and resulted in less EC permeability after TNF-α. Compared to mitoTEMPO and P110, ensifentrine exhibited superior protection against mitochondrial dysfunction after PLY exposure. In addition, in the presence of ensifentrine, the quantity of EV release and their extracelllular mitochondrial content were both dramatically reduced. In contrast to control EV
PLY
, EV
PLY
from ensifentrine-pretreated AEC demonstrated no barrier disruptive properties.

Conclusions:
Mitochondrial dysfunction in AEC contributes to vascular endothelial injury in ALI through mechanisms involving the release of barrier-disruptive EVs, which can be effectively targeted by inhibiting PDE3/4.
Abstract 4135708: Obesity and the risk of cardiac death in coronary artery disease
Authors: Holmstrom Lauri , Hannula Maria , Tulppo Mikko , Hookana Ida , Perkiomaki Juha , Huikuri Heikki , Junttila Juhani
Published: November 2024

Background:
The prevalence of obesity is increasing worldwide reaching epidemic proportions. Obesity increases the risk of coronary artery disease (CAD), but there is little prospective evidence about the effect of obesity on the risk of cardiac death in CAD patients.

Aim:
We aimed to investigate the effect of obesity and the risk of cardiac death in a prospective cohort of CAD patients.

Methods:
We have prospectively enrolled 1,946 patients with CAD (mean age 66.9±8.6, 68% male), with a mean follow-up of 8.7±2.2 years. BMI was measured at baseline and was categorized into 4 groups: 1) BMI 18.5-24.9 kg/m
2
(normal weight, reference group), 2) BMI 25-29.9 kg/m
2
(overweight), 3) BMI 30-34.9 kg/m
2
(class 1 obesity), and 4) BMI >35 kg/m
2
(class 2 obesity). The primary endpoint was cardiac death and secondary endpoints were sudden cardiac death/arrest (SCD/SCA), non-sudden cardiac death, non-cardiac death, and heart failure (HF) hospitalization. Statistical analysis was performed with Cox regression and was adjusted for age, sex, type 2 diabetes, CCS class, kidney function (eGFR), systolic and diastolic blood pressure, LDL, smoking, SYNTAX score, and left ventricle ejection fraction.

Results:
The prevalence of BMI 18.5-24.9 kg/m
2
was 18.5% (n=359), BMI 25-29.9 kg/m
2
was 47.8% (n=929), BMI 30-34.9 kg/m
2
was 24.0% (n=466), and BMI>35 kg/m
2
was 9.7% (n=189). During the follow-up, cardiac death occurred in 156 subjects, SCD/SCA in 75 subjects, non-sudden cardiac death in 81 subjects, and non-cardiac death in 197 subjects. BMI >35 kg/m
2
was associated with an increased trend of cardiac death (adjusted HR 1.92, 95% CI 0.92-4.01; p=0.08) and an increased risk of non-sudden cardiac death (adjusted HR 4.11, 95% CI 1.58-10.68; p=0.004) and HF hospitalization (adjusted HR 2.83, 95% CI 1.06-7-54; p=0.04), but not with SCD/SCA (adjusted HR 0.79, 95% CI 0.24-2.56; p=0.69) or noncardiac death (adjusted HR 0.85, 95% CI 0.43-1.69; p=0.64). The risk of cardiac death or secondary endpoints was not increased in patients with overweight or class 1 obesity.

Conclusions:
Class 2 obesity was associated with an increased risk of non-sudden cardiac death and heart failure hospitalization among CAD patients. Obesity may have adverse long-term effects on cardiac function and prognosis among CAD patients, supporting the benefit of optimal weight control therapy.
Abstract 4135726: Prospective validation and implementation pilot study of an emergency department heart failure risk stratification tool: STRIDE-HF
Authors: Sax Dana , Huang Jie , Mark Dustin , Rana Jamal , Solomon Mathew , Norris Robert , Reed Mary
Published: November 2024

Background:
We previously found the STRIDE-HF emergency department (ED) risk tool accurately predicted risk of a 30-day serious adverse event (SAE), including 30-day mortality, cardiopulmonary resuscitation, intra-aortic balloon pump insertion, intubation, new dialysis, myocardial infarction, or coronary revascularization.

Research question:
We sought to prospectively validate STRIDE-HF and describe safety of the deployed model in a clinical pilot. We hypothesized that performance would decrease slightly with prospective evaluation and that real-time risk display would contribute to safe disposition decisions.

Goals:
1) To prospectively validate KPCARES-HF across 21 community EDs among ED patients with acute heart failure (AHF) from January 1, 2023 – December 31
st
, 2023; and 2) to describe outcomes among patients predicted to be very low risk and discharged home in the clinical pilot.

Methods:
For prospective validation, we report 30-day mortality rates by risk strata. We assess model performance using area under the receiver operator curve (AUROC) and sensitivity at a key clinical threshold. We describe rates of 30-day SAE among patients predicted to be very low risk and discharged after ED or observation unit care in the clinical pilot.

Results:
There were 13,274 ED patients in the prospective validation; median age was 76, 50.8% were female, and 44.5% were non-White. We found 11.4%, 24.8%, 31.9%, and 31.9% of patients were very low, low, moderate, and high risk, respectively, while 21.6%, 15.2% and 63.0% were discharged, observed, and admitted, respectively.

Among discharged patients, 29.2% and 13.3% were moderate or high risk, respectively, and 30-day mortality rates among these patients were 2.2% and 8.4%, respectively. Among 8,363 admitted patients, 27.7% were very low or low risk.

Conclusions:
STRIDE-HF maintained high predictive accuracy with prospective validation in this diverse, multi-center cohort. Our findings suggest that use of STRIDE-HF might help better align risk with admission decision and can be safely used to assist providers in identifying patients who may be stable for outpatient care.
Abstract 4135745: Prematurity Predicts Neurodevelopmental Outcomes in Congenital Heart Disease
Authors: Katz Jenna , Gauvreau Kimberlee , Butler Samantha , Sadhwani Anjali , Levy Phillip , Kaza Aditya , Nathan Meena , Newburger Jane
Published: November 2024

Background:
Neurodevelopmental (ND) impairment is common in both prematurity and congenital heart disease (CHD). Preterm infants with CHD may have a “double hit,” with worse ND impairments than seen in prematurity or CHD alone. We analyzed whether gestational age (GA) at delivery predicted ND outcomes in children with CHD.

Methods:
We performed a single-institution retrospective study of children who underwent infant heart surgery from 2007-2020 and returned for ND evaluation after discharge. Exclusion criteria were 1) trisomy 21 and 2) PDA ligation alone. The Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessed ND between ages 6-40 months. Patients were stratified into 4 GA groups: very/moderately preterm (≤33 weeks), late-preterm (34-36 weeks), early-term (37-38 weeks) or term/post-term (≥39 weeks). Hierarchical linear regression evaluated potential predictors of Bayley-III composite scores including GA category, demographic, medical, and surgical variables.

Results:
Among 1350 infants, 513 (38%) had a Bayley-III at median age 28 months [IQR 19, 34]. Of these, 448 (87%) were full-term and 65 (13%) preterm. In univariate analyses, children born preterm vs. full term had lower Bayley-III cognitive, language, and motor scores, explaining from 2.4% (language) to 6.2% (motor) of the variance in Bayley composite scores. In the final models, GA remained a strong independent predictor of motor and cognitive scores. Children with GA ≤33 weeks had the worst outcomes, with age-adjusted cognitive and motor composite scores 11 and 15 points lower, respectively, than those of term infants (Figure). Other significant risk factors included lower primary caregiver education, Black race, longer hospital length of stay, and genetic diagnosis. These models ultimately explained 17-26% of the variance in Bayley scores, with the highest explained variance in the motor domain.

Conclusions:
Adjusting for other patient and medical factors, preterm infants with CHD have worse cognitive and motor outcomes; risk is highest in those born at ≤33 weeks. Further work is needed to identify potentially modifiable factors to tailor prenatal, postnatal and perioperative care of infants with CHD born prematurely.
Abstract 4135746: Assessing Coronary Artery Disease Severity: Leveraging Inflammatory Markers As a Prognostic Indicators
Authors: Turnbull Scott , Dugal Jasmine , Gill Randeep , Wang Shawn , Cross Chad , Mubder Mohamad
Published: November 2024

Introduction:
Cardiovascular disease continues to be the leading cause of death and a significant cause of morbidity in the United States. In recent years, there has been increased interest in the role of inflammation in predicting and modifying the risk of coronary artery disease. Of the multitude of inflammatory markers studied subsequently, two of the most easily and widely obtained is the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR), which can be calculated from a complete blood count with differential. Multiple retrospective studies have demonstrated that the NLR and MLR have been used to diagnose ACS, predict mortality at a year after ACS, and risk stratify patients prior to percutaneous coronary intervention.

Research Question:
Are the NLR/MLR useful tools in predicting the severity of coronary artery disease (CAD) in patients admitted to a tertiary medical center in Southern Nevada for ACS between 2021 and 2023?

Methods:
A sample of n=344 patients was used to examine the potential significance of NLR/MLR to diagnose ACS and for predicting CAD severity. Traditional diagnostic test evaluation was used for determining CAD with a ratio of NLR=3.5 + MLR=0.35 (data medians) as the cut-off value. Patient risk group status (1:low risk to 4:high risk) was used as a binary outcome to test NLR/MLR between low and high risk groups using a nonparametric MWW test of medians. Additionally, ROC analysis was used to estimate an optimized cut-off for NLR/MLR as determined by AUC.

Results:
Results demonstrate for predicting ACS using the median NLR, sensitivity=88.07; specificity=14.88; PPV=52.01; NPV=54.35), LR(+)=1.03 and LR(-)= 0.80, using the median MLR results showed sensitivity=87.28; specificity=14.11; PPV=50.84; NPV=52.17, LR(+)=1.01 and LR(-)= 0.90. Subpopulation analysis demonstrated a statistically significant difference in NLR between “high risk ACS” vs “Low Risk ACS” (p<0.001). Examination of the ROC curve for predicting the high-risk group suggested an optimized cutoff of NLR=3.7; however, AUC was only 0.617, and sensitivity and specificity were not improved compared to using the median NLR.

Conclusion:
Our findings suggest that an NLR greater than 3.7 may indicate multivessel involvement or proximal/left main disease in CAD patients. However, due to its low specificity and AUC, NLR alone cannot reliably distinguish between single-vessel and multivessel CAD.
Abstract 4135780: Predictors of Engagement in a Coaching Intervention for Heart Failure Caregivers
Authors: Kim Sue Hyon , Hirschman Karen , Ryan Quinn , Riegel Barbara
Published: November 2024

Background:
Even the best intervention will not be effective without engagement in the experience. We developed and tested a virtual health coaching intervention ("ViCCY”, Virtual Caregiver Coach for You) for informal caregivers of patients with HF in a RCT. Of the 125 caregivers in the intervention group, completion rates varied (mean 6 ± 4 sessions, median 9; 21% no sessions). The aim of this study was to identify factors associated with intervention engagement defined as receipt of ≥8 of 10 intervention sessions over a 6-month period based on core intervention content.

Methods:
This explanatory sequential mixed methods study was conducted in two phases. First quantitative data were analyzed with respect to number of completed sessions, sociodemographics, and the Credibility-Expectancy Questionnaire measuring expectations regarding intervention effectiveness. We used multivariable logistic regression to quantitatively identify salient predictors of caregivers’ intervention engagement. Then, based on the number of sessions completed, 24 caregivers assigned to ViCCY were interviewed to explore individual, family, community, and societal factors associated with intervention engagement. Transcribed interviews were coded using content analysis.

Results:
Each one hour increase in hours caregiving was associated with reduced odds of completing ≥8 sessions. Race other than White and income insufficient to make ends meet were associated with reduced odds of completing ≥8 sessions. Each unit increase in intervention credibility was associated with increased odds of completing ≥8 sessions. Interviews with participants who completed some sessions revealed common challenges such as the patient’s HF progression and life events including caregiver health issues, balancing multiple responsibilities, and interpersonal issues. Reluctance to accept help from an unfamiliar individual through a virtual network and perceiving additional resources as burdensome also hindered participation. Practical issues such as finding a suitable space for virtual meetings and scheduling conflicts interfered. In those who did not complete any sessions, the main reason for non-engagement was misunderstanding of what to expect in the intervention.

Conclusions:
The daily lives of HF caregivers are influenced by caregiving demands exacerbated by social determinants of health. These issues may reduce the capacity of caregivers to accept help and ultimately act as a barrier to program engagement.
Abstract 4135835: Prevalence of Diabetes Mellitus in Calcutta Schoolteachers and its Relationship with Cardiovascular Risk as Assessed by the ASCVD Model
Authors: Ray Madhab , Guha Dr. Santanu , Ray Bipasha , Saxena Varun , Menon Rohan , Desai Virang , Ray Meghna , Desai Vivaan , Sagar Dey Trisha , Goel Neev , John Lisa , Soohoo Julie , John Maria , Sarkar Arja , Gogada Khushal , Pal Anushri , Ghosh Ahana , Sikder Sonali , Viswanathan Badri , Mandal Srijan , Karak Avik , Chowdhury Basabendra , Chaudhuri Sudipta , Hazra Prakash , Goldberg Robert , Bhatt Deepak , Selker Harry
Published: November 2024

Introduction:
Cardiovascular disease (CVD) is rising in prevalence in India with economic development and the adoption of a Western lifestyle.

Hypothesis:
The increase in incidence and prevalence of CVD is possibly due to a rise in the incidence of risk factors like diabetes mellitus (DM), hypertension, hyperlipidemia, lack of physical activity and obesity, among various other causes.

Aims:
1. To estimate the prevalence of DM in the community of Calcutta schoolteachers

2. To examine the relationship between the prevalence of DM and CVD risk as assessed by the different traditional CVD risk factors (age, sex, hypertension, current smoking, DM, and hyperlipidemia).

Methods:
We recruited 4,150 schoolteachers from 400 schools in Calcutta, India between June, and August 2019 with approval of the Tufts IRB and the local Ethics Committee. Participants were asked questions about their different risk factors to ascertain their cardiovascular risk by the ASCVD risk calculator. Baseline values (total cholesterol 170 mg/dL, HDL-C 50 mg/dL, no DM) were used when a participant’s glycemic status or lipid profile was not available. Based on the risk score, participants were stratified as mild (<5%), moderate (5-10%), or high (>10%) risk for developing ASCVD. A total of 240 participants were randomly selected from a stratified sample of the participants for evaluation for diabetes using HbA1c. DM was diagnosed when the Hb A1 C was 6.5% or more.

Results:
The mean age of the participants was 44 years, and 41% were male. Out of a total of 4,150 participants, 85.7% (3,558) were in the low-risk for CVD category, 9.0% (374) were moderate-risk, and 5.3% (218) were high-risk. Among the 240 screened for DM, 17.1% (41) were found to have the condition, and 41.3% (99) were pre-diabetic. There was no significant difference in prevalence of DM between men and women in the overall study population and in the mild risk group. However, more women in the medium risk group and more men in the high-risk group were found to be diabetic (p value <0.001 in both). Some participants were reclassified based on their new diagnosis of DM.

Conclusions:
The prevalence of DM was high among Calcutta schoolteachers, which contributes to being at increased risk for ASCVD. Most participants were unaware of their DM or cardiovascular risk, highlighting the need for increased testing and awareness. The estimates from this study may be used to understand the community burden of DM and cardiovascular risk.
Abstract 4135872: Effects of In-vivo Contact Force on Pulsed Field Ablation Lesion Size in Porcine Ventricles
Authors: Koya Taro , Otsuka Naoto , Tri Jason , ying yang , Asirvatham Samuel , Nguyen Duy
Published: November 2024

Background:
Pulsed field ablation (PFA) is an innovative modality for treating arrhythmias that is mostly non-thermal and renders myocardial tissue non-viable by creating pores in cardiac cell membranes. The impact of contact force (CF) on PFA efficacy is not well characterized.

Hypothesis:
We hypothesize that, while contact is necessary for PFA, increasing CF will not have a significant effect on
in vivo
ablation lesion size.

Aim:
We seek to investigate the effects of CF on acute PFA lesions in a beating porcine heart model.

Methods:
The ventricles of 7 porcine animals were ablated
in vivo
with PFA (500V, at 20μs for 50 pulses separated by 200ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). CF was measured before and after each PFA application using CARTO 3. Lesions were divided into standard CF (5-15g), high CF (16-30g), and very high CF (>31g).

Results:
A total of 46 lesions were analyzed. Gross pathology showed no significant difference in maximum width, lesion depth, and lesion volume between the three groups (
Figure 1A-B
). Linear regression showed a decrease of 0.003 mm in depth (depth = -0.003 × CF + 1.8, R = 0.05), an increase of 0.01 mm in width (width = 0.01 × CF + 5.7, R = 0.09), and a decrease of 0.05 mm
3
in volume (volume = -0.05 × CF + 26.8, R = 0.03) for each additional gram of CF (
Figure 1C
).

Conclusion:
While contact is necessary, increasing CF did not have a significant effect on in-vivo PFA lesion dimensions in a beating porcine heart model.
Abstract 4135905: The Impact of Emergent Atrial Fibrillation in Patients With Newly Diagnosed Heart Failure and Differences in Risk Among Preserved vs. Reduced Ejection Fraction
Authors: May Heidi , Knight Stacey , Le Viet , Anderson Jeffrey , Knowlton Kirk , Cutler Michael , Packer Douglas
Published: November 2024

Background:
Atrial fibrillation (AF) and heart failure (HF) are associated with an increased risk of adverse events, with their diagnoses often coexisting. The impact of AF in HF needs additional study, with further delineation among HF type. Therefore, this study sought to determine the degree of AF burden among newly diagnosed HF patients and whether differences in risk exist between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) patients.

Methods:
Patients with new-onset HF between 2000-2019 were studied. To be included, patients had to have 1-year of follow-up, an ejection fraction (EF) measurement within 30 days of HF diagnosis, and no history of cancer. EF was used to define HFrEF (EF <40%) and HFpEF (EF
>
40%). Multivariable Cox hazard regression was used to evaluate the risk of death and HF hospitalization at 1- and 3-years.

Results:
A total of 21,925 patients were studied with HFrEF (n=7931 [36.2%]) and HFpEF (n=13,994 [63.8%]). HFpEF patients were older (74 vs. 65 years) and more often female (53.7% vs. 33.1%). Prevalent AF was 40.5% (n=8879), being more common in HFpEF compared to HFrEF (65.2% vs. 34.8%). Among AF patients, HFpEF patients were also older (76 vs. 72 years) and more often female (52.7% vs. 30.8%) compared to HFrEF. The presence of AF was associated with an increased risk of HFpEF (OR=1.11, p=0.001). Prevalent AF was associated with an increased risk of death and follow-up HF hospitalization (Table). Death at 1-year and 3-years were similar between the HF groups (Table). However, the risk of HF hospitalization was greater among HFrEF patients (Table). Similar associations persisted when AF patients were propensity matched (Table).

Conclusions:
Among a newly diagnosed HF population, AF was common (40%) and was associated with an increased risk of HFpEF, death, and HF hospitalization. These results provide a rationale for aggressive management of HF and AF patients and the need for a randomized clinical trial to determine optimal therapy by ablation and 4-pillar HF therapy.
Abstract 4135951: Single Nuclei RNA Sequencing Reveals Distinct Cellular Composition of Pericoronary Adipose Tissue
Authors: Regan Jessica , Kwee Lydia , de Calvacamp Caroline , Corey Kristin , Dewan Krish , Gross Ryan , Jain Vaibhav , Gregory Simon , Bowles Dawn , Shah Svati
Published: November 2024

Introduction:
Adipose tissue is a metabolically active organ with local paracrine interactions on adjacent tissues. Pericoronary adipose tissue (PcAT) is an emerging cardiovascular disease (CVD) risk factor and likely has paracrine effects on coronary vasculature that may promote coronary artery disease (CAD) development. PcAT may be functionally and clinically distinct from epicardial adipose tissue (EAT) given its proximity to the coronary artery adventitia. The cellular composition of PcAT and EAT and whether they have unique inflammatory cell signatures and functional expression at a single cell level has not been explored.

Hypothesis:
PcAT will have diverse cellular composition with heightened inflammatory cell content compared to EAT.

Methods:
Visual dissection of paired EAT not adjacent to an epicardial coronary artery and PcAT in direct apposition to an epicardial artery (left anterior descending artery) was performed from a single human heart immediately after explant (prior to heart transplantation). Nuclei were isolated using the Chromium Nuclei Isolation Kit (10x Genomics) with RNAse inhibitor. Cells were counted with a Cellometer K2 and Chromium Next GEM Single Cell libraries were prepared, followed by reverse transcription, PCR and NovaSeq 6000 platform sequencing. Raw sequence reads from single nuclei RNA-seq (snRNA-seq) were processed and after QC filtering, cells were clustered using Seurat. Clusters were annotated using singleR.

Results:
In PcAT and EAT, >7000 cells were successfully extracted with 73755 and 48750 mean snRNA-seq reads per cell, respectively. snRNA-seq cellular composition analysis delineated a heightened inflammatory milieu and distinct cellular composition of human PcAT vs. EAT. A UMAP (Uniform Manifold Approximation and Projection) plot displays higher inflammatory cell infiltrate with a neutrophil predominance and lesser adipocyte composition in PcAT compared with EAT (
Figure 1)
.

Conclusions:
We have generated snRNA-seq data from human PcAT and shown distinct cellular composition compared to EAT. Given the proximity of PcAT to coronary vasculature, these results are supportive of paracrine inflammatory effects and highlight adipose tissue biology in cardiovascular disease. Understanding this biology may identify novel therapeutic targets for CVD.
Abstract 4135975: Anticoagulation versus Antiplatelets in Coronary Artery Ectasia and Acute Coronary Syndrome: A Systematic Review and Meta-analysis
Authors: Hernandez Pastrana Sarai , Doma Mohamed , Fatima Syeda Rubab , Hemdanieh Maya , Kritya Mangesh , Huang Wilbert , Naji Zahra , Lingamsetty Shanmukh sai pavan , Mesadri Gewehr Douglas , Latapi Ruiz Esparza Ximena , Martignoni Felipe , Araiza Diego
Published: November 2024

Introduction:
Coronary artery ectasia (CAE) is a rare but well-recognized anatomical abnormality of the coronary arteries with a prevalence of up to 9% in patients presenting with acute coronary syndrome (ACS). While anticoagulants have been suggested to reduce recurrent events, the optimal antithrombotic therapy in CAE and ACS remains unclear.

Research Question:
What is the comparative effect of anticoagulation therapy versus no anticoagulation in patients with CAE and ACS receiving background antiplatelet therapy?

Goals:
To perform a systematic review and meta-analysis evaluating the efficacy of anticoagulation in preventing major adverse cardiovascular events (MACE) among patients with CAE and ACS.

Methods:
We searched PubMed, Embase, and Cochrane to identify studies comparing the use of anticoagulants versus no use of anticoagulants as part of the antithrombotic therapy in patients presenting CAE and ACS, and reported MACE. Statistical analysis was performed using R version 4.2.2 adopting the Mantel-Haenszel random-effects model. Heterogeneity was assessed using Cochrane's Q statistic and Higgins and Thompson’s I2 statistics. Pooled risk ratios were used to evaluate the effectiveness of anticoagulant therapy in CAE and ACS.

Results:
We included 3 studies, including 1 randomized controlled trial and 2 observational studies, comprising a total of 441 patients, of whom 162 (36.7%) received anticoagulants, including vitamin K antagonists (warfarin and acenocoumarol) or direct oral anticoagulants (rivaroxaban, apixaban, and dabigatran). Time of follow-up ranged from 12 to 52 months, mean age was 57.9 ± 11.4 years, and 388 (87.9%) were male. We found no significant difference in MACE between patients who received anticoagulation and patients who did not (RR 0.64; 95% CI 0.31, 1.32; p=0.22; I2 = 0%). Additionally, there was no difference in the risk of re-infarction (RR 0.71; 95% CI 0.43, 1.18; p=0.19; I2 = 0%). Finally, there was no significant difference in risk of bleeding between both groups (RR 1.41; 95% CI 0.70, 1.85; p=0.19; I2 = 0.59%).

Conclusion:
Our findings suggest that, among patients with CAE and ACS, anticoagulation does not reduce the risk of MACE or re-infarction as compared with no anticoagulation.
Abstract 4136016: Higher aircraft noise exposure associates with worse heart structure and function
Authors: Topriceanu Constantin-Cristian , Gong Xiangpu , Shah Mit , Shiwani Hunain , Eminson Katie , O Atilola Glory , Jephcote Calvin , Adams Kathryn , Blangiardo Marta , Moon James , Hughes Alun , Gulliver John , Rowlands Alex V , Chaturvedi Nishi , O'Regan Declan , Hansell Anna L , Captur Gabriella
Published: November 2024

Introduction:
Aircraft noise is a concern for communities living near airports, but its impact on heart structure and function is unknown.

Methods:
Night-time (L
night
) and weighted 24-hour day (L
den
) aircraft noise levels were provided by the UK Civil Aviation Authority for 2011 (Fig.1). Health data came from UK Biobank (UKB) participants living near four UK major airports (Heathrow, Gatwick, Manchester, and Birmingham) who had cardiovascular magnetic resonance (CMR) imaging starting from 2014 and self-reported no hearing difficulties. Generalized linear models investigated the associations between aircraft noise exposure and CMR metrics (derived using a validated convolutional neural network to ensure consistent image segmentations), after adjustment for demographics, socio-economic, lifestyle, and environmental covariates. Mediation by cardiovascular (CV) risk factors was also explored. Downstream associations between CMR metrics and major adverse cardiac events (MACE) were tested in a separate prospective UKB subcohort (n=26,658) to understand the potential clinical impact of noise-associated heart remodeling.

Results:
Of 3,635 UKB participants included, 3% experienced higher aircraft noise L
night
(≥45decibels) and 8% higher L
den
(≥50decibels). Participants exposed to higher L
night
had 7% [95% confidence interval: 4–10%] higher left ventricular (LV) mass and 4% [2–5%] thicker LV walls with a normal septal:lateral wall thickness ratio (Fig.2 A1). This LV concentric remodeling is relevant since 7% higher LV mass associates with 32% higher odds of MACE. They also had worse LV myocardial dynamics (Fig.2 A2) (e.g., 8% [4–12%] lower global circumferential strain which associates with 37% higher odds of MACE). Overall, a hypothetical individual experiencing the typical CMR abnormalities associated with higher L
night
exposure may have 5-times higher odds of MACE. Body mass index and hypertension appeared to mediate 20-50% of the observed associations. Findings were similar in those exposed to higher L
den
(Fig.2 B1-2). Participants who did not move home during follow-up and were continuously exposed to higher aircraft noise levels had the worst CMR phenotype.

Conclusion:
Higher aircraft noise exposure associates with adverse LV remodeling, potentially due to noise increasing the risk of obesity and hypertension. Findings are consistent with the existing literature on aircraft noise and CV disease, and need to be considered by policymakers and the aviation industry.