bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4137770: Development of a User-Friendly Self-Screening Tool for Assessing Metabolic Syndrome Risk in young adults from economically challenged regions
Authors: Nascimento-Ferreira Marcus , Xavier Jacqueline , Cunha Shirley , Oliveira Tiago , Marin Kliver , De Moraes Augusto Cesar
Published: November 2024

Background:
Metabolic syndrome is a cluster of conditions that increase the risk of heart disease and diabetes. Early identification and management are crucial, particularly in economically challenged regions where access to healthcare may be limited.

Research Questions/Hypothesis:
User-friendly self-report data accurately predict metabolic outcomes.

Aims:
To develop and validate nomograms for individualized estimation of metabolic syndrome risk.

Methods:
Data from 521 college students (60.1% aged 17-20 years; 68.7% female; 28.0% white) were collected in 2022/2023 from two Brazilian cities. These cities are located in the country's poorest states, with Gini indices of 0.56 and 0.43. The potential predictors include demographic and economic variables, school-related factors, behaviors, and body weight. Based on predictors for abdominal obesity identified through multilevel logistic regression, we created a nomogram model. We performed the Hosmer-Lemeshow test to assess model calibration and used a bootstrapping approach (B = 150) for internal validation. To evaluate external validity, we assessed metabolic syndrome in a subset of 375 students. The area under the receiver operating characteristic curve (AUROC), with a threshold of 0.70, was used to evaluate the model's discrimination accuracy.

Results:
We identified 114 (23.0%) college students who were abdominally obese. We found ten variables associated with the primary outcome: age, biological sex, physical education facilities, enrollment in sports competition (during elementary school); grade retention, preferred subject, physical education classes per week; enrollment in sports training (during secondary school); adherence of 24-hour movement behaviors and body weight. The proposed nomogram showed acceptable performance in the AUROC (0.94 [95% CI: 0.92-0.96). The calibration assessment indicated reasonable consistency of our model (p > 0.05). In the internal validation, we observed a decreased predictive capability (AUROC = 0.86).

Conclusion:
The 24h-MESYN risk score offers an effective self-screening tool for college students from diverse racial and ethnic backgrounds in economically challenged regions to assess their risk of developing metabolic syndrome.
Abstract 4137781: Relationship between Race, Predelivery Cardiology Care and Cardiovascular Outcomes in Pre-eclampsia/Eclampsia among a Commercially Insured Population
Authors: Bolakale-Rufai Ikeoluwapo , Knapp Shannon , Khan Sadiya , Tucker Edmonds Brownsyne , Brewer LaPrincess , Mohammed Selma , Johnson Amber , Mazimba Sula , Addison Daniel , Breathett Khadijah
Published: November 2024

Background:
Inequities in Preeclampsia/Eclampsia (PrE/E) persist. It is unknown if the receipt of cardiology care relates to future risk of major adverse cardiovascular events (MACE) in Black and White patients with PrE/E. We sought to determine the cumulative incidence of MACE by race and whether predelivery cardiology care was associated with the hazard of MACE up to 1-year post-delivery for Black and White patients with PrE/E.

Methods:
Using Optum’s Clinformatics® Data Mart Database (CDM), we identified Black and White patients with PrE/E who had a delivery between 2008 to 2019. MACE was defined as the composite of heart failure, acute myocardial infarction, stroke, and death. Cumulative incidence functions were used to compare the incidence of MACE by race. Cox regression models were used to assess the hazard of MACE by cardiology care for Black and White patients.

Results:
Among 29,336 patients (83.4% White, 16.6% Black, mean age of 30.9 years) with PrE/E, 11.2% received cardiology care (10.9% White, 13.0% Black). Black patients had a higher incidence of MACE than White patients at 1-yr post-delivery (2.7% vs 1.4%). After adjusting for age and clinical comorbidities, receipt of cardiology care was associated with lower hazard of MACE for White patients (HR= 0.68, 95%CI: 0.50-0.92 p=0.013) but not Black patients (HR: 1.22, 95% CI: 0.82-1.81; p= 0.328). The interaction effect between race and cardiology care was statistically significant (p=0.013)

Conclusions:
Among a well-insured population of patients with PrE/E, Black patients had a higher cumulative incidence of MACE up to a year post-delivery. However, cardiology care significantly lowered the hazard of MACE for only White women. This observation does not suggest that cardiology care is detrimental to Black individuals but underscores the necessity to investigate why outcomes are disparate among these racial groups.
Abstract 4137805: Loss to Follow-Up Among Adults with Congenital Heart Defects: A Report from Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE)
Authors: Dailey Schwartz Andrew , Shi Caroline , Aldoss Osamah , Fundora Michael , Gaitonde Mansi , Hiremath Gurumurthy , John Anitha , McHugh Kimberly , Raghuveer Geetha , Kochilas Lazaros , Oster Matthew
Published: November 2024

Background:
Many of the 1.4 million adults with congenital heart disease (CHD) are lost to follow up (LTF). We aimed to identify factors associated with LTF and compare to those who remained in care.

Methods:
In the Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE), we performed a cross-sectional survey in 2021-2023 of CHD survivors with a history of intervention at 11 centers in the Pediatric Cardiac Care Consortium, a large US-based registry of CHD procedures. Participants reported their cardiac history, general health, education, income, health insurance, healthcare utilization, and marital status. LTF was defined as having seen a cardiologist three or more years ago.

Results:
Among the 3109 respondents with CHD (median age 33) there were 1157 (37%) LTF and 1952 (63%) in care. Age, sex, marital status, and household income were not risk factors for LTF; but lack of health insurance, lower severity of CHD, and increasing time since last heart surgery were. Notably, respondents who reported being told in adolescence about the lifelong need for a cardiologist were almost three times as likely to report being in care (79% vs 28%, p<0.0001). Among women, most reported no LTF if counseled about concerns with pregnancy or told to avoid pregnancy. The most common reasons for being LTF for 5 years or more (N=857) included feeling well (60%), not thinking there was a need for lifelong care (49%), and a doctor told them they no longer needed to see a cardiologist (47%). Those LTF were more likely to report excellent or very good general health, physical health, and quality of life than those not LTF. There were no differences in self-assessment of mental health between groups.

Conclusion:
Adults with CHD and LTF were more likely to report less severe heart defects, a younger age at last surgery and a lack of counseling about the need for lifelong care.
Abstract 4137829: Comprehensive Single-Cell Atlas of the Human Lung in Pulmonary Arterial Hypertension
Authors: Hong Jason , Wong Brenda , Brownstein Adam , Graves Tammy , Aldred Micheala , Dai Zhiyu , Yang Xia , Eghbali Mansoureh
Published: November 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a complex cardiopulmonary disease characterized by progressive vascular remodeling. Although various immune and vascular cell populations have been implicated in the pathobiology of PAH, a comprehensive assessment of the various cell types in human PAH lungs is still lacking.

Methods:
Single-nucleus RNA sequencing was performed on lung samples from the Pulmonary Hypertension Breakthrough Initiative using the 10x Genomics Chromium Fixed RNA Profiling workflow. Rigorous quality control measures were implemented, including the detection and removal of ambient RNA using CellBender and doublets using scDblFinder. Data normalization and dimensionality reduction were performed using Seurat, and alignment by sample and sequencing batch was conducted using Harmony. Cells were annotated by mapping onto the Human Lung Cell Atlas using Azimuth. Differential gene expression analysis was conducted using a robust pseudobulk approach with edgeR to limit false positive findings. Gene set enrichment analysis was performed using the Hallmark pathways.

Results:
Lung samples from a total of 67 individuals were profiled, including 42 PAH and 25 age- and sex-matched control lungs. After quality control filtering, over 800,000 cells were captured, with a median of 12,000 cells per sample. Clustering uncovered over 30 cell types, representing endothelial, stromal, immune, and epithelial lineages of the lung. A median of 2,500 transcripts and 1,500 genes were detected per cell. Differentially expressed genes between PAH and control were detected in all major cell populations (FDR < 0.05). Comparative analysis across all cell types revealed interferon response in monocyte subpopulations and endothelial-to-mesenchymal transition in endothelial subpopulations as top upregulated pathways.

Conclusion:
Comprehensive single-nucleus profiling of human lungs in PAH revealed extensive gene and pathway dysregulation across diverse cell types. This rich dataset provides a valuable resource for the research community, offering opportunities to advance and refine our understanding of the cellular pathobiology of PAH.
Abstract 4137836: Association of AHA PREVENT Risk Score with Cardiovascular Mortality Across Social Determinants of Health: A Nationwide Retrospective Cohort Study
Authors: Stephens Daniel , Parcha Vibhu , McClure Trevor , Cobbs Parker , Nordberg Megan , Clarkson Stephen
Published: November 2024

Introduction/Background:
The AHA PREVENT risk calculator was recently developed to accurately predict the risk of cardiovascular disease (CVD) risk, including incident heart failure, stroke, and coronary heart disease. However, the risk prediction of this tool for CVD mortality overall and among groups with increasing social determinants of health (SDOH) burden in a multi-ethnic nationally representative cohort of American adults is unclear.

Methods:
This retrospective study included adult NHANES participants (age > 30 years) from 1998-2018 cycles without known CVD. Individuals without data for risk estimation were excluded. AHA PREVENT risk was scored from 0 to 100. Multivariable-adjusted Cox regression models were used to estimate the risk of CVD mortality, accounting for 7 SDOH measures (employment, family income, food security, health access, health insurance, housing instability, and being married or living with partner). Population was stratified based on cumulative SDOH burden (1, 2, 3, 4, 5, > 5 unfavorable SDOH markers). Model discrimination was assessed using C-statistics in these groups.

Results:
Among 19,887 participants (median age 53 years, 49% Female, 54% White, 19% Black), a 1% increase in AHA PREVENT Risk score calculation was associated with 13% higher risk of CVD mortality (HR
adj
1.13, 95% CI: 1.12-1.14) with C-statistic of 0.91. While AHA PREVENT Risk score was predictive of CVD mortality across the SDOH burden strata, there was a decline in C-statistic from 0.91 among those without any unfavorable SDOH to 0.81 among those with > 5 unfavorable SDOH measures.

Conclusion:
The AHA PREVENT Risk score is predictive of CVD mortality even when accounting for SDOH measures. However, the risk discrimination decreases among individuals with a higher SDOH burden. Further investigation is needed to identify means to improve CVD risk prediction among disadvantaged people with high unfavorable SDOH burden.
Abstract 4137846: Smooth muscle expression of RNA editing enzyme
ADAR1
controls vascular integrity and progression of atherosclerosis
Authors: Weldy Chad , Li Qin , Monteiro Joao , Guo Hongchao , Galls Drew , Gu Wenduo , Cheng Paul , Ramste Markus , Li Daniel , Palmisano Brian , Sharma Disha , Worssam Matthew , Zhao Quanyi , Bhate Amruta , Kundu Ramendra , Nguyen Trieu , Li Jin Billy , Quertermous Thomas
Published: November 2024

Mapping the genomic architecture of complex disease has been predicated on the understanding that genetic variants influence disease risk through modifying gene expression. However, recent discoveries have revealed that a significant burden of disease heritability in common autoinflammatory disorders and coronary artery disease is mediated through genetic variation modifying post-transcriptional modification of RNA through adenosine-to-inosine (A-to-I) RNA editing. This common RNA modification is catalyzed by ADAR enzymes, where ADAR1 edits specific immunogenic double stranded RNA (dsRNA) to prevent activation of the double strand RNA (dsRNA) sensor MDA5 (
IFIH1
) and stimulation of an interferon stimulated gene (ISG) response. Multiple lines of human genetic data indicate impaired RNA editing and increased dsRNA sensing to be an important mechanism of coronary artery disease (CAD) risk. Here, we provide a crucial link between observations in human genetics and mechanistic cell biology leading to progression of CAD. Through analysis of human atherosclerotic plaque, we implicate the vascular smooth muscle cell (SMC) to have a unique requirement for RNA editing, and that ISG induction occurs in SMC phenotypic modulation, implicating MDA5 activation. Through culture of human coronary artery SMCs, generation of a conditional SMC specific
Adar1
deletion mouse model on a pro-atherosclerosis background, and with incorporation of single cell RNA sequencing cellular profiling, we further show that Adar1 controls SMC phenotypic state, is required to maintain vascular integrity, and controls progression of atherosclerosis and vascular calcification. Our data implicates MDA5 activation to occur in SMC phenotypic modulation and accelerates formation of chondromyocytes in a distinct cellular lineage trajectory — indicating a cell type and context specific requirement of RNA editing. Through this work, we describe a fundamental new mechanism of CAD, where RNA editing and sensing of dsRNA in a cell type and context specific mechanism mediates disease progression, bridging our understanding of human genetics and disease causality.
Abstract 4137855: Hybrid Coronary Revascularization versus Traditional Coronary Artery Bypass Grafting for Left Main Disease
Authors: Hebbo Elsa , Barker Madeleine , Gold Daniel , Elhage Hassan Malika , Sawan Mariem , Halkos Michael , Jaber Wissam , Sandesara Pratik
Published: November 2024

Background:
The current guideline-recommended intervention for left main (LM) disease is coronary artery bypass grafting (CABG). Hybrid coronary revascularization (HCR) combines robotic coronary artery bypass and percutaneous coronary intervention (PCI) and offers a less invasive approach for patients with LM and multivessel coronary artery disease. We aim to compare clinical outcomes at 30 days, 6 months and 1 year between HCR and CABG in patients with LM disease.

Methods:
We retrospectively screened 761 patients who underwent bypass for LM disease between 2019 and 2023 at a single institution. A total of 118 patients who underwent either HCR (n=59) or CABG (n=59) were included after propensity matching for baseline characteristics. The primary endpoint was major adverse cardiovascular events (MACE), defined as death, myocardial infarction, repeat revascularization and stroke, at 30 days, 6 months and 1 year, which was assessed using chi-squared tests. Secondary outcomes are individual components of MACE at 30 days, 6 months and 1 year. Kaplan-Meier curves were used to visualize the difference in 1-year cumulative MACE-free survival across groups coupled with a log-rank test.

Results:
The mean age was 68.93±11 years for HCR patients and 68.41±10.11 years for CABG patients (p=0.394). SYNTAX score was high (> 33) for 49.1% of HCR patients and 67.3% of CABG patients (p=0.15). Hospital length of stay was shorter for HCR compared to CABG (4.07 ± 1.21 days vs. 7.58 ± 7.71 days, p<0.001). MACE events were significantly lower in the HCR group at 30 days (0% vs 10.2%; p=0.01), 6 months (0% vs 17%; p=0.002) and 1 year (2.4% vs 20.5%; p=0.01). The cumulative MACE-free survival at 1 year was significantly higher in the HCR group (p=0.007). There were no significant differences in secondary outcomes at any time point with the exception of lower repeat revascularization at 6 months in the HCR group (0% vs 10.9%; p=0.02).

Conclusion:
This retrospective study demonstrates that HCR is a viable alternative to CABG for LM disease. While randomized clinical trial data is still needed, this less invasive approach is a promising treatment strategy for patients with high surgical risk.
Abstract 4137870: Nasal Etripamil Spray efficacy for Acute Paroxysmal Supraventricular Tachycardia: A Systematic Review, Meta-Analysis and Trial Sequential Analysis.
Authors: Queiroz Ivo , Barbosa Lucas , Defante Maria Luiza Rodrigues , X. Mendes Beatriz , Antunes Vanio do Livramento Junior , Romeiro Pedro , Mazetto Roberto , Silva Catarina , Bulhoes Elisio , Guida Camila
Published: November 2024

Background:
Acute paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia. Etripamil, a novel calcium channel blocker via nasal spray, has shown promise for PSVT management. This meta-analysis and trial sequential analysis (TSA) evaluates the efficacy and safety of nasal Etripamil for treating PSVT.

Methods:
We systematically searched Pubmed, Embase, and Cochrane databases for studies assessing the efficacy and safety of Etripamil for PSVT. The main outcome was conversion to sinus rhythm(CSR) within 15 minutes. Secondary outcomes included adverse events(AE). Meta-analysis was performed using random-effects models, and TSA was employed to assess the robustness of the evidence and required information size.

Results:
Three randomized controlled trials (RCTs) and two extensive trials involving 1,652 participants were analyzed. Nasal Etripamil significantly increased the CSR within 15 minutes compared to placebo (RR 1.87 95% CI; 1.39-2.52, p <0.001; Figure A). Outcome TSA suggested a low risk of type 1 error; therefore, this result may be conclusive (Figure B). For the AEs both a pairwise and single-arm meta-analysis of studies was performed with 1 AEs being statistically significant in the single-arm plot, Nasal Discomfort (22.11 95% CI; 16.02-29.70 events per 100 observations, p <0.01 Figure C). In the pairwise, the overall was statistically significant and it favored placebo (RR 3.93, 95% CI; 2.46-6.27, p <0.001 Figure D).

Conclusion:
Nasal Etripamil is effective and safe for the treatment of acute PSVT, offering a non-invasive alternative to traditional therapies. Larger-scale RCTs are warranted to confirm these findings and explore long-term outcomes.
Abstract 4137891: Treated HIV infection is not associated with carotid vascular inflammation or plaque progression as assessed by dynamic contrast magnetic resonance imaging
Authors: Shakil Saate , Chen Daniel , Isquith Daniel , Sapp Jamie , Pommier Isabella , Chu Baocheng , Guo Yin , Canton Gador , Balu Niranjan , Yuan Chun , Hatsukami Thomas , Maynard Charles , Zhao Xue-qiao , Kim Francis
Published: November 2024

Background:
Inflammation and immune dysregulation are thought to drive residual cardiovascular disease risk among persons living with HIV (PLWH) despite effective viral suppression with antiretroviral therapy (ART).

Question:
We investigated differences in carotid vascular inflammation and atherosclerosis in a longitudinal cohort of virally suppressed PLWH (n = 50; on stable ART with CD4 >250 cells/mm
3
, viral load <200 copies/mL for >6 months) and HIV-uninfected controls (n = 51) matched for age, sex, hypertension, diabetes, smoking, hyperlipidemia, and family history of premature coronary artery disease.

Methods&Results:
Participants were
>
40 years old at enrollment, 8% female, and had a high prevalence of cardiovascular risk factors (
Table 1
). Measures of carotid inflammation and capillary permeability (

K
trans

), neovascularization (

V
p

), and wall thickness were assessed at baseline, 1 year, and change over 1 year by dynamic contrast-enhanced magnetic resonance imaging. Both PLWH and controls demonstrated a reduction in systolic and diastolic blood pressures and total cholesterol over 1 year; however, the difference was not significant by HIV status. PLWH had a significant reduction in triglycerides compared with controls (-48.8 mg/dL vs 12.8 mg/dL; p = 0.026). HIV was not associated with baseline, follow-up, or change in markers of systemic inflammation assessed by plasma cytokines (C-reactive protein, interleukin-6, interleukin-1ß), nor vascular inflammation or plaque as assessed by

K
trans

,

V
p

, carotid wall thickness, or percent wall volume (
Tables 2
&
3
).

Conclusions:
In contrast to other studies of chronically treated and virally suppressed PLWH, HIV infection was not associated with carotid inflammation or plaque.
Abstract 4137895: Serum High-density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events after Stent Implantation in Patients with Stable Angina Pectoris
Authors: Kashima Yumi , Nakagawa Masashi , Kure Yusuke , Matsuo Masanori , Sakamoto Yuya , Shimeno Kenji , Matsumura Yoshiki , Matsumoto Ryo , Abe Yukio , Naruko Takahiko
Published: November 2024

Background:
Poor clinical outcomes for patients undergoing hemodialysis (HD) after drug-eluting stent (DES) implantation have been reported. High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease, and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. The aim of this study was to investigate the relationship between plasma MPO and serum PON-1 levels after implantation of DES in patients with stable angina pectoris (SAP) with and without HD.

Methods:
Serum PON-1 concentrations and PON-arylesterase activity were measured in 183 patients with SAP after DES implantation (HD group, n=37; non-HD group, n=146) with a sandwich ELISA method. Cardiovascular events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction, cerebral infarction and other non-fatal events including unstable angina pectoris or coronary revascularization.

Results:
Serum PON-1 concentrations and PON-arylesterase activity were significantly lower in the HD group than in the non-HD group (PON-1 concentrations, P<0.0001; PON-arylesterase activity, P<0.0001). In addition, plasma MPO in patients undergoing HD were significantly higher than in patients not undergoing HD (P<0.0001). Moreover, plasma MPO showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity (concentration: R= -0.24, P=0.0013; arylesterase-activity: R=-0.24, P=0.0014). Cardiovascular event rates were significantly higher in the HD group than in the non-HD group (67.6% vs. 43.8%, P<0.01). Kaplan-Meier survival analysis showed that the low-PON-1 group (<58.0 mg/mL, median) had a significantly worse outcome than the high-PON-1 group (
P
=0.013). Multivariate analysis showed that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.93; 95% confidence interval, 1.10 to 3.40,
P
=0.024).

Conclusions:
These findings demonstrate that plasma MPO have a significant inverse correlation with PON-1 in patients undergoing HD and suggest that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression and destabilization of human coronary atherosclerotic lesions in patients with SAP who undergo HD following DES implantation.
Abstract 4137900: Differences in Echocardiographic Findings Between Epicardial Vasospastic Angina Phenotypes Affect Response to Medical Therapy
Authors: Shibata Keita , Ikeda Naoko , furuya takahiro , Sato Chisato , Nishikura Tenjin , Wakabayashi Kohei , Tanno Kaoru
Published: November 2024

Background:
The phenotype of epicardial vasospasm is classified as focal or diffuse. However, its echocardiographic characteristics are unknown. Furthermore, patients with diffuse vasospasms have poorer responses to medical therapy than patients with focal spasms because of more extensive areas of endothelial dysfunction. We hypothesized that there are differences in echocardiographic findings between the patients with diffuse and focal vasospasm, which might affect response to medical therapy.

Methods:
The present study was a single-center retrospective cohort study that included 77 consecutive patients diagnosed with vasospastic angina (VSA) undergoing coronary spasm provocation test using acetylcholine from 2014 to 2024. The patients with a history of cardiomyopathy and significant obstructive coronary artery disease were excluded. Diffuse VSA was defined as vasospasm in 2≧ adjacent coronary segments, and focal VSA was defined as vasospasm in one isolated coronary segment. Patients were divided into diffuse VSA group (n=45) and focal VSA group (n=32). Left ventricular function was assessed using 2D speckle tracking echocardiography. After the diagnosis of VSA and the administration of medical treatment for VSA, an emergency room (ER) visit with a chest pain attack was recorded as the event of poor response to medical therapy.

Results:
There was no significant difference in the follow-up period and baseline characteristics (Table). LVEF was similar between the two groups (63.1±5.8% vs. 62.9±7.6%,
p
=0.87). In contrast, the left ventricular global longitudinal strain (LV-GLS) was significantly lower in the diffuse VSA group than in the focal VSA group (17.4±2.8% vs. 20.2±2.4%
p
<0.001). There is no difference in medical therapy for VSA (Table). Observation of ER visits with a chest was more frequent in the diffuse VSA group [diffuse VSA group (20/45, 44.4%) vs. focal VSA group (3/29, 9.3%),
p
<0.001]. Kaplan-Meier curves showed that the diffuse VSA group had a higher cumulative rate of ER visits with a chest pain attack (Log-rank
p
<0.001). On multivariable Cox regression analysis, diffuse VSA (HR=4.2, 95% CI: 1.10-16.06,
p
=0.030) and low LV-GLS (HR =1.16, 95%CI: 1.01-1.34,
p
=0.031) were an independent risk factor for poor response to medical therapy.

Conclusion:
Patients with diffuse VSA had lower LV-GLS than patients with focal VSA. Moreover, diffuse VSA and lower LV-GLS were associated with poor response to medical therapy after diagnosis of VSA.
Abstract 4137902: Layer-specific Gene Expression Associated with Intima Hyperplasia in Arterio-venous Fistula
Authors: He Yong , Hu Qiongyao , Cai Guoshuai , Berceli Scott
Published: November 2024

Background:
The mechanism of hemodialysis arteriovenous fistula (AVF) vein intima hyperplasia (IH) may be specific to its layers (intima, media, and adventitia) but is poorly understood. To address this gap, we studied layer-specific transcriptomics related to IH in veins of two-stage AVF creation.

Methods:
Vein samples were collected during the initial creation of brachial artery-basilic vein AVF (1st stage) and vein transposition surgery 6 weeks later (2nd stage) and were sectioned in OCT. Tissues from each layer were separately collected by laser microdissection. Following Takara’s SMARTer Stranded Total RNA-Seq Pico Input protocol, libraries were constructed and sequenced in NovaSeq. The sequencing reads were processed by fastp, aligned to genome GENCODE 45 by STAR and gene-level counts were estimated by RSEM. Intima was assessed by histology. Layer-specific differentially expressed genes in pre-access or AVF veins associated with IH in AVF veins were detected by edgeR and further identified the enriched pathways and predicted functions using Qiagen IPA.

Results:
44 veins were collected from 22 patients. 13,522 protein-coding genes that had a raw count of at least 10 in more than 70% of samples were included in analysis. 10 AVF veins had severe IH. Among the layers of pre-access vein, intima had the largest number of genes significantly associated with severe AVF IH and most or all these genes were upregulated (35/4, 26/2, 5/0 for the number of up/downregulated genes in intima, media, and adventitia of pre-access vein, respectively); cellular movement and immune cell trafficking were more strongly activated in intima of pre-access vein with severe AVF IH. No genes in any layer of AVF vein were significantly associated with severe AVF IH. From 1
st
to 2
nd
stage, more genes significantly changed expression in intima with severe AVF IH than intima without severe AVF IH (197/150 vs 144/93 for up/downregulated genes), while media (20/4 vs 149/31) and adventitia (99/27 vs 196/70) were the opposite; TGFB1, angiotensinogen, and TNF were more strongly activated in intima, while cell survival and migration were diminished in media and adventitia with severe AVF IH, respectively.

Conclusion:
Intima of pre-access vein has more genes associated with severe AVF IH. The layer-specific gene expression changes during AVF development and predicted functions are associated with AVF IH. These data can be used to develop layer-specific therapies to reduce AVF IH.
Abstract 4137917: Eligibility and Preventable CVD Events in US Adults with Cardiovascular Disease and Overweight or Obesity: Projections from the SELECT Trial
Authors: YAN Hongmei , Karthikeyan Hridhay , FAN WENJUN , Yang Qin , Wong Nathan
Published: November 2024

Background:
The Trial to Evaluate Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT) showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with preexisting CVD and overweight or obesity.

Purpose:
To estimate the number of US adults with CVD and overweight or obesity that may be eligible for semaglutide based on SELECT eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SELECT.

Methods:
We included US adults from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 who had eligibility criteria from SELECT. This included patients aged
>
45 years who had preexisting CVD and a BMI of
>
27kg/m
2
but no history of diabetes. Using NHANES sample weighting, we estimated the number of SELECT-eligible US adults and primary composite and secondary CVD endpoints that would occur based on SELECT treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on mean 3.3-year follow-up).

Results:
Among 8783 (projected to 77.9 million [M]) adults with overweight or obesity, we estimated 493 (4.1 million) (5.61%) to fit SELECT eligibility criteria. Compared to SELECT trial participants, our sample had a higher proportion of Black participants and was older with higher levels of diastolic blood pressure, total, LDL and HDL-cholesterol, and lower BMI, HbA1c, eGFR and triglycerides. Prior myocardial infarction was less common, but stroke was more common in our sample. From SELECT semaglutide and placebo primary composite CVD event rates of 6.5% and 8.0%, respectively, we estimated 79949 and 98399 CVD events would occur annually, the difference being 18450 potentially preventable CVD events. Moreover, we similarly estimated 104,549 and 357,928 annual preventable cases of diabetes and pre-diabetes, respectively. The Figure shows the estimated number of primary and secondary CVD outcomes that could be prevented annually.

Conclusion:
Semaglutide may prevent many fatal and non-fatal CVD events, as well as incident cases of diabetes and pre-diabetes if provided to US adults meeting SELECT eligibility criteria. More efforts are needed to educate clinicians and patients on the benefits of semaglutide 2.4mg in those with preexisting CVD and overweight or obesity.
Abstract 4137919: Electrical Storm Caused by Chagasic Cardiomyopathy Successfully Treated with Ventricular Aneurysmectomy
Authors: Munoz-Moreno Juan Manuel , Lobato-Jeri Carlos Jhonatan , Requena Armas Carlos , Becerra-Gonzales Victor , Mendoza Cesar
Published: November 2024

Introduction:
Chronic Chagasic cardiomyopathy (CCC) is a serious complication of Chagas disease that can manifest as LV dysfunction, ventricular aneurysms, and ventricular arrhythmias. Management of the electrical storm in CCC is challenging, especially when it is refractory to catheter ablation.

Case Presentation:
A 59-year-old woman from southern Peru presented to the ED with palpitations and dyspnea for 1 week. Physical exam was normal. ECG showed Q waves in III and AVF leads. TTE revealed an LVEF of 45% with an inferolateral LV aneurysm. Coronary angiography showed no lesions. CCC was suspected and serology was ordered, which was positive for
T. cruzi
. Cardiac MRI confirmed the presence of a 32x22mm basal inferolateral LV aneurysm. During hospitalization, she experienced 4 episodes of unstable monomorphic ventricular tachycardia (VT) within 24 hours, requiring defibrillation with 200J, vasopressor support, and invasive mechanical ventilation. The diagnosis of electrical storm secondary to CCC was proposed, for which amiodarone infusion was started until complete impregnation was achieved. Additionally, support was provided with IABP and specific antiparasitic treatment with benznidazole. Electrophysiology determined that the probable focus of the VT was situated at the level of the LV aneurysm. Therefore, ablation with endocardial-epicardial mapping was performed. However, the patient continued to experience recurrent episodes of VT. Consequently, in a multidisciplinary discussion, it was decided to perform a ventricular aneurysmectomy, which was successful. The patient's clinical progress was favorable, with initiation of GDMT and placement of a single-chamber ICD for secondary prevention. After one year of outpatient follow-up, the patient remains free of VT recurrences.
Conclusion:
Ventricular aneurysmectomy is a successful management approach for patients with CCC who present with electrical storm refractory to antiarrhythmic drugs and catheter ablation, and whose VT is believed to originate from the aneurysm. The diagnosis of CCC is highly arrhythmogenic and should be suspected at an early stage, given the patient's demographics and the presence of LV aneurysm in the absence of coronary artery disease.
Abstract 4137922: Cardiovascular Prognosis of Statin Users Developing Diabetes in Secondary Prevention:
A Prospective Multicenter Study
Authors: Zhang Yiwen , Li Pengfei , Ji Hongwei
Published: November 2024

Background:
In primary prevention, statin use with new-onset diabetes mellitus (DM) was associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. In high-risk and secondary prevention settings, the cardiovascular prognosis of statin users progressing to new-onset DM remains unclear.

Methods:
We collected data from inpatients with or without baseline ASCVD from four medical centers affiliated to Qingdao University. Patients were categorized into 4 phenotypes: (1) statin non-users without diabetes; (2) statin users with incident diabetes; (3) statin users with pre-existing diabetes; and (4) statin users without diabetes. The primary outcome was ASCVD events. The stratified Cox proportional hazard model was used to investigate the association between the four distinct phenotypes and the risk of ASCVD.

Results:
Among 12,800 high-risk patients, over a median follow-up of 118 days (interquartile range, 48-379 days), 1447 ASCVD events were documented. Compared with statin non-users without diabetes, statin users without diabetes (hazard ratio [95% confidence interval], 0.77 [0.65, 0.91], P=0.001) and statin users with pre-existing diabetes (0.80 [0.66, 0.99], P=0.035) were associated with lower risk of ASCVD, whereas statin users with new-onset diabetes were not (0.91 [0.70, 1.19], P=0.50), overall P for trend =0.013.(
Figure 1
) In patients with baseline ASCVD (i.e., secondary prevention settings), we observed similar findings (
Figure 2
)

Conclusions:
In high-risk patients with pre-existing ASCVD, new-onset diabetes after statin use was likely associated with compromised cardiovascular benefits of statins.
Abstract 4137933: High ABSI is associated with elevated risk of cardiovascular events
Authors: Kajikawa Masato , Maruhashi Tatsuya , kishimoto shinji , Yamaji Takayuki , Harada Takahiro , Nakano Yukiko , Mohamad Yusoff Farina , Higashi Yukihito
Published: November 2024

Background:
A Body Shape Index (ABSI) has been reported to have associations with cardiovascular risk factors. However, there is no information on the association between ABSI and incidence of cardiovascular events.

Methods:
We investigated the associations between ABSI and first major cardiovascular events (death from cardiovascular disease, nonfatal acute coronary syndrome, and nonfatal stroke) in 1857 subjects from the database of Flow-Mediated Dilation Japan registry and from Hiroshima University Vascular Function registry.

Results:
The areas under the curves of ABSI to predict the first major cardiovascular events were 0.672 (95% confidence interval [CI], 0.568-0.761) in men and 0.749 (95% CI, 0.624-0.842) in women. The subjects were divided into two groups based on the cutoff value of ABSI for predicting first major cardiovascular events: a low ABSI group (<0.0822 in men and <0.0814 in women) and a high ABSI group (≥0.0822 in men and ≥0.0814 in women). During a median follow-up period of 41.6 months, 56 subjects died (23 from cardiovascular causes), 16 had nonfatal acute coronary syndrome, and 14 had nonfatal stroke. The Kaplan-Meier curves for first major cardiovascular events were significantly different between the two groups (men, P<0.001; women, P<0.001). Multivariate analysis revealed that high ABSI remained an independent predictor of first major cardiovascular events (men: hazard ratio, 2.33; 95% CI, 1.07 to 5.06; P=0.033; women: hazard ratio, 8.33; 95% CI, 1.06 to 65.49; P=0.044).

Conclusions:
High ABSI is independently associated with incidence of cardiovascular events. ABSI calculation should be performed for evaluation of risk of cardiovascular events.
Abstract 4137942: Comparing Outcomes in Low versus High Activated Partial Thromboplastin Time-guided Anticoagulation Monitoring during Extracorporeal Membrane Oxygenation
Authors: Khoury Fadi , Ma Mariel , Specht Hayley , Chiang I-Hui
Published: November 2024

Introduction:
Systemic anticoagulation in Extracorporeal Membrane Oxygenation (ECMO) aims to reduce the risk of patient and circuit thrombosis, but requires monitoring due to risk of bleeding. Activated partial thromboplastin time (aPTT) is one of many tests utilized for this purpose. However, it lacks validation in ECMO patients and its clinical utility necessitates further analysis.

Aim:
We aim to elucidate associations between low versus high aPTT-guided anticoagulation monitoring and total time, survival, bleeding, and thrombotic events during ECMO.

Methods:
A retrospective review was conducted on 93 patients requiring ECMO at our institution between January 2020 and March 2021. Study inclusion required more than 2 days on ECMO and maintenance on anticoagulation with aPTT targets predominantly greater (>) or less than (<) 60 seconds (s). Final cohort was 74 subjects; 30 subjects with majority aPTT targets <60s composed the control “low” aPTT group and 44 subjects with aPTT targets >60s composed the “high” aPTT group. Primary outcomes were survival to decannulation, survival to discharge, average time on ECMO, and incidence of bleeding and thrombotic events during ECMO. Bleeding and thrombotic events were classified into subtypes and incidence of each was recorded. Statistical analyses were performed with Fisher’s exact, Pearson’s chi-square, and Student’s t-tests with an alpha level of .05 on IBM SPSS software.

Results:
The high group required a longer average time on ECMO (29.5 days versus 14.3 days; p = .002; 95% CI [5.5; 24.7]). Chi-square tests did not show an association between the low versus high groups and survival to decannulation (22/30 and 35/44; p = .533), survival to hospital discharge (17/30 and 30/44; p = .312), or overall incidence of bleeding (18/30 and 20/44; p = .219) and thrombotic events (7/30 and 14/44; p = .427). Regarding subtypes of events, Fisher’s exact test showed an association between aPTT target >60s and severe epistaxis (1/30 in the low and 9/44 in the high group; two-tailed p = .042). Though not significant, a greater incidence of oxygenator failure and circuit thrombosis was recorded in the high group.

Conclusions:
Our findings did not establish a relationship between aPTT target <60s or >60s and survival, bleeding, or thrombotic events. However, aPTT target >60s was associated with longer average ECMO time and severe epistaxis. Further investigation of aPTT-guided anticoagulation monitoring in ECMO patients is needed.
Abstract 4137989: Notched P-wave by digital ECG analysis was associated with new-onset atrial fibrillation onset and ischemic stroke
Authors: Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi
Published: November 2024

Background:
A bimodal P wave in lead II reflects left atrial remodeling and is described as a notched P wave. A notched P wave is usually defined as a dip over the smallest unit of electrocardiography (ECG) recording paper, 40 ms, but automated analysis of ECGs has shown that even a notch of 20 ms is associated with cardiovascular events. A notched P wave is also known to predict atrial fibrillation (AF) after catheter ablation. However, the relationship between automatically assessed notched P waves and new-onset AF and ischemic stroke in patients without documented AF has not been clarified.

Hypothesis:
A notched P-wave by digital ECG analysis was associated with both new-onset AF and ischemic stroke.

Methods:
We enrolled 4,216 subjects from the Cardiovascular Prognostic Coupling Study in Japan (Coupling Registry) who had one or more cardiovascular risk factors. Twelve-lead electrocardiography was conducted, and the peak-to-peak distance in the M shape was calculated automatically using a 12-lead ECG analysis system. We compared two definitions: P-waves defined as “notched” at the the peak-to-peak (“M shape”) distance in lead II of ≥20 ms or ≥40 ms. New-onset AF was confirmed through routine medical care as well as annual ECGs. We defined the primary endpoint as new-onset AF and the secondary endpoint as ischemic stroke.

Results:
The mean follow-up period was 53 ± 17 months, during which 17 AF cases developed. When a notched P-wave was defined as ≥20 ms (n = 319), it was a significant predictor of both new-onset AF (hazard ratio [HR] 2.91, 95% confidence interval [CI] 1.41–6.01, p=0.004) and ischemic stroke (HR 3.02, 95% CI 1.56–5.83, P=0.001). A notched P-wave defined as ≥40 ms (n = 63) was also a predictor of new-onset AF (HR 4.57; 95% CI:1.42–14.71, p = 0.011) and ischemic stroke (HR 3.84, 95% CI 1.20–12.29, P=0.024).

Conclusions:
A notched P-wave by digital ECG analysis was associated with ischemic stroke as well as the new-onset AF.
Abstract 4137991: Association of the 2022 AHA/ACC/HFSA Heart Failure Staging and Cardiovascular and Kidney Outcomes in Patients with Diabetes and Kidney Disease: A Secondary Analysis of the SCORED Trial
Authors: Odutayo Ayodele , Bhatt Deepak , Sridhar Vikas , Szarek Michael , Davies Michael , Banks Phillip , Girard Manon , Pitt Bertram , Steg Philippe , Cherney David
Published: November 2024

Introduction:
The 2022 AHA/ACC/HFSA heart failure (HF) classification newly incorporates cardiac biomarkers to identify patients at risk of HF.

Research Question:
Given shared risk factors between HF and other cardiorenal events, the HF stages may also guide prognosis and management of cardiovascular (CV) and kidney-related events beyond HF.

Aims:
Examine the association of HF stage with CV and kidney events.

Methods:
SCORED was a randomized trial in diabetes with kidney disease comparing sotagliflozin (sota) v. placebo on CV death, hospitalizations for HF, and urgent HF visits. SCORED participants were grouped by HF stage
post hoc
. Stage A: No HF, normal cardiac biomarkers (NT-proBNP; <125 pg/mL, hs-cTnT; <14 ng/L) and normal cardiac structure/function by echocardiography. Stage B (pre-HF): No HF but elevated NTproBNP, hsTNT or abnormal echocardiography. Stage C/D: symptomatic HF. Endpoints of interest included the primary composite endpoint (CV death and HF-related events), major adverse CV events (MACE), and kidney-related composites (See Figure caption). Using Cox regression, we examined the association between HF stage and these endpoints, and whether the effect of sota v. placebo varied by HF stage.

Results:
There were 741 patients in stage A, 6560 in stage B (pre-HF) and 3283 in stage C/D (established HF). The mean NTproBNP and hs-cTnT increased with HF stage. Stepwise increases in HF stage were associated with a 2-4 fold higher incidence of the primary, MACE and kidney endpoints in the placebo group, although the incidence of the kidney-specific composite was similar in stage B and C/D (Figure). The relative risk reduction with sota v. placebo for all endpoints was similar irrespective of HF stage (p-interaction>0.05), with higher absolute benefit in each HF stage (Figure). The absolute benefit for the kidney-specific endpoint was comparable for stage B and C/D.

Conclusions:
Increasing HF stage is associated with higher risk of HF, MACE, and kidney events, but the risk of kidney events is similar in stage B (pre-HF) and stage C/D (established HF). Sota has similar relative benefits for all endpoints, irrespective of HF stage, with a corresponding increase in absolute benefits at higher stages.
Voices of Desolation
Authors: Košťálová Petra
Published: November 2024

The paper deals with the phenomenon of the so-called Great Flight, which could be (within the context of Ottoman history) considered equivalent of Thirty Years’ War and its impacts in Central-Europe and elsewhere. Armenian primary sources depict this time generally as “bitter times of sorrow”, making references on forced deportations of urban or rural population (surgun), climate changes, crop failures, epidemics, raids of djelâli or levend rebels, war campaigns and scorched earth, famines and others. To explain the phenomenon of Armenian identity strategies during so turbulent 17th century helps to understand better later development, as well as National Revival period, while many contemporary topoi, such as the lamentation over the lost homeland and the emphasized motif of exile, remained valid until the mid-19th century only to be further modified and re-actualized.
On the Legal System of the First Republic of Armenia (1918–1920)
Authors: Minasyan Edik
Published: November 2024

This article examines the development of the judicial and legal systems in the First Republic of Armenia (1918–1920), highlighting key reforms and challenges. It explores the establishment of various courts, including conciliation, district, and appellate courts, as well as the introduction of a jury court and notarial activities. Despite progressive reforms aimed at democratizing the legal system, such as the creation of jury courts and the regulation of investigatory bodies, widespread malfeasance plagued state administration. Efforts to combat corruption through the establishment of the Extraordinary Investigative Commission and Extraordinary Court proved ineffective, leading to their abolition in 1920. The article also discusses the failure to adopt a constitution, largely due to the republic’s short-lived existence and unresolved political crises. This research draws on primary sources including materials from the National Archives of the Republic of Armenia, parliamentary and government session minutes from 1918–1920, official records, statistical data, periodicals, and contemporary writings.