bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4142564: A Body Shape Index at Age 25-64 Predicts Mortality and CHD Hospitalization
Authors: Shafran Itamar , Krakauer Nir , Krakauer Jesse , Cohen Gali , Gerber Yariv
Published: November 2024

Introduction:
Obesity is a known risk factor for cardiovascular disease (CVD) morbidity and mortality. A body shape index (ABSI) is a waist circumference (WC) measure of abdominal obesity independent of body mass index (BMI) that has been shown to predict mortality and numerous clinical outcomes.

Aims:
To study the predictive value of ABSI in conjunction with BMI for all-cause mortality and coronary heart disease (CHD) hospitalization among adult participants.

Methods:
Participants (n=2,225) were drawn from the First Israeli National Health and Nutrition Survey (1999-2001), constituting adults aged 25-64. Baseline anthropometrics, including weight, height, and WC, were measured and expressed as their allometric indices: BMI (weight/height
2
) and ABSI [WC/(BMI
2/3
*height
1/2
)]. Follow-up lasted through 2021 for mortality and 2022 for hospitalizations. Cox regressions assessed the adjusted risk of all-cause mortality and CHD hospitalization.

Results:
The baseline mean [SD] age was 43 [11] years, and 50% were women. The correlation between BMI and WC was 0.78, and 0.02 for BMI and ABSI. Over a median follow-up of 21 years, 247 (11.1%) deaths occurred. The multivariable-adjusted hazard ratios (HRs) for mortality per 1 SD increase in BMI and ABSI were 1.11 (95% CI: 0.97; 1.27) and 1.55 (95% CI: 1.33; 1.79), respectively (Table). ABSI exhibited a significant association with mortality risk across all standard BMI categories; adjusted for demographics and classic CVD risk factors, the HRs (95% CIs) per 1 SD increase in ABSI were 1.38 (1.01; 1.88) for individuals with a BMI of 18.5-24.9, 1.70 (1.34; 2.16) for BMI 25.0-29.9, and 1.46 (1.13; 1.87) for BMI ≥30.0. Among CVD-free participants at baseline (n=2,146), 267 (12.4%) were hospitalized for CHD during follow-up. The latter had higher ABSI (0.082 vs. 0.078, P<.001) and BMI (28.1 vs. 26.7, P<.001) than individuals who remained free of CHD. An increase in the adjusted HR was seen for both ABSI [1.34 (95% CI: 1.15; 1.55)] and BMI [1.16 (95% CI: 1.01; 1.33)] (Table).

Conclusion:
In a 20-year prospective study of a middle-aged cohort, baseline ABSI was a stronger predictor of mortality than BMI and predicted CHD hospitalization independently of BMI.
Abstract 4142565: Dysfunction of left atrial physiology in patients with pAF despite return to sinus rhythm
Authors: Feseha Simon , Bibby Dwight , Fang Qizhi , Namjou Armeen , Hang Sachiyo , Olgin Jeffrey , Schiller Nelson
Published: November 2024

Background:
Knowledge of physiologic and anatomic abnormalities that attend the spectrum of atrial fibrillation (AF) is incomplete. Left atrial physiology in patients who have developed atrial fibrillation and have converted to sinus rhythm may be a productive focus for exploration.

Hypothesis:
We hypothesize that left atrial function is altered in patients with a history of paroxysmal AF despite conversion to sinus rhythm and may precede development of AF.

Methods:
33 patients with paroxysmal atrial fibrillation (pAF group) and 40 healthy age matched patients (control group) underwent echocardiography while in sinus rhythm. 28 patients with risk factors for AF (risk group) were compared to control.

Results:
Table 1 shows baseline characteristics of age matched control and pAF groups, with mean age of 60 and 62. Of the pAF group, 58% had a history of hypertension and trended towards obesity (Table 1, p<0.001). Left atrial end systolic volume index (LAESVI) and left atrial end diastolic volume index (LAEDVI) was increased in pAF (36 and 19) compared to controls (28 and 11) (Table 2, p<0.001). Emptying fraction was diminished in pAF group when compared to controls with 46% and 59% (Figure 3, p<0.001). LA global longitudinal strain is diminished in pAF at -29% compared to controls at -33% (Table 2, p=0.014). Emptying fraction was diminished in risk group at 53% compared to control group 59% (Figure 1, p=0.007).

Conclusion:
The left atrium remains significantly altered in both its physiology and anatomy in atrial fibrillation despite conversion to sinus rhythm, LA volumes are increased throughout the cardiac cycle and LA contractile performance (strain) is reduced. Left atrial abnormalities precede development of AF in risk group.
Abstract 4142574: Impaired Autophagy Augments Necroptosis Signaling in the Diabetic Kidney Following Ischemia/Reperfusion.
Authors: TAKAHASHI REO , Saga Yukika , Hosoda Ryusuke , Tatekoshi Yuki , Kuno Atsushi
Published: November 2024

Background:
Diabetes mellitus (DM) elevates the risk of acute kidney injury (AKI); however, the underlying mechanisms are not fully elucidated. Necroptosis, a form of regulated cell death mediated through activation of RIPK1/RIPK3/MLKL signaling, contributes to the development of AKI. We previously reported that suppression of autophagy after renal ischemia/reperfusion (I/R) underlies the aggravation of AKI in type 2 DM.

Hypothesis:
Impaired autophagy amplifies necroptosis signaling in the diabetic kidney following I/R.

Methods:
AKI was induced by unilateral nephrectomy and 30-min renal artery occlusion/24-hour reperfusion in the contralateral kidney in OLETF, obese type 2 DM rats, and its non-diabetic control LETO. To inhibit autophagy in LETO, chloroquine (CQ, 10 mg/kg/day) was subcutaneously administered from 7 days before I/R. Rapamycin was injected to OLETF 30-min prior to ischemia to restore autophagic activity in the kidney. Renal tissues sampled before and after I/R were analyzed.

Results:
The serum creatinine (sCr) levels after I/R were higher in OLETF than in LETO (3.8±0.3 vs. 1.9±0.4 mg/dl, P<0.05). CQ treatment elevated sCr levels in LETO while rapamycin decreased the levels in OLETF. Immunoblot analyses showed that renal protein levels of RIPK1, RIPK3, and MLKL were similar in LETO and OLETF at baseline, but RIPK1 and RIPK3 were increased after I/R in both rats. Notably, the upregulation of RIPK3 after I/R were more pronounced in OLETF than in LETO. Suppression of autophagy by CQ enhanced the increase in RIPK3 levels by I/R in LETO, while restoration of autophagy by rapamycin reduced the RIPK3 levels in OLETF. Immunostaining for RIPK3 revealed that tubular cells were sites of RIPK3 upregulation observed in OLETF and CQ-treated LETO. To determine whether changes in RIPK3 protein levels were regulated at the transcription level, we measured RIPK3 mRNA level. qPCR analysis of renal tissues demonstrated that RIPK3 mRNA levels were increased by I/R in LETO and OLETF, but the upregulation was more pronounced in OLETF than LETO. The upregulation of RIPK3 mRNA after I/R was enhanced by CQ treatment in LETO and was suppressed by rapamycin in OLETF, suggesting that the impairment in autophagy promoted transcription of RIPK3.

Conclusion:
Compromised autophagy augments RIPK3-mediated necroptosis signaling via the upregulation of RIPK3 transcription in the diabetic kidney following I/R.
Abstract 4142589: GLP-1 receptor agonists slow the progression of subclinical cardiovascular risk as detected from 12-lead electrocardiograms
Authors: Kaisinger Lena , Buergel Thore , Steinfeldt Jakob
Published: November 2024

Background:
GLP-1 receptor agonists (GLP1RA) agonists have been shown to reduce cardiovascular events in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, it is unclear whether early subclinical therapeutic changes can be detected from routine 12-lead electrocardiograms (ECGs).

Methods:
We finetuned a neural network (NN) from Pheiron’s phenotyping platform to predict subclinical risk markers from 12-lead ECGs using data from Dandelion Health, comprised of longitudinal, multimodal real-world clinical data for 106,289 patients receiving care from Sharp Healthcare in the US. Based on the finetuned NN, we predicted risk markers within an independent cohort of 48,376 patients with a history of T2D, ASCVD, or obesity and emulated a target trial to evaluate the subclinical effect of GLP1RA. The primary analysis compared percentile rank transformed ECG markers for GLP1RA and non-GLP1RA patients using inverse probability weighted (IPW) linear regression models, adjusted for key variables including demographics, comorbidities, medications, HbA1c, and BMI at baseline. Sensitivity analyses included unadjusted models, models with only covariate adjustments, and propensity score-matched models.

Results:
The emulated trial study cohort was, on average, 59.6 [SD 15.9] years old, predominantly female (56%), and racially diverse: 46.6% White, 25.3% Hispanic, 9.6% Asian, and 4.6% Black. Compared to the control group, the GLP1RA cohort had a higher baseline risk profile (BMI: 35.1 [SD 7.6] vs. 31.0 [SD 6.0], HbA1c: 7.1 % [SD 1.8] vs. 5.8 % [SD 0.9]) but cardiovascular risk progressed slower during the observation time: Each year of GLP1RA treatment was linked to percentile risk reductions of -1.65 (p<0.001) for all-cause mortality, -1.74 (p<0.001) for myocardial infarction, and -1.74 (p<0.001) for stroke. These findings were directionally consistent across all sensitivity analyses.

Conclusions:
Our findings suggest treatment with GLP1RA slows the progression of subclinical cardiovascular risk, as detected from routine 12-lead ECGs. This illustrates the potential of ECG-based monitoring to guide therapeutic interventions and establish treatment efficacy.
Abstract 4142648: Cardiac Catheterization in Kidney Transplant Patients Presenting with Non-ST Segment Elevation Myocardial Infarction: A Five-year Nationwide Analysis
Authors: Al Akeel Mohannad , Eldawud Daoud , Jha Mayank , Harikrishna Arya , Jain Hritvik , Abdulfattah Ammar , Alamro Yazan , patel jeetendra
Published: November 2024

Background:
Cardiovascular disease is a significant cause of death among kidney transplant (KT) patients. The potential for contrast-induced nephropathy renders cardiac catheterization challenging for patients with non-ST segment elevation myocardial infarction (NSTEMI).

Aims:
To identify and evaluate the rates of all-cause mortality, intensive care unit (ICU) admission, cardiac catheterization, and length of stay between KT patients and non-KT patients who were admitted for NSTEMI.

Methods:
Our retrospective analysis utlized data from the Nationwide Inpatient Sample Database (NIS) from January 2016 to December 2020. A total of number of 31,51,154 non-KT were compared with 11,935 KT patients were admitted for NTSEMI. We identified patients who were admitted to the hospital in the US with discharge diagnosis of NSTEMI comapring their outcomes based on their renal transplant status. A multivariate logistic and linear regression analysis were conducted and adjusted for confounding variables such as age, gender, race, insurance, income, hospital region, and medical comorbidities to evaluate outcomes of interest. The adjusted odds ratio (aOR) and 95% confidence intervals (CI) were calculated.

Results:
Our analysis showed that patients with KT were less likely to undergo cardiac catheterization (aOR = 0.66, 95% CI: 0.60-0.73) compared to non-KT patients. There was no significant difference in the risk of cardiac arrest (aOR = 0.72, 95% CI: 0.43-1.22), ICU admissions (aOR = 1.09, 95% CI: 0.95-1.25), and the length of stay was found to be comparable in between the two groups. However, there was an increased risk of all-cause mortality (aOR = 1.28, 95% CI: 1.083-1.527) in KT patients when compared to non-KT patients.

Conclusion:
For NSTEMI, KT patients underwent cardiac catheterization significantly less frequently than their non-KT patients. patients Additionally, patients with KT had a higher risk of mortality than non-KT patients. Nonetheless, the risk of cardiac arrest, ICU admission, and duration of stay were comparable among the two groups, indicating that the potential side effects associated with left heart catheterization should not outweigh the benefits of performing left heart catheterization in KT patients.
Abstract 4142671: Machine-learning versus traditional risk scores for predicting clinical outcomes after coronary artery bypass graft surgery: a systematic review and meta-analysis
Authors: Gupta Aashray , Zaka Ammar , Mutahar Daud , Muston Benjamin , Tyagi Daksh , Farag Maria , Lombardo Alexander , Parvez Razeen , Stretton Brandon , Kovoor Joshua , Mridha Naim , Ramponi Fabio , Chan Justin , Gould Paul , Sivagangabalan Gopal , Zaman Sarah , Thiagalingam Aravinda , Chow Clara , Kovoor Pramesh , Bacchi Stephen , Bennetts Jayme , Maddern Guy
Published: November 2024

Background:
Coronary Artery Bypass Graft Surgery (CABG) is the most commonly performed operation in cardiac surgery and results from isolated CABG are used as benchmark to rate cardiac surgery programs in the US by the Society of Thoracic Surgeons (STS). Accurate and reliable mortality risk prediction of CABG patients is essential for developing targeted treatment strategies. Traditional risk scores such as the STS score and EuroSCORE II offer moderate discriminative value, and have limited utility in predicting outcomes for high-risk patients. Machine learning (ML) models have emerged as an alternate method that may offer improved risk assessment. This study aims to compare machine learning models with traditional risk scores for predicting all-cause mortality in patients undergoing CABG.

Methods:
PubMed, EMBASE, Web of Science and Cochrane databases were searched until 18
th
May 2024 for studies comparing ML models with traditional statistical methods for event prediction of CABG patients. The primary outcome was comparative discrimination measured by C-statistics with 95% confidence intervals between ML models and traditional methods in estimating the risk of all-cause mortality. A secondary aim was to compare model calibration between ML models and traditional risk scores, adhering to guidelines for predictive algorithm comparisons.

Results:
A total of 27 studies were included (568,190 patients). The summary C-statistic of all ML models across all endpoints was 0.82 (95% CI, 0.78-0.85), compared to traditional methods 0.73 (95% CI, 0.70-0.75). The difference in C-statistic between all ML models and traditional methods was 0.09 (p<0.0001). One model undertook external validation, and calibration was inconsistently reported.

Conclusion:
ML models demonstrated superior discrimination of all-cause mortality for CABG patients compared to traditional risk scores. Whilst there is great potential for ML models to be integrated into electronic healthcare systems to improve pre-operative risk stratification, and guide clinical decision making, the methodological and validation limitations pose a hurdle for immediate clinical implementation.
Abstract 4142679: Involvement of PCSK9 in progression of coronary atherosclerosis through molecular mechanisms beyond LDL-cholesterol regulation in patients with chronic coronary disease.
Authors: Ragusa Rosetta , Rocchiccioli Silvia , Del Turco Serena , Morlando Antonio , Basta Giuseppina , Neglia Danilo , Caselli Chiara
Published: November 2024

Background:
PCSK9, a key regulator of serum LDL-cholesterol levels, is associated with presence and severity of atherosclerosis, but data on the association between PCSK9 and coronary disease progression are lacking
.

Hypothesis:
Beyond the well-known role on the LDL-C regulation, PCSK9 has been hypothesized to interfere with inflammation and endothelial function affecting atherogenesis.

Aims:
The purpose of the present study is to evaluate whether PCSK9 is associated with coronary plaque progression in patients with chronic coronary disease (CCD) and to assess its molecular involvement on fundamental processes conditioning the atherosclerotic process.

Approach:
PCSK9 plasma levels were measured in 202 CCD patients (68±7 years of age; 58% males) undergoing coronary computed tomography angiography at baseline and after a follow up period of 6.5±1.1 years to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volumes (PV). Molecular pathways linked with PCSK9 were further studied by RNA-sequencing of whole blood and
in vitro
studies using Human Umbilical Vein Endothelial Cells (HUVEC).

Results:
PCSK9 plasma levels were positively related with LDL-C and HDL-C as well as ICAM1, IL6 and MMP9 (Fig A). At multivariate analysis, plasma PCSK9 was associated with annual increase of Necrotic Core PV (Coefficient 3.499, SE 1.507, P=0.022), independently from cardiovascular risk factors, LDL-C, and statin use (Fig B). At RNA-seq analysis, plasma PCSK9 was linked to the expression of genes involved in the regulation of innate-immuno response and cytokine mediated signal pathways (Fig C). A significant increase in ICAM-1, VCAM-1, MCP1 and IL6 expression was observed after treatment of HUVEC with increasing concentration of PCSK9 (Fig D).

Conclusion:
In CCD patients, PCSK9 is independently associated with progression of necrotic core PV, possibly reflecting the activity on inflammatory/endothelial pathways conditioning adverse plaque phenotypes. Understanding these mechanisms might shed further light on the therapeutic benefits of PCSK9 inhibitors beyond LDL-C regulation.
Abstract 4142683: Piezo2 channels expressed in cardiac ganglionated plexus modulate atrial fibrillation susceptibility
Authors: Li Xunjun , Jiang Hong , Yu Lilei
Published: November 2024

Background:
Pressure overload of the atria has been postulated to play a significant role in the development of atrial fibrillation. Piezo is a mechanosensitive channel protein and studies have revealed that piezo overexpressed in cardiomyocytes and fibroblasts can promote atrial fibrillation. However, whether pizeo is involved in cardiac ganglionated plexus and its role in atrial fibrillation remains unclear.

Hypothesis:
The aim of this study is to investigate whether piezo is expressed in the cardiac ganglionated plexus and plays an important role in atrial fibrillation.

Methods:
Cardiac ganglionated plexus were collected from 6 specimen with high left atrial pressure (high-LAP) or normal left atrial pressure (normal-LAP). Beagles were randomly allocated into sham group, AF group and piezo2-/- group. Atrial electrophysiological parameters, wov, left atrial pressure, neural function, neural activity and tissue of ganglionated plexus were detected.

Results:
Compared to the normal-LAP specimen, high-LAP resulted in an elevation of piezo2 in ganglionated plexus. RAP-induced increase in left atrial pressure promotes atrial fibrillation by overexpression of piezo2 increasing the function, activity, inflammation and oxidative stress levels of ganglionated plexus. Piezo2 -/- ameliorated atrial fibrillation susceptibility and showed a mild neuranagenesis. Moreover, notch signaling pathway maybe a significant mechanism.

Conclusions:
Piezo2-mediated mechanical transduction promotes atrial fibrillation by increasing ganglionated plexus activity and facilitating nerve regeneration, possibly through notch signaling.
Abstract 4142708: DIgital REgistry for CardiomeTabolic conditions – Diabetes Mellitus (DIRECT-DM): A Large, Pragmatic, Multisite, Diverse Longitudinal Registry of Type 2 Diabetes
Authors: Pedroso Camargos Aline , Dhingra Lovedeep , Aminorroaya Arya , Khera Rohan
Published: November 2024

Background:
Despite the rising prevalence of T2DM, contemporary information on its longitudinal care and outcomes is limited and largely derived from small, self-selected cohorts. We describe the development and patterns of care of a digital pragmatic cohort of all T2DM patients seeking care in the multisite network of an integrated health system.

Methods:
DIRECT-DM is a digital registry of T2DM patients seeking care across multiple hospitals and community practices in CT and RI from 2013 to 2023. From 223,932 individuals with T2DM, those with regular care (≥1 visit every 2 years) were included in the longitudinal cohort. Mortality was derived from the CT Death Index, healthcare resource utilization (HRU) was tracked across all care settings, and exposomic drivers of outcomes were linked via zip-code-based community and environmental characteristics, including data drawn from census, surveys, and air quality metrics. In this report, we describe the cohort’s characteristics, patterns of HRU, particularly in those with CV disease and factors associated with HRU using multivariate Poisson regression.

Results:
DIRECT-DM included 106,881 T2DM individuals with a median age of 63 years (IQR 52-73), 50% women and 16% Black, who were followed for a median of 5.4 years (3.1-7.5), and 9% died. There were 2.3M healthcare visits, including 1.5M hospitalizations, 250K emergency department visits, and 1.9M outpatient visits with 11.4% of CV-related principal diagnoses. In the DIRECT-DM cohort, where 31.5% had established CV disease, the burden of HRU increased with the comorbidities burden, with those having CV disease experiencing the highest HRU (3.7 median visits/year for ASCVD [1.9-6.8] and 4.4 [2.2-8.0] for HF). However, for the same age, sex, and comorbidity profile, lack of health insurance (IRR 0.94; 0.92-0.97), low income (IRR 0.97; 0.96-0.98), and Black vs. White race (IRR 0.98; 0.98-0.99) were associated with lower HRU.

Conclusions:
DIRECT-DM is a pragmatic T2DM registry in a diverse high-risk population, identifying key factors associated with HRU among T2DM patients. While there was an expected increased HRU in established CV disease, there was a lower-than-expected HRU among racially and socioeconomically disadvantaged populations.
Abstract 4142743: VEIN-SCORE: a new risk score for chronic venous insufficiency in patients who experienced leg swelling
Authors: Shim Chi Young , Kim Kyu , Lee Hyun-Jung , Cho Iksung , Hong Geu-Ru , Ha Jong-Won
Published: November 2024

Backgrounds:
Chronic venous insufficiency (CVI) is a condition of the venous wall and/or valves’ dysfunction in the leg veins prone to venous thrombosis and reducing quality of life. This study sought to find risk factors of CVI and develop a dedicated risk score model to predict the presence of chronic venous insufficiency in patients who experience leg edema

Methods:
In a total of 1,226 patients (age 65.2± 15.0, 662 women) with leg swelling, specialized protocols for venous function tests were applied for diagnosis of CVI in a single center vascular ultrasound laboratory from Mar 2015 to Dec 2020 after exclusion of the presence of deep vein thrombosis. Duplex ultrasound scan on the greater and lesser saphenous veins was performed with patients erect or as upright as possible. Using a tilt table, patients’ position was flexibly changed. For the distal augmentation to assess for venous incompetence, we used the Hokanson
®
E20 Rapid Cuff Inflator. Pathologic reflux is defined by reversal of flow greater than 500 milliseconds in duration. The new CVI scoring system was calculated from logistic regression model. The VEIN-score were compared with cardiovascular risk scoring system established for other purposes.

Results:
607 patients (49.5%) were diagnosed with CVI. The final risk score ranged from 0 to 6 points and included six parameters: age ≥ 65 years, male sex, obesity (body mass index ≥ 25 kg/m
2
), hypertension, atrial fibrillation, and a history of myocardial infarction, which were derived from the results of logistic regression model (
Figure A
). The incidence of CVI gradually increased from 39% to 100%, as the score increased from 0 up to 6 points (
Figure B
). The new scoring system showed modest predictive value (C-index: 0.575, 95% CI: 0.544-0.606, cut-off value 3), higher than the CHA
2
DS
2
-VASc score and H
2
FPEF score.

Conclusions:
Old age, male sex, obesity, history of atrial fibrillation and myocardial infarction were significant risk factors for CVI. We propose VEIN-SCORE as a dedicated risk score model to predict chronic venous insufficiency in patients with leg swelling.
Abstract 4142747: Role of Cardiomyocyte Mechanotransduction in Triggering Atrial Arrhythmias in Pulmonary Hypertension
Authors: Bronk Peter , Zhang Peng , Wang Eric , Lu Yichun , Banerjee Debolina , Stanley Madigan , sellke frank , Radice Glenn , Choudhary Gaurav , Tran Cao , Choi Bum-rak
Published: November 2024

Introduction:
Pulmonary arterial hypertension (PAH) is a chronic disease associated with atrial fibrillation (AF). Chronic pressure overload in right atria (RA) may disrupt cardiomyocyte mechanotransduction resulting in remodeling that triggers arrhythmias. The mechanosensitive adaptor protein, vinculin, interacts with Nav1.5 as well as indirectly stabilizing connexin-43 gap junctions.

Goal:
To show that the influence of chronic overload in RA under conditions of PAH disrupts mechanotransduction signaling and increases susceptibility to arrhythmias.

Methods:
We used the Sugen/Hypoxia (Su/Hx) rat model of PAH for optical mapping of action potentials in isolated right atria as well as immunohistochemistry of atrial tissue.

Results:
PAH rats have enlarged RA (82.2 ± 22.3 mg PAH vs. 38.5 ± 4.7 mg control, p=0.02, t-test). In comparison to controls, isolated RA of PAH rats show slower conduction velocity (CV) (0.4 ± 0.07 mm/ms PAH vs. 0.5 ± 0.06 mm/ms control, p=0.02, t-test) together with increased local heterogeneity, an increase in APD (Fig. 1A) and APD dispersion (11.2 ± 3.7 ms PAH vs. 5.6 ± 1.3 ms control, p=0.006, t-test). Traditionally, AF is usually associated with shorter APD, so the prolonged APD we recorded in PAH RA represents a unique electrophysiological change. This electrical remodeling in PAH rats promotes conduction block in the posteromedial RA and reentry formation (Fig. 1B). Immunohistochemistry shows that vinculin is reduced at N-cadherin cell-cell contacts and redistributed to the lateral membrane in PAH RA (Fig. 2) with a 2D FFT radial sum intensity major to minor peak ratio: 1.02 ± 0.002 vs 1.008 +/- 0.001 control, p=0.02, t-test.

Conclusion:
RA of PAH rats show high arrhythmia risks compared to controls. The unique electrophysiological changes could be a critical feature of AF in PAH. Vinculin redistribution may create a substrate for RA arrhythmias and may play an important role in regulating the electrical remodeling of RA in PAH.
Abstract 4142757: Adiponectin receptor agonist alleviates heart failure with preserved ejection fraction by regulating NLRP3/Caspase-1/IL-1β and Pl3K/Akt signaling pathway
Authors: Cheng Siyi , Yu Lilei , Zhou Xiaoya
Published: November 2024

Background:
Treating and managing heart failure with preserved ejection fraction (HFpEF) remains challenging. With the gradual increase in the number of obese individuals, diabetics, and cases of hypertension, HFpEF prevalence accounts for half of the total number of patients with heart failure. HFpEF, for which no specific treatment exists, is the most challenging problem.

Objective:
To investigate the cardioprotective effects and mechanisms of an adiponectin receptor agonist, AdipoRon, as an anti-inflammatory agent in a two-hit HFpEF mice model.

Methods:
A mouse model of HFpEF was induced using a 60% high-fat diet plus 5.0g/L L-NAME drinking water for 12 weeks. AdipoRon (50 mg/kg) or a comparable volume of saline via gavage once daily was administered to the two-hit HFpEF mice model for four weeks. Cardiac function was evaluated by echocardiography, while molecular biology techniques were employed to determine the effect of AdipoRon.

Results:
The oral adiponectin receptor agonist, AdipoRon, inhibited HFpEF inflammation by downregulating NLRP3, caspase-1, IL-1β and IL-18, and suppressing the TLR4/NF-κB/TNF-α signaling pathway. This improved cardiac functional phenotypes, including cardiac diastolic dysfunction, pulmonary congestion, myocardial hypertrophy, reduced exercise tolerance, and glucose intolerance. AdipoRon improved heart rate variability (HRV) , decreased serum norepinephrine(NE), which inhibiting inflammation-induced cardiac sympathetic over-activation. AdipoRon dramatically reversed HFpEF-induced down-regulation of PI3K, Akt, and GSK3β phosphorylation, improved glucose metabolism and attenuated the cardiac damage associated with glucose accumulation. Our findings indicated AdipoRon’s ability to downregulate the expression of Bax/Bcl-2, inhibiting cardiomyocyte apoptosis, attenuating myocardial injury, and effectively improving cardiac function and ventricular remodeling.

Conclusion:
AdipoRon attenuated inflammatory response, improved cardiac function and phenotypes, and ameliorated impaired myocardial glucose metabolism and apoptosis in HFpEF mice. This was achieved by modulation of NLRP3/Caspase-1/IL-1β, Pl3K/Akt, and TLR4/NF-κB/TNF-α signaling pathways.
Abstract 4142856: Integrative Bulk And Single-Cell Meta-Analysis Defines SPP1+ Foamy Macrophage Contributing To Atherosclerosis Progression
Authors: Huang Shengkang , Yang Ziang , Fang Chenglong , Feng Wei
Published: November 2024

Background:
Atherosclerosis (AS) progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes and crucial pathogenic cell subsets remain controversial.

Methods:
We performed an integrated meta-analysis of single-cell sequencing data from our center along with four other scRNA-seq libraries (GSE247238, GSE235436, GSE155512, GSE159677) to generate a comprehensive map of human atherosclerotic plaques, including both coronary arteries with no discernible atherosclerotic lesions and diseased carotid plaques. To validate our conclusions, three independent datasets were used, including two bulk transcriptomics datasets and one proteomics dataset (GSE28829, GSE16315 and PXD031052). Besides, the Biobank of Karolinska Endarterectomy (BiKE) dataset was used for Kaplan–Meier (KM) analysis. Comparative analyses were performed between the groups, including cellular compositional analysis, cell type–resolved transcriptomic changes, and functional analysis.

Results:
The final integrated single-cell dataset, comprising 134,710 cells, consisted of 8 major cell types. The annotated cell subpopulations were generally present across the various studies, but their proportions varied between different studies. Pathway analysis identified that the most significantly impacted pathways were those associated with immune cell functions and cellular metabolism. Notably, SPP1 is highly expressed in macrophages. Survival analysis showed significantly lower ischemic event-free survival in the high SPP1 expression group compared to the low expression group. Besides, compared to atherosclerotic plaques with early stage (EA), non-intraplaque hemorrhage (IPH), and non-calcified conditions, SPP1 expression was highly up-regulated in all stages of plaque progression, including advanced plaques (AA), hemorrhagic plaques, and calcified plaques. Meanwhile, the differences in cellular composition and transcriptomic profiles between the lesion and non-lesion groups further highlighted the significance of lipid metabolism-related SPP1
hi
foamy macrophages.

Conclusions:
We created a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases. SPP1
hi
foamy macrophages contributed importantly to AS progression.
Abstract 4142887: Disentangling Abdominal Aortic Aneurysms and Coronary Artery Disease Through Circulating Proteomics
Authors: Vanmaele Alexander , da Veiga Fernandes de Mira Jose , Hoeks Sanne , Bouwens Elke , Akkerhuis K. Martijn , de Bruin Jorg , ten Raa Sander , Fioole Bram , Daemen Joost , Van Mieghem Nicolas , Van Geuns Robert-jan , Serruys Patrick , Verhagen Hence , Boersma Eric , Kardys Isabella
Published: November 2024

Introduction:
The prevalence of abdominal aortic aneurysms(AAA) is at least twice as high in patients with coronary artery disease(CAD), and about half of the AAA-patients have clinically relevant CAD. Detecting concomitant disease and intervening on pathophysiological mechanisms could potentially improve survival in these patients.

Research Questions:
Which circulating biomarkers and biological mechanisms can distinguish AAA and CAD?

Aims:
To differentiate the circulating proteomic profiles and biological pathways associated with AAA and CAD.

Methods:
Patients with AAA and/or stable CAD from two prospective cohort studies were age, sex, and comorbidity matched 1:1:1 (AAA only, AAA and CAD, CAD only). 369 plasma proteins were simultaneously measured in both cohorts using the Olink Explore Cardiometabolic I panel. We investigated differences in proteomic profiles using univariable linear regression and multivariable logistic elastic net regression. Differences in biomarker interactions(pathways) were studied through differential network analysis.

Results:
Each matched group consisted of 53 patients. Overall, the mean age was 70 years and 92% were men. In AAA-patients, the baseline median(25
th
-75
th
percentile) maximum diameter was 46(43,50) mm. The proteins IRAG2 and CORO1A were significantly downregulated in AAA-patients with CAD, compared to AAA only. After multivariable selection, only IRAG2 was independently associated with the presence of CAD in AAA-patients. Protein interactions in six pathways differed in AAA-patients with CAD, compared to AAA only(Figure 1A). Moreover, the IGFBP7, CD59, REG1A and CST3 proteins were univariably, significantly upregulated in CAD-patients with AAA, compared to CAD only. Multivariable selection in the proteomic profile proposed PLA2G2A, CD59 and REG1A as independently informative biomarkers for the presence of AAA in CAD-patients. In 14 biological pathways, proteins interacted differently in CAD-patients with AAA, compared to CAD only(Figure 1B).

Conclusion(s):
A small set of proteins differed between phenotypes. While the average level of most biomarkers was the same, many protein interactions, in pathways implied in AAA by basic research, differed between AAA- and CAD-patients.
Abstract 4142910: Role of High-Sensitivity Troponin I and Troponin T in Prediction of Sudden Arrhythmic Death in Patients with Coronary Artery Disease
Authors: Mao Jessica , Cuk Natasha , Tseng Chi-Hong , Liu Yunxian , Kadish Alan , Moorthy M. Vinayaga , Cook Nancy , Morrow David , Albert Christine
Published: November 2024

Introduction:
While implantable cardiac defibrillators (ICDs) can prevent sudden arrhythmic death (SAD), less than 30% of SAD patients meet criteria for implantation. Improved risk stratification and prediction is necessary to identify individuals at risk.

Objective:
The purpose of this study was to evaluate the role of high-sensitivity troponin T (hs-TnT) and high sensitivity troponin I (hs-TnI) in predicting SAD.

Methods:
We prospectively evaluated the associations of hs-TnT and hs-TnI with the incidence of SAD in 5,764 participants enrolled in the PREDETERMINE study, which enrolled individuals with history of coronary artery disease (CAD) not meeting criteria for ICD implantation with left ventricular ejection fraction (LVEF) above 30%. Using multivariable Cox proportional hazards models, hs-TnT and hs-TnI were evaluated as continuous (log-transformed) variables, by quintile, and dichotomously by clinical thresholds. Spearman coefficients were calculated to assess biomarker correlations.

Results:
Over a median 8.1 years follow-up, 4.3% (n=249) of the study cohort experienced SAD. Within our cohort, hs-TnT and hs-TnI were highly correlated with a Spearman coefficient of 0.77. After multivariable adjustment, both hs-TnT and hs-TnI were associated with increased risk of SAD (HR 1.18, 95% CI 1.03-1.36 per 1-SD change for hs-TnT, and HR 1.19, 95% CI 1.04-1.37 per 1-SD change for hs-TnI). Risk for SAD was elevated in the highest quintile of hs-TnT (HR 2.53, 95% CI 1.47-4.37) and the highest quintile of hs-TnI (HR 3.23, 95% CI 1.86-5.60) compared to the lowest quintile. Elevated hs-TnT ≥19 ng/L (median) was associated with increased risk of SAD (1.69, 95% CI 1.27-2.25), as was hs-TnI ≥ 8.5 ng/L (HR 1.69, 95% CI 1.29-2.23).

Conclusion:
In our large, prospectively enrolled cohort of participants with CAD and LVEF above 30%, both increased hs-TnT and hs-TnI were each significantly associated with similarly increased risks of SAD. Among individuals who are at risk for SAD but do not qualify for prevention with ICD implantation, measurement of high-sensitivity troponin in conjunction with clinical data may help to identify those most likely to benefit from preventative therapy.
Abstract 4142913: Characteristics and Prognosis of In-Hospital Onset Non-ST-Segment Elevation Acute Myocardial Infarction in Patients Hospitalized for Non-Cardiac Diseases: Comparison of Cardiology Referral vs. Non-Referral
Authors: Zhu Lei , Gu Tian-Shu , Zhang Ze , Hu Su-Tao , Jiang Chao , Zhang Yu-Kun , Zhang Jing-Kun , Wu Xue , Liu Xing , Liu Tong , Chen Kang-Yin
Published: November 2024

Background:
NSTEMI accounts for the majority of the in-hospital MI. However, whether differences exist between in-hospital NSTEMI patients referred to cardiology and those who are not remains unclear.

Aims
This study aims to compare the characteristics and prognosis of in-hospital NSTEMI patients referred to cardiology with those who are not.

Methods:
Data for this study were obtained from a retrospective cohort comprising patients from 72 hospitals between 2010 and 2023. Patients who developed NSTEMI during hospitalization were identified and classified into the referral and the non-referral group based on whether they were referred to cardiology. The primary endpoint was Major Adverse Cardiovascular and Cerebrovascular Events (MACCE), comprising cardiovascular death(CD), recurrent MI, stroke, and repeat revascularization at 1 year. The secondary endpoints were in-hospital all-cause mortality, 1-year all-cause mortality, CD, and Net Adverse Clinical Events (NACE), including CD, recurrent MI, BARC≥3 bleeding events, and repeat revascularization. Kaplan-Meier curves were used to depict survival between the two groups. A multivariable Cox regression model, adjusted for age, sex, Killip classification, and medical history, was utilized to analyze the association between referral and 1-year outcomes. Additionally, multivariate logistic regression analysis was employed to examine the factors related to in-hospital mortality.

Results:
The study included 6218 patients were in the non-referral group (mean age 73 years, 43.4% women) and 1260 in the cardiology referral group (mean age 70.8 years, 43.4% women). The non-referral group was less likely to take antiplatelet drugs, statins, or undergoing PCI (p<0.001). Multivariate logistic regression showed that cardiology referral was a significant factor affecting in-hospital mortality (OR: 0.405, 95%CI: 0.310-0.528). All the 1-year endpoints-free survival rates were better in the referral group than in the non-referral group (Log-rank p<0.001). Multivariate Cox regression analysis showed that referral were associated with a lower risk of 1-year MACCE (HR: 0.878, 95%CI: 0.801-0.964), NACE (HR: 0.882, 95%CI: 0.805-0.967), all-cause mortality (HR: 0.729, 95%CI: 0.658-0.808) and CD (HR: 0.743, 95%CI: 0.657-0.840).

Conclusion:
In-hospital NSTEMI patients referred to cardiology had better outcomes compared to those who were not, partly due to higher rates of revascularization and adherence to guideline-recommended medical therapy.
Abstract 4142955: Clinical Outcomes and Healthcare Resource Utilization Following Percutaneous Coronary Intervention for ST-segment-elevation Myocardial Infarction in Adult Patients Treated in US Hospitals
Authors: Krishnaswami Shanthi , Clark Brendan , Tyagi Manu , Sinha Meenal , Donato Bonnie MK , Wittrup-Jensen Villum , Cao Zhun
Published: November 2024

Background:
ST-segment-elevation myocardial infarction (STEMI) is estimated to affect approximately 250,000 people in the US each year, leading to significant burden of morbidity and mortality. Evidence on long-term outcomes following percutaneous coronary intervention (PCI) for STEMI is limited.

Aims:
To assess clinical and economic outcomes following PCI among patients with STEMI.

Methods:
This retrospective study utilizing data from Premier PINC AI™ Healthcare Database was conducted among adult patients (age ≥ 18 years) discharged from US hospitals for PCI with a primary diagnosis of STEMI, between October 1, 2016 and December 31, 2021 (index date). The study included mortality data from an external data source that captures death dates for approximately 85% of the US population. Clinical outcomes, healthcare resource use, and costs (adjusted to 2022 US dollars) following first PCI discharge were assessed for a minimum of 1 year. Outcomes at 3-year follow up were assessed among a subset of patients with an index date on or before December 31, 2019. Multivariable regression was used to identify risk factors for key outcomes.

Results:
A total of 180,691 patients underwent PCI for STEMI in 633 US hospitals during the study period. Median age of patients was 62 years, with majority being male (71%), White (79.1%), and with Medicare as the primary payor (42.9%). At index visit, 13.8% of patients had ventricular tachycardia, 8.8% had ventricular fibrillation, with a median cost of $17,582, and a mortality rate of 5.5%. Within 1-year, there were 1,966 (1.1%) additional deaths, 16.4% of patients were readmitted, 12.6% newly diagnosed with heart failure (HF), 3.6% with atrial fibrillation, and 1% experienced recurrent STEMI. The median total study cost at 1-year was $21,010. In patients with 3-year follow up data (n=63,469), the mortality rate was 7.5%. Charlson Comorbidity Index (CCI) score ≥4 (vs <4) at index visit was most strongly associated with higher risk of death at follow up periods: 1-year (HR: 4.1, 95% CI: 3.66 to 4.49), 3-year (HR: 3.7, 95% CI: 3.21 to 4.27), higher odds of readmissions (1,3-year: OR: 2.2, 95% CI: 2.08 to 2.37), HF incidence (OR: 3.0 to 3.2, 95% CI: 2.89 to 3.35) and had 74% higher costs (p<0.05).

Conclusion:
This study highlights the risk factors associated with long-term negative clinical outcomes and higher cost following PCI for the treatment of STEMI.
Abstract 4143004: A Stepwise Approach to Identifying and Assessing the Content Validity of Patient-Reported Outcome (PRO) Measures for Use with Adults with Acute Heart Failure
Authors: OConnor Meaghan , Loughlin Anita , Waldman Laura , Rucker Sloan , Vaghela Shailja , Kwon Namhee , Sikirica Vanja
Published: November 2024

Different patient-reported outcome (PRO) measures have been used and validated in studies of patients with heart failure (HF), including disease-specific measures like the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ). However, there is limited research available regarding the content validity (i.e., comprehensiveness, relevance, and comprehensibility) of those measures specifically as it relates to patients with acute HF (AHF).

This study used a stepwise approach to identify PRO measures used in AHF studies and evaluate their content validity through a landscape analysis, concept mapping, and cognitive debriefing (CD) interviews with US-based patients.

A landscape analysis was performed to identify PRO measures used in AHF studies. To assess concept coverage, items in each PRO measure were mapped to concepts (i.e., signs/symptoms and impacts on daily life) from the AHF conceptual model developed by Moshkovich et al. (2020). PRO measures with the most comprehensive and/or appropriate concept coverage were further evaluated through CD interviews with US adults who had been hospitalized for AHF within the last six months.

The landscape analysis resulted in the identification of 15 PRO measures for use in AHF; nine were deemed appropriate for concept mapping. Following mapping, four measures were selected for further research based on their comprehensive concept coverage (KCCQ, PROMIS®+HF-27), effectiveness at measuring health utility (EQ-5D-5L), and suitability for measuring shortness of breath (a dyspnea numeric rating scale [NRS]). The KCCQ, in particular, showed good concept coverage, addressing more than half (n=12) of the key concepts in the Moshkovich et al. (2020) model. Twenty adults with AHF, representing NYHA classes I (n=4), II (n=8), and III (n=8), a mean age of 64 years (range: 39-81), and an average of 110 days since hospitalization (range: 26-183), participated in CD interviews. Participants found each measure easy to understand and answer, with items relevant to their experience of AHF. Participants found the recall periods, ranging from 24-hours to 2-weeks, appropriate and easy to use.

This study’s stepwise approach allowed for the systematic identification and evaluation of the content validity of four PRO measures—the KCCQ, dyspnea NRS, EQ-5D-5L, and PROMIS®+HF-27—for use with adults with AHF. This research fills a gap in the current published literature regarding measures appropriate for use with adults with AHF.
Abstract 4143007: Pericoronary fat attenuation index as a Novel Tool to predict the morbidity of new-onset atrial fibrillation in patients with myocardial infarction with nonobstructive coronary artery disease
Authors: Huang Sizhuang , Yu Mengyue , Xu Haobo
Published: November 2024

Background:
Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is a special syndrome with clear evidence of myocardial ischemia, but no clear stenosis of coronary artery imaging sign. The pericoronary fat attenuation index (FAI) could reflect the local coronary inflammation as a novel imaging marker. This study focuses on the correlation between FAI and the morbidity of new-onset atrial fibrillation (NOAF) in MINOCA patients.

Methods:
This study was a single-center, observational clinical cohort study. Patients who underwent coronary angiography and diagnosed with MINOCA in Fuwai Hospital from January 2015 to December 2019 and met the inclusion criteria were enrolled. We mainly explored the correlation between the FAI of right coronary artery and left circumflex and morbidity of AF. Kaplan-Meier analyses and Cox regression analyses were performed to evaluated cumulative NOAF hazard ratio during a 77.2-month follow-up. ROC analyses were also adapted in this study to detect the best cut-off value for FAI in predicting NOAF.

Results:
A total of 592 MINOCA patients with coronary CT angiography were enrolled, including 40 (8.0%) with NOAF. CT was performed within two months before or after the onset of MI. Patients in higher median group of FAI had an apparently higher rate of NOAF (8.8% vs 4.7%; P<0.05) during the follow-up time. After adjusted for multiple clinically relevant variables, higher FAI was still associated with an increased risk of NOAF (HR=1.71; 95% CI: 1.23-2.39 P<0.001). Moreover, AMR had an AUC of 0.722 for NOAF prediction with the best cut-off value of -74.395 HU.

Conclusions:
FAI score of main atrial coronary artery (RCA and LCX ), which may capture the risk of inflammation, is closely related to the atrial function. Higher FAI was a risk factor for NOAF in patients with MINOCA, which had high specificity and sensitivity for predicting NOAF in MINOCA patients. Assessment of FAI score derived from CCTA may increase predictability for NOAF in this special population.