bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4139423: Glycemic Changes After Peer Group Exergaming and Step Goal Activities Among Adolescents With Type 1 Diabetes
Authors: Lukasik James , Nally Laura , Jeon Sangchoon , Granados Alvaro , Weinzimer Stuart , Ash Garrett
Published: November 2024

Adolescents with type 1 diabetes (T1D) experience both psychosocial and self-management barriers to physical activity (PA). We previously reported on a peer support intervention with group exergaming and step-counting goals for adolescents with T1D. The intervention yielded high participation, motivation, perceived group cohesion, and participant satisfaction. The purpose of the present sub-study was to assess 24hr continuous glucose monitoring (CGM) changes following the biweekly 20-40min group exergaming sessions (Nintendo Ring Fit Adventure) across the 6-week intervention, adjusted for other daily PA tracked by smartwatch (Fitbit Inspire 2). Participants (n=15) were mean age 15.6 [SE=0.4] years, 7 non-Hispanic white, 6 female, 1 non-binary, mean A1c 8.9%±0.6%. They provided 75.3% of possible 24hr CGM readings (n=12 Dexcom G6, n=3 Abbott Libre 2) and 70.5% of possible 24hr Fitbit readings, thus 1,008 person-hours with CGM and Fitbit. In a 2-level linear model (i.e., within-person biometrics from CGM and Fitbit, after adjustment for between-person HbA1c and age), hours ≤24hr after exergaming sessions - compared to hours >24hr after them – had lower average glucose (185mg/dL [95% CI 173,196] vs 192mg/dL [177,214], t=-2.66,
P
<.01) and higher probability of glucose being in the clinical target range of 70-180mg/dL (OR=1.18 [95% CI 1.06,1.32], t=2.98,
P
<.01). Increased hourly Fitbit steps further contributed to lowering average glucose (standardized β=-0.65 (SE=0.11), t=-2.37,
P
<.01) and increasing probability of being in the clinical target glucose range (β=0.021±0.003), t=6.26,
P
<.01). Whereas, increased hourly Fitbit heart rate contributed to elevating average glucose (β=0.52±0.08), t=6.52,
P
<.01) and decreasing likelihood of being in the clinical target glucose range (β=-0.012±0.002), t=-5.20,
P
<.01). In conclusion, both peer group exergaming and Fitbit steps were followed by glucose being modestly lower and more often in the clinical target range, suggesting our intervention was an implementable strategy to aid in glucose management but may require increasing the volume of exercise. Fitbit heart rate elevations independent of PA may signal sympathetic nervous system activation (e.g., from mental stress) and partially predict elevation of glucose. Further research should test dose response to varying amounts of exergaming, refine the optimal time window duration after exergaming to observe glucose effects, and examine other CGM metrics.
Abstract 4139455: Do Congenital Heart Defects in Offspring Signal Early Signs of Maternal Cardiometabolic Dysregulation and Increased Risk of Cardiovascular Disease Later in Life?
Authors: Bircan Emine , Orloff Mohammed , Hays Laura , Ying Jun , Eswaran Hari , Nembhard Wendy
Published: November 2024

Introduction:
A recent study suggested an association between a history of delivering a child with congenital heart defects (CHDs) and development of cardiovascular diseases (CVDs) later in life; however, little is known about this possible association.

Research Question:
Do women with a CHD-affected pregnancy have a higher risk of CVD compared to women who had a pregnancy unaffected by a structural birth defect?

Goals:
To determine the CVD risk among women with a history of a CHD-affected pregnancy.

Methods:
A total of 1,423 women who delivered an infant with at least one of selected CHDs, and 1,020 women who delivered a live-born infant with no structural birth defects were identified from the Arkansas site of the National Birth Defects Prevention Study (August 1997 – December 2011) and linked to the Arkansas All-Payers Claims Database (2000-2022) to identify cases of CVD. CVD was identified using International Classification Diagnostic Ninth (ICD-9) and Tenth (ICD-10) codes and was categorized as ischemic, cerebrovascular, essential hypertension, other heart diseases, other CVDs, and any CVDs. Women were followed from the estimated date of delivery of their offspring (in years) until the date of the first CVD event, death, or the end of the study (January 1, 2023), whichever occurred first. Unadjusted and adjusted hazard ratios (aHR) with corresponding 95% confidence intervals (CIs) were calculated from Cox Proportional Hazard regression analyses.

Results:
Both adjusted and unadjusted models showed women with CHD-affected pregnancies had a higher risk of developing any type of CVD than those with no structural birth defects. Women with CHD-affected children had a 1.40 times risk of developing any type of CVD (aHR=1.4, 95% CI: 1.1, 1.8) after adjusting for potential confounders. For specific types of CVD, the risk was (aHR=3.7, 95% CI: 1.1, 13.1) for developing ischemic heart disease.

Conclusion:
Women with CHD-affected pregnancies have an increased risk of developing CVD in later life. CHD-affected pregnancies may be early signs of cardiometabolic dysregulation and CVD in later life. Additional studies are needed to further investigate this possible association.
Abstract 4139456: Integrin α5β1 contributes to pathological remodeling of the right ventricle in pulmonary arterial hypertension
Authors: Lemay Sarah-Eve , Montesinos Monica , Grobs Yann , Bourgeois Alice , Romanet Charlotte , Sauvaget Melanie , Breuils Bonnet Sandra , Theberge Charlie , Martineau Sandra , Lippa Blaise , Goodwin Bryan , Lin Albert , Wang Hua , Dowling James , Lu Min , Qiao Qi , McTeague T. Andrew , Moy Terence I. , Potus Francois , Provencher Steeve , Boucherat Olivier , Bonnet Sebastien
Published: November 2024

Introduction:
Right ventricular (RV) function is an important prognosis factor in pulmonary arterial hypertension (PAH). In response to pressure overload, the RV undergoes morphological changes driven by the accumulation of extracellular matrix (ECM) elements and cardiomyocyte hypertrophy. Integrins (Itg) are members of the cell adhesion receptor superfamily. Through ECM-binding, Itg are known to transduce extracellular cues to cardiac cells resulting in the activation of pro-hypertrophic and pro-fibrotic signaling pathways. Among them, integrin α5β1 is one of the most abundant heterodimers in cardiac tissue. We thus hypothesized that α5β1 signaling promotes pathological RV remodeling.

Methods&Results:
Using Western blot (WB), we found elevated levels of Itgα5 and Itgβ1 protein in RV isolated from PAH patients compared to controls. Similar findings were observed in monocrotaline (MCT) and pulmonary artery banding (PAB) rats. In adult rat cardiomyocytes, pharmacological inhibition of α5β1 decreased phenylephrine-induced hypertrophy and reversed established hypertrophy induced by MCT treatment (assessment of cell surface area by F-actin labeling). In human RV fibroblasts (RVFB) inhibition of α5β1 prevented TGFβ1-induced activation of control RVFB and decreased proliferation and activation of RVFB derived from PAH patients (WB PCNA, αSMA, COL1; immunofluorescence Ki67).
In vivo
, inhibition of α5β1 using a small molecule inhibitor or a blocking-antibody improved RV dysfunction (CO, TAPSE, RVFAC, RV strain, as assessed by echocardiography, right heart catheterization and cardiac magnetic resonance imaging) and diminished RV hypertrophy and fibrosis (Fulton index, H&E and Masson’s trichrome staining) in MCT-injected rats with established PAH and PAB rats.
Ex vivo
, inhibition of α5β1 attenuated cardiomyocyte hypertrophy and RV fibrosis in human precision-cut RV slices exposed to phenylephrine and TGFβ1.

Conclusion:
Our results suggest that integrin α5β1 plays a key role in pathological RV remodeling in PAH.
Abstract 4139492: Impact Of Valvular Heart Diseases On In Hospital Outcomes Of Patients With Immune Thrombocytopenic Purpura - A Nationwide Analysis
Authors: Jayakumar Jayalekshmi , Ginjupalli Manasa , Sekandlapuram Rohit , Gaddam Mrunanjali , Vachhani Bhavyakumar
Published: November 2024

Background:
There are multiple studies showing high prevalence of valvular heart diseases(VHD) in patients with Immune Thrombocytopenic Purpura(ITP) and the need for prompt pre-operative treatment while attempting surgical repair of valves. A reciprocal occurrence of high valvular complications in suboptimally treated ITP were also reported in literature. This could be multifactorial and can be attributed to increased platelet destruction from shear stress and turbulent flow from stenotic or regurgitant valves, increased platelet reactivity, acquired platelet dysfunction and dilutional effect. In this study, we tried to analyze the in-hospital outcomes of ITP in patients who have VHD.

Methods:
We queried the National inpatient sample 2016-2020 using ICD-10 codes to identify VHD hospitalizations(stenotic and regurgitant mitral, tricuspid, aortic and pulmonary valves). This population was stratified with the prevalence of ITP. Complication rates for bleeding, sepsis, pulmonary hypertension, infective endocarditis, acute embolic stroke and arrhythmia were compared in these cohorts using chi-square test. Multivariate regression analysis was further performed to study the impact of VHD on mortality, length of stay and total hospitalization charges in the subpopulation of ITP hospitalizations after adjusting for relevant confounders.

Results:
We identified 8,279,973 VHD hospitalizations with a mean age of 73.58 without ITP and 73.72 with ITP, of which 48.6 % were females. The prevalence of ITP in this subpopulation was 0.27%(N = 22, 995). As compared to ITP hospitalizations without VHD, hospitalizations with VHD had a statistically significant higher occurrence of epistaxis, hemoptysis, hematuria, gastrointestinal bleed, intracranial bleed, sepsis, pulmonary hypertension, arrhythmia and infective endocarditis(Table 1). In the subgroup of hospitalizations with ITP, multivariate regression analysis revealed higher odds of mortality, increased length of stay and higher hospital charges with VHD than those without VHD.(Table 2)

Conclusion:
Valvular heart diseases have significant impact on the in hospital outcomes of patients admitted with ITP. Considering the possibility of reciprocal influence, there is a further scope for prospective studies to establish bidirectional association which can give way to promising options to improve outcomes in patients with valvular heart disease who develop ITP and can also aid in pre-operative risk stratification for valvular surgeries
Abstract 4139501: Transthoracic Transmitral Atrial Flow is Independently Associated with Ischemic Stroke Risk in Patients with Paroxysmal Atrial Fibrillation
Authors: Chua Su-kiat , Huang Pang-Shuo , Chen Jien-jiun , Chiu Fu-chun , Hwang Juey Jen , Wang Chih-hsien , Tsai Chia-Ti
Published: November 2024

Background:
Atrial fibrillation (AF) is a major risk factor for ischemic stroke. Prior studies have shown that reduced blood flow velocity in the left atrial appendage, measured by the invasive transesophageal echocardiography (TEE) procedure, is associated with higher stroke risk. However, TEE is an invasive procedure with inherent risks. In this study, we aimed to investigate whether transmitral atrial flow velocity (MVA) obtained through the non-invasive transthoracic echocardiography (TTE) technique could also predict the risk of stroke in patients with AF.

Methods:
We conducted a longitudinal cohort study of 10,150 patients with paroxysmal AF who underwent TTE to assess MVA. The patients were followed up from January 2010 to December 2021, with the primary outcome being hospitalization for ischemic stroke.

Results:
Over a mean follow-up of 4.26±3.52years, 2419 (23.8%) patients developed ischemic strokes (5.59% per 100 person-years). Patients with MVA < 50 cm/s had a higher stroke incidence rate than those with MVA ≥ 50 cm/s (6.57% vs 5.47%, P<0.001). On multivariable analysis adjusting for CHA
2
DS
2
-VASc score, MVA was independently associated with stroke incidence. Every 10 cm/s reduction in MVA velocity conferred 4% higher stroke risk (adjusted hazard ratio [HR] 0.96 [0.94-0.97], P<0.001). AF patients with MVA < 50 cm/s had a 39% increase in stroke risk compared to those with MVA ≥ 50 cm/s (adjusted HR 1.39 [1.22-1.58], P<0.001). In patients with CHA
2
DS
2
-VASc score 0 or 1, the stroke incidence increased from 1.33 % to 2.28% when they had MVA < 50 cm/s, which was similar to those with CHA
2
DS
2
-VASc score 2 points (2.51 %).

Conclusions:
Reduced transthoracic MVA independently predicts higher ischemic stroke rates in paroxysmal AF patients. MVA assessment easily enhances risk stratification and could help guide targeted stroke prevention therapies, especially in low-risk patients with CHA
2
DS
2
-VASc scores of 0 or 1.
Abstract 4139502: Projected Impact of GLP-1 adoption on 5-year coronary stent rates among Medicare beneficiaries with cardiovascular disease
Authors: Rathore Saif , Epstein Andrew , Zuk Eric , Curtis Jeptha
Published: November 2024

Background:
Semaglutide reduced 5-year rates of coronary revascularization by 23% in SELECT. The impact of broader adoption of glucagon-like peptide 1 (GLP-1) agonists on coronary stent use among elderly patients with cardiovascular (CV) disease is unclear.

Methods:
To project the impact of GLP-1 adoption on 5-year rates of coronary stent use, we analyzed claims data for the 5% random sample of fee-for-service Medicare and Medicare Advantage beneficiaries identified in 2016 (n=1,847,213). Patient risk for CV events was derived using the REGARDS study administrative CV risk algorithm. Five-year observed coronary stent use was based on treatment in 2017–21. The unadjusted association between derived CV event risk and observed stent use was modeled as a flexible linear spline. Projected impact of increased GLP-1 use on patients’ 5-year risk of stent use was calculated by applying SELECT estimates of coronary revascularization reduction (HR 0.77 95% CI 0.68–0.87) to patients’ REGARDS-derived CV event risk and estimating stent use at the GLP-1-driven reduced derived CV event risk level. We projected impact on 5-year stent use as GLP-1 use increased from 0% to 100% of beneficiaries under 4 CV risk-based adoption scenarios: highest CV risk first; lowest CV risk first; median CV risk patients first (base case); and random adoption.

Results:
Sixty percent adoption of GLP-1 (current statin use) by median CV risk patients first would reduce coronary stent use overall by 6.9% (95% CI 3.6%–9.8%). Impact varied by role of CV risk in GLP-1 adoption, with 60% use in highest CV risk patients first resulting in 21.5% (95% CI 14.3%–25.8%) reduction as opposed to 5.9% (95% CI 3.3%–8.3%) if driven by population with 60% lowest CV risk (Figure). Adoption by 25% highest CV risk would achieve 70% benefit of complete population use. Reductions varied more than two-fold across hospital referral regions (HRRs) in the base case, ranging from 4.5% (95% CI 2.4%–6.1%) to 9.2% (95% CI 4.7%–13.3%); the highest CV-risk-first approach impact ranged from 13.6% (95% CI 9.0%–16.8%) to 30.7% (95% CI 20.7%–35.6%).

Conclusion:
GLP-1 adoption by Medicare beneficiaries comparable to current statin use could reduce coronary stent use nationally by 6.9% if focused on median CV risk, but up to 21.5% if focused on highest CV risk patients first. Impact varies by HRR, with high GLP-1 use among highest CV risk patients reducing stent use as much as >30%.
Abstract 4139555: Transitions Between Heart Failure States in Adult Patients with Congenital Heart Disease
Authors: Zhang Emily , Wang Qiyu , Fan Yining , Liu Aihua , Yang Yi , Marelli Ariane
Published: November 2024

Background:
The growing number of adult congenital heart disease (CHD) patients facing heart failure (HF) related complications after the age of 40 has become a major concern. There is a lack of data to capture the dynamic nature of HF progression across the adulthood, with the consideration of various contributing factors. This application of multistate models paves a promising way to accurately track health state changes, thus to provide data to inform surveillance and interventions to prevent disease progression, potentially improving personalized treatment plans for a significant patient population.

Aims:
This study aimed to (1) determine the expected time a patient remains in each HF state, based on predisposing factors; (2) evaluate the probabilities that, across different ages, a patient will either remain at the same state, transition to the next HF state, or die; (3) identify the risk factors of transitioning between health states related to HF among CHD patients.

Methods:
The dataset was derived from the Quebec CHD database which encompasses 137,493 patients, spanning 35 years of follow-up from 1983 to 2017. We constructed a multistate model to include 6 states: no HF history (0HF), having one (1HF), two (2HF), three (3HF) or more than four HF events (4+HF), and death. Each HF state transition was modeled by Cox proportional hazards regression using the same predictors, including sex, presence of severe congenital heart defects, and comorbidity history.

Results:
The study included 83,669 adult patients with CHD. Among them, 32,934 HF events and 16,348 deaths were observed during a total of 1,732,942 person-years of follow-up. With each HF occurrence, patients showed faster progression to subsequent HF events. Patients with severe CHD lesion had nearly two decades fewer HF-free years compared to those with non-severe lesions (Figure). Early age of initial HF increased the risk of additional HF events and mortality. Comorbidities such as diabetes and chronic kidney disease markedly reduced the duration that a CHD patient remains HF-free.

Conclusion:
The study findings highlight the need for early intervention and personalized treatment strategies in managing HF progression in CHD patients.
Abstract 4139565: Association of transcatheter edge-to-edge repair with clinical outcomes in atrial functional mitral regurgitation
Authors: Naser Jwan , Massad Faysal , Scott Christopher , Borlaug Barry , Pellikka Patricia , Kennedy Austin , Simard Trevor , Enriquez-Sarano Maurice , Nkomo Vuyisile , Michelena Hector , Pislaru Sorin
Published: November 2024

Background:
Atrial functional mitral regurgitation (AFMR) constitutes ~25% of ≥moderate MR and has been associated with a high prevalence and incidence of HFpEF. Transcatheter edge-to-edge repair (TEER) has shown effectiveness in improving symptoms in AFMR, but its impact on mortality and HF hospitalizations is unknown.

Objective:
Evaluate rates of mortality and HF hospitalizations in patients with ≥moderate AFMR treated with TEER and compare them to conservative management.

Methods:
Consecutive adults with ≥moderate AFMR (functional MR with left atrial enlargement, ejection fraction≥50%, and absent >mild left ventricular enlargement) were identified retrospectively. Ecxlusion criteria were previous cardiac surgery, ≥moderate aortic regurgitation/stenosis, infiltrative/hypertrophic cardiomyopathy, regional wall motion abnormalities or malignancy. Propensity score matching was performed (1:1 ratio) between patients treated with TEER and patients treated conservatively based on age, sex, EuroScore II, effective regurgitant orifice area, and the integrative MR severity. To ensure similar technique in evaluation in the 2 groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group [median 65 (IQR 29-111) days].

Results:
Overall, 46 patients with ≥moderate AFMR treated by TEER and 46 treated conservatively were included,
Table 1
. Patients undergoing TEER had more frequent atrial fibrillation and NYHA class ≥III. MR improved to ≤moderate in 93% of patients undergoing TEER on procedural transesophageal echocardiography,
Figure 1
. On 1–3-month post-TEER follow-up, 64% had NYHA class I/II (vs 33% pre-TEER),
Figure 1
. Over median 2.2 (IQR 1.2-3.1) years, 32 patients died (rate 13%/year in each group, log-rank p=0.85),
Figure 2
. When adjusted for baseline NYHA, rates of HF hospitalizations were not different between the groups (Wald-test p-value=0.48). Residual ≥moderate AFMR in the TEER group was not associated with mortality (log-rank p=0.83), but ≥1 class improvement of NYHA in patients with baseline NYHA >1 was associated with decreased mortality,
Figure 2
.

Conclusion:
MR severity and NYHA class improved with TEER for AFMR, and improved NYHA class was associated with decreased mortality. However, the association of TEER with decreased risk of mortality or HF hospitalization remains unproven, and larger randomized studies are needed to evaluate the potential role of TEER on these outcomes in AFMR.
Abstract 4139575: Feasibility and safety of left bundle branch area pacing in amyloid light chain cardiac amyloidosis
Authors: Yu Jiaqi , Yang Deyan , Wang Jiaqi , Fan Jingbo , Liu Yongtai , Gao Peng , Deng Hua , Chen Taibo , Cheng Zhongwei , Zhang Lihua , Lai Jinzhi , Qin Xiaohan , Cheng Kangan , Li Jian , Fang Quan
Published: November 2024

Background:
Left bundle branch area pacing (LBBAP) has been persuasively adopted in clinical practice to achieve electrical and mechanical synchrony of the left ventricle. However, LBBAP in amyloid light chain cardiac amyloidosis (AL-CA) patients has not been studied in detail.

Hypothesis:
LBBAP could be a feasible and safe approach to rectify the conduction system diseases of AL-CA patients.

Aim:
To study the feasibility and safety of LBBAP in AL-CA patients.

Methods:
Consecutive patients with AL-CA and newly implanted pacemaker in our centre between 1st January 2022 and 31st December 2023 were retrospectively included. The diagnosis of AL-CA was confirmed according to the current ESC position statement. Indications for pacemaker fulfilled the current ESC guideline. All patients underwent attempts of LBBAP or right ventricular pacing (RVP) based on operators’ preference.

Results:
A total of 10 patients were included. RVP was chosen initially in 1 patient and LBBAP was attempted in 9 patients. LBBAP were successfully performed in 6 patients (66.7%, 6/9). Three patients crossed over to RVP group because LBBAP was failed to achieve
(Fig.1)
.

Baseline clinical characteristics and pacing parameters was compared between LBBAP group and RVP group (
Table.1
). Duration of intrinsic QRS was similar and paced QRS was wider in RVP group (
P
=0.029).

During follow-up, one patient in LBBAP group died from sudden death 15 days after implantation, while 2 patients in RVP group died from sudden death and pneumonia 55 days and 17 days after implantation, respectively. Seven patients visited our centre at three-month follow-up without adverse events and interrogation reports were summarized in
Fig.1
.

Conclusion:
LBBAP appears to be a reasonable method for physiological pacing for patients with AL-CA and bradycardia, but its impact on long-term prognosis needs further investigation.
Abstract 4139609: Impact of Metformin on Cardiovascular Outcomes in Breast Cancer Patients Receiving Chest Radiation Therapy
Authors: Idowu Abiodun , Adebolu Olayinka , XObomanuX XElvisX , Okwuosa Tochi
Published: November 2024

Introduction:
Metformin has anti-inflammatory and anti-oxidant properties that have been associated with protective effects against radiation in animal studies. However, there is limited evidence demonstrating similar effects in humans. This study evaluated the impact of metformin on cardiovascular outcomes in breast cancer patients receiving chest radiotherapy.

Methods:
A retrospective propensity-matched analysis of women aged 18-65 with breast cancer who received chest radiotherapy between January 1, 2000, and December 31, 2018, using the TriNetX database. The patients were categorized into two groups - metformin users (used metformin within 3 months before or after exposure to chest radiation therapy) and metformin non-users. Adjusted odds ratio (aOR) for outcomes was calculated and the Kaplan-Meier survival curve using log-rank tests for a five-year follow-up was performed. All analyses were performed using R software.

Result:
131 patients were propensity-matched to each group (Table 1). None of the patients was dialysis-dependent or had chronic liver disease and none was taking SGLT2i. The median number of days of follow-up was 1825 days. Major adverse cardiovascular events – MACE, a composite of all-cause mortality, Heart failure, Myocardial infarction, and cerebrovascular accident - were comparable between metformin users and non-users (19.8% vs 19.3%, aOR: 1.03, 95%CI: 0.54-1.97, p=0.923). Survival probability at 5 years was also comparable in both groups (78.5% vs 79.1%, Hazard ratio = 1.04, 95% CI (0.59 – 1.86), p=0.89) (fig. 1).

Conclusion:
Metformin use around the time of radiation therapy did not significantly lower or increase the future risk of MACE in breast cancer patients.
Abstract 4139632: Narciclasine Reverses Vascular Aging and Atherosclerosis by Suppressing SPP1-mediated Inflammation Signals
Authors: Fang Zhiyi , Wang Linghuan , Fang Yan , Chen Renzheng , Zhang Weiwei , Li Hui , Chen Sijia , Shen Xiaoying , Zhang Yingjie , Cao Ruihua , Cao Feng
Published: November 2024

Objective:
The senescence of smooth muscle is one of the significant risk factors in atherosclerosis progression in which the vascular inflammation plays an important role on dysfunction. This study is designed to explore the novel vascular aging inflammation biomarkers and screen the potential molecular interventional targets through bioinformatic analysis.

Methods&Results:
The transcriptional analysis on GSE16487 database from 15 human vascular tissue samples, 8 from less than 60 yro (young group) and 7 from older than 75 yro (Aged group). The comparison between two groups contained 252 (114 upregulated and 138 downregulated) DEGs with minimum 1.5-fold change. As shown in FigA-B, 114 upregulated genes were mainly involved in 5 biological processes and 5 signaling pathways using GO and KEGG functional enrichment analysis. PPI network results indicated that 9 genes had interactions at medium confidence (score＞0.415), which are mainly included the GO and KEGG inflammation-related terms
leukocyte cell-cell adhesion, Cytokine-cytokine receptor interaction, TGF-beta signaling pathway
and
regulation of T cell activation
(Fig C). Furthermore, the association between 9 genes and vascular aging was validated in an independent cohort (GSE117715, GSE116277, GSE130727) and senescent VSMCs induced by 250 μM oleic acid (OA). ssGSEA analysis results revealed a higher abundance of Tem and Th2 cells within aged vascular tissues, indicating that the local inflammation activated the immune system and immune cell recruitment (p<0.05) (Fig D). To further screen novel therapeutics, all DEGs expression data were uploaded to CMap database. The results showed that narciclasine, known as RhoA activator, may alleviate inflammation-related vascular aging by regulating SPP1-mediated cytokines release(Fig E-G).
In vitro
experiments demonstrated that narciclasine alleviated senescence of VSMCs(p<0.05).
In vivo
experiments revealed that narciclasine treatment reduced aortic plaque area and diminished lipid core size within atherosclerotic plaques in ApoE
-/-
mice fed a high-fat diet(p<0.05).

Conclusion:
The 9 inflammatory biomarkers were screened and validated in senescent VSMCs. The compound narciclasine can regulate SPP1-mediated cytokines release to suppress inflammation signals and alleviate vascular aging. This research explores potential inflammation-related biomarkers and interventional targets for alleviating vascular aging.
Abstract 4139637: Artificial Intelligence ECG Mapping of Biventricular Pacing QRS Morphology Predicts Response to Cardiac Resynchronization Therapy
Authors: Oliver Kendall , Hull Stephanie , Velasquez Mariana , Hall Peter , Ho Gordon , Han Frederick , Hoffmayer Kurt , Hsu Jonathan , Raissi Farshad , Feld Gregory , McCulloch Andrew , Choudhuri Indrajit , Villongco Christopher , Birgersdotter-Green Ulrika , Krummen David
Published: November 2024

Background:
Cardiac resynchronization therapy (CRT) is an important treatment modality for patients with heart failure and electrical dyssynchrony. A current limitation is that approximately 30% of patients do not respond, and identification of patients at greater risk for suboptimal outcome remains challenging.

Hypothesis:
We hypothesized that an artificial intelligence (AI) ECG mapping system would identify maladaptive ECG activation patterns in non-responders to CRT-defibrillator (CRT-D) therapy.

Aims:
We endeavored to analyze the biventricular-paced 12-lead ECG QRS complex using a novel AI tool and compare the projected segment of origin between responders and non-responders.

Methods:
We enrolled patients with heart failure 6 months or more after CRT-D implantation. ECG samples obtained during routine clinical follow-up during LV, RV, and BiV pacing were analyzed with an AI-based ECG mapping system. The projected segments of origin for each pacing setting were noted using a validated 30 segment ventricular model. CRT responders were defined as ≥5% increase in LVEF at 6 to 12 months post-implantation.

Results:
Of 49 study patients, 35 were responders (age 74±9 y, LVEF 28±9%, 31% female) and 14 were non-responders (age 68±12 y, LVEF 32±5%, 20% female). LVEF increased in responders by 15±7% and decreased in non-responders by 3±5% (p<0.001). Biventricular-paced ventricular activation patterns were significantly different between responders and non-responders: in non-responders, 8 of 14 patients (57.1%) had an activation pattern identified as mid to apical anterior or anteroseptal (Figure A) versus 6 of 35 responders (Figure B, 17.1%, p= 0.012). Left ventricular and right ventricular activation mapping results were not predictive.

Conclusions:
A maladaptive biventricular-paced electrical activation pattern, localized to the mid- or apical anteroseptal region of the LV, is associated with non-response to CRT. Studies of intraprocedural noninvasive LV activation mapping to improve target LV pacing site selection and response to CRT are underway.
Abstract 4139660: Human IL-8 BAC Transgenic Mice Reveal the Causative Role of IL-8 in Neointima Hyperplasia
Authors: Zhang Wei , Pan Lihua , wu xiaoliang , Dong Kunzhe , Long Xiaochun
Published: November 2024

Interleukin-8 (IL-8, aka CXCL8) is a chemokine produced by multiple proinflammatory cells. A high level of serum IL-8 is correlated with increased risk of cardiovascular diseases; diseased vessels frequently express high levels of IL-8. Despite these correlations, it remains largely unknown whether IL-8 plays a causative role in vascular disease owing to the lack of mouse ortholog of
IL-8
and thus knockout mouse models. To address the knowledge gap, we applied a bacterial artificial chromosome (BAC) transgenic (Tg) mouse model which carries the whole
IL-8
gene locus as well as the surrounding regulatory elements to enable the pathophysiological expression of IL-8 in mice. As expected, the expression of IL-8 in the BAC Tg mice is substantially induced by vascular injury and ex vivo culture condition. To determine the role of IL-8 in vascular stenosis, we subjected BAC Tg mice to complete carotid artery ligation injury. We found that neointima formation is significantly increased in BAC Tg mice compared with WT controls; the neointima in Tg mice displays increased accumulation of MAC2 and PCNA positive cells. To further pinpoint the causative role of IL-8 in the phenotype seen in BAC Tg mice, we applied IL-8 antibody to neutralize IL-8 produced in the injured carotid arteries using Pluronic gel immediately after ligation surgery in the BAC Tg mice. We found IL-8 antibody significantly attenuated neointima formation compared with IgG control. Our studies, for the first demonstrated a causative role of IL-8 in neointima formation, suggesting that IL-8 is a potential therapeutic target for vascular stenosis. Our study also indicates BAC
IL-8
Tg could serve as a useful tool for investigating the role of IL-8 in various vascular pathologies.
Abstract 4139708: Social determinants of health in early pregnancy and racial and ethnic differences in cardiovascular health 2-7 years after delivery
Authors: Huang Xiaoning , Petito Lucia , Yee Lynn , Cameron Natalie , Haas David , Mercer Brian , Parry Samuel , Saade George , Silver Robert , Simhan Hy , Reddy Uma , Varagic Jasmina , Licon Ernesto , Greenland Philip , Lloyd-Jones Donald , McNeil Rebecca , Kershaw Kiarri , Grobman William , Khan Sadiya , venkatesh kartik
Published: November 2024

Background:
Racial and ethnic disparities exist in cardiovascular health (CVH) in pregnancy. While social determinants of health (SDOH) affect CVH, the extent to which SDOH assessed in early pregnancy explain racial and ethnic differences in CVH postpartum remains to be defined.

Objective:
This study examines the relative contribution of SDOH in early pregnancy to racial and ethnic differences in maternal CVH 2-7 years after delivery.

Methods:
This is a secondary analysis of the prospective nulliparous pregnancy outcomes study: Monitoring Mothers-to-be Heart Health Study (nuMoM2b-HHS) cohort. The outcome was maternal CVH defined using the American Heart Association’s Life’s Essential 8 (LE8) framework, which included body mass index, blood pressure, lipids, fasting glucose, diet, physical activity, sleep health, and smoking status, and calculated as a score of 0-100. We used the Blinder-Oaxaca decomposition to quantify the statistical contributions of differences in demographic (age and nativity), socioeconomic status ([SES], education, income, insurance, and health literacy), and psychosocial (resilience, social support, anxiety, depression, and stress) factors in early pregnancy to differences in mean postpartum CVH between the two largest self-identified minoritized racial and ethnic groups (non-Hispanic [NH] Black and Hispanic) and NH White individuals.

Results:
Of 4,161 assessed pregnant individuals, 17.7% identified as Hispanic, 15% as Black, and 67.3% as White. After adjusting for demographic, SES, and psychosocial factors, the average CVH score in White individuals was 12.2 (SE 1.2) points higher (better) than in Black individuals and 3.3 (SE 0.8) points higher than in Hispanic individuals (
Figure
, all p<0.001). If the distribution of SES factors among Black and Hispanic individuals were similar to White individuals, the CVH score would be 6.6 (SE 0.8) points higher (better) in Black individuals (i.e., 50% of the CVH difference) and 3.9 (SE 0.6) points higher in Hispanic individuals (i.e., 100% of the CVH difference).

Conclusions:
The majority of racial and ethnic differences in CVH 2-7 years after delivery were explained by differences in SES factors present in early pregnancy. Public health and structural policies that target SES factors in or before pregnancy may reduce racial and ethnic disparities in postpartum maternal CVH.
Abstract 4139711: Does Left Ventricular Dysfunction Assessed by Global Longitudinal Strain Affect Outcomes After Transcatheter Aortic Valve Implantation?
Authors: matsubara yuki , Yamano Michiyo , Yamano Tetsuhiro , Fujimoto Tomotaka , Yashige Masaki , Zen Kan , Nakamura Takeshi , Matoba Satoaki
Published: November 2024

Background:
Left ventricular (LV) global longitudinal strain (GLS) has been reported to decline before LV ejection fraction (EF) in patients with aortic stenosis (AS). The decrease in LVEF has been reported to result in poor prognosis after transcatheter aortic valve implantation (TAVI). However, the relationship between the degree of LV dysfunction caused by AS and the post-procedural outcomes has not been fully elucidated.

Research questions:
Is there a difference in the clinical outcome after TAVI according to the degree of LV dysfunction?

Aim:
The purpose of this study is to determine the relationship between the degree of LV dysfunction and outcomes after TAVI.

Methods:
This was a single-center, retrospective cohort study, in which 150 of 347 consecutive patients undergoing TAVI were included, excluding atrial fibrillation, inadequate echo image for analysis, and loss to follow-up echocardiography. The degree of LV dysfunction was classified into Grade I (EF ≥50%, GLS ≤-15%), Grade II (EF ≥ 50%, GLS > -15%), and Grade III (EF < 50%), and baseline echocardiographic parameters and changes from baseline to intermediate follow-up (6 months to 1 year) were compared between groups.

Results:
Baseline characteristics showed significant differences in the incidence of symptomatic heart failure. Baseline echocardiographic parameters were significantly impaired according to grade progression (Table). Although patients with Grade III showed improvement in cardiac function, significant differences remained in LV diastolic diameter, LV mass index, LVEF, and LV-GLS compared with those with Grade I. On the other hand, patients with Grade II showed improvement in LV diastolic diameter, LV mass index, and LVEF, resulting in values comparable to Grade I. However, regarding LV-GLS, although patients with Grade II showed improvement as well as Grade III, it did not improve to the same level as Grade I (Figure).

Conclusions:
The present study suggests that patients with impaired LV-GLS without reduced LVEF have a better improvement in cardiac function after TAVI compared to patients with reduced LVEF. The optimal timing of TAVI may be in the earlier stages of the deterioration of LV-GLS.
Abstract 4139718: Five-Year Real-World Clinical Outcomes After Intravascular Imaging Device-Guided Percutaneous Coronary Intervention with Paclitaxel-Coated Balloon versus Durable-Polymer Everolimus-Eluting Stent
Authors: Ariyasu Wataru , Ishihara Takayuki , masuda masaharu , Okamoto Shin , Nanto Kiyonori , Tsujimura Takuya , Matsuda Yasuhiro , Hata Yosuke , Uematsu Hiroyuki , NAKAO SHO , Kusuda Masaya , Kudo Satoshi , Fujii Subaru , Mano Toshiaki
Published: November 2024

Background:
Paclitaxel-coated balloon (PCB) has been used for the treatment of coronary artery disease in the small native coronary artery and its safety and efficacy have been reported in clinical trials.

Research Questions:
The real-word long-term outcomes after intravascular imaging device-guided percutaneous coronary intervention (PCI) with PCB have not fully elucidated.

Aims:
To elucidate the long-term outcome after PCB treatment.

Methods:
This was a single-center, retrospective and observational study. We enrolled 1226 lesions from 713 patients which were treated by intravascular imaging device-guided PCI with PCB (342 lesions from 211 patients) or durable-polymer everolimus-eluting stent (DP-EES, 784 lesions from 502 patients) which diameter was less than 3.0 mm in the native coronary arteries. Long-term clinical outcomes were compared between PCB and DP-EES. Primary outcome was major adverse cardiac event (MACE) defined as a composite of cardiac death (CD), myocardial infarction (MI), target vessel revascularization (TVR) and device thrombosis. Secondary outcomes were all-cause death, CD, MI, target lesion revascularization (TLR), TVR and device thrombosis. Cumulative incidences of clinical outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) of PCB relative to DP-EES for MACE were estimated through a multivariable Cox model and an inverse probability weighted (IPW).

Results:
Cumulative 5-year incidence of MACE was similar between PCB and DP-EES (18.5% vs. 20.7%, P=0.78, Figure). Cumulative 5-year incidences of all-cause death (23.2% vs. 16.8%, P=0.12), CD (8.0% vs. 7.0%, P=0.81), MI (2.2% vs. 2.5%, P=0.97), TLR (5.9% vs. 8.9%, P=0.35), TVR (12.6% vs. 14.4%, P=0.90) and device thrombosis (0% vs. 0.6%, P=0.20) were also similar between PCB and DP-EES. Even after adjustment for baseline characteristics, cumulative 5-year incidence of MACE was similar between PCB and DP-EES (multivariate and IPW adjusted HRs 0.72 [95% CI: 0.37-1.39], P=0.33 and 0.67 [95% CI: 0.21-2.07], P=0.48, respectively).

Conclusion:
PCB demonstrated comparable 5-year clinical outcomes with intravascular imaging device-guided PCI compared to DP-EES.
Abstract 4139757: COVID-19-Related Changes in Dalily Life, Concerns, and Their Associations with Sleep Disturbances
Authors: Cho Sung-il , Kim Young-Mee
Published: November 2024

Background:
The COVID-19 pandemic has significantly exacerbated sleep problems. Pandemic-related lockdowns and drastic changes in daily life have disrupted sleep patterns, resulting in a marked increase in sleep disturbances.

Research questions:
This study aims to investigate the primary factors contributing to the increase in sleep disturbances during the COVID-19 pandemic in Korea. By utilizing nationally representative data encompassing various variables, this study seeks to identify COVID-19-related factors associated with sleep disturbances during the pandemic.

Method:
We analyzed data from the nationally representative Korea Community Health Survey conducted in 2020, including 216,809 adults. Changes in daily life due to COVID-19 were assessed by asking participants to score their current situation compared to their pre-pandemic situation, ranging from 100 (no change) to 0 (complete cessation of daily activities). COVID-19 concerns were assessed with five questions: 1) fear of contracting the virus; 2) fear of mortality if infected; 3) fear of blame from others; 4) concerns about the health of vulnerable family members; and 5) concerns about economic impacts. Sleep disturbances were defined as sleeping 5 hours or less per night on average. Logistic regression analyses with a complex sample design were performed to examine the relationship between COVID-19-related factors and sleep disturbances, adjusting for socioeconomic and health-related variables.

Results:
A high level of lifestyle changes due to COVID-19 (OR = 1.15, 95% CI = 1.11–1.19) and high COVID-19 concerns (OR = 1.04, 95% CI = 1.01–1.08) were associated with an increased likelihood of sleep disturbances. Conversely, resting during COVID-19 symptoms (OR = 0.81, 95% CI = 0.76–0.87), having support during quarantine (OR = 0.93, 95% CI = 0.89–0.97), and trust in the government and neighbors (OR = 0.92, 95% CI = 0.89–0.96) were associated with a decreased likelihood of sleep disturbances.

Conclusion:
These findings suggest that sleep disturbances during the COVID-19 pandemic were mediated by lifestyle disruptions and high levels of concern. Social support and trust mitigated the impact of COVID-19-related risk factors. As part of preparedness, improving the environment to facilitate adequate rest during illness, ensuring strong social support, and fostering high levels of trust in the government and neighbors may be important to protect sleep health during future public health emergencies.
Abstract 4139776: Correlation of Skin Sympathetic Nerve Activity (SKNA) with Renal Sympathetic Nerve Activity (RSNA) in Rats: A Novel Non-Invasive Indicator of Sympathetic Activity
Authors: Nakashima Ryosuke , Shinohara Keisuke , Ikeda Shota , Matsumoto Sho , Yoshida Daisuke , Ono Yoshiyasu , Nakashima Hiroka , Miyamoto Ryohei , Abe Kohtaro
Published: November 2024

Introduction:
The sympathetic nervous system plays a crucial role in cardiovascular regulation and in the pathophysiology of cardiovascular diseases such as hypertension, arrhythmias, and heart failure. Therefore, assessment of sympathetic nerve activity is important for understanding the pathophysiology in patients with cardiovascular disease. In humans, the gold standard for indicators of sympathetic nerve activity is muscle sympathetic nerve activity recording, but this is invasive and not a versatile method because it requires special techniques and equipment. Recently, skin sympathetic nerve activity (SKNA) has been reported as a novel indicator of cardiac sympathetic nerve activity derived from non-invasive ECG recording in humans. However, the utility and validation of SKNA have not been fully established.

Research Question:
Does SKNA truly reflect sympathetic nerve activity?

Aims:
To evaluate whether SKNA correlates with renal sympathetic nerve activity (RSNA), an established measure of sympathetic activity, in experimental animals.

Methods and Results:
Blood pressure, heart rate, RSNA, and SKNA were measured simultaneously in Sprague-Dawley rats under anesthesia. RSNA was recorded directly using bipolar electrodes, and SKNA was isolated from body surface ECG recordings by band-pass filtering to remove electrocardiograms and electromyograms. Changes in RSNA and SKNA were evaluated when blood pressure was altered by intravenous phenylephrine or nitroprusside and when the sympathetic nervous system was blocked by intravenous hexamethonium, a ganglion blocker. Baroreceptor reflexes functioned; RSNA decreased when blood pressure was raised with phenylephrine and increased when blood pressure was lowered with nitroprusside. SKNA was altered similarly to these RSNA responses (Figure A). In addition, administration of the ganglion blocker hexamethonium markedly attenuated RSNA, and SKNA was attenuated similarly to RSNA. Changes in SKNA in response to phenylephrine or nitroprusside were significantly correlated with changes in RSNA (r
2
=0.54, p <0.05; Figure B).

Conclusion:
SKNA correlates with RSNA, an established measure of sympathetic activity, in rats. Our study confirms that SKNA can be an alternative, novel indicator of sympathetic activity. This non-invasive SKNA recording will allow for application to animal experiments under unanesthetized awake conditions.
Abstract 4139802: The Safety and Efficacy of Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jafar Uzair , Khan Muhammad Sami , Hashmi Tallal Mushtaq , Ijaz Maryam , Jehangir Hanzala , Jagani Sanjna Devi , Munawar Irja , Khalid Ayesha , Maqsood Maham , Akram Muhammad Faiq , Saeed Usman , Ahmad Adeel
Published: November 2024

Background:
SGLT2 inhibitors improve cardiovascular outcomes in patients with heart failure and chronic kidney disease. However, the evidence on their efficacy in patients who have had acute myocardial infarction is still lacking. This systematic review and meta-analysis aimed to assess the safety and efficacy of SGLT2 inhibitors on cardiovascular outcomes in patients with a recent acute myocardial infarction.

Methods:
We searched various electronic databases including MEDLINE (via PubMed), Embase, the Cochrane Library, and Clincaltrials.gov to retrieve randomized controlled trials comparing SGLT2 inhibitors to placebo in patients with acute myocardial infarction. We performed statistical analysis on RevMan 5.4 using the random effect model. We reported dichotomous outcomes as relative risk (RR) along with 95% confidence intervals (CI) and continuous outcomes as mean difference (MD) along with 95% CI.

Results:
Our meta-analysis included 6 RCTs involving 11,256 patients. SGLT2i significantly decreased the rate of hospitalization for heart failure (RR 0.73, 95% CI: 0.61-0.88, I2=0%) with no significant change in mortality (RR 1.05, 95% CI: 0.78-1.40, I2=25%). There was no significant change between the two groups when assessing the rate of all-cause hospitalization (RR 1.00, 95% CI: 0.84-1.17, I2=%), cardiovascular death (RR 1.03, 95% CI: 0.83-1.28, I2=%), hepatic injury (RR 1.99, 95% CI: 0.54-7.40, I2=%), ketoacidosis (RR 2.00, 95% CI: 0.18-22.01, I2=%), hypoglycemia (RR 0.80, 95% CI: 0.21-2.97, I2=%), or lower limb amputation (RR 1.80, 95% CI: 0.60-5.36, I2=%). The mean change in NT-pro BNP (MD -0.28 95% CI: -0.61-0.05, I2=0%] and LVEF at follow-up (MD 0.62, 95% CI -0.73-1.97, I2=0%] were also comparable between the two groups.

Conclusion:
SGLT2i reduces the rate of hospitalization for heart failure with no change in mortality or other cardiovascular outcomes. Further high-quality and large-scale RCTs are required to confirm or refute our findings and provide more reliable results.