bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4121378: Non-invasive, Automated Approach to Estimate Septal Curvature as a Surrogate of Mean Pulmonary Arterial Pressure for Pediatric Pulmonary Hypertension Patients
Authors: Fujiwara Takashi , Lu Vivian , Ivy Dunbar , Fonseca Brian , Malone LaDonna , Frank Benjamin , Neves da Silva Helio , Sassoon Daniel , Burkett Dale , Browne Lorna , Barker Alex
Published: November 2024

Background:
Pediatric pulmonary hypertension (PH) is diagnosed and monitored using echocardiography and right heart catheterization. Recently, non-invasive measurements using cardiac MRI have also been investigated for patient monitoring. A promising measurement is MRI-based septal curvature, which has excellent correlation with mean pulmonary arterial pressure (mPAP). However, this approach requires significant manual interaction and is subject to observer-dependent measurement variability.

Hypothesis:
Automated septal curvature computation can predict mPAP and is less observer-dependent than the manual approach.

Aims:
To develop an automated approach to measure septal curvature and compare its performance with a manual approach in pediatric PH patients.

Methods:
Pediatric PH patients (mPAP≥25mmHg) who had both a clinical cardiac MR exam and right heart catheterization were retrospectively enrolled. From the mid-slice of short-axis stack images for the ventricles, time-resolved contours for both ventricles were automatically generated with cvi42, and imported to a custom MATLAB tool to automatically compute normalized septal curvature (Fig.1). The minimum normalized curvature (a 7-point average around the minimum value in a cardiac cycle) was computed to investigate its association with mPAP and a composite outcome (death or referral for heart/lung transplant). The new and manual approaches were conducted by two observers to test interobserver agreement. Pearson correlation, univariable logistic regression, receiver-operating characteristic curve, area under the curve (AUC), and intraclass correlation coefficients (ICC) were conducted. P<0.05 was considered statistically significant.

Results:
Twenty-seven patients (14.3±5.4 years; mPAP, 44 [35.5–57] mmHg) were enrolled. Minimum normalized curvature was correlated with mPAP (r=0.78, p<0.001; Fig.2A). Logistic regression found significant association between outcomes and minimum curvature (AUC, 0.88; 95% CI, 0.74–1.00; p<0.001; Fig.3AC). The proposed approach found excellent interobserver agreement (ICC, 0.98; 95% CI, 0.96-0.99) and was similar or superior to the manual one in all performance metrics (manual: correlation with mPAP: r=0.67, p<0.001; AUC: 0.84, 95% CI, 0.69–0.99, p=0.004; ICC: 0.89, 95% CI, 0.81-0.94; Figs.2B,3BD).

Conclusion:
The proposed automated approach to compute septal curvature is less observer dependent than the manual approach and could be a robust tool to follow up pediatric PH patients.
Abstract 4121793: A Pressure-Volume Loops Approach Predicts Outcomes After Double Switch Operation For Congenitally Corrected Transposition Of The Great Arteries with Intact Ventricular Septum
Authors: Thatte Nikhil , Hammer Peter , Marx Gerald , Beroukhim Rebecca , Gauvreau Kimberlee , Callahan Ryan , Prakash Ashwin , Emani Sitaram , Hoganson David , Del Nido Pedro , Ghelani Sunil
Published: November 2024

Background:
Double switch operation (DSO) for congenitally corrected transposition of the great arteries with intact ventricular septum (ccTGA) has a high rate of post-DSO LV dysfunction.

Hypothesis:
LV pressure-volume area (PVA), a surrogate of myocardial O
2
consumption, is a superior marker of LV preparedness and is associated with adverse outcomes after DSO.

Aims:
1. Derive a mathematical relationship to estimate LV PVA (ePVA) from catheterization (pressure) and imaging (volumetric) data, using directly measured PVA (mPVA) as reference 2. Assess if lower ratio of LV ePVA to RV ePVA (as an internal control) is associated with adverse outcome after DSO.

Methods:
Aim 1: Using conductance catheter derived invasive subpulmonary LV PV loops, mPVA was recorded as the sum of stroke work (SW) and potential energy (PE). A mathematical relationship was established with standard catheterization/imaging data to estimate ePVA. Aim 2: In a retrospective cohort, LV:RV ePVA ratio was calculated as above, and along with standard clinical metrics, assessed for relationship with a composite outcome of ≥ moderate LV dysfunction, transplant, or death post-DSO.

Results:
Aim 1: In 20 PV loop studies in 18 pre-DSO patients, there was a strong linear correlation between measured and estimated SW and PE (R
2
> 0.9 and p<0.0001 for both). ePVA yielded high agreement and low bias compared to mPVA (mean bias 0.5±11%). Aim 2: Composite outcome occurred in 6/42 DSO patients (14%). LV:RV ePVA ratio (0.57 [0.49, 0.61] vs 0.90 [0.73, 1.1], p<0.001) and LV:RV pressure ratio (0.80 [0.77, 0.87] vs 1.13 [1.01, 1.23], p<0.001) were lower in those with adverse outcome. There were no differences in other pre-operative parameters. On time to event analysis, lower LV:RV ePVA ratio was the strongest determinant (HR 39, 95% CI 15-100; C Index 0.94), while lower LV:RV pressure ratio was the only other predictor (HR 24, 95% CI 13-42; C Index 0.88). In 8 patients with borderline pressure ratios of 0.77-0.88, ePVA ratio was an excellent discriminator - 3 patients with ePVA ratio of ≥0.67 had good outcomes, whereas 5 patients with ePVA ratio <0.67 had adverse outcomes.

Conclusion:
LV:RV ePVA ratio >0.67 is a strong and novel predictor of LV preparedness for DSO in patients with ccTGA.
Abstract 4121890: Resting Heart Rate Trajectories over 25 Years: Patterns, Predictors, and Prognostic Impact in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Meng Ning , Mok Yejin , Soliman Elsayed , Chen Lin , Ballantyne Christie , Solomon Scott , Matsushita Kuni
Published: November 2024

Background:
Abnormal resting heart rate (RHR) is associated with cardiovascular events and mortality. Longitudinal RHR trajectories may offer unique prognostic, but research exploring these trajectories over extended periods and their prognostic implications is limited.

Methods:
Using data from 5,794 participants in the Atherosclerosis Risk in Communities (ARIC) study, we first characterized RHR trajectories over 25 years (from visit 1 [1987-89] to visit 5 [2011-13]) with latent class growth mixture models. Then, we determined the predictors of those trajectories using multinomial logistic regression (n=5,432 with data on predictors of interest). We ran Cox models to quantify the associations between RHR trajectories with cardiovascular outcomes (coronary heart disease, heart failure, stroke) and all-cause mortality (n=4,329 free of cardiovascular disease at baseline).

Results:
We identified one typical pattern (stable/slight decline, 88.4%) and three atypical patterns (stable-slight increase, 9.2%; increase-decrease, 2.0%; stable-sharp increase, 0.4%) (Figure-Left panel). Obesity, ever smoking, a history of heart failure, and lower education levels predicted the atypical patterns. The stable-increase (combined for slight and sharp) trajectory was significantly and robustly associated with heart failure and all-cause mortality (Figure-Right panel). The increase-decrease trajectory showed a hazard ratio of ~2 for coronary heart disease, although statistical significance was restricted in the demographically adjusted model.

Conclusions:
We identified one typical (stable/slight decline) and three atypical (increase-decrease, stable-slight increase, and stable-sharp increase) RHR trajectories over 25 years. The atypical trajectories, particularly the stable-increase pattern, were associated with poorer prognosis. These findings highlight the value of monitoring long-term RHR trajectories for cardiovascular risk assessment.
Abstract 4122092: Carotid plaque progression predicts persistent endothelial dysfunction in an infarct-related coronary artery in STEMI survivors
Authors: Horikoshi Takeo , Nakamura Takamitsu , Yoshizaki Toru , Kobayashi Tsuyoshi , Sato Akira
Published: November 2024

Background and Aim:
Persistent coronary endothelial vasomotor dysfunction predicts future coronary events; however, performing multiple invasive endothelial function tests is difficult in actual clinical practice. This study examined whether carotid plaque changes can predict persistent coronary endothelial dysfunction using serial assessments of the coronary vasomotor response to acetylcholine (ACh) in the infarct-related artery (IRA) among patients with ST-elevation acute myocardial infarction (STEMI).

Methods:
This study included 169 consecutive patients with a first acute STEMI due to the left anterior descending coronary artery (LAD) occlusion who underwent successful reperfusion therapy with percutaneous coronary intervention. The vasomotor response to ACh in the LAD was measured within two weeks of acute myocardial infarction (AMI) (first test) and repeated at six months (second test) after AMI under optimal anti-atherosclerotic therapy. Ultrasonography of the bilateral common carotid artery (CCA) and internal carotid artery (ICA) was performed during the acute phase, and the thickest intima media thickness (IMT) of either artery was measured as the maximum IMT. After six months, the IMT at the site of maximal IMT was measured to determine whether there was an increase or decrease in IMT.

Results:
Finally, 87 STEMI patients analyzed in this study. At 6 months, 25 patients (28.7%) showed carotid plaque progression. In a multivariable adjusted analysis, carotid plaque progression was identified as an independent predictor of persistent coronary endothelial dysfunction, both in terms of coronary diameter response [OR 3.22, 95% confidence interval1.13 - 9.15, P = 0.03] and coronary flow response [OR 2.65, 95% confidence interval 1.01 - 7.00, P = 0.04].

Conclusions:
Carotid plaque progression could independently predict persistent endothelial vasomotor dysfunction in the IRA of STEMI survivors.
Abstract 4122249: Deletion of macrophage dynamin-related protein 1 exacerbates left ventricular remodeling after myocardial infarction by impairing mitochondrial quality maintenance machinery
Authors: Kondo Yuki , Koga Junichiro , Orkhonselenge Nasanbadrakh , Nishimura Yosuke , Nomura Masatoshi , Kataoka Masaharu
Published: November 2024

Background:
Macrophage-mediated inflammation plays an important role in the healing process after myocardial infarction (MI). We have previously reported in macrophages that inhibition of dynamin-related protein 1 (Drp1), which induces mitochondrial fission, restrains skewing toward inflammatory phenotype. It is, however, obscure whether macrophage Drp1 promotes left ventricular (LV) remodeling after MI.

Aims:
The aim of this study is to elucidate the role of macrophage Drp1 in the mechanisms of LV remodeling after MI.

Methods:
C57Bl/6J mice specifically deficient Drp1 in Lysozyme-M
+
macrophages (Drp1KO) were created by Cre/loxP technology and underwent ligation of the left anterior descending coronary artery at 8 to 12 weeks of age.

Results:
Deletion of macrophage Drp1 decreased LV ejection fraction (38±14 vs. 23±9% at day 28. N=9, p<0.05) and increased LV diameter (LVDd/Ds 5.7±0.4/4.8±0.3 vs. 4.6±0.2/3.7±0.3mm at day 28, N=9, p<0.05) (Figure). Survival rates until 28 days after MI were significantly lower in Drp1KO mice (25 vs. 64%. N=24 and 33, p<0.05). Deletion of Drp1 led to sustained macrophage accumulation and fibrosis of infarcted tissues. TEM revealed that mitophagosomes are decreased in Drp1-deficient macrophages in infarcted hearts. In
ex vivo
cultured macrophages, siRNA-mediated knockdown of Drp1 impaired mitochondrial fission and LC3-dependent mitophagy. In these macrophages, inhibition of Drp1 by Mdivi-1 for 96 hr, but not for 24 hr, induced mitochondrial DNA (mtDNA) leakage to the cytosol accompanied by increased expression of inflammatory cytokines. Hypoxia and starvation, in addition to Mdivi-1, induced leakage of mtDNA and expression of inflammatory cytokines at 24 hr. These results suggest that impairment of mitochondrial quality maintenance machinery causes leakage of mtDNA that induces inflammation.

Conclusions:
Macrophage Drp1 protects the heart from sustained inflammation and adverse cardiac remodeling after MI. Drp1-LC3-mediated mitophagy could be a mechanism that maintains mitochondrial quality and prevents excessive inflammation after MI.
Abstract 4122256: Health Status Outcomes of Nicorandil in Patients With Angina Pectoris: A Prospective, Multicenter, Registry-Based Study
Authors: Zeng Yong , zhao xiliang
Published: November 2024

Background:
Coronary artery disease (CAD) exerts a considerable impact on mortality from cardiovascular disease. Approximately half of patients with CAD initially present with angina pectoris. The GREAT study is designed to establish a large cohort of Chinese patients with angina pectoris and compare the effectiveness of different anti-angina regimens, using the Seattle Angina Questionnaire.

Method:
The GREAT (reGistRy study of medical thErapy in patients with Angina pecToris) Registry is a multicenter, prospective, observational, cohort study that enrolled 1556 adult CAD patients with angina pectoris from nine hospitals in China. The study included patients currently receiving or eligible to receive oral anti-anginal regimens. The cohort was classified into nicorandil and non-nicorandil groups based on the treatment therapies. The primary outcome was the Seattle Angina Questionnaire summary score (SAQ-SS) changes from baseline to 12 months. The SAQ-SS averages the domains of physical limitation, angina frequency, and quality-of-life scores.

Results:
From September 2021 to May 2022, a total of 1575 patients were screened, of whom 1556 met the inclusion criteria and were included (
Figure 1
). Among the patients at the full analysis set (FAS, N=1528), 28.5% were women, and the median age was 61 years. Baseline variables were well balanced after propensity score matching, with both groups containing 450 patients. In the nicorandil group, patients showed a significantly greater increase in mean SAQ-SS score at Month 12 compared to the non-nicorandil group (17.6±14.0 vs 15.1±13.0; difference: 0.19; 95% CI, 0.05-0.32; p=0.003). In addition, patients in the nicorandil versus the non-nicorandil group reported a significantly greater mean improvement in the SAQ-QoL domain (18.9±21.4 vs 16.3±20.4; p=0.042) and SAQ-PL domain (11.7±16.9 vs 10.0±17.0; p=0.001). Over 12 months, a higher proportion of patients in the nicorandil group, compared to the non-nicorandil group, reported substantial improvements in SAQ-SS, with 24.1% experiencing large improvements (20-29 points) and 18.2% reporting very large improvements (≥30 points) versus 20.7% and 12.0%, respectively (p=0.005 across all categories) (
Figure 2
).

Conclusion:
This real-world data indicates that nicorandil-based anti-angina regimens are associated with a greater health status outcome improvement compared to those not using nicorandil in CAD patients.
Abstract 4122948: Lipoprotein(a) associated risk of atherosclerotic cardiovascular disease is independent of C-reactive protein
Authors: Engel Thomas Peter , Vedel-Krogh Signe , Afzal Shoaib , Nordestgaard Borge , KAMSTRUP PIA
Published: November 2024

Background:
Elevated lipoprotein(a), present in 1 in 5 individuals, is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent studies have reached contrasting conclusions on whether low-grade inflammation measured by elevated C-reactive protein (CRP) modifies the risk of ASCVD from high lipoprotein(a). We tested the hypothesis that high lipoprotein(a) associates with risk of recurrent ASCVD irrespective of elevated or low CRP. Additionally, we performed meta-analyses of previous studies on lipoprotein(a)-associated ASCVD risk stratified by CRP levels and by incident or recurrent events.

Methods:
We included 3,543 individuals with prevalent ASCVD from the Copenhagen General Population Study (CGPS), a contemporary, prospective Danish cohort study. Hazard ratios (HR) for ASCVD were examined using multivariable adjusted Cox regressions stratified by CRP (<2 mg/L and ≥2 mg/L). Random-effects meta-analyses in primary (incident events) and secondary (recurrent events) prevention were conducted separately, including studies on lipoprotein(a) and risk of ASCVD stratified by CRP.

Results:
During a median of 7.5 years of follow-up of 3,543 CGPS participants with established ASCVD, 1,425 experienced a recurrent ASCVD event. Multivariable adjusted HRs for ASCVD for high vs. low lipoprotein(a) were 1.41 (95% confidence interval: 1.19-1.67) and 1.31 (1.08-1.59) in individuals with low or elevated CRP with no evidence of effect modification (Figure 1A, p for interaction=0.11). When risk estimates for ASCVD were summarized in separate meta-analyses for primary and secondary prevention settings, a 50 mg/dL higher lipoprotein(a) was robustly associated with increased risk of ASCVD irrespective of CRP levels (Figure 1B). In primary prevention, a 50 mg/dL higher lipoprotein(a) associated with similar summary HRs of 1.18 (1.15-1.20) in low CRP vs. 1.16 (1.14-1.19) in elevated CRP, and likewise in secondary prevention settings, with similar HRs of 1.10 (1.07-1.14) and 1.14 (1.10-1.17), respectively.

Conclusion:
High lipoprotein(a) was associated with increased risk of ASCVD irrespective of CRP levels both in primary and secondary prevention settings.
Abstract 4123371: Hyperoxia is not a significant predictor of ICU mortality and is likely a surrogate parameter for reduced native cardiac function in patients supported with VA-ECMO
Authors: Ruaysungnoen Ryan , Obrien Connor , Baik Alan , Baudart sylvie , strehlow anja
Published: November 2024

Intro:
Hyperoxia has been associated with adverse outcomes in VA-ECMO patients. Whether hyperoxia represents a mechanism of mortality or is a surrogate for worse cardiac function is unknown.

Aim:
To determine patient characteristics, lab values, and hemodynamic parameters associated with increased mortality in VA-ECMO patients.

Methods:
Single-center retrospective cohort study at UCSF in VA-ECMO patients (2020-2023). Patients were categorized into 3 groups: Dead, Advanced Therapy-Free Survivors, and Advanced Therapy Survivors (survived to ICU discharge with LVAD or heart transplant). Wilcox rank sum and two sample proportion tests were performed. In-hospital mortality was evaluated using multiple logistic regression.

Results:
Of 179 patients, 87 died and 92 survived to ICU discharge. Of the survivors, 22 received advanced therapies. Compared to Advanced Therapy-Free Survivors, Dead patients had higher PaO2 levels (297[95% CI,164-400], p = 0.01). Dead and Advanced Therapy Survivors groups had similarly high PaO2 levels, but the latter group showed less acidosis and were more likely to have HFrEF (59%; 13/22; p = 0.02). ECMO support and VIS scores were similar. The multivariate model showed PaO2 is not associated with mortality (adjusted OR, 1.002 [95% CI, 0.99-1.004]; p = 0.131).

Conclusion:
Hyperoxia was associated with both death and advanced therapies, but did not predict mortality in a multivariate model. Advanced therapy survivors and patients that died were more likely to have HFrEF, suggesting that high PaO2 at cannulation reflects a proximal mixing cloud due to weak native cardiac function. Future work will analyze ECHO parameters to examine the association between hyperoxia and reduced cardiac output in VA-ECMO patients.
Abstract 4123530: Disparities in Hypertension Treatment Intensification among Adults in a Large United States Healthcare System
Authors: Meche Aster , Boonyasai Romsai , Hsu Yea-Jen , Greer Raquel , Mehta Hemalkumar , Alexander G Caleb , Segal Jodi , Cooper Lisa , Jackson John
Published: November 2024

Background:
There are racial/ethnic and socioeconomic status (SES) disparities in hypertension control, even in populations with regular care. It is unclear if clinical inertia by clinicians contributes to these disparities.

Objectives:
To quantify racial/ethnic and SES disparities in treatment intensification (TI) among adults with hypertension.

Methods:
We performed a retrospective cohort study using electronic health records from Johns Hopkins primary care practices from January 2018 to December 2022. We included non-Hispanic Black (Black) and non-Hispanic White (White) adults with at least 2 elevated blood pressure readings (>=140/90 mm Hg) in the 12 months prior to the index primary care visit and a diagnosis of essential hypertension. We excluded patients with diagnoses of end-stage renal disease, liver disease, dementia, and metastatic solid tumor. Patients could contribute multiple index visits. We measured SES using the national Area Deprivation Index, which comprises 17 neighborhood-level SES indicators, and dichotomized the population into high and low median SES groups. We defined TI as a change in antihypertensive class or dose increase within 14 days of the index visit. We balanced covariates reflecting clinical need at the index visit (age, sex, blood pressure readings, cardiometabolic comorbidities, body mass index) and the index visit’s calendar time across racial/ethnic and SES groups using inverse probability weighting. We estimated annual race/ethnic and SES specific TI rates and risk difference measures of disparity with 95% confidence intervals (CI) using a clustered bootstrap.

Results:
The cohort included 25,287 patients (11,800 Black, 13,487 White) with 79,898 eligible visits. Black patients were more often younger, female, and residing in low SES areas compared to White patients. In 2018, TI rates for Black patients (37%, 95% CI: 36-38%) were slightly lower than rates for White patients (39%, 95% CI: 38-40%). In 2022, the disparity persisted, with the Black patients’ TI rate lower by 3% (95% CI: -5%, -1%). Similarly, low SES patients had lower TI rates than high SES patients by 2% to 3% over the study period.

Conclusion:
Black patients and those from low SES consistently had modestly lower rates of TI compared to White patients and those from high SES. It will be important to identify the drivers and clinical implications of these treatment disparities.
Abstract 4123826: Very Short-Term Blood Pressure Variability Determined by Pulse Transit Time Predicts Major Adverse Cardiac and Cerebrovascular Event in Patients with Heart Failure
Authors: Sato Yu , Yoshihisa Akiomi , Ohashi Naoto , Takeishi Ryohei , Sekine Toranosuke , Nishiura Kazuto , Ogawara Ryo , Ichimura Shohei , Kimishima Yusuke , Yokokawa Tetsuro , Miura Shunsuke , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Nakazato Kazuhiko , Takeishi Yasuchika
Published: November 2024

Introduction:
It has been reported that day-to-day blood pressure (BP) variability (BPV) is associated with major adverse cardiac and cerebrovascular events (MACCE) in patients with heart failure (HF). However, the clinical significance of beat-to-beat BPV is unclear.

Methods and Results:
We recruited data on patients with HF who underwent nighttime pulse transit time (PTT)-based continuous beat-to-beat BP measurement (n = 379, median age 71, male sex 53.6%). Standard deviation (SD) of PTT-based BP was considered as BPV. The primary outcome was MACCE defined as coronary artery disease, stroke, or death due to HF, acute coronary syndrome or ventricular fibrillation. Median values (25th and 75th percentiles) of SD of PTT-based systolic, diastolic, and mean BP were 4.2 (3.5, 5.3), 3.3 (2.7, 4.1), and 3.4 (2.8, 4.1) mmHg, respectively. During the follow-up period of median 1,083 days after BPV evaluation, 43 patients experienced MACCE. When patients were divided into three tertiles based on the systolic, diastolic, and mean BPV, MACCE occurred more frequently in those with higher tertiles of BPV (
Figure
). In the Cox proportional hazard analysis, systolic, diastolic, and mean BPV as continuous variables were associated with MACCE (hazard ratio, 1.191, 1.228, and 1.243, respectively).

Conclusion:
Beat-to-beat BPV was associated with MACCE in patients with HF.
Abstract 4124039: Aging-Associated Protein Medin Induces Human Coronary Artery Endothelial Proinflammatory and Prothrombotic Activation
Authors: Karamanova Nina , Morrow Kaleb , Maerivoet Alana , Madine Jillian , Li Ming , Migrino Raymond
Published: November 2024

Background:
Age is the most important risk factor for coronary artery disease (CAD), independent of traditional risk factors such as hypertension, diabetes (DM), hyperlipidemia and smoking, through poorly understood mechanisms. Medin, a cleavage product of MFGE8 protein that forms the most common human amyloid, accumulates in the vasculature with age, including the coronary arteries. Although medin amyloid has been implicated in various diseases such as Alzheimer’s disease, vascular dementia and aortic aneurysms, its role in CAD remains unknown. Medin was shown to induce changes characteristic of vascular aging, such as endothelial and smooth muscle dysfunction in human donor cerebral arteries. Medin also induced proinflammatory activation of human brain microvascular endothelial cells through NFκB activation .

Aims:
To determine the effects of medin on pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells (HCAECs).

Methods:
Primary HCAECs (passages 6-8) were exposed for 20 hours to physiologic doses of recombinant medin (0.5, 1 and 5 µM) and gene expression of pro-inflammatory proteins (IL-6, IL-8, IL-1b and intercellular adhesion molecule (ICAM)-1), prothrombotic protein (plasminogen activator inhibitor (PAI)-1) and anticoagulant membrane protein thrombomodulin were quantified using rtPCR and compared. Separately, HCAECs were exposed to medin (0.5, 1 and 5 µM) with or without small molecule specific inhibitor of NFκB (RO106-9920, 10 uM) for 20 hours and protein expression of IL-6 in conditioned media was measured using ELISA.

Results:
Medin caused dose-dependent increases in gene expressions of pro-inflammatory cytokines IL-6, IL-8, IL-1b, ICAM-1 (Figure 1 A-D). Medin caused a dose-dependent increase in PAI-1 and a dose-dependent decrease in thrombomodulin (Fig. 1 E-F). Co-treatment with RO106-9920 prevented medin-induced increase in IL-6 protein expression (Fig. 1G).

Conclusions:
Medin induces pro-inflammatory and prothrombotic activation of human coronary artery endothelial cells. The proinflammatory activation is likely NFκB-dependent. Medin is a promising potential novel mediator of CAD and vascular aging.
Abstract 4124323: Extensive atrial cardiomyopathy indicated by left atrial low-voltage areas predicts subsequent stroke after atrial fibrillation ablation
Authors: Kudo Satoshi , Matsuda Yasuhiro , Masuda Masaharu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Tsujimura Takuya , Hata Yosuke , Uematsu Hiroyuki , NAKAO SHO , Kusuda Masaya , Ariyasu Wataru , Fujii Subaru , Ooka Hirotaka , Mano Toshiaki
Published: November 2024

Background:
Atrial fibrillation (AF) is a leading cause of stroke. However, predictors of stroke after AF ablation have not been well clarified, therefore, evidences of anticoagulation therapy after the procedure have been limited. Although left atrial low-voltage areas (LVAs) reflects atrial cardiomyopathy, which is a potential cause of thromboembolism, there are few reports of an association between LVAs and stroke. The purpose of this study was to investigate the association between atrial cardiomyopathy assessed by LVAs and stroke in patients undergoing AF ablation.

Methods:
The study design was a single center, retrospective observational study. This study included 1,486 (age, 68 ± 10 years; female, 501 [34%]; persistent AF, 905 [61%]) consecutive patients who underwent initial AF ablation from December 2014 to March 2022. The definition of LVAs were areas with a bipolar voltage of <0.5 mV in the left atrium. The area of LVAs in the whole left atrium was divided into 3 groups, namely <5cm
2
, 5-20 cm
2
and ≥20 cm
2
. Stroke after AF ablation was followed for 60 months.

Results:
Of 1,486 patients, LVAs were found in 352 (24%) patients, and 25 (1.7%) patients developed stroke (hemorrhagic stroke, 4 [16%] patients; ischemic stroke 21 [84%] patients). Freedom from stroke was significantly lower in patients with LVAs than in those without (<5cm
2
: 98.3%, 5-20 cm
2
: 95.4%, ≥20 cm
2
: 88.8%, p<0.001). Additionally, LVAs ≥20 cm
2
was an independent predictor of the development of stroke after AF ablation (hazard ratio 4.9, 95% confidence interval: 2.0-12; p=0.001, adjusted by estimated glomerular filtration rate and AF recurrence after ablation).

Conclusion:
In patients with initial AF ablation, freedom from stroke after AF ablation was significantly lower in patients with LVAs ≥20 cm
2
than in patients with LVAs 5-20 cm
2
and in patients with LVAs <5cm
2
. Particularly, LVAs ≥20 cm
2
was an independent predictor of the development of stroke after AF ablation.
Abstract 4124370: DAPT for 1-Month Followed by P2Y12 Inhibitor Monotherapy Versus DAPT for 12-Months After Percutaneous Coronary Intervention: A Systematic Review and Meta Analysis of Randomized Controlled Trials
Authors: Pascoal Capela , Ribeiro Goncalves Ocilio , Saugo Faria Hilária , Francisco Antonino , de Souza Faria Giovana , Bombassaro Masiero Barbara , Doma Mohamed , Manuel Valdano , Tinajero Shirley
Published: November 2024

Background:
Dual antiplatelet therapy (DAPT) is well established as standard of care following percutaneous coronary intervention (PCI). Recent trials have shown a potential benefit in the reduction of hemorrhagic events with a shorter course of DAPT. However, the optimal duration of DAPT following PCI remains unclear.

Question:
Is 1 month of DAPT followed by P2Y12 inhibitor monotherapy superior to the standard 12-month DAPT regimen in terms of cardiovascular outcomes in patients post-PCI?

Methods:
Medline, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for randomized clinical trials (RCTs) comparing 1-month vs. 12-months of DAPT followed by P2Y12 inhibitor monotherapy post-PCI. The outcomes of interest were cardiovascular death, myocardial infarction, and major bleeding. We used R version 4.1.2 (The R Foundation, 2021) to pool the data using a random-effects model. Heterogeneity was assessed with I2.

Results:
We included three RCTs reporting data from 22,413 patients, of whom 11,180 (49.8%) were treated with 1-month of DAPT, followed by P2Y12 inhibitor monotherapy. Follow-up ranged from 12 months to 24 months. The incidence of all-cause death (RR 1.20; 95% CI 0.95-1.51; p=0.12) and myocardial infarction (RR 0.86; 95% CI 0.71-1.05; p=0.14) were not significantly different between the groups. However, major bleeding (RR 0.51; 95% CI 0.26-0.99; p=0.048) was significantly reduced with a short course of DAPT followed by P2Y12 inhibitor monotherapy, as compared with standard 12 months of DAPT.

Conclusion:
Following PCI, a transition from DAPT to P2Y12 inhibitor monotherapy at 1-month is associated with a significant reduction in major bleeding as compared with standard DAPT for 12-months, with no significant change in the incidence of all-cause mortality or myocardial infarction.
Abstract 4124531: Digital Health Intervention to Enhance Optimization of Heart Failure Care: From Reciprocal Innovation using Human-Centered Design to Pilot Study
Authors: Polachini Beatriz , Ciminelli Ana Luiza , Lino Rafael , Bramucci Victoria , RIBEIRO EDMAR , Rezende Lilian , Spaulding Erin , Sandhu Alexander , Azizi Zahra , Beaton Andrea , Longenecker Chris , Ribeiro Antonio Luiz , Brant Luisa
Published: November 2024

Introduction:
Guideline-directed medical therapy (GDMT) for Heart Failure with reduced ejection fraction (HFrEF) reduces adverse events by 70%, but is underutilized. The Human Centered Design (HCD) methodology can be useful to build a strategy to optimize GDMT centered on patients’ demands and perspectives. We aimed to reciprocally innovate a telephone-based digital health intervention (DHI) from a Brazilian trial to an app co-developed for a US trial and iterate it again to the Brazilian context using HCD. We will evaluate the app’s usability and utility to facilitate HF GDMT optimization, considering barriers of the Brazilian public health system users, such as low literacy and socioeconomic status.

Methods:
Mixed methods study. Steps were carried out according to HCD method: (1) empathizing and identifying challenges, (2) suggesting solutions, (3) prototype development, (4) ranking features for feasibility and utility (5) engineering work and (6) prototype testing. In stages 1-3, semi-structured interviews were held with 10 HF patients and 2 health professionals. Steps 4 and 5 were done by the research team. In stage 6, we conducted a pilot study with 10 HFrEF patients, with at least one GDMT drug with an optimization gap. The primary outcome was the app’s usability assessed by an engagement score, and the app’s utility at 4 weeks. Secondary outcomes included change in self-care score using the European Self-Care Behavior Scale. After step 6, new interviews were carried out to capture the user experience and identify new iterations. Interviews were recorded and transcribed for content analysis.

Results:
The average engagement score was 80% (SD 16) and the app’s utility score was 82% (SD 8). The average self-care score increased by 32% (SD 25) at the end of the pilot. The main challenges were lack of knowledge about HF and self-care. Technical difficulties and lack of trust in the app to handle health data were mentioned. In the pilot, patients reported the app was easy to use and contributed to self-care and understanding of HF. Among the DHI components, teleconsultation was best evaluated, followed by the educational videos. The greatest challenge was connecting the blood pressure cuff and scale via Bluetooth.

Conclusion:
The app was well accepted and considered useful by patients. User contributions were fundamental to create tools that facilitate engagement and utility. The final product will be evaluated in a randomized, multicenter, clinical trial.
Abstract 4124532: A Meta-Analysis on the Effect of Chronic Total Occlusion of Coronary Arteries on Cardiovascular Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement
Authors: Goyal Aman , Tariq Muhammad Daoud , Zahra Rubab , Jain Hritvik , Khan Rozi , MAHALWAR GAURANGA
Published: November 2024

Background and Aims:
Transcatheter aortic valve replacement (TAVR) has revolutionized the management of severe aortic stenosis, particularly prevalent in elderly patients. These patients often present with coexisting coronary artery disease (CAD) due to shared risk factors. There is evidence suggesting that underlying CAD may result in poorer outcomes for patients undergoing TAVR. Chronic total occlusion (CTO), representing a severe manifestation of CAD, could therefore be hypothesized to worsen prognosis in TAVR patients, although data supporting this hypothesis are limited. Our meta-analysis aims to consolidate all available data concerning patients undergoing TAVR with concurrent CTO.

Methods:
We conducted a thorough literature search across major bibliographic databases, including PubMed, Embase, Cochrane Library, and SCOPUS, from their inception until May 15, 2024, to identify studies comparing outcomes of TAVR in patients with and without CTO. Pooled odds ratios (OR) with 95% confidence intervals (CIs) were calculated using the random-effects model via Comprehensive Meta-Analysis Software. The primary outcome assessed was in-hospital mortality, with several secondary endpoints also evaluated. Statistical significance was determined at p<0.05.

Results:
Eight studies, encompassing a total of 540,910 patients undergoing TAVR (11,679 with CTO; 529,231 without CTO), were included in this meta-analysis. TAVR in patients with CTO was associated with significantly increased odds of in-hospital mortality (OR: 1.25; 95% CI: 1.05, 1.49; p=0.011;

I
2

=0%) and acute myocardial infarction (periprocedural) (OR: 1.68; 95% CI: 1.48, 1.91; p<0.001;

I
2

=0%). However, no significant difference was observed in all-cause mortality (OR: 1.18; 95% CI: 0.71, 1.96; p=0.525;

I
2

=59.37%), acute kidney injury (OR: 1.32; 95% CI: 0.94, 1.85; p=0.11;

I
2

=72.12%), and stroke (OR: 1.06; 95% CI: 0.89, 1.28; p=0.509;

I
2

=0%) (see Figures 1 and 2).

Conclusion:
CTO emerges as a substantial risk factor for patients undergoing TAVR, elevating the risk of in-hospital mortality and acute myocardial infarction. Considering a heart team's multidisciplinary approach in patients with underlying CTO may be advisable during TAVR, allowing for a comprehensive assessment of the benefits versus risks of revascularization prior to TAVR.
Abstract 4124585: Identification of Low-Value Carotid Ultrasound Tests: A Comparison of Administrative Claims Versus Chart Review
Authors: Beale Robert , Kini Vinay
Published: November 2024

Introduction/Background:
Low-value care is defined as care where harms or costs outweigh patient benefits. Prior studies have suggested that approximately 1 of every 10 carotid ultrasound tests are low-value because they were performed among patients without neurologic symptoms or a history of stroke. However, these studies have used administrative claims data that may not account for all patient symptoms or include all guideline-recommended indications. We assessed the validity of a claims-based measure of low-value carotid ultrasound testing compared to a reference standard of chart review.

Hypothesis:
Claims-based measures overestimate the proportion of carotid ultrasound tests classified as low-value care.

Methods:
We conducted a retrospective cohort study of Medicare fee-for-service beneficiaries attributed to an accountable care organization with administrative claims data linked to electronic health record data. Using Current Procedural Technology codes, the first 150 patients that underwent carotid ultrasound in 2021 were identified. We applied a claims-based algorithm used by researchers and policymakers to identify if testing was low-value or appropriate. We used linked electronic health record data to assess appropriateness of testing using the 2012 American Heart Association clinical practice guidelines. We assessed agreement between claims and chart review using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Cohen’s Kappa.

Results:
Among 150 patients (mean age 76, 55% male, 86% white) who underwent carotid ultrasound, 76 tests (51%) were considered low value by the claims measure and 63 (42%) by chart review. Claims based measures were 67% sensitive, 61% specific, with a PPV of 55% and NPV of 62%. Cohen’s Kappa coefficient was 0.27 (CI 0.11 - 0.42), indicating only fair agreement between claims and chart review.

Conclusion:
We found that an often-used claims-based measure to identify low-value carotid ultrasound testing misclassifies a substantial proportion of tests as low-value. Using claims-based measures alone for assessing provider quality and making payment decisions could harm provider reputations and erode trust in the quality reporting system.
Abstract 4125281: Detection of Acute Myocardial Infarction and Ischemia From Lead-I ECG Using Deep Learning
Authors: Davarmanesh Parmida , Jabbour Gabriel , Lin Qian , Tenison Irene , Stultz Collin , Alam Ridwan
Published: November 2024

Introduction:
While smartwatches that acquire Lead-I electrocardiogram (ECG) have shown promise in detecting arrhythmias, the detection of ischemic events using Lead-I alone remains understudied. We aim to build and evaluate a deep-learning model to determine whether Lead-I ECG can identify ischemia/infarction in a 12-lead ECG.

Methods:
We developed a deep-learning model that can identify MI/ischemia using only Lead-I ECG signal as input. For this task, we utilized PTB-XL, a large publicly available dataset of 12-Lead clinical ECG with associated diagnostic labels. Our experiment utilized 8781 ECGs whose labels were validated by at-least one cardiologist with 100% confidence scores. This dataset includes 1391 ECGs that are labeled as either ischemic ST/T changes or MI, and 7390 ECGs with either “normal” labels or non-ischemic ST/T abnormalities. We split the dataset in training, validation, and holdout sets (80-10-10) with equal stratification of the diagnosis classes. The holdout test set contains 909 non-ischemic ECGs and 233 ECGs with MI/ischemia diagnosis, 106 of which are labeled as acute MI or ischemic ST/T changes and 127 labeled as other MI chronicity. The discriminatory ability of the model is evaluated with the Area Under the receiver-operating Curve (AUC), sensitivity, specificity, and the predictive values. We further analyze the model’s capability in discriminating the cohort of acute MI and ischemia diagnoses from other MI as well as from the non-ischemic cohort.

Results:
The model has an AUC of 0.88 for discriminating an MI/ischemia vs normal. Using a threshold corresponding to 80% sensitivity, the corresponding specificity is 79% and the negative and positive predictive values are 94% and 50% (Table-1). Although the model was trained to identify the combined class of MI/ischemia, it can differentiate acute MI and ischemia cohorts from other MI as well as from non-ischemic diagnoses with p-values<10
-4
(Table-2). Lastly, with the same threshold, the sensitivity for detecting acute inferior myocardial infarctions or inferior ischemia – a class that is difficult to detect with Lead-I alone – is 82%.

Conclusions:
Our deep learning model, which was trained on Lead-I ECG alone, can effectively detect acute MI and ischemia that would have been identified using a 12-lead ECG. This method presents a proof-of-concept for applications in home settings. Further prospective validation using wearable ECG monitors that record lead-I is warranted.
Abstract 4125587: Vasomotor function and its regulation by perivascular adipose tissue in metabolic syndrome vary depending on severity and combination of metabolic parameters
Authors: Kagota Satomi , Maruyama-Fumoto Kana , Shinozuka Kazumasa
Published: November 2024

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease. Because perivascular adipose tissue (PVAT) regulates arterial tone by releasing vasorelaxing/vasocontracting factors, the effects of PVAT on vasomotor function have been heterogeneously reported. Various PVAT functions can result from the severity or combination of metabolic parameters in MetS. Therefore, we compared the effects of mesenteric arterial PVAT on the nitric oxide-dependent vasorelaxation response among the three metabolic syndrome (MetS) model strains.

We compared male OLETF, Zucker fatty (ZF), and SHRSPZF (SPZF) rats aged 20 weeks to lean controls, LETO, ZF
+/+
, and Wistar-Kyoto (WKY) rats. To determine the effects of PVAT on vasodilators, we used organ bath techniques to assay nitroprusside-induced relaxation of isolated mesenteric arterial ring preparations with intact or removed PVAT.

The waist circumference to length ratio in OLETF and ZF rats was higher than that in SPZF rats, and the systolic blood pressure was higher in SPZF rats than in the other groups. In the serum, there was no significant difference in triglyceride levels. Still, glucose and thiobarbituric acid reactive substance levels were higher in OLETF and SPZF rats than in ZF rats. Relaxation in ZF rats did not change compared to that in ZF
+/+
rats and the presence of PVAT. In contrast, relaxation in OLETF rats was lower than in LETO rats, and there was no difference between the presence and absence of PVAT. However, relaxation in SPZF rats was lower than in WKY rats, and relaxation increased to the same level as in WKY rats in the presence of PVAT.

This study unveils novel insights, suggesting that high serum glucose and oxidative stress cause arterial dysfunction, whereas high blood pressure induces PVAT functional changes. These findings underscore the complex interplay between metabolic disorders and vascular health, potentially paving the way for more targeted interventions in patients with MetS.
Abstract 4125691: A machine learning approach to examining the associations of minority stressors and physical activity among sexual and gender minority adults
Authors: Lopez Veneros David , Ensari Ipek , Bhilegaonkar Riya , Sharma Yashika , Caceres Billy
Published: November 2024

Introduction:
Physical activity (PA) is an important modifiable factor for cardiovascular disease (CVD). Sexual and gender minority (SGM; e.g., lesbian/gay, bisexual, transgender) adults face higher risks of inadequate PA and CVD due to increased exposure to minority stressors, such as experienced and anticipated discrimination, which may influence SGM adults’ willingness to engage in PA. To our knowledge, researchers have not investigated the impact of minority stressors on objectively-measured PA among SGM adults.

Goal:
Using k-means clustering, we sought to identify whether clusters characterized by greater exposure to minority stressors were associated with lower moderate and vigorous PA (MVPA) and higher sedentary behavior among SGM adults.

Methods:
This daily diary study included an online sample of SGM adults living in the United States. Participants completed daily surveys about personally experienced discrimination and anticipated discrimination (i.e., expectation of experiencing discrimination) and wore wrist accelerometers for 28 days to objectively measure PA. We used k-means clustering to identify clusters based on reports of experienced and anticipated discrimination. We first determined the optimal number of clusters using established partition criteria. Next, we ran linear regression models (adjusted for demographic factors) to examine the associations of minority stress clusters with MVPA and sedentary time per week.

Results:
Among 42 SGM adults (mean age 27.0±7.7 years) with 1133 person-days of accelerometry data (~3% missing data), we identified four minority stress clusters: low anticipated/low experienced (LALE; reference group); low anticipated/high experienced (LAHE); high anticipated/low experienced (HALE); and high anticipated/high experienced discrimination (HAHE). Participants in the HALE cluster (n=12) engaged in 202 fewer minutes of MVPA than those in the LALE cluster (n=7). Participants in the LAHE cluster (n=10) had 123 fewer minutes of vigorous PA than those in the LALE cluster. No differences were identified for sedentary time.

Conclusions:
This is the first study to examine the association of minority stressors with objective PA among SGM adults. Participants in the HALE and LAHE clusters engaged in significantly lower PA than those with low levels of both experienced and anticipated discrimination. Findings underscore the importance of assessing minority stressors and the need for interventions to improve PA among SGM adults.