tbuckley/cabot-search huggingface dataset:
Abstract 4125500: Obesity-Related Left Atrial Functional Change Becomes Apparent in Infancy
Authors: Kenji Harada, Yukiko Harada, Miho Hatakeyama-Sasaki, Yuichi Nakamoto, Manatomo Toyono
Journal: Circulation (2024)

Background: Impaired left atrial (LA) function is observed in obese patients, however, there is little information on when LA dysfunction begins to appear. To clarify this issue, we assessed LA volume and function in obese infants. Methods: Two-dimensional speckle-tracking echocardiography was performed in 96 infants aged 4 months. Subjects were divided into 3 groups according to body mass index (BMI): normal (n=53), &lt;17 kg/m 2 ; overweight (n=28), 17 to 19.9 kg/m 2 ; obese (n=15), ≧20 kg/m 2 . LA maximal volume, LA minimal volume, and LA pre-atrial contraction volume and LA longitudinal strain (reservoir, conduit, and booster) were measured. LA total emptying fraction, passive emptying fraction, and active emptying fraction were calculated. Results: Systolic blood pressure was significantly higher in the obese group than in the normal group (Table). LA maximal volume, minimal volume, and pre-atrial contraction volume increased significantly with increasing BMI (r = 0.53, 0.54, and 0.63, respectively, p &lt;0.01). Compared with the normal group, reservoir LA strain was significantly lower in the overweight and obese groups. Conduit LA strain and passive emptying fraction were significantly lower in the overweight and obese groups than those in the normal group (Table). Reservoir LA strain, conduit LA strain, and passive emptying fraction decreased significantly with increasing BMI (r = -0.28, -0.27, and -0.33, respectively, p &lt;0.01). There was no significant difference in booster LA strain among the 3 groups. Compared with the normal group, LA active emptying fraction was significantly higher in the obese group (Table). Conclusions: Higher BMI is associated with impaired reservoir and conduit LA function and higher booster LA pump function, which may be compensatory. Thus, obesity-related changes in LA functional begin to appear in infancy. Our data support prevention of obesity in early childhood because higher BMI is responsible for significant changes in LA function in early life.
Abstract 4125581: Association Between Life’s Essential 8 and Premature Atherosclerotic Cardiovascular Disease: A Cross-sectional Study Among Young Adults in the United States
Authors: Yitao Han, Yuxiong Chen, Zhongjie Fan
Journal: Circulation (2024)

Background: Among patients presenting with atherosclerotic cardiovascular disease (ASCVD), the proportion of young individuals has increased in recent years. Life’s Essential 8 (LE8), containing two domains of health behaviors and health factors, is an updated monitoring measurement of cardiovascular health by assessing 8 modifiable risk factors. Objective: The objective of this study is to investigate the potential relationship between the LE8 score and a history of premature ASCVD among young adults residing in the United States. Methods: This population-based cross-sectional study utilized data from the National Health and Nutrition Examination Survey spanning 2005 to 2018, focusing specifically on adults aged 20 to 45. LE8 score was measured and categorized into low (0-49), moderate (50-79), and high (80-100) levels (Figure 1). Premature ASCVD status was determined by interviews conducted at enrollment, encompassing a self-reported composite disease history of coronary heart disease, angina pectoris, heart attack, and stroke. Following descriptive statistics, weighted multivariable logistic regression and restricted cubic spline models were employed to evaluate the associations between the LE8 score and premature ASCVD. Additionally, subscale and subgroup analysis were developed. Results: Among 17,499 participants, 9846 were eligible for analysis (weighted mean age, 32.7 years; male, 50.3%), and 167 had premature ASCVD history (weighted percentage, 1.46%). The weighted mean LE8 score of the study population was 71.99 (0.3). Following the adjustment for potential confounders, individuals with higher LE8 scores exhibited a reduced risk of developing premature ASCVD (Table 1). A nonlinear relationship was observed and similar patterns were also identified in the association of health behaviors and health factors scores with premature ASCVD (Figure 2). This inverse association was consistently observed across various subgroups, including sex, age strata, ethnicity, education, and income levels, with no significant interactions identified. Conclusions: The LE8 score and its subscale scores exhibited a negative, nonlinear association with premature ASCVD. Maintaining a healthy lifestyle and controlling modifiable risk factors are crucial in preventing premature ASCVD in the younger demographic. Further studies, encompassing prospective cohorts, are needed to confirm this finding.
Abstract 4125992: Eicosapentaenoic Acid (EPA) Increases Expression of Nrf2-mediated Antioxidant Response Element and Heme Oxygenase-1 in Cytokine-Activated Endothelial Cells
Authors: Samuel Sherratt, Peter Libby, Richard Dunbar, Deepak Bhatt, Preston Mason
Journal: Circulation (2024)

Background: Endothelial cell (EC) nuclear factor erythroid 2-related factor (Nrf2) translocates to the nucleus during inflammation to mediate transcription of genes in the antioxidant response elements (ARE). An ARE regulates mRNA encoding HMOX-1, thioredoxin (TXN), and NAD(P)H quinone oxidoreductase-1 (NQO1), among others. Parkinson disease protein 7 (PARK7) and p62 work independently to prevent Keap1-mediated degradation of Nrf2 during oxidative stress. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced CV events (REDUCE-IT). We tested the effects of EPA on ARE protein expression in ECs from multiple tissues during cytokine challenge. Methods: Human brain, pulmonary and vascular ECs were treated with IL-6 (12 ng/mL) for 2 hours and then incubated with EPA (40 µM) for 24 h. Global proteomic analysis performed by LC-MS measured relative protein expression. Significant (p&lt;0.05) changes between treatment groups &gt;1-fold were analyzed by differential enrichment analysis of proteomics data (DEP) and included in gene set enrichment analyses (GSEA). Significantly modulated pathways within the Gene Ontology (GO) database were identified as those with an adjusted-p value &lt;0.05. Results: Proteomic analysis revealed that EPA significantly modulated ≥600 proteins in ECs distinct from IL-6 challenge alone. In EC, EPA significantly modulated the “cellular response to oxidative stress” pathway (GO: 0034599) relative to IL-6 alone. Within this GO pathway, EPA increased levels of catalase (1.2-fold, 1.1-fold, 1.1-fold) and mitochondrial glutathione reductase (1.1-fold, 1.1-fold, 1.1-fold) in brain, pulmonary, and vascular ECs, respectively. We also observed a consistent increase in brain, pulmonary, and vascular ECs of p62 (1.3-fold, 1.2-fold, and 1.2-fold, respectively), and ARE members HMOX-1 (1.5-fold, 1.7-fold, and 2.1-fold, respectively), and NQO1 (1.1-fold, 1.2-fold, and 1.3-fold, respectively). TXN was increased in pulmonary and vascular ECs (1.1-fold and 1.2-fold, respectively) with EPA. Mitochondrial TXN (also called TXN2) increased in brain ECs with EPA 1.1-fold. EPA also significantly increased levels of PARK7 1.1-fold. Conclusions: During inflammation, EPA enhanced expression of cytoprotective proteins in the ARE, notably HMOX-1, along with its regulators, in ECs from multiple tissues. Augmented endogenous antioxidant pathways may contribute to EPA’s clinical benefits.
Abstract 4125076: Catheter Ablation Alone Versus Catheter Ablation With Combined Percutaneous Left Atrial Appendage Closure For Atrial Fibrillation: A Systematic Review and Meta-analysis
Authors: Joey Junarta, Muhammad Siddiqui, Ehab Abaza, Peter Zhang, Aarash Roshandel, Chirag Barbhaiya, Lior Jankelson, David Park, Larry Chinitz, Anthony Aizer
Journal: Circulation (2024)

Background: Combined catheter ablation (CA) with left atrial appendage closure (LAAC) may produce comprehensive treatment for atrial fibrillation (AF) whereby rhythm control is achieved and stroke risk is reduced without the need for chronic oral anticoagulation. However, the efficacy and safety of this strategy is still controversial. Aim: To investigate the efficacy and safety of a combined CA with LAAC approach to treat AF in patients moderate-to-high-risk for bleeding. Methods: This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus, and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Risk of bias was assessed using the Modified Newcastle-Ottawa scale and Cochrane risk of bias tool. Eligible studies reported outcomes in patients with AF who underwent combined CA and LAAC versus CA alone. Studies performing CA without pulmonary vein isolation were excluded. Results: Eight studies comprising 1878 patients were included (2 RCT, 6 observational). Pooled results showed no difference in arrhythmia recurrence (risk ratio [RR] 1.05; 95% confidence interval [CI] 0.84-1.30), stroke or systemic embolism (RR 0.71; 95% CI 0.26-1.94), total procedure time (mean difference 31.45 minutes; 95% CI -5.91-68.81), or major periprocedural complications (RR 1.28; 95% CI 0.28-5.89) when comparing combined CA and LAAC versus CA alone. Conclusion: Combined CA with LAAC for AF is associated with similar rates of arrhythmia free survival, stroke, major periprocedural complications, and procedure time when compared to CA alone. A combined strategy may be as safe and efficacious for patients moderate-to-high-risk for bleeding events to negate the need for chronic oral anticoagulation.
Abstract 4125059: Techniques and Outcomes of Atrial Fibrillation Ablation in Patients with Persistent Left Superior Vena Cava
Authors: Ting-Wei Ernie Liao, Lingyu Xu, MirMilad Pourmousavi Khoshknab, Carli Peters, David Callans, Francis Marchlinski, Robert Schaller, David Frankel, Jeffrey Luebbert, Gustavo Guandalini, Saman Nazarian
Journal: Circulation (2024)

Introduction/Background: Persistent Left Superior Vena Cava (PLSVC) presents unique challenges for atrial fibrillation (AF) ablation due to its arrhythmogenic potential and complex anatomical variations. Understanding tailored approaches and outcomes in patients with PLSVC and AF is essential for improving procedural success and safety. Research Questions/Hypothesis: This study aims to investigate the efficacy and outcomes of tailored ablation strategies in patients with PLSVC and AF. Goals/Aims: To evaluate the procedural safety, acute success, and AF recurrence rate post-ablation in patients with PLSVC, and to determine the optimal ablation strategies for this population. Methods/Approach: This retrospective cohort study included 16 patients with PLSVC who underwent 21 AF ablation procedures between August 1, 2008, and February 14, 2024, at the Hospital of the University of Pennsylvania. Procedures involved pre-ablation imaging, 3D electroanatomical mapping, pulmonary vein isolation (PVI), and targeted ablation strategies focusing on PLSVC-related triggers. The primary endpoints were procedural safety and AF recurrence post-ablation. Results/Data: The cohort's mean age was 51.9 ± 17.9 years, 31.2% of whom were female. Triggers from the PLSVC were identified in 66.7% of procedures. Tailored ablation strategies were employed to isolate PLSVC-left atrium/coronary sinus connections or directly target the induced triggers, with a success rate of 85% in achieving isolation or targeted ablation once triggers were induced. The recurrence rate of arrhythmia post-ablation was 58.3% in the patient-based analysis and 70.6% in the procedure-based analysis. No major complications occurred. Conclusion(s): This study highlights the significance of recognizing PLSVC as a potential source of AF triggers. The single procedure success rate is low compared to patients without PLSVC. Further studies are warranted to enhance outcomes in this challenging AF population.
Abstract 4125281: Detection of Acute Myocardial Infarction and Ischemia From Lead-I ECG Using Deep Learning
Authors: Parmida Davarmanesh, Gabriel Jabbour, Qian Lin, Irene Tenison, Collin Stultz, Ridwan Alam
Journal: Circulation (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&lt;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 4125188: Cardiac Specific Biomarkers of Progression in Duchenne Muscular Dystrophy Detected Using Aptamer-Based Proteomics
Authors: Mark Naguib, Jaclyn Tamaroff, William Burnette, Rachel Harris, Meng Xu, James Slaughter, Larry Markham, Jonathan Soslow
Journal: Circulation (2024)

Background: Duchenne muscular dystrophy (DMD) is an X-linked, progressive neuromuscular disorder characterized by cardiac and skeletal myopathy. The cardiac and skeletal muscle manifestations have different ages of onset and rates of progression, suggesting variability in the pathophysiology of dystrophin loss within the respective muscle groups. Hypothesis: We hypothesized that proteomics with comprehensive clinical phenotyping would identify novel biomarkers that correlate with cardiac but not skeletal disease progression in boys with DMD. Methods: This single-center cohort study of 56 DMD subjects performed cardiac magnetic resonance (CMR), including left ventricular ejection fraction (LVEF), late gadolinium enhancement (LGE), and myocardial circumferential strain (ECC). Fifty-one subjects underwent quantitative muscle testing, and 33 underwent actigraphy (MSK indices). Aptamer-based technology (SomaScan, SomaLogic, Boulder, CO) evaluated 1128 proteins in plasma sampled at the time of CMR. Correlations between serum protein levels and cardiac or MSK indices were tested using Benjamini-Hochberg corrected p-values (q-values). Results: The mean age of DMD subjects was 15.5 years old +/- 4.30. Twenty-six subjects had left ventricular dysfunction (LVEF &lt;55%), 45 subjects had LGE, and 45 were non-ambulatory. Of 1128 proteins analyzed, 208 demonstrated a significant correlation for cardiac but not MSK indices (Figure 1). Figure 2 lists the 20 proteins with the strongest correlations, which included biomarkers of inflammation, calcium regulation in myocytes, and cell adhesion. Conclusion: We detected 208 novel proteins that correlate with cardiac-specific DMD disease progression. These proteins provide a better understanding of the underlying differences of cardiac disease, compared to MSK disease in DMD and provide clues to potential cardiac therapeutic options.
Abstract 4126893: Feasibility and Acceptability of a Nurse-Pharmacist Post-Discharge Telehealth Model of Care for Heart Failure Patients
Authors: Joshua Bennetts, Cameron Robson, Aisha Weismantel-Savage, Julie Mani, Trent Williams, Aaron Sverdlov, Doan Ngo
Journal: Circulation (2024)

Background: Suboptimal medication management is common in patients with heart failure (HF), particularly during transitions-of-care. To date, there are few studies assessing the feasibility of a nurse-pharmacist post-discharge telehealth service for medication optimisation in patients with HF. We performed a feasibility study to determine service uptake and acceptability, and ability to identify medication-related issues for HF patients as they transition from hospital to home. Methods: HF patients were referred to an existing post-discharge telehealth service and offered medication reconciliation and education in addition to their usual care; a service we termed ‘MedRec’ (MR). Primary outcomes were feasibility, measured through recruitment and successful MR completion, and acceptability, measured by an investigator-developed survey. Secondary outcomes were medication-related issues detected during MR. Results: A total of 100 HF patients were offered a post-discharge MR. Mean age of patients was 68.5 ±14.2 years, and mostly male sex (62%). Pharmacist MRs were requested by 80% of patients. In total 62 MRs (77.5%) were performed; 9 patients declined MR during follow-up and an additional 9 patients were uncontactable. Mean time to MR following nurse referral was 10.98 ±9.74 days. Drug-related toxicity or adverse effect presentation was identified in 25 (40.3%) MR recipients at the time of consultation and subsequently required general practitioner follow-up. Medication compliance issues were detected by the pharmacist in 13 (20.9%) patients; forgotten doses being the most common concern. Undertreated medical conditions, such as symptomatic HF and chronic pain, were identified in 12 (19.3%) MR recipients. Medications prescribed without any apparent indication were found in 8 (12.9%) patients. Drug or disease management information was requested by 35 (56.4%) MR recipients. A total of 35 (56.5%) post-MR surveys were successfully completed. All participants who completed a post-MR survey agreed that a post-discharge telehealth MR was an acceptable form of education provision. Engagement with a pharmacist MR was perceived to ease anxiety associated with understanding medication-related changes and empowered greater medication self-management. Conclusions: A post-discharge nurse-pharmacist telehealth service is a feasible and acceptable model of care. Inclusion of a routine MR post-discharge may be an effective means of maintaining continuity of care for HF patients.
Abstract 4125294: Fontan-Related Lymphatic Complications are Associated with Extracardiac Outcomes and Morbidity
Authors: Riley Boyd, Christina Laternser, Shivani Patel, Karl Migally, sheetal patel
Journal: Circulation (2024)

Background: Patients born with single ventricle anatomy palliated with the Fontan procedure are at risk of lymphatic complications (LC), including plastic bronchitis, protein losing enteropathy, ascites, and hypoalbuminemia. The mechanism of LC, associated risk factors, and impact on outcomes are not well understood. Aim: We aimed to describe the prevalence of Fontan-related LC, expand on their association with previously reported risk factors, and explore the impact on mortality and transplantation. Methods: We performed a single-center, retrospective, cross-sectional cohort study of patients with Fontan circulation seen between 2009-2022, including those with cardiac catheterization and echocardiography within six months. Univariate comparisons were completed comparing those with and without LC. Results: A total of 144 Fontan patients were included with mean age of 23.6±11.9 years, with average of 18.8±10.5 years after their Fontan. Of those, 68 patients (48.6%) had at least one LC. There was no difference in demographic or anthropometric data in those with versus without LC, however patients with LC had their Fontan at an older age (5.6 vs 3.8 years, p =0.001). The presence of LC was associated with higher likelihood of thromboembolism (25% vs 7.9%, p =0.005), arrhythmia (45.6% vs 21.1%, p =0.002), lower estimated glomerular filtration rate (102.0±25.5 vs 111.6±17.9, p =0.02) and higher Fontan mean pressures noted on catheterization (14.8±3.8 vs 12.1±3.8 mmHg, p &lt;0.001). Notably, LC were not related to the presence of moderate to severe ventricular dysfunction or moderate to severe atrioventricular valve regurgitation. Fontan patients with LC had higher rates of transplantation (25.4% vs 4%, p &lt;0.001) and mortality (18% vs 4%, p =0.006). Conclusions: Fontan-related LC are associated with extra-cardiac morbidities and greater transplant and mortality rates. Our study suggests that LC are associated with venous congestion and not necessarily dependent on cardiac function.