tbuckley/cabot-search huggingface dataset:
Abstract 4138321: Marine Microplastic Levels and the Prevalence of Cardio-Metabolic Diseases in Coastline Counties: An Ecological Analysis
Authors: Bhargav Makwana, sumanth khadke, Ashish Kumar, Khurram Nasir, Sudip Sheth, Rikin Shah, Rishi Wadhera, Yixin Kong, Ana Navas-Acien, Gary Adamkiewicz, Sanjay Rajagopalan, Sadeer Al-Kindi, Sourbha Dani, Susan Moffatt-Bruce, Sarju Ganatra
Journal: Circulation (2024)

Background: Micro- and nanoplastics are an emerging risk factor for the development of cardiovascular diseases. The association of marine microplastic levels (MMLs) with the burden of cardiometabolic diseases at a population level remains unexplored. Aim: To investigate the association between the average microplastic concentration in the ocean water body within 200 nautical miles of US coastline surveyed between 2015 and 2020, assigned to its most adjacent coastline county, and the prevalence of type 2 diabetes (T2D), coronary artery disease (CAD), and stroke in those counties. Methods: Microplastic concentration data within 200 nautical miles of the US coastline was spatially analyzed in ArcGIS Online to calculate mean MMLs. The coastal counties were stratified into four categories based on MMLs in the adjacent ocean water body: low (0-0.005 pieces/m 3 ), medium (0.005-1 pieces/m 3 ), high (1-10 pieces/m 3 ), or very high (≥10 pieces/m 3 ). BRFSS 2019-2020 survey data was used to correlate with the prevalence of type 2 diabetes (T2D), coronary artery disease (CAD), and stroke in these counties. Univariate and population-weighted multivariate quasi-Poisson regression adjusted for median county age, sex, physician access, and baseline community vulnerability theme of the US climate vulnerability index (CVI) was used to evaluate unadjusted and adjusted associations between disease prevalence and MMLs. Results: The mean age of the population was 43 ± 6 years. The mean prevalence of T2D, CAD, and stroke was significantly higher in counties with very high MMLs (13.03%, 8.94%, and 4.17%, respectively) compared to low MMLs (11.23%, 7.43%, and 3.51%, respectively, p &lt; 0.001). The counties with very high MMLs exhibited an 18% higher adjusted prevalence of T2D (PR: 1.18 [1.13 – 1.23], p &lt; 0.001), 7% higher adjusted prevalence of CAD (PR: 1.07, [1.03 – 1.11], p &lt; 0.001), and 9% higher adjusted prevalence of stroke (PR: 1.09, 95% CI: 1.05 – 1.13, p &lt; 0.001) compared to those with low levels. Conclusion: Our study establishes a significant association between marine microplastic levels and cardiometabolic disease prevalence in coastal counties.
Abstract 4138344: High fat diet induced the premature senescence of white adipose tissue through downregulating SIRT1 expression and promoting its S-nitroslyation modification
Authors: Qunyan Xiang, Liling Guo, Jin Xu, Yingying Xie, Liyuan Zhu, Tie Wen, Ling Liu
Journal: Circulation (2024)

Background and Objectives: The dysfunction of subcutaneous white adipose tissue is one of the early manifestations of obesity, which was associated with accelerated cellular process in aging induced by high fat-diet. The premature senescence of adipose-derived mesenchymal stem cells (AMSCs) is the key factor contributing to the aging of subcutaneous white adipose tissue. However, the underlying mechanism was not clear. Here, we explored the role and mechanism of obesity on the aging of white adipose tissue and AMSCs, and evaluated the anti-aging effect of resveratrol on this process. Methods: Subcutaneous white adipose tissue in non-elderly obese individuals and mice fed with high fat-diet was obtained to detect the TG metabolism and premature senescence. Then the postprandial triglyceride-rich lipoproteins (TRL) after high-fat diet was extracted, and the role and mechanism of TRL on the senescence of AMSCs were explored. Finally, the anti-aging effect of resveratrol on the white adipose tissue and AMSCs was evaluated. Results: Postprandial TG metabolism was abnormal in non-elderly obese humans and mice, and high-fat diet remarkably aggravated white adipose tissue senescence in mice (Fig. 1). TRL induced the premature senescence of AMSCs, with the downregulation of of silent mating-type information regulation 2 homolog 1 (SIRT1) via protein kinase B/forkhead box protein O1 pathway. Besides, the S-nitrosylation of SIRT1 was increased which was regulated by ten-eleven translocation 1/S-nitrosoglutathione reductase pathway. Resveratrol, a SIRT1 agonist, inhibited the TRL-induced AMSCs senescence, resulting in the amelioration of white adipose tissue senescence in obese mice (Fig. 2). Conclusions: These findings established a new mechanism for high-fat diet-induced white adipose tissue senescence and provided a potential therapeutic strategy for high-fat diet induced white adipose tissue senescence and metabolic disorders.
Abstract 4138334: Identification and Immunological Characterization of Arrhythmia-Related Molecular Clusters in Ischemic Cardiomyopathy
Authors: Hui Yang, Chenlu Wu, Shenghua Zhou
Journal: Circulation (2024)

Ischemic cardiomyopathy, a severe cardiac condition resulting from prolonged myocardial ischemia, is characterized by ventricular dilation, dysfunction, and an increased risk of life-threatening arrhythmias. Arrhythmia, a common complication in ischemic cardiomyopathy, is associated with poor clinical outcomes. Recent studies have indicated that the molecular heterogeneity of ischemic cardiomyopathy may contribute to the development of arrhythmias. Therefore, our study aimed to explore arrhythmia-related molecular clusters in ischemic cardiomyopathy and establish a prediction model for risk stratification. Based on gene expression profiles of ischemic cardiomyopathy patients, we analyzed the dysregulation of arrhythmia-associated genes and the associated immune characteristics (Figure 1A-C). Using unsupervised clustering analysis, we identified distinct arrhythmia-related molecular clusters in ischemic cardiomyopathy patients (Figure 1D-F). Cluster-specific differentially expressed genes were further identified using weighted gene co-expression network analysis (WGCNA). Functional enrichment analysis revealed significant differences in biological processes and pathways between the clusters (Figure 1G-H). Subsequently, we developed a prediction model using a random forest algorithm, which showed superior performance in distinguishing patients with different arrhythmia risks (Figure 1I-J). This forest model demonstrated excellent performance in one external validation datasets with AUC values of 0.891. In conclusion, our study provides novel insights into the molecular basis of arrhythmias in ischemic cardiomyopathy and establishes a prediction model with potential clinical utility for risk stratification and targeted therapies. Further investigation into the specific mechanisms underlying the identified molecular clusters may reveal new therapeutic targets for the management of arrhythmias in ischemic cardiomyopathy patients.
Abstract 4138278: A Titin Missense Variant Causes Atrial Fibrillation
Authors: Mahmud Arif, Hanna Chen, Michael Hill, Miles Barney, Arvind Sridhar, Asia Owais, Jaime DeSantiago, Dawood Darbar
Journal: Circulation (2024)

Background: Rare loss-of-function variants in TTN , the gene encoding the sarcomeric protein titin, have been causally associated with atrial fibrillation (AF). Missense TTN variants ( TTN mv) are generally regarded as benign in relation to dilated cardiomyopathy, but their role in AF is unknown. Hypothesis: TTN mv are associated with clinical outcomes and AF pathogenesis. Aims: We aimed to determine if TTN mv are associated with AF/heart failure (HF) hospitalizations and investigate if a rare missense variant ( TTN -T32756I) caused AF using human induced pluripotent stem cell-derived atrial cardiomyocytes (iPSC-aCMs). Methods: Whole exome sequencing was performed in 131 adults at an urban academic healthcare system who identified as non-Hispanic Black (NHB) or Hispanic/Latinx (HL). Multivariable Cox proportional hazard models were used to assess cumulative risk of AF/HF hospitalization. Isogenic TTN -T32756I iPSC-aCM mutants were generated using the CRISPR-Cas9 technique. We used confocal microscopy to assess sarcomeric integrity, MuscleMotion to assess contractility, and optical voltage mapping and patch-clamping to assess the electrophysiological (EP) properties. Results: We identified 137 TTN mvs in 76/131 (58.0%) of subjects, which were most commonly in the TTN A-band. 64 AF-related and 110 HF-related hospitalizations occurred after a median follow-up time of 4.16 years. Hospitalization risk was higher in TTN mv carriers (HR 1.81, Fig. 1A ). We also identified three patients with early-onset AF who shared a rare missense variant T32756I. TTN-T32756I -iPSC-aCMs displayed aberrant contractility ( Fig. 1B-D ), shortened action potential duration ( Fig. 1G-H ), increased activity of cardiac K + channel ( Fig. 1I ), and dysregulated Ca 2+ homeostasis ( Fig. 1J ) without compromising sarcomeric integrity ( Fig. 1E-F ). The titin-binding protein, Four-and-a-Half Lim domains 2 (FHL2), also has increased binding with KCNQ1 and its modulatory subunit KNCE1 in TTN-T32756I -iPSC-aCMs, which may enhance the slow delayed rectifier K + current ( I ks ). Suppression of FHL2 normalized I ks , supporting FHL2 as a mediator of the increased I ks ( Fig. 1K) . Conclusion: In a single-center multi-ethnic AF cohort, TTN mv were associated with increased AF/HF hospitalization, and the T32756I- TTN mv causes ion channel remodeling and an AF-like EP phenotype. These findings establish a mechanistic link between TTN mv, K + ion channels, and sarcomeric regulatory proteins that may represent a novel therapeutic target.
Abstract 4138330: Clinical outcomes in rheumatic mitral stenosis and the novel Yeo’s index
Authors: Ryan Leow, Tony Li, Jackie Chiu, Meei-Wah Chan, William Kong, Kian-Keong Poh, Ivandito Kuntjoro, Ching-Hui Sia, Tiong-Cheng Yeo
Journal: Circulation (2024)

Introduction: Yeo’s index, the product of the mitral leaflet separation index and dimensionless index of mitral valve, was recently described to accurately identify severe rheumatic mitral stenosis (MS). We aimed to study the association between Yeo’s index and clinical outcomes in patients with rheumatic MS. Methods: We studied 297 patients with rheumatic MS. Clinical and echocardiographic data were obtained from the electronic medical record and Yeo’s index was measured in all cases. The outcome studied was a composite of all cause death, heart failure (HF) hospitalisation, mitral valve intervention and stroke or transient ischaemic attack. We also performed subgroup analysis of patients without pre-existing atrial fibrillation (AF) to assess for association with new onset AF. Results: After a median follow up of 6.3 years, 145 patients (48.8%) developed the composite outcome. Yeo’s index ( p &lt;0.001), mitral valve area (MVA) by pressure half-time (PHT) ( p= 0.028) and planimetry ( p &lt;0.001), age ( p =0.016), history of diabetes mellitus ( p =0.029), previous HF ( p =0.021), left ventricular ejection fraction ( p =0.022), and pulmonary artery systolic pressure ( p =0.007) were univariately associated with the composite outcome. Yeo’s index remained independently associated ( p &lt;0.001, HR 0.094, 95% CI 0.260-0.340) with the composite outcome in multivariate analysis. In subgroup analysis of patients without pre-existing AF, Yeo’s index was independently associated ( p =0.024, HR 0.354, 95% CI 0.143-0.874) with new onset AF. MVA by PHT and planimetry were not associated with new onset AF. Conclusion: Yeo’s index was independently associated with clinical outcomes in patients with rheumatic MS.
Abstract 4138303: Stress Hyperglycemia Ratio Predicts MACE and All-cause Mortality in Acute Coronary Syndrome Patients: A Meta-Analysis Comparing Patient with Diabetes Mellitus and Non-Diabetes Mellitus
Authors: Ramya S D Kanagala, Neha Kanthala, Joanne Mathew, Maneeth Mylavarapu, Sachin Singh, Lovekumar Vala, Riya Dhadhal, Ali Danish, Nanush Damarlapally, Adil Mohammed, Hafeezuddin Ahmed, meshal alsulami, Rupak Desai
Journal: Circulation (2024)

Background: A higher stress hyperglycemic ratio (SHR) has been reported to be associated with adverse cardiac outcomes. However, the role of SHR in predicting clinical outcomes by comparing patients with and without diabetes mellitus is yet to be explored. Objective: To evaluate the prognostic value of the SHR for predicting major adverse cardiovascular (MACE) and all-cause mortality in ACS patients with and without diabetes mellitus. Methods: Per PRISMA guidelines, we comprehensively reviewed PubMed, Google Scholar, and SCOPUS for eligible studies reporting on SHR and its association with MACE (8 studies) and all-cause mortality (7 studies) in ACS patients. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a binary random-effects model, with results displayed as forest plots. Heterogeneity was assessed using I2 statistics, and a leave-one-out sensitivity analysis was performed. P&lt;0.05 was considered significant. Results: A total of 15 studies with 45,774 patients with ACS were included in the analysis. The majority of patients were males (72.6%) with a mean age of 62.8 years. High SHR was associated with higher odds of MACE (1.93 [1.54–2.42]) and all-cause mortality (1.91 [1.58–2.31]) (Fig. 1). Subgroup analysis revealed increased odds of all-cause mortality (1.69 [1.34–2.11] for patients with diabetes vs 2.12 [1.65–2.71] for patients without diabetes) and MACE (1.60 [1.30–1.97] for patients with diabetes vs 1.44 [1.28–1.62] for patients without diabetes), all p&lt;0.01. (Fig. 2). Additionally, the leave-one-out sensitivity analysis demonstrated that excluding any particular study did not significantly affect outcomes (p&lt;0.05). Conclusions: In patients with ACS, SHR is an independent predictor of MACE and all-cause mortality, irrespective of diabetes status. Strict glycemic control strategies may improve outcomes in this high-risk population. These findings underscore the importance of early recognition and management of stress hyperglycemia in ACS patients.
Abstract 4138345: Incidence and Predictors of Infective Endocarditis in Bacteremic Patients
Authors: Ahmed Alturki, Jacinthe Boulet, Mohammed Abalhassan, Laurie Fiorentino, Yi Fan, Vivian Loo, Thao Huynh
Journal: Circulation (2024)

Background: Infective endocarditis (IE) is a serious disease, with a high mortality rate.There has been a shift in the composition of organisms causing infective endocarditis. We aimed to provide a contemporary incidence of IE among bacteremic patients stratified by bacterial pathogens. We also sought to evaluate the predictors of IE in bacteremic patients. Methods: We included patients at a large quaternary centre in Canada. All bacteremias during the period from 2014 to 2016 were identified and data was collected on the following variables – patient demographics, organism, comorbidities, pre-disposing factors, clinical findings, pertinent biochemistry, performance of echocardiography, and diagnosis of IE. Diagnosis of IE was made using the modified Duke’s criteria. Logistic regression was used to identify predictors of IE. Results: There were 1,708 patients with bacteremia included in this analysis. The mean age was 64.5±17.0 years old; 39.7% were females and 77.4% were community acquired bacteremia. In addition, 47.0% had hypertension, 29.9% had diabetes mellitus, 17.5% had chronic kidney disease and 25.2% were immunosuppressed. There were 102 (6.0%) patients with confirmed infective endocarditis (IE). The proportion of bacteremic patients who developed IE was 13.2% in 281 patients with methicillin-sensitive Staphylococcus aureus, 5.4% in 56 patients with methicillin-resistant S. aureus, 2.4% in 292 patients with S. epidermidis, 9.9% in 121 patients with Streptococcus viridans group, 16.5% in 91 patients with Enterococcus, 1.3% in 303 patients with Escherichia coli, 38.5% in 13 in patients with Streptococcus bovis, and 9.5% in 21 patients with Propionibacterium acnes. Predictors of IE were intravenous drug use (odds ratio [OR]=8.64, 95% confidence interval [CI] 3.50- 21.3; p&lt;0.0001), prosthetic heart valve (OR= 2.10, 95% CI 1.01- 4.39; p=0.049), structural heart disease (OR= 12.2, 95% CI 3.35- 44.67; p= 0.0002) and community acquired bacteremia (OR= 2.06, 95% CI 1.11- 3.82; p=0.02). CONCLUSIONS: Methicillin-sensitive Staphylococcus aureus is the commonest cause overall of IE followed by viridans group streptococcus. Streptococcus bovis and Enterococcus bacteremia have the highest incidence of IE. Knowledge of the incidence rates of IE among various pathogens may guide diagnostic testing such as pursuing more advanced imaging procedures for patients with increased risk of IE.
Abstract 4138340: Cav-1/FGF2 Axis Mediates Endothelial-Mesenchymal Transition Promoting Aortic Valve Calcification
Authors: Zhihui Zhu, Yongqiang Lai
Journal: Circulation (2024)

Background: Calcific Aortic Valve Disease is a common cardiac condition with no effective medication available; severe cases require surgery. Endothelial-to-mesenchymal transition is a key pathological process, yet the genetic regulatory mechanisms involved remain unclear. Research Questions: Investigating the mechanism of Cav-1/FGF2 axis-mediated endothelial-mesenchymal transition in aortic valve calcification. Methods: Histopathology, immunohistochemical staining, and western blot analysis were performed on 5 non-calcified and 5 calcified aortic valves. Proteomic sequencing was conducted on these samples. Single-cell RNA sequencing on 3 calcified aortic valves focused on valve endothelial and interstitial cells to explore key genes and functions in EndoMT. In vivo and in vitro experiments, along with single-cell multi-omics sequencing, elucidated the role and mechanism of the Cav-1/FGF2 axis in EndoMT using endothelial cell-specific EndoMT knockout mouse models and cell models. Results: Proteomics and single-cell sequencing results indicated that Cav-1 is involved in the Endothelial-to-mesenchymal transition process in Calcific Aortic Valve Disease. Cav-1 plays a crucial role in the intermediate transition of EndoMT, interacting significantly with FGF2. Immunohistochemical staining showed high expression of Cav-1 in calcified aortic valves. In vitro experiments demonstrated that Cav-1 mediates Endothelial-to-mesenchymal transition in valve endothelial cells, promoting aortic valve calcification. Molecular docking analysis revealed potential direct interaction between Cav-1 and FGF2 proteins. Elevated Cav-1 gene expression increases the number of cell surface caveolae, enhancing cell surface area, which promotes FGF2 binding to its receptor and activates the TGF-beta receptor, both of which facilitate EndoMT through the Smad pathway. Conclusion(s): Activation of the Cav-1/FGF2 axis promotes endothelial-mesenchymal transition, thereby promoting aortic valve calcification.
Abstract 4138310: Successful Endovascular Closure of Ascending Aortic Pseudoaneurysm Using Atrial Septal Defect Occluder
Authors: Wahab Jahangir Khan, Muhammad Asif, Christopher Paa, Michael Bacharach, John Wagener
Journal: Circulation (2024)

Introduction: Ascending aortic pseudoaneurysms are mostly related to either surgery or non-surgical trauma. Any pseudoaneurysm arising from graft anastomoses, regardless of size or location, must be repaired due to the potential for catastrophic rupture. Traditional surgical intervention has a high mortality rate, but percutaneous treatment has emerged as an alternative. We present such a case of pseudoaneurysm treated by percutaneous intervention using a 6-mm Amplatzer device. Case: A 77-year-old female with a history of type A aortic dissection s/p emergent repair with a 32 mm tube graft one year ago presented with chest pain radiating to her back. Initial vital signs showed a BP of 185/105, SaO2 98% on RA, 98.3 F, HR 98 bpm, and RR 24/min. A chest CT scan suggested a pseudoaneurysm at the proximal anastomotic site of the aortic graft (Figs. 1A and B). Serial troponin and EKGs were unremarkable for acute ischemia. Multiple quaternary centers declined intervention due to the high risk of redo sternotomy for open repair and patient frailty. After multidisciplinary discussions, it was felt that percutaneous closure with an Amplatzer device was possible without coronary obstruction. In the catheterization lab, a TEE probe was placed to visualize the pseudoaneurysm of the ascending aorta (Fig. 1C). Angiography showed the aneurysm coming off the posterior aorta just above the noncoronary cusp, with the neck measuring ~6 mm (Fig. 1D). The aneurysm was successfully engaged using an 8-French sheath and an 8-French AL1. Based on measurements from the TEE and the angiogram, a 6 mm ASO device was used. After device deployment and release, aortograms showed that the pseudoaneurysm was excluded (Fig. 1H). Assessment with TEE and CTA showed no residual flow in the pseudoaneurysm (Fig. 1 E–G). Conclusion: Using an atrial septal occluder, endovascular intervention may be a safe and effective alternative to surgery for treating the ascending aortic pseudoaneurysm, especially in patients with a high prohibitive surgical risk. Longitudinal follow-ups are needed to comment on long-term mortality benefits for these individuals.
Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment
Authors: Hannah Hart, Prabhjot Grewal, Karan Sud, Edgar Argulian, Abel Casso
Journal: Circulation (2024)

Background: Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction. Case: A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT &gt; 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up. Discussion: With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.