tbuckley/cabot-search huggingface dataset:
Abstract 15369: Once-Weekly Insulin Icodec versus Once-Daily Long-Acting Insulin for Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Mohamed T Abuelazm, Mohamed A Elzeftawy, Ibrahim Gowaily, amr badr, Ahmed Mazen Amin, Ahmed A. Ibrahim, Ahmed Saad Elsaeidy, Shafaqat Ali, Basel Abdelazeem
Journal: Circulation (2023)

Introduction: Insulin Icodec is a novel basal insulin analog with once-weekly subcutaneous administration. Compared to once-daily long-acting insulin (insulin glargine and degludec), insulin icodec was associated with improved glycemic control. We aim to estimate the efficacy and safety of Insulin Icodec versus long-acting insulin in type II diabetic patients. Methods: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 29th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Our primary outcome was glycated hemoglobin (HbA1C) change. Results: We included five RCTs with a total of 1,611 patients. Insulin icodec was associated with significantly decreased HbA1C (MD: -0.16 with 95% CI [-0.32, -0.01], P = 0.04) and increased percentage of time with glucose in range (TIR) (MD: 4.24 with 95% CI [1.51, 6.98], P = 0.002). However, insulin icodec was associated with increased body weight (MD: 0.63 with 95% CI [0.59, 0.67], P = 0.00001). Furthermore, there was no difference regarding hypoglycemic events incidence (RR: 1.13 with 95% CI [0.96, 1.34], P = 0.14), any serious adverse events (AEs) (RR: 1.04 with 95% CI [0.71, 1.53], P = 0.84), or AEs leading to withdrawal (RR: 1.36 with 95% CI [0.55, 3.37], P = 0.5). However, insulin icodec was associated with increased any AEs incidence (RR: 1.10 with 95% CI [1.00, 1.20], P = 0.04). Conclusions: Insulin icodec was associated with decreased HbA1C, increased TIR, similar hypoglycemic, and serious AEs. However, it was also associated with increased body weight and the incidence of any AEs. Further large-scale phase III real-world RCTs are required to confirm insulin icodec efficacy and safety.
Abstract 18303: Characteristics of Clinical Studies Evaluating Thrombolysis and Novel Catheter-Based Interventions for Pulmonary Embolism
Authors: John H Bertot, Khaled Abdelrahman, Ozan Unlu, Ryan Watson, Ajar Kochar
Journal: Circulation (2023)

Introduction: Novel treatment approaches for pulmonary embolism (PE) including catheter directed thrombolysis (CDT), percutaneous thrombectomy (PT), and systemic thrombolysis (ST) are under investigation. However, characteristics of studies of these interventions are not well described. We sought to evaluate the state of studies pertaining to advanced PE therapies. Methods: The ClinicalTrials.gov (CTG) database was queried using search terms specific to advanced therapies and PE between January 1, 2000, and June 30, 2022, with unrelated, withdrawn, and terminated studies excluded. Advanced therapies were defined as studies evaluating either systemic thrombolysis, CDT, and/or PT. Geographic data from enrollment was gathered using zip codes of study sites. Descriptive characteristics related to studies were explored, and ANOVA was used to compare mean trial enrollment between interventions. Results: Of 700 total results, our search yielded 56 eligible studies (8.0%) investigating advanced PE therapies, among which 39.3% studies evaluated CDT, 32.1% evaluated ST, and 28.6% evaluated MT. Most studies were interventional (76.7%) rather than observational (23.3%). The primary study endpoint was most commonly a surrogate endpoint (60.7%), with mortality (5.4%) or a composite including mortality (21.4%), or other endpoints (12.5%) were less frequent (Figure). Mean enrollment was 206.4 in ST, 101.5 in CDT, and 103.7 in PT studies, with no significant difference in study size between intervention type (p=0.207). The USA was the most frequent trial sponsor (41.1%), and within the USA, trial sites were most commonly in large, urban areas and demonstrated geographic variation. Conclusion In conclusion, there is a paucity of studies evaluating advanced therapies for PE with substantial heterogeneity in design and geography. These data highlight the need for further high-quality studies to inform clinical decision making for the treatment of PE.
Abstract 18302: Impact of Guideline-Directed Statin Intervention in Secondary Prevention Patients Stratified by Diabetes Status
Authors: Saarang S Mulukutla, Jianhui Zhu, Floyd W Thoma, Oscar C MARROQUIN, Khurram Nasir, Eugenia Gianos, Anum Saeed
Journal: Circulation (2023)

Background: The 2018 ACC/AHA Cholesterol guidelines recommend that patients with diabetes and known ASCVD should be prescribed high-intensity statin therapy. We analyzed statin use and associated ASCVD outcomes in patients with diabetes and ASCVD across a healthcare network. Methods: Using EMR data, statin utilization was analyzed on patients with established ASCVD (CAD, ischemic stroke, TIA and PAD) stratified by diabetes status. Statin use was divided as: (1) no statin , (2) less than guideline-directed statin intensity (&lt;GDSI), and GDSI. Cox regression models were used to assess HRs and incidence rate per 1000-person years for secondary ASCVD outcomes (MI, ischemic stroke/TIA and all-cause death) in the population. Results: Over a median follow up of 6 years, out of 38,309 secondary prevention patients, 34.3% had diabetes. Over 30% of patients in both groups received no statin or &lt;GDSI. Patients with diabetes and no statin use had higher incidence of MI (107 vs 37 per 1000PY), stroke (44 vs 17) and death (122 vs 45) than those on GDSI. In comparison to GDSI, patients receiving &lt;GDSI or no statin were at significantly higher risk for all adverse outcomes in a graded manner (Table). Conclusions: In a contemporary real-world practice, there is an underutilization of GDSI amongst patients with known ASCVD with or without diabetes. Patients with diabetes suffer worse consequences as a result of this underuse. Efforts to ensure guideline implementation and optimal statin use can curtail burden of future ASCVD events.
Abstract 15334: Laminin Alpha 2 Increases the Protective Effect of Exosomes in Human IPSC-Derived Cardiomyocytes During Ischemia-Reperfusion
Authors: Fernanda Mesquita, Madelyn King, Camila Hochman Mendez
Journal: Circulation (2023)

Acute myocardial infarction (AMI) is a leading cause of death and disability worldwide. With early treatment, restoration of blood flow to ischemic myocardium can be achieved and therefore reduce mortality risk. Evidence suggests that mesenchymal stromal cell (MSC)-derived exosomes (EXO) promote myocardial repair after AMI due to paracrine activity. Laminin alpha 2 (LAMA2) is a major cardiac extracellular matrix (ECM) component and can be used to produce cardiac-specific EXO. Here we coated MSC-derived EXOs in LAMA2 to enhance their recognition by human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). We hypothesized that LAMA2-coated MSC-EXO would confer protective effects on CMs during ischemia-reperfusion. The LAMA2-EXO had a similar yield of particles, with a size range of 130nm as the control (gelatin-EXO). No cytotoxic effect was observed in CMs after 3-day exposure to LAMA2-EXO. CMs were then treated with LAMA2-EXO two hours prior to 4h ischemia (1% O 2 , 5% CO 2 , and glucose-free media). LAMA2-EXO had a 2-fold protective effect compared to non-treatment, and after 1.5h of reperfusion (5% CO 2 , CM-enriched media) CMs treated with LAMA2-EXO recovered faster than the control group. Conversely, due to the laminin 511/411 ECM component of endothelial cells (ECs), we did not see a significant protective effect nor a difference between LAMA2-EXO vs. the control in the EC ischemia-reperfusion group. This is the first report of suggesting the specificity of LAMA2-EXO to treat CM post-exposure to ischemia-reperfusion injury. Overall, these results indicate that LAMA2-EXO can be a promising treatment to target CM survival in ischemic cardiovascular disease.
Abstract 16590: Left Ventricular Remodelling Following Transcatheter Mitral Valve Replacement With the Innovalve System
Authors: Orly Goitein, David Meerkin, Victor Guetta, Ehud Schwammenthal, ADI BUTNARU, Avi Avner, Charanjit Rihal, Ehud Raanani
Journal: Circulation (2023)

Introduction: Transcatheter Mitral Valve Replacement (TMVR) using a trans-septal approach is a new therapeutic option for patients with severe mitral regurgitation (MR). However, both surgical as well as currently under-testing trans-catheter approach, are shown to cause decrease in LV function. The Innovalve TMVR is a novel self-expandable transcatheter mitral valve prosthesis, delivered trans-septally using femoral venous access. It is deployed in an intravalvular posterior position after subvalvular anchoring by rotation of 6 circumferential arms Hypothesis: TMVR procedure (Innovalve system) leads to LV anatomical and functional changes Methods: CT was performed before the Innovalve TMVR procedure, and after 3 to 6 months. CT protocol included retrospective ECG gating with full cardiac cycle coverage. LV end diastolic and end systolic diameters (LVEDD, LVESD) were measured in the left ventricular outflow tract orientation at the most basal level. Tip to tip papillary muscle distance was measured in the short axis orientation at the most basal slice demonstrating the papillary muscle tips. LV ejection fraction (LVEF) was calculated using the end systolic and end diastolic volumes. All measurements were performed at end systole and end diastole before MTVR and after 3-6 months using a dedicated platform (3Mensio). Results: Ten patients (7 males) average age 69+/-10 years, underwent the Innovalve TMVR procedure. Average LVESD decreased from 52±15 mm at baseline to 44±15mm (P=0.016) at 3-6 months. Similarly, LVEDD decreased from 60±14 mm at baseline, to 52±13mm at 3-6 months (P=0.039). Average papillary muscle tip to tip distance at end diastole (ED) decreased from 31.7±7mm at baseline to 28.4±6.5mm at 3-6 months (P=0.047).A trend of LVEF improvement was evident with an increase from 35%±12 average at baseline compared with 39%±12 average after 3-6 months (P=0.346). Conclusions: These preliminary results show that the TMVR procedure using the Innovalve system may result in favourable LV reverse remodelling changes including reduction of LVESD, LVEDD and ED papillary muscle distances, with improved LVEF. This encouraging data might suggest favourable postprocedural structural LV change.
Abstract 16767: Utilization Trends and Sex Disparities in Cardiac Magnetic Resonance Imaging for Cardiovascular Diseases: Insights From TriNetX, a Large Database Analysis
Authors: Aparna Narendrula, Rochell Issa, David Chen, Christopher Nguyen, Wai Hong W Tang, David Kaelber, Deborah H Kwon
Journal: Circulation (2023)

Introduction: Cardiac magnetic resonance imaging (CMR) is an important imaging modality for diagnosing cardiovascular diseases and optimizing therapeutic management. We assessed CMR utilization and potential sex disparities for myocarditis, Takotsubo cardiomyopathy (CM), heart failure, and amyloidosis. Methods: Using the TriNetX database, we conducted a comprehensive analysis, querying adults with diagnoses of these four diseases. CMR risk within 1 year of ICD-10 diagnosis was assessed. Trends in CMR incidence proportion and prevalence between 2015 and 2022 were examined. Odds ratios were used to assess the presence of both sex disparities and temporal differences in CMR utilization for myocarditis in the COVID-19 era. Results: Overall increasing prevalence and incidence proportion of CMR for these four diagnoses are presented in Figure 1. CMR utilization for patients with myocarditis (10.4%), remained consistent between 2019 and 2020. However, the odds of CMR slightly increased in 2021 and then declined in 2022. CMR utilization for Takotsubo, heart failure, and amyloidosis diagnoses was lower, 2.4%, 1.3%, and 4.4%, respectively. Odds ratios revealed higher likelihood of CMR ordered for males than females diagnosed with Takotsubo CM [OR 1.352* (1.143, 1.599)], heart failure [ OR 1.248* (1.221,1.277)], and amyloidosis [OR 1.375* (1.261,1.499)]. Conclusions: Despite CMR's diagnostic and prognostic utility in patients with suspected myocarditis, heart failure, Takotsubo CM, and amyloidosis, CMR utilization is rising but low, with significant sex disparities in referral patterns. Further studies are needed to determine how increased CMR utilization impacts cardiovascular disease diagnosis, patient outcomes, and sex disparities.
Abstract 18340: Several De-Regulated Chemokine Pathways Characterize Long COVID Syndrome
Authors: Mariann Gyongyosi, Emilie Han, Dominika Lukovic, Kevin Hamzaraj, Jutta K Bergler-Klein, Ena Hasimbegovic
Journal: Circulation (2023)

Introduction: The diagnosis of the Long COVID multi-organ syndrome is impeded by lack of circulating biomarkers. Hypothesis: We hypothesized, that post-COVID syndrome is associated with circulating protein de-regulation, enabling diagnosis of long COVID syndrome. Methods: Consecutive patients (70% female, 55±8y) with long COVID syndrome (n=70, 64.3% female, 49±6y) and non-diseased, non-vaccinated healthy controls (n=23, 70% female, 55±8y) of the Vienna POSTCOV Registry (EC 1008/2021) were included, and blood samples were collected. Proteomics was performed by using the Olink proteomics technology (Olink Proteomics, Uppsala, Sweden), by using cardiovascular, Immunologic, inflammation and neurologic protein (3x96 protein) panels. Protein-protein interaction network were built by selecting the significantly dysregulated proteins from the 4 panels, and were classified into functional groups. Results: Multiplex protein panel revealed 34 significantly de-regulated proteins as compared to controls. Gene ontology categorized the 29 upregulated proteins into several pathways with significant (false discovery rate &lt;0.05) functional enrichment in biological processes (eg. death-inducing signaling complex assembly or positive regulation of tumor necrosis factor-mediated signaling pathway), and in molecular function (catalytic activity). Downregulated proteins were in association with chemokine-mediated signaling pathway and chemokine activity (Figure). KEGG pathway analyses revealed upregulated apoptosis, TNF- and NF-κB signaling pathways, but unchanged ACE2 receptors in patients with long COVID syndrome. Conclusions: Several de-regulated chemokine pathways characterize long COVID syndrome and may serve as a combined biomarker panel for long COVOD diagnosis and target drug prediction.
Abstract 18239: Diabetes Status Does Not Modify the Association Between Prolonged Exposure to Elevated Fasting Blood Glucose and Midlife Cognitive Function
Authors: Soo Jung Kang, Ileana De Anda-Duran, XUANYI JIN, Camilo A Fernandez, Owen T Carmichael, Lydia A Bazzano
Journal: Circulation (2023)

Introduction: The association between type 2 diabetes mellitus (T2DM) and cognitive function(CF) has been well established. However, whether the impact of elevated fasting blood glucose(FBG) levels on CF according to T2DM status remains unclear. Hypothesis: We hypothesized that the impact of elevated FBG on midlife CF would be greater in people with T2DM than in those without T2DM. Methods: We studied 673 midlife participants of the Bogalusa Heart Study (age at baseline 36.7 ± 4.4 years, follow-up period 12.6 ± 1.0 years, age at midlife 49.2 ± 4.5 years, 63% women, 30.2% Black) with ≥3 measurements of FBG across the follow up period. Midlife T2DM status was defined as having FBG≥ 126 mg/dL or taking anti-diabetic medications at the time of midlife neuropsychological (NP) examination. Elevated FBG was defined as FBG≥ 100 mg/dL. Exposure duration of elevated FBG (ED_FBG) was defined as the time interval from initial detection of elevated FBG to midlife NP examination. Participants were classified into 3 distinct NP profiles (optimal, average, and mixed-low) using cluster analysis based on their NP performance, with mixed-low signifying worse CF. Associations between ED_FBG and NP profiles were analyzed using multinomial logistic regression models, adjusting for education status. Stratified analysis of the multinomial regression models according to midlife T2DM status, race and sex were performed. Results: Prevalence of midlife prediabetes and T2DM were 34.0% (n=229) and 11.1 % (n=75), respectively. A total of 120 participants (17.8%) were exposed to ED_FBG during the follow-up period. Mean ED_FBG was 9.1 ± 3.2 years. Mean ED_FBG was significantly longer in Black participants and men. The OR for having a mixed-low CF compared to optimal CF was 1.09 for a 1-year increase in ED_FBG (95% CI 1.02, 1.16), adjusted for education status. Stratified analysis according to midlife T2DM status, race, and sex did not yield significant results. Conclusions: Prolonged exposure to elevated FBG from early adulthood was associated with worse midlife cognitive function regardless of midlife T2DM status. Therefore, even among those without T2DM, prolonged exposure to elevated FBG may affect cognition.
Abstract 18385: Platelet Transcriptome in Type 2 Diabetes Provides Insight Into Peripheral Artery Disease and Cardiovascular Events
Authors: Matthew A Muller, Jonathan D Newman, Elliot Luttrell-Williams, Kelly Ruggles, Tessa A Barrett, Jeffrey Berger
Journal: Circulation (2023)

Background: Platelets are integral to atherothrombosis and peripheral artery disease (PAD), processes that are accelerated in diabetes. We evaluated the platelet transcriptome, generated a platelet RNA score, and investigated whether it could serve as a novel biomarker of PAD severity and major adverse cardiovascular events (MACE). Methods: We performed RNA sequencing on circulating platelet samples obtained from 133 patients enrolled in the platelet activity and cardiovascular events in PAD study. The transcriptome was (1) compared in PAD patients with Type 2 Diabetes (T2D) (n=73) vs without T2D (n=60), and (2) correlated with platelet aggregation responses to submaximal epinephrine (0.4uM). Using the overlap of transcripts identified by these approaches, we scored each sample based on a rank-based phenotypic metric (Singscore) to develop a T2D-specific platelet RNA score. This platelet score was compared in PAD patients with (vs without) critical limb ischemia (CLI), and PAD patients with (vs without) incident MACE (myocardial infarction, stroke, or death) after multivariable adjustment. Results: Overall, 384 transcripts were differentially expressed in PAD patients with vs without T2D (P&lt;0.01; 195 upregulated and 189 downregulated). Gene set enrichment analysis noted upregulation of pathways related to cell chemotaxis, acute inflammatory response, and platelet alpha granules in T2D. Among these 384 genes, 102 significantly correlated with platelet aggregation (P&lt;0.01) and were used to create a T2D platelet RNA score. To evaluate its clinical significance, this score was 3- times higher in PAD with (vs without) CLI (P=0.002). Further, after adjusting for age, sex, race, T2D, hypertension and coronary artery disease, the platelet score above (vs below) the median was associated with increased MACE (HR 2.8, 95% CI 1.4 to 5.6, P = 0.003). Conclusions: These findings demonstrate a unique platelet transcriptome in T2D that is associated with PAD severity and future risk of cardiovascular events. This work provides an important step toward the use of platelet RNA to unlock novel molecular mechanisms and inform future clinical outcomes.
Abstract 15339: CAD Polygenic Risk Score and Incident Complex Coronary Revascularization in Adults With Atherosclerosis
Authors: Sachit Singal, Frederick Kamanu, Giorgio Melloni, Carolina Roselli, Robert Giugliano, Patrick T Ellinor, Marc S Sabatine, Christian T Ruff, Nicholas A Marston, Brian A Bergmark
Journal: Circulation (2023)

Introduction: A CAD polygenic risk score (CAD PRS) was previously shown to predict major vascular events among patients with established ASCVD. Whether genetic risk can predict the need for complex coronary revascularization procedures, including complex PCI or CABG, has not been established. Methods: The FOURIER trial randomized 27,564 patients with established ASCVD to evolocumab or placebo with a median follow-up of 2.2 years. Of these, 14,298 had genotype data and were used in this analysis. The CAD PRS was previously derived in a CAD GWAS and includes 2,293,205 SNPs. Clinical records were reviewed for coronary revascularization events to determine procedural characteristics and coronary anatomy. Complex revascularization was defined as complex PCI [multivessel PCI, &gt;3 lesions, &gt;3 stents, total stent length &gt;60mm, or bifurcation PCI] or CABG. Associations between the CAD PRS and revascularization events were analyzed by PRS quintile. Results: Patients with higher CAD PRS were significantly more likely to undergo complex coronary revascularization than those with low genetic risk (Q5 vs Q1: HR 1.71; 95% CI 1.23-2.37; P=0.002) (Fig A), with a greater than 2-fold higher risk of complex PCI (HR 2.11; 1.33-3.35) and a numerically higher risk of CABG (HR 1.28; 0.80-2.05). These findings were directionally consistent for the individual components of complex PCI, including multivessel PCI (HR 1.71; 0.97-3.00), &gt; 3 lesions (HR 1.85; 0.73-4.68), &gt; 3 stents (HR 3.77; 1.75-8.12), stent length &gt;60 mm (HR 2.07; 0.88-4.87), and bifurcation PCI (HR 2.17; 0.39-11.98) (Fig B). Conclusions: Among patients with established ASCVD, a CAD PRS predicted incident complex coronary revascularization procedures. Genetic prediction of advanced coronary disease requiring specific complex interventions has not previously been shown, and these findings may have the potential to yield novel approaches for reducing the need for these high-risk and costly procedures.
Abstract 15332: Obesity is Associated With Acute Kidney Injury in STEMI Undergoing PCI: A National Representative Cohort Study
Authors: Congyan Ye, Guangzhi CONG, Shaobin JIA, Xueping Ma, Ru Yan
Journal: Circulation (2023)

Background: Acute kidney injury (AKI) is a frequent and serious complication after percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, the relationship between obesity and the risk of AKI in this specific patient population has not been previously examined. Methods: We conducted a retrospective analysis of adult discharges from the National Inpatient Sample (NIS) between 2016 and 2019. ICD-10 codes were used to identify patients with STEMI who undergoing PCI. All patients were further sub-categorized into obese and non-obese cohorts. The primary outcome was the incidence of AKI. Multivariable regression models adjusting for demographics, hospital characteristics, and co-morbidities were used to examine differences in AKI incidence in the two groups of patients. Subgroup analysis and interaction tests were used to test whether this relationship was stable across groups. Results: A total of 62,599(weighted national estimate of 529,106) patients were included in the study, out of which 9.80% (n=6137) had AKI. Obese comprised 19.78% (n=1214) of the AKI cohort. Obese patients were on average younger, male, white race and had more comorbidities. There was a significant positive association between obesity and the incidence of AKI (aOR 1.20, 95% CI 1.10-1.31). This significant positive association was more pronounced in female patients (aOR 1.49, 95% CI 1.25-1.79, p&lt;0.001, P-interaction=0.014). The incidence of AKI in STEMI patients after PCI increased steadily during the 4-year study period, and the adjusted trend showed that the incidence of AKI in obese patients was consistently higher than in non-obese patients. Conclusions: Obesity was independently associated with a greater risk for acute kidney injury among adults with STEMI undergoing PCI, especially in female patients. Further studies examining management strategies and best practices in obese patients with STEMI are warranted.