tbuckley/cabot-search huggingface dataset:
Abstract 4145690: Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Atrial Fibrillation Recurrence After Catheter Ablation in Patients with Diabetes: A Systematic Review and Meta-Analysis
Authors: Sawai Singh Rathore, Ibrahim Al Shyyab, Ameer Farrukh, hamam aneis, Sem Josue Nsanh Yao, Vanessa Vidaurre Corrales, Zario Wint, Ashish Kumar
Journal: Circulation (2024)

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated cardiovascular benefits beyond glycemic control, including potential anti-arrhythmic effects. The impact of SGLT2 inhibitors on atrial fibrillation (AF) recurrence following catheter ablation in diabetic patients is an area of emerging interest. The purpose of this meta-analysis was to evaluate the impact of SGLT2 inhibitors on AF recurrence following catheter ablation in patients with diabetes. Methods: A comprehensive literature search was carried out using PubMed, Embase, and Google Scholar databases for the studies comparing SGLT2 inhibitors with other antidiabetic drugs in AF patients undergoing catheter ablation. Using random effect models, Mantel-Haenszel odds ratios and associated 95% confidence intervals were produced to report the overall effect size. Statistical significance was set at p &lt; 0.05. Egger's regression test and Begg-Mazumdar's rank test were used to assess publication bias. The primary endpoint was the reoccurrence of atrial fibrillation after catheter ablation during the follow-up period, which varied between studies and ranged from 12 to 33 months. Results: The analysis included six studies, involving a sample size of around 5,765 AF patients. Our study reported that the use of SGLT2 inhibitors in diabetic patients undergoing catheter ablation for AF was associated with lower odds of AF reoccurrence (OR: 0.46; 95% CI: 0.32 to 0.65; p&lt;0.0001) compared with other antidiabetic medications. This outcome has moderately associated heterogeneity, with I2 of 59%. Egger's regression test and Begg-Mazumdar's rank test showed no evidence of publication bias (p &gt; 0.05). Conclusion: The use of SGLT2 inhibitors was associated with improved outcomes post-catheter ablation for AF diabetic patients. Further large-scale, randomized controlled trials are warranted to confirm these findings and elucidate the underlying mechanisms.
Abstract 4145678: Enhanced Cardiovascular Risk Prediction of Calcium Scoring Computed Tomography Scans by Incorporating Pericardial Fat Characteristics: A Machine Learning Gradient Boost Analysis of Data Derived from a Deep Learning Segmentation Model of a Community-Based Cohort
Authors: Elham Mahmoudi, Francisco Lopez-Jimenez, Betsy Medina, Jose Medina-Inojosa, Bradley Erickson
Journal: Circulation (2024)

Introduction: Calcium scoring computed tomography (CAC) is a widely available and inexpensive modality of screening for atherosclerosis. This study aims to improve the predictive value of CAC by incorporating pericardial fat characteristics in a CatBoost model. Methods: A sample of 7,000 non-contrast clinically indicated CAC scans were randomly selected from a cohort of consecutive Olmsted County MN residents. Known history of atherosclerotic cardiovascular disease or impaired images were excluded. A pericardial fat segmentation model, trained on 191 images of the same dataset with a dice similarity score of 94%, was applied to 6,194 CT scans; Volume and mean Hounsfield unit (mHU) of the output masks were added to age at imaging, radiologist-measured calcium score, male gender, diabetes, and smoking (Figure 1). A 70,20 and 10% split was used to produce the training, validation and test set, respectively. Features were inputted to CatBoost classifier, as the best model tested, to predict four outcomes: acute coronary syndrome (ACS), heart failure (HF), ischemic stroke, and all-cause mortality. Model was evaluated by area under the ROC curve (AUC) on the unseen test set. Results: Mean age was 55.2 (8.8), 55.2 (8.8) and 54.8 (8.5) years in the training, validation and test sets, respectively, and 65%, 67% and 66% of the populations were male. The mean AUC, obtained through bootstrapping with 100 iterations, was 0.81 [0.77-0.85], 0.86 [0.60-0.92], 0.80 [0.73-0.87] and 0.87 [0.81-0.91] for HF, ACS, stroke and death, respectively; The same analysis excluding pericardial fat measurements showed a 3% reduction in the AUC for all of the investigated outcomes (Figure 2). Conclusion: Our study presents a robust risk prediction model for ACS, HF, stroke, and mortality based on CAC scans. The improved performance of the model by incorporating pericardial fat characteristics, highlights the potentials of deep learning in timely inexpensive risk prediction in large populations.
Abstract 4146509: L-Lactic Acid Reduces Infarct Size After Ischemia In Isolated Mouse Hearts Through Acidosis, MCT1-Mediated Uptake, And Metabolic Reprogramming
Authors: Marina Cler, Soledad Perez-Amodio, Laura Valls-Lacalle, Elena Martinez, Ignasi Barba, Gino Freddy Sena Ganse, Elisabeth Engel, Antonio Rodriguez-Sinovas
Journal: Circulation (2024)

Introduction: Lactic acid is increasingly recognized as an alternative fuel source for various tissues, including the brain and heart. It is acknowledged as a protective compound in tissues such as the brain, particularly under conditions like traumatic brain injury or ischemia-reperfusion. However, its potential as a cardioprotective agent remains controversial. Aims: We aimed to (1) evaluate the impact of acute L-lactic acid administration at reperfusion onset on myocardial infarct size in isolated mouse hearts after transient global ischemia, and (2) elucidate the underlying mechanisms. Methods: Isolated mouse hearts underwent 35 min global ischaemia followed by 60 min of reperfusion and were randomly assigned to experimental groups. Control hearts (n=7) received standard Krebs buffer, while L-lactic acid-treated hearts received Krebs containing 8 or 20 mmol/L L-lactic acid for the first 15 minutes of reperfusion (n=5). To assess the contribution of acidosis to the observed effects, 5 hearts were treated with acidic Krebs (pH 7.0) for the same time period. To evaluate the role of import of L-lactic acid through monocarboxylate transporter 1 (MCT1) in those effects, additional hearts (n=6) were treated with L-lactic acid and 1 μmol/L AR-C141990 hydrochloride. Results: L-lactic acid induced a concentration-dependent reduction in infarct size, achieving a 23% reduction at 20 mmol/L (from 44.74±2.24 to 21.46±1.93%, ANOVA and Tukey’s tests, p=0.0006). This protective effect was associated with reduced lactate dehydrogenase release and improved functional recovery during reperfusion. Perfusion with an acidic Krebs also reduced infarct size, but to a lesser extent than L-lactic acid (see Figure). MCT1 inhibition with AR-C 141990 attenuated the protective effect of L-lactic acid to the levels seen with the acidic Krebs (see Figure). 1 H NMR spectroscopy revealed significant metabolic changes in L-lactic acid-treated hearts, with pathway enrichment analysis indicating nearly a 3-fold enrichment in pyruvate metabolism, fatty acid biosynthesis, and gluconeogenesis, suggestive of a metabolic shift. Conclusions: These findings support a cardioprotective role for L-lactic acid against ischemia-reperfusion injury, attributable to both acidosis and MCT1-mediated uptake, leading to metabolic reprogramming.
Abstract 4146499: Commercial Pricing of Percutaneous Coronary Intervention in The United States
Authors: Chen Wei, Ishan Paranjpe, Pranav Sharma, Nancy Song, roy lan, Maitreyi Sahu, Joseph Dieleman, Kevin Schulman, Alexander Sandhu
Journal: Circulation (2024)

Background: The 2021 Price Transparency Final Rule required hospitals to publicly disclose commercial prices for all medical services. Using data made available by this legislation, we investigated variation in inpatient prices for percutaneous coronary intervention (PCI). Hypothesis: We hypothesized that there would be substantial differences in commercial prices between and within hospitals and that this variation would be associated with factors such as market competitiveness rather than patient outcomes. Methods: PCI hospitalization prices (MS-DRG 247-251) were obtained from Turquoise Health and linked to hospital characteristics. The association between price and hospital factors such as the Herfindahl–Hirschman index (HHI) for market competitiveness was evaluated using linear models. We also included hospital acute myocardial infarction (AMI) specific mortality and readmission rates made publicly available by Medicare. Results: Median commercial prices (N = 523 hospitals) were 1.7-1.9x higher than Medicare rates (Fig 1A). Self-pay prices were 2.4-3.0x higher. There was strong price correlation across DRG codes (Fig 1B). Across hospitals, the 90th percentile price was &gt;2.5x the 10th percentile price. Within hospitals, the 90th percentile price was 1.7-2.1x the 10th percentile price. Prices varied greatly by region, with the Pacific being the most expensive and Midwest the least. For PCI with drug-eluting stents (DRG 246-247), teaching hospitals had higher prices than non-teaching hospitals (95% CI: +$4,000-5,000) whereas investor-owned hospitals had lower prices (95% CI: -$6,000-$9,000). Higher prices were not linked to hospital readmission and mortality statistics for AMI. On a system level, less competitive markets had significantly higher markups over Medicare rates (Fig 1C). Conclusion: Prices for PCI hospitalization vary significantly within and between hospitals and appear associated with hospital and system-level characteristics.
Abstract 4146425: Impact Of Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-Like-Peptide-1 Agonists On Cardiovascular and Renal Outcomes In Patients With Type 2 Diabetes Mellitus (T2DM) and Autoimmune Diseases: A Global Retrospective Study
Authors: Anderson Anuforo, Alexander Somerville, Jenish Bhandari, Mahnoor Sherazi, Kamal Gautam, Eloho Olojakpoke, Toluwalase Awoyemi, Helena Makri, bhavya poudyal, anuj kadel, Prabhjeet Sandhu, Dan Draytsel, Michelle Melfi, Andras Perl, Cynthia Taub
Journal: Circulation (2024)

Background: Type 2 diabetes mellitus (T2DM) and autoimmune diseases are independent risk factors for cardiovascular disease. Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and Glucagon-like-peptide-1 agonists (GLP1a) have shown cardiovascular benefits. This study compared the cardiovascular impacts of these medications in patients with autoimmune disease and T2DM. Methods: In May 2024, we queried the TriNetX Global collaborative network across 120 healthcare organizations for adults ≥18 yo diagnosed with T2DM and any of 28 autoimmune (15 connective tissue and 13 organ-specific) diseases between 01/01/05 and 06/30/23. We created 3 cohorts based on at least 3 months of SGLT2i use alone or GLP1a use alone, or neither SGLT2i nor GLP1a use during the study period (control). We conducted propensity score matching (PSM) for over 30 covariates and compared outcomes between cohorts. Cox Model analysis was used to calculate the hazard ratios (HR), 95% confidence intervals (CI), and log-rank p-values at five years. Results: In the control cohort, we identified 692,259 eligible patients, 49,458 patients on GLP1a, and 25,002 patients on SGLT2i. Compared to the control cohort, the SGLT2i cohort had a 28% lower risk of the primary composite outcome (HR 0.72; 95% CI: 0.68 – 0.76) and reduced all-cause mortality (HR 0.59; 0.56 – 0.63), acute MI (HR 0.86; 0.79 – 0.94) and ischemic stroke (HR 0.84; 0.77 – 0.91). Compared to the control cohort, the GLP1a cohort had a 28% lower risk of the primary composite outcome (HR 0.72; 95% CI: 0.69 – 0.75) as well as all-cause mortality (HR 0.54; 0.51 – 0.57), acute MI (HR 0.85; 0.80 – 0.91) and ischemic stroke (HR 0.90; 0.85 – 0.95) but higher risk of gastroparesis (HR 1.24; 1.12 – 1.38). We observed lower risks of cardiac arrest, heart failure, venous thromboembolism (VTE), adverse renal outcomes, and hospitalizations in both SGLT2i and GLP1a cohorts compared to controls. Further analysis between the SGLT2i and the GLP1a cohorts revealed lower risks of heart failure, acute kidney injury, end-stage renal disease (ESRD), or dialysis dependence in the SGLT2i cohort but higher risks for ventricular arrhythmias, and diabetic ketoacidosis. Wrist sprain was used as a falsification endpoint. Conclusion: Among patients with T2DM and autoimmune disease, SGLT2i and GLP1a use correlated with a significant reduction in cardiovascular morbidity and all-cause mortality and were associated with a reduced risk of renal failure, VTE, and hospital admission.
Abstract 4146424: Evaluating <u>reported ethnicity</u> , <u>genetic ancestry</u> and three-way local-ancestry <u>admixture</u> with <u>preeclampsia</u> in GenPE, <u>a multi-center case-control study of Colombian women</u>
Authors: Nataraja Sarma Vaitinadin, Kathryn Gray, Charles Dupont, Matthew Maher, RICHA SAXENA, Juan Casas, Claudia Colmenares, Norma Serrano, Ayush Giri
Journal: Circulation (2024)

The role of genetic ancestry (GA) in hypertensive pregnancy disorders in Latin-American women is poorly understood. Using data from a multi-center case-control study (GenPE) of preeclampsia (PE) in young Colombian women (median age = 19) of predominantly low socioeconomic status (2364 controls and 1811 cases), who identify as Afro-Caribbean (AFR-C), White Hispanic (HISP), Amerindian, and Mixed ethnicity, we evaluated associations between 1) reported ethnicity, and 2) empirically estimated GA, with PE . We performed 3-way admixture mapping using European (EUR), African (AFR) and Amerindian (AMR) ancestry references from the Human Genome Diversity Project using the FLARE software to estimate local and global ancestry in GenPE samples. Statistical significance threshold, for three-way local ancestry analyses, was empirically estimated using STEAM (P = 3.45x10 -6 ). In multivariable logistic regression models for reported ethnicity, AFR-C were 33% more likely to have PE (OR = 1.33; P = 0.02) than HISP women . In models evaluating empirically estimated global GA , AFR was positively associated (OR per 10% increase in ancestry = 1.05; P = 0.002) , while AMR (OR = 0.91; P = 0.035) and EUR (OR = 0.95; P = 0.009) were inversely associated with PE. Additionally, adjusting for reported ethnicity in models evaluating global GA and PE changed estimates only marginally for AFR (OR = 1.04; P = 0.025) and EUR (OR = 0.92; P = 0.009). Evaluation of GA and PE in a subset of women who reported AFR-C ethnicity , showed stronger estimates for all global ancestries: AFR (OR = 1.11; P = 0.013, EUR (OR = 0.82; P = 0.026), and AMR (OR = 0.83; P = 0.01). Association analyses with AFR local GA identified three loci associated with PE . The top locus at chromosome 11, rs2021740 (a smooth muscle enhancer in OTOG1 and near MYOD1 ), each additional allele of AFR origin associated with 27% increased odds of PE (OR = 1.27; P = 1.13x10 -7 ). The A-allele for this variant is found in greater frequency in AFR reference populations (22%) than in EUR (5%). Subgroup analyses with HELLP syndrome (279 cases and 2364 controls) shows intriguingly opposite findings with increased risk for global AMR and EUR ancestry and decreased risk for AFR ancestry. Using a genetically diverse hispanic population , we show genetic ancestry is associated with PE independent of reported ethnicity and further demonstrate the power of admixture mapping to identify a candidate locus for PE .
Abstract 4146512: Modifiability of Post-Exercise Oxygen Uptake Recovery Patterns: A Substudy of the SEQUOIA-HCM Randomized Trial
Authors: Chloe Newlands, Catharine Griskowitz, Joseph Campain, Shaina McGinnis, Ilya Giverts, Fabely Moreno, Isabela Landsteiner, Brian Claggett, Caroline Coats, Ian Kulac, Matthew Lee, Martin maron, Iacopo Olivotto, Anjali Owens, Daniel Jacoby, Stephen Heitner, Stuart Kupfer, Fady Malik, Lixin Meng, Amy Wohltman, Rajeev Malhotra, Gregory Lewis
Journal: Circulation (2024)

Background: Recent heart failure studies show that post-exercise VO 2 recovery (VO 2 Rec) patterns track closely with exercise cardiac output and outcomes, but not with peripheral oxygen (O 2 ) extraction. In patients with obstructive hypertrophic cardiomyopathy (oHCM), studies of VO 2 Rec changes with effective cardio-specific interventions are lacking. We hypothesized that treatment with aficamten, a next-in-class cardiac myosin inhibitor, would shorten VO 2 Rec in patients with oHCM. Methods: SEQUOIA-HCM is the pivotal phase 3 trial of aficamten in symptomatic patients with oHCM (New York Heart Association functional class [NYHA FC] II-III, peak VO 2 [pVO 2 ] ≤90% predicted, respiratory exchange ratio ≥1.05). Patients were randomized 1:1 to aficamten or placebo for 24 weeks with the primary endpoint of change from baseline (BL) in pVO 2 . For this analysis, VO 2 Rec was measured as the time taken after exercise cessation for VO 2 to decline by 12.5% (t 12.5% ), 25%, or 50% of pVO 2 . Response rates for achieving clinically meaningful threshold reductions (&gt;15 seconds) in t 12.5% , and correlations with changes in cardiac function (echocardiographic parameters/cardiac biomarkers) were assessed. Results: Among 282 randomized patients (mean age 59.1±12.9 years, 115 female [41%]), 263 (93%) had CPETs at BL and W24 with VO 2 Rec values as shown ( Table ). At W24, t 12.5% improved by 8sec (95% CI, -12, -5sec, p&lt;0.001) in the aficamten group compared to the placebo group. Those treated with aficamten were more likely to improve t 12.5% by ≥15sec (OR 3.7 95% CI 1.9-6.9, NNT=4.8) than those on placebo. Shortening of t 12.5% correlated with reduced NT-proBNP, high-sensitivity cardiac troponin I, left ventricular outflow tract gradient, and improved NYHA FC and Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (all p&lt;0.005). Conclusion: This is the first study to establish that VO 2 Rec is modifiable in response to cardio-specific intervention (aficamten) in patients with oHCM. VO 2 Rec (t 12.5% ) shortened proportionally and in parallel with other metrics of improved cardiac function, underscoring the benefits of aficamten for oHCM, and supporting inclusion of VO 2 Rec as a routine metric for evaluating cardio-specific interventions for oHCM.
Abstract 4146369: Association of Midlife Systemic Inflammatory Markers and Interval Change with Cognition: Insights from the HeartSCORE Study
Authors: Khaled Abdoun, Justin Swanson, Steven Reis, Anum Saeed
Journal: Circulation (2024)

Introduction: Systemic inflammation may be associated with risk for neuroinflammation and cognitive decline. We investigated the association of midlife inflammatory markers and their 1-year change with Montreal Cognitive Evaluation (MoCA) score in a longitudinal cohort. Methods: In the Heart Strategies Concentrating on Risk Evaluation (HeartSCORE) study, baseline serum levels of high-sensitivity c-reactive protein (hs-CRP|), interleukin-6 (IL-6), CD40L, and intercellular adhesion molecule-1 (ICAM-1) were measured, along with their one-year changes (delta). Using linear regression, association of inflammatory biomarkers and interval change with MoCA scores taken 10-12 years later, were examined in models adjusted for traditional risk factors (age, sex, race, smoking, smoking, triglycerides, high density lipoprotein and total cholesterol, systolic and diastolic blood pressure, hypertension, diabetes, metabolic syndrome, antihypertensive use, statin use, and aspirin use). Model 2 added the one-year change in each biomarker. Results: Among 673 participants (mean age [SD]: 59 [6.8] years), 63.9% were women and 31.6% were self-reported Black. While univariate modelling showed an inverse association of IL-6 with MoCA; this was not significant when adjusted for covariates. Baseline ICAM levels had a significant inverse association with MoCA scores [β: -0.47 (-0.93 --0.02) p&lt;0.05] in fully adjusted models (Table). One year change in these markers did not show any statistically significant association with MoCA scores. Conclusion: Midlife ICAM, known to initiate neuro and systemic inflammatory responses, may be an early risk marker for cognitive impairment. Future studies can examine the mechanisms of ICAM and its role in inflammatory cascade and neurocognitive decline.
Abstract 4146398: Single-Nucleus Transcriptome Profiling Identifies Phenotypic Shift in Pulmonary Vascular Endothelial Subpopulations in Pulmonary Arterial Hypertension
Authors: Jingbo Dai
Journal: Circulation (2024)

Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive rise in pulmonary vascular resistance and occlusive vascular remodeling, leading to right heart failure and premature death. Endothelial cell (EC) damage and dysfunction is a key feature of pulmonary vascular remodeling and PAH. However, the understanding of how different EC subpopulations contribute to this process is limited. Methods: We utilized single-nucleus RNA sequencing (snRNAseq) to provide transcriptome insights into cellular composition changes within idiopathic PAH (IPAH) and donor lungs. Principal component analysis (PCA) for dimensional reduction was performed based on the variable genes previously identified and cells are clustered using uniform manifold approximation and projection for dimensions reduction (UMAP) algorithm. Differentially expressed gene (DEG) analysis and cell pseudotime trajectory analysis were performed to identify biological pathway changes and differentiation states of EC subpopulations. Results: Our data revealed 4 distinct EC subsets in human lungs: general capillary EC (gCap), alveolar specific capillary EC (aCap), pulmonary venous EC (PVEC), and pulmonary arterial EC (PAEC). The EC proportion in the whole lung diminished markedly in IPAH patients. Differentially expressed gene (DEG) analysis led to identification of IPAH-related biological process in different EC subsets including aberrant vasoconstriction and cell autophagy in PAEC. The function of aCap in IPAH lungs was skewed from a pro-gas/substance exchange to a pro-inflammation state. Transcriptionally distinct gCap subpopulations were enriched in specific biological processes and could be distinguished into 3 major clusters: angiogenic gCap, inflammatory gCap, and quiescent gCap. Moreover, we identified a skewed cellular distribution from the angiogenic gCap to inflammatory gCap in IPAH lungs. Conclusions: The current study complements efforts to establish a lung cellular atlas and provides a blueprint of molecular/cellular changes associated with EC dysfunction in IPAH at single-nucleus level. EC dysfunction in the pathogenesis of IPAH is centered on EC phenotypic shift and skewed intercellular signaling pattern. Thus, targeting the genes that underlying the EC identity shift and dedifferentiation process may serve as a novel therapeutic strategy to reverse pulmonary vascular remodeling in PAH.