tbuckley/cabot-search huggingface dataset:
Abstract 4147208: Life’s Essential 8 and Association with Adverse Cardiovascular Disease Events: Is Inflammation the Missing 9 <sup>th</sup> Factor?
Authors: Ian Pollack, Justin Swanson, Claudia Bambs, Steven Reis, Anum Saeed
Journal: Circulation (2024)

Background: Recent data show that inflammation leads to residual atherosclerotic cardiovascular disease (ASCVD) risk. The recently revised AHA’s Life’s Essential 8 (LE8) optimal cardiovascular health advisory does not include inflammation as a modifiable risk factor for optimal cardiovascular health. We investigated the role of inflammation as a ninth component of LE8. Methods: Measures of cardiovascular health and inflammation biomarkers data were evaluated among 1,869 patients (age 59.0±7.45 years, 65.7% female, 41.9% self-identified as Black) enrolled in the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study. Multivariable adjusted regression models were used to examine the association of LE8 quartiles with incident ASCVD events and all-cause mortality. We then tested the association of inflammatory markers (interleukin-6 [IL-6] and C-reactive protein [hs-CRP]). Results: Over a median of ~12 years, ideal level of blood glucose was associated with significantly lower risk of ASCVD (HR 0.26, CI 95% [0.12-0.58]; p=0.001). A similar trend was seen for ideal BP (HR 0.45, [0.18-1.12]; p=0.086). For all-cause mortality, no smoking emerged as the main protective factor (HR 0.29 CI95% 0.16-0.53, p&lt;0.001). Overall, highest quartile of LE8 Score was significantly associated with lower risk of ASCVD events and all-cause mortality (HR 0.14, [0.04-0.48];p&lt;0.01) ( Table ). In stratified analysis, age and IL-6 levels (HR 1.54 (1.05-2.25); p=0.03) were independently associated with a higher risk of ASCVD events despite higher LE8 scores. Conclusion: Despite optimal health parameters, as identified by optimal Life’s Essential 8 scores, high IL-6 levels are independently associated with residual risk of ASCVD events. Utility of adding IL-6 as a ‘necessary ninth’ modifiable parameter needs to be explored further.
Abstract 4147197: Deletion of PKM2 in macrophages fosters stabilization but not regression of atherosclerotic plaques
Authors: Flavio Dionisio, Filip Prica, Yeqian Zhu, Anna Gisslinger, Linda Andersson, Eva Bengtsson, Harry Bjoerkbacka, Steffen Massberg, Christian Schulz, Lukas Tomas
Journal: Circulation (2024)

High-risk human atherosclerotic plaques show a metabolic profile characterized by a high glycolytic flux. Pyruvate kinase M2 is an important regulator of increased glycolytic activity and deletion of PKM2 in macrophages induces a reparatory macrophage phenotype. Given these results, we hypothesized that inhbiting glycolysis in macrophages by deleting PKM2 might induce atherosclerotic regression and present a viable therapeutic target. For this, we employed LDL receptor antisense oligonucleotides in LysM Cre PKM2 flox , allowing us temporal control of the LDL receptor knockdown and thus the induction of atherosclerosis regression by normocholesterolemia after a period of atherosclerotic development. After 16 weeks of Western Diet and ASO treatment, we found no difference in plaque size between PKM2 cKO and littermate PKM2 WT controls. We verified these results in a second centre in Sweden by transplanting either PKM2 cKO or PKM2 WT bone marrow into LDL receptor knockout mice and analysing the plaque area over the entire aortic root after 16 weeks of Western Diet. Despite similar plaque sizes between the two genotypes, we found that plaque collagen content was increased in PKM2 cKO compared to PKM2 WT mice (58±11 vs. 46±9%, p&lt;0.05) whereas CD68 area was significantly decreased (39±10 vs. 23±9%, p&lt;0.05) - mirroring previous results from another group. In line with these results, we found a trend towards more effective efferocytosis in vitro in PKM2 cKO compared to PKM2 WT macrophages. In order to test the effect of PKM2 knockout on plaque regression, we treated PKM2 cKO and PKM2 WT mice with Western Diet and ASOs for 16 weeks, after which we stopped ASO injections and fed them a chow diet for another 4 weeks to induce normocholesterolemia and plaque regression. After 20 weeks of treatment, we did not see a difference in plaque size or markers of plaque stability (lipid/collagen/macrophage content). These findings confirm previous results that PKM2 knockout in macrophages leads to a more stable phenotype in progressing plaques. Nonetheless, after a short period of normocholesterolemia - comparable to initiated statin treatment in patients - this advantage of non-functional PKM2 is lost. We conclude that PKM2 does not appear to be a promising therapeutic target to ameliorate atherosclerosis progression and initiate regression.
Abstract 4146890: Analysis of In-Hospital Outcomes of Transcatheter Edge-to-Edge Repair of Mitral Valve in Patients with and without COVID-19: Insights from the National Inpatient Sample Data (2020-2021)
Authors: Siddharth Agrawal, Maharshi Raval, Aalesh Shah, Labdhi Sanghvi, Hitesh Bhatia, Sajid Siddiq
Journal: Circulation (2024)

Background: COVID-19 has introduced new complexities in the management of patients undergoing the transcatheter edge-to-edge repair (TEER) procedure of the mitral valve. This study compares outcomes of mitral valve TEER in patients with and without COVID-19, utilizing data from the National Inpatient Sample (2020-2021). Methods: We conducted a retrospective cohort study on 23,465 patients without COVID-19 and 85 patients with COVID-19 undergoing mitral valve TEER. Multivariate logistic regression was employed to compare outcomes, adjusting for potential confounders. Primary outcomes included mortality and major complications, while secondary outcomes encompassed specific procedural complications. Results: Patients with COVID-19 were younger (mean age: 73.176 vs. 76.178 years, p-value &lt;0.001) and exhibited differences in gender distribution (male: 64.71% vs. 54.80%, female: 35.29% vs. 45.20%, p=0.4125) Patients with COVID-19 exhibited a significantly higher prevalence of mortality (OR: 16.331, 95% CI: 4.842-55.08, p&lt;0.001), transfusion (OR: 5.424, 95% CI: 1.511-19.47, p=0.01), post-procedure shock (OR: 7.521, 95% CI: 2.731-20.708, p&lt;0.001), intra-procedure stroke (OR: 7.892, 95% CI: 2.87-21.704, p&lt;0.001), mechanical ventilation (OR: 13.918, 95% CI: 4.072-47.562, p&lt;0.001), acute renal failure (OR: 7.523, 95% CI: 2.454-23.059, p&lt;0.001), sudden cardiac arrest (OR: 26.127, 95% CI: 7.2-94.803, p&lt;0.001), cardiogenic shock (OR: 7.971, 95% CI: 2.894-21.955, p&lt;0.001), septic shock (OR: 23.176, 95% CI: 5.226-102.78, p&lt;0.001), and sepsis (OR: 18.371, 95% CI: 4.926-68.51, p&lt;0.001). The odds of bleeding (OR: 2.983, 95% CI: 0.94-9.47, p=0.064) did not significantly differ between groups. Patients with COVID-19 had a longer length of stay (LOS) (coefficient: 11.26409 days, p=0.001) and higher total hospitalization cost (coefficient: $230,944.2, 95% CI: $107,037.8-$354,850.5, p&lt;0.001). Conclusion: Patients with COVID-19 undergoing mitral valve TEER procedure face elevated risks of mortality, post-procedure shock, stroke, mechanical ventilation, acute renal failure, sudden cardiac arrest, cardiogenic shock, septic shock, and sepsis compared to those without COVID-19. Additionally, they experience longer hospital stays and incur higher total health charges. Clinicians should consider these heightened risks when evaluating the appropriateness of mitral valve TEER in COVID-19 patients. Further research is warranted to explore strategies for risk mitigation in this population.
Abstract 4146723: Integrating Multi-Omics, Phenotypic, and Social Determinants for Stroke Prediction in Atrial Fibrillation: Advancing Precision Health Using Machine Learning
Authors: Zahra Azizi, Trisha Gupte, Jiayan Zhou, Pik Fang Kho, Rodrigo Guarischi-Sousa, Estella Chen, Daniel Panyard, Shoa CLARKE, Themistocles Assimes
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) is linked to an elevated risk of ischemic stroke (IS) and mortality. However, the performance of existing clinical scoring systems in assessing these outcomes is at best moderate. The blood proteome serves as a vital indicator of biological processes related to complex disorders. Consequently, there exists an opportunity to enhance the predictive accuracy of such risk scores by incorporating blood proteomic data. Purpose: In this study, we aim to evaluate the combined influence of genomics, proteomics, biomarkers, phenotypic, and social determinants of health (SDOH) on AF outcomes to better understand a precision health framework in managing AF. Methods: We analyzed patients with AF in the UK Biobank cohort who underwent proteomics measurements using the Olink Proximity Extension Assay. The primary endpoint was the incidence of IS.We assessed the intersection of multi-omics,comorbidities,SDOH and traditional CHA2DS2-VASc score to identify the most important factors associated with IS.We employed multi-step machine learning algorithms to evaluate 3,083 features, including Step1,which involved separate models for each feature type,followed by Step 2,where a combined model was used to assess the complex relationship between these features.The area under the curve (AUC) was used to compare the discriminative ability of the model with the addition of each feature group for predicting IS.Grid search and 10-fold cross-validation were performed to identify the best hyperparameters,and we calculated the mean AUC for the final models.SHAP values were reported for the top 30 features in the final XGBoost model (Figure1). Results: Among 4,842 patients with AF(mean age 67.2±9.5 years,61.8% female),5.2% experienced an IS within 9.9±7.5 years after AF diagnosis.The mean CHA2DS2-VASc score was 2.3±1.4, with 60.14% on anticoagulation therapy.The AUC for the CHA2DS2-VASc score at baseline was 0.493.Adding SDOH, polygenic scores, phenotypic data, proteomics, and biomarkers improved the model's discriminative ability (Figure 1.A), with a combined model AUC of 0.619 (95% CI: 0.592-0.645)(Figure 1.B).The top 30 features in the final model, primarily proteins, are shown in Figure 1C. Conclusion: A small number of plasma proteins can substantially enhance risk prediction of IS in the setting of AF. Further validation could enable a single-source,personalized assessment of stroke risk in patients with AF as a gateway to personalized risk reduction therapy.
Abstract 4146868: Mapping 3’ untranslated regions reveal compromised alternative polyadenylation in human right ventricle failure
Authors: Rajarajan Thandavarayan, Rahul Neupane, Rajasekaran Mahalingam, Erik Suarez, Eric Wagner, Hari Krishna Yalamanchili, Ashrith Guha
Journal: Circulation (2024)

Background: Right ventricular failure (RVF) impacts the prognosis of pulmonary arterial hypertension (PAH). Alternative polyadenylation (APA) generates transcript diversity and is implicated in diseases, including left heart failure. However, understanding genome-wide polyadenylation maps in RVF patients with PAH is limited, with no studies investigating RVF-specific APA events. Objective: This study mapped 3' untranslated regions (3'UTRs) to explore APA dynamics in RVF development, comparing healthy donors and RVF from patients with PAH. Methods and Results: RV tissues were obtained from patients with failing RV from heart and double lung transplant recipients. Poly(A)-ClickSeq (PAC-seq) RNA sequencing and PolyA-miner algorithm were used. Analysis revealed significant changes in cleavage site usage, identifying 690 genes with altered APA patterns in RVF. Notably, our investigation uncovered a significant finding related to CPSF6, a key factor involved in APA regulation. We observed a substantial lengthening of the 3'UTR in CPSF6, suggesting disrupted polyadenylation events in RVF. Intriguingly, this lengthening coincided with a noticeable decrease in CPSF6 protein levels, indicating a potential regulatory mechanism affecting its expression. Additionally, 530 genes had shortened 3'UTRs enriched for RNA binding and hypertrophic cardiomyopathy pathways, while 160 genes had lengthened 3'UTRs enriched for RNA surveillance and ribosomal RNA binding. Disease-specific APA signatures in RVF patients with PAH were identified. Conclusion: The present study highlights the significant role of APA in human RVF exerting its influence on multiple pathways and regulating specific gene expression. These findings offer insights into RVF in PAH patients and may guide the identification of therapeutic targets and strategies for improved management of the condition.
Abstract 4146753: Digital Health Interventions After An Acute Coronary Syndrome: A Systematic Review And Meta-analysis Of Randomized Controlled Trials
Authors: Mangesh Kritya, Shanmukh sai pavan Lingamsetty, Priyanshi Maurya, Mohamed Doma, Sarai Hernandez Pastrana, Syeda Rubab Fatima, Wilbert Huang, Zahra Naji, Maya Hamdanieh, Felipe Martignoni
Journal: Circulation (2024)

Background: The role of digital health interventions (DHI) in addition to usual care (UC) in patients discharged after an acute coronary syndrome (ACS) remains uncertain. Hypothesis: DHI improves medication adherence, and systolic blood pressure (BP) control and reduces mortality in patients after an ACS. Purpose: To ascertain the efficacy of adding DHI to UC in patients discharged after an ACS through a systematic review and meta-analysis. Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing DHI plus UC versus UC alone in patients discharged after an ACS. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Our outcomes of interest were medication adherence (as per the studies' definitions), all-cause mortality, and systolic BP. Statistical analyses were performed using R software version 4.4.0. Results: We included 22 RCTs comprising 20,587 patients, of whom 14,079 (68.4%) were randomized to DHI + UC. The mean age was 59.5 years and 58.5% were male. About 15% had diabetes mellitus at baseline while 54% had hypertension. In the pooled analysis, DHI plus UC significantly increased medication adherence (RR 1.06; 95% CI 1.01 to 1.13; p=0.03; Fig. 1) and reduced systolic BP (MD -3.16 mmHg; 95% CI -5.53 to -0.79; p&lt;0.01; Figure 2A) compared with UC alone. There was no significant difference between groups in terms of all-cause mortality (RR 0.87; 95% CI 0.52 to 1.44; p=0.58; Figure 2B). Conclusion: In this meta-analysis of RCTs among patients discharged after an ACS, UC with DHI significantly improved medication adherence and lowered systolic BP relative to UC alone, without significantly affecting mortality.
Abstract 4147741: The Effect of Anemia on the Mechanisms of Exercise Intolerance in Adults with HFpEF
Authors: Giorgio Manferdelli, Denis Wakeham, Michael Leahy, Rachel Skow, Claire Kissel, Tiffany Brazile, James MacNamara, Paul Fadel, Mark Haykowsky, Benjamin Levine, Satyam Sarma, Christopher Hearon
Journal: Circulation (2024)

Introduction: Anemia (males: [Hb] &lt;13.5 g/dL, females: &lt;12 g/dL) is common in heart failure with preserved ejection fraction (HFpEF) and associated with exercise intolerance. The hemodynamic effect of anemia and the mechanism by which anemia impairs exercise capacity in patients with HFpEF are unclear. We investigated the effects of anemia on exercise hemodynamics and oxygen transport and utilization (VO 2 ) during a cardiopulmonary exercise test (CPET) and single leg knee extension exercise (SLKE) in patients with HFpEF. Methods: Patients with HFpEF (n=57) classified as non-anemic (n=33, 67% female, age: 70±7 y, BMI: 39.3±5.8 kg/m 2 , [Hb]: 13.7±1.5 g/dL) or anemic (63% female, age: 71±7 y, BMI: 34.7±5.9 kg/m 2 , [Hb]: 11.2±0.9 g/dL) completed CPET on a seated upright cycle ergometer. A subgroup (n=20 non-anemic; 14 anemic) also completed SLKE to exhaustion. During CPET we measured VO 2 (indirect calorimetry), arterio-venous O 2 difference (Δa-vO 2 ; arterial and right heart catheters) and cardiac output (Qc; Direct Fick). During SLKE we measured femoral artery blood flow (LBF; Doppler ultrasound), Δa-vO 2 (pulse oximetry and femoral venous catheter) and leg VO 2 . We also measured total hemoglobin mass (tHbmass; carbon monoxide rebreathing) and plasma volume. Data were compared via independent samples t-tests. Results: The anemic group had lower relative tHbmass (g/kg lean mass; Figure 1A) compared to non-anemic, with no difference in plasma volume (Figure 1B). Peak VO 2 during CPET was similar between groups (non-anemic: 1.32±0.39 vs anemic: 1.24±0.44 L/min, P =0.269), but the anemic group had a higher Q c -VO 2 slope (Figure 1C&amp;D) and a lower Δa-vO 2 (non-anemic: 12.6±1.8; anemic: 10.7±1.4 mL/dL, P &lt;0.001). During SLKE, no difference was detected in peak leg VO 2 , LBF, Δa-vO 2 , or diffusive capacity (all, P &gt;0.175); however, the anemic group had a significantly greater LBF-VO 2 slope (Figure 1D). Conclusion: Patients with HFpEF and anemia present with a hyperdynamic circulation during exercise despite similar peak VO 2 to non-anemic peers. [Hb] modifies the coupling of oxygen delivery and demand and may be a key mechanism responsible for hyperdynamic circulatory responses to exercise in patients with HFpEF and anemia.
Abstract 4147138: Cardiovascular and Bleeding Outcomes of Proton-Pump Inhibitor and Clopidogrel Co-therapy after Percutaneous Intervention: A Meta-Analysis
Authors: Mobeen Haider, Mohammad Hamza, Sahib Singh, junaid Mir, Nismat Javed, Yousra Khalid, Yasar Sattar, Subanandhini Subramaniam Parameshwari, Prasanna Sengodan
Journal: Circulation (2024)

Introduction: Clinical studies have shown conflicting results regarding the effect of proton pump inhibitors (PPIs) on the antiplatelet action of clopidogrel in coronary artery disease (CAD) patients. We conducted a meta-analysis to evaluate cardiovascular, gastrointestinal, and mortality outcomes in 6 months of concurrent use of these medications. Methods: We searched PubMed and Embase, screened 1071 articles, and included seven articles meeting our inclusion criteria: randomized control trials comparing the PPI group to the control group (no PPI) in patients on clopidogrel with CAD for six months. The outcomes of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), heart failure (HF), arrhythmia, bleeding, all-cause death, and cardiovascular (CV) death. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated using a random-effects model. We assessed heterogeneity between studies and p-value was assigned to &lt;0.05 for statistical significance. Results: Seven studies with a total of 5146 patients (PPI group: 2585, No-PPI: 2561). Our analysis shows that use of PPI with clopidogrel is associated with less bleeding outcomes (RR: 0.30, CI:0.19-0.49; p-value:&lt;0.0001). Table 1. Our analysis showed no difference with regard to myocardial infarction (RR: 0.96; CI: 0.51-1.79, p-value:0.897), major cardiovascular events (RR: 0.99; CI: 0.74-1.32, p-value: 0.944), the onset of heart failure (RR: 0.78; CI: 0.27-2.25, p-value: 0.643), arrhythmias (RR: 0.86; CI: 0.30-2.43, p-value: 0.775), cardiovascular mortality (RR: 0.78; CI: 0.29-2.07, p-value: 0.623), and all-cause mortality (RR: 0.77; CI: 0.39-1.51, p-value: 0.451). Figure 1. Conclusions: In patients taking clopidogrel, proton pump inhibitors are associated with decreased bleeding outcomes. Our study showed no difference in terms of cardiovascular and mortality outcomes. Further randomized controlled trials are needed to evaluate these results.
Abstract 4146722: Incidence and Risk Factors for Atrial Arrhythmia in Adults with Systemic Right Ventricle
Authors: Shisheer Havangi Prakash, Rimsha Ahmad, Anca Chiriac, Heidi Connolly, Alexander Egbe, Abhishek Deshmukh, Samuel Asirvatham, Keerthika Vijayakumar, Malini Madhavan
Journal: Circulation (2024)

Introduction: The incidence and risk factors for atrial arrhythmia (AA) [atrial fibrillation (AF) and atrial flutter (AFL)] in adults with systemic right ventricle (SRV), specifically congenitally corrected-TGA (cc-TGA) and D-TGA palliated with atrial switch procedures, is not well understood. This study aims to better define these risks. Methods: Adults with SRV presenting to the Mayo Clinic between 1971 and 2022 were identified. Clinical characteristics, ECG and echocardiographic parameters were recorded at first evaluation. Sustained AA (&gt; 30s) incidence at follow-up was documented using ECG. Cox regression analysis identified associations of incident AA. Results: Among 447 patients with SRV (mean age 34.7±14.8, 55.9% male, cc-TGA n=247; D-TGA post-atrial baffle n=200), AA was documented in 231 (51.6%) at a mean age of 37.5±18.8y. Isolated AF was observed in 88 (38.1%), isolated AFL in 71 (30.7%), and both AF and AFL in 72 (31.2%) patients. Univariate analysis showed significant predictors of AA as: age (HR:1.03, p&lt;0.001), male sex (HR:1.49, p=0.026), NYHA class≥2 (HR:1.98, p&lt;0.001), ventricular pacing (HR:1.64, p=0.019), QRS duration (HR:1.008, p&lt;0.001), SRV enlargement (HR:1.73, p=0.01), SRV ejection fraction (HR:0.979,p=0.012), left atrial enlargement (HR:1.947, p=0.006), hypertension (HR:1.57, p=0.047), CKD (HR:0.991, p=0.021), and obesity (HR:1.66, p=0.023). In multivariable analysis, age (HR:1.032, p&lt;0.001) and QRS duration (HR:1.007, p=0.013) were significant predictors of AA. Kaplan Meier analysis of time from first evaluation to incidence of AA is shown in the figure. AA was associated with heart failure in 56 (26.7%) patients. During 11.2±10.5 years of follow-up, mortality occurred in 50 (21.6%) with AA and 19 (8.8%) without AA. Conclusion: Atrial arrhythmia occurred in more than half of patients with SRV, predominantly in the third decade of life. Significant associations of AA included advancing age, longer QRS duration, enlargement of pulmonary venous atrium, reduced SRV function, hypertension and obesity. AA was associated with heart failure in one-fourth of patients and higher mortality. Close monitoring and early intervention in patients with risk factors may help mitigate the development of AA.