tbuckley/cabot-search huggingface dataset:
Abstract 4143799: Dose-Dependent Inhibition of Lp(a) Oxidation by Eicosapentaenoic Acid (EPA) Compared to a Fibrate and Statin due to Lipid Interactions and Antioxidant Properties
Authors: Samuel Sherratt, Peter Libby, Deepak Bhatt, Preston Mason
Journal: Circulation (2024)

Background: Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Levels of oxidized Lp(a) were more predictive of CV events and endothelial dysfunction than non-oxidized forms in patients. The omega-3 fatty acid EPA reduced CV events in high-risk patients, including those with elevated Lp(a) (REDUCE-IT). EPA inhibits lipid oxidation due to scavenging activity and lipophilicity. We compared the effects of a pharmacologic concentration of EPA on oxidation rates for Lp(a) versus LDL compared to a fibrate and statin, along with lipid affinity. Methods: Lp(a) was enriched to 66% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) and LDL (50 µg/ml) were incubated at 37°C for 30 min with EPA at various concentrations (10 – 100 µM) compared to equimolar fenofibric acid or rosuvastatin (10 µM). Samples then underwent copper sulfate-induced oxidation (20 µM) monitored by formation of malondialdehyde (MDA). Lipid affinity of each agent was measured by UV/Vis spectroscopy using lipid vesicles containing phosphatidylcholine and cholesterol at a 0.3:1 ratio. Drug concentrations in vesicles versus buffer were measured and compared to standard curves. Results: Lp(a) enriched ApoB particles underwent time-dependent oxidation by 51-fold, peaking after 2 h (4.13 ± 0.10, p&lt;0.001). EPA significantly inhibited Lp(a) oxidation in a dose and time-dependent manner; after 2 h, EPA inhibited oxidation from 31 to 69% ( p &lt;0.001) at 5 concentrations while fenofibric acid and rosuvastatin lacked antioxidant activity. Similar distinct antioxidant effects of EPA were observed in non-modified LDL. The antioxidant activity EPA correlated with higher lipid affinity that was significantly greater than fenofibric acid and rosuvastatin ( p &lt;0.001). Conclusions: EPA inhibited oxidation of Lp(a) enriched plasma in a dose-dependent fashion due to potent scavenging mechanism and high lipid affinity. The fibrate or statin tested did not exert similar antioxidant effects. The potent antioxidant actions of EPA may contribute to reduced events in REDUCE-IT, including in subjects with elevated Lp(a).
Abstract 4143464: Comparison of The Burden of Cardiovascular-Kidney-Metabolic Syndrome Components in Heart Failure with Preserved Ejection Fraction clinical trials and Heart Failure in the General United States Population
Authors: Michael Hammond, Nicole Cyrille-Superville, Michael Givertz, Akshay Desai, Margaret Redfield, Julio Chirinos, Dalane Kitzman, Alain Bertoni, Barry Borlaug, Gregory Lewis, Kavita Sharma, Javier Lopez, Sanjiv Shah, Sadiya Khan, Laura Rasmussen-Torvik
Journal: Circulation (2024)

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) have a high burden of comorbidities. To recognize the complex interplay of obesity, diabetes, and chronic kidney disease (CKD) in patients with cardiovascular disease, the cardiovascular-kidney-metabolic (CKM) syndrome was recently defined, but data on the burden of CKM in HFpEF is limited. Aim: We sought to describe the prevalence of CKM components in HFpEF leveraging data from control participants in clinical trials and NHANES. Methods: We analyzed data presented in publications from four randomized clinical trials that enrolled participants with HFpEF (all of which are available via NHLBI BioLINCC and will be included in the extant HeartShare dataset): TOPCAT, RELAX, NEAT-HFpEF, and INDIE. We abstracted baseline demographic and clinical variables from study publications to define CKM components (e.g., body mass index [BMI], diabetes status, hypertension, CKD status). We compared prevalence of CKM in these trials with a representative sample of US adults with self-reported history of heart failure (HF) from NHANES 2011-2018. Results: We included 1937 patients with HFpEF from four trials with enrollment between 2006-2016 and 715 adults representing 5.6 million adults aged ≥40 years with a self-report of HF between 2011-2018 from NHANES ( Table ). Mean age was similar among enrolled trial participants with HFpEF and those with HF in NHANES (~68-69 years). Mean BMI was in the obesity range and was similar among trial participants with HFpEF and HF in NHANES (31-35 kg/m 2 ). A significant proportion of individuals had hypertension in HFpEF trials (&gt;80%) and in the NHANES sample with HF (89%). The proportion of stage ≥ 3 CKD in HFpEF trials (≥ 37%) was similar to the NHANES sample with HF (37%). Results are shown in Table . Conclusions: Patients with HFpEF enrolled in clinical trials and those with HF in general population are significantly enriched with CKM components that may contribute to morbidity and mortality. Similar prevalence estimates were observed despite variability in trial inclusion criteria and heterogeneity in defining HFpEF and highlight CKM as a central target for HFpEF management.
Abstract 4143606: Ficolin-1 Genetic Polymorphisms in Chronic Chagasic Cardiomyopathy
Authors: Pamela Fontana, Fabiana Andrade, Karita Lidani, Helena Placido, Sandra Catarino, Iara de Messias-Reason
Journal: Circulation (2024)

Background: Chagas disease (CD) is an infectious disease caused by the protozoa Trypanosoma cruzi , affecting around 6-7 million people in Latin America. Although most infected individuals remain asymptomatic throughout their lives, annually 2-5% of them progress to chronic chagasic cardiomyopathy (CCC), digestive megasyndromes, or both. Ficolins are innate immunity proteins that play a crucial role in the lectin pathway (LP) of complement activation. They recognize pathogen-associated molecular patterns and mediate the clearance of apoptotic cells and cellular debris. Genetic polymorphisms of components of LP have been associated with clinical forms of CD; however, the relationship between Ficolin-1 ( FCN1 ) gene polymorphisms and CD remains unclear. Hypothesis: We hypothesize that polymorphisms in the FCN1 gene, previously related to its expression, are associated with clinical forms of CD, possibly impacting LP activation. Goals: To investigate the association of genetic variants of the FCN1 gene with the clinical forms of chronic CD. Methods: We evaluated three single-nucleotide polymorphisms (SNPs): rs2989727G&gt;A (c.-1981G&gt;A), rs17039495 (-399G&gt;A) and rs10858293 (+33G&gt;T) by sequence-specific amplification in 200 patients with chronic CD (23.5% asymptomatic, 52% CCC, 10% digestive form, and 14.5% cardiodigestive form) from Southern Brazil, and 210 T. cruzi seronegative controls. Logistic regression models were adjusted for sex, age, and self-identified ethnicity, followed by Bonferroni correction. Results: The haplotypes GGG, AGT, AGG, GAT, and AAT were more frequently found in patients, while GGG, AGT, AGG, and AAT were more common in controls. We observed a higher frequency of the G allele (p=0.004; OR 1.49; 95% CI 1.14, 1.99) of SNP rs2989727 and the GG genotype (p=0.010; OR 1.82; 95% CI 1.10, 3.03) in CD patients, particularly those with symptomatic forms (p=0.008; OR 1.51; 95% CI 1.11, 2.03; and p=0.012; OR 2.05; 95% CI 1.17, 3.59) and CCC (p=0.013; OR 1.54; 95% CI 1.10, 2.16, and p=0.013; OR 2.16; 95% CI 1.18, 3.97), compared to the control group. Conclusion: The FCN1 rs2989727 variant is associated with chronic CD and CCC, likely due to its impact on FCN1 gene expression.
Abstract 4143765: Partial Cardiac Denervation To Prevent Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting: A Randomized Controlled Trial
Authors: Ziang Yang, Xieraili Tiemuerniyazi, Fei Xu, Yang Sun, Peng Yan, Liangxin Tian, Chao Han, yan zhang, Shiwei Pan, Zhan Hu, Wei Zhao, Wei Feng
Journal: Circulation (2024)

Background: Postoperative atrial fibrillation (POAF) is commonly seen in patients undergoing coronary artery bypass grafting (CABG), increasing the risk of both short-term and long-term clinical adverse events. This study aimed to evaluate the effectiveness of partial cardiac denervation, which is achieved by cutting off the ligament of Marshall (LOM) and resecting the fat pad along the Waterston groove, on the prevention of POAF after CABG. Methods: In this single-center randomized controlled study, patients planned for isolated CABG were recruited during August 2022 and December 2023, then randomized into the intervention group (CABG + partial cardiac denervation) and the control group (CABG only) in a 1:1 pattern. All the participants were continuously monitored for the incidence of POAF through electrophysiologic device till day 6 after the operation, and invited to follow-up visits 30 days after discharge. The primary endpoint was the incidence of POAF, while the secondary endpoints were the safety and economics outcomes. Results: A total of 430 patients were enrolled (215 in the intervention vs. 215 in the control). The mean age was 61.9 ± 7.8 years, and 18.4% of them were female. Baseline characteristics were well balanced after ramdomizaiton. All participants underwent successful CABG and each one in the intervention group received scheduled partial cardiac denervation procedure. Compared with the control group, the 6-day incidence of POAF was significantly lower in the intervention group (18.1% vs. 31.6%, p=0.001). The time-to-event analysis also showed a significant reduction in the occurrence of POAF in the intervention group (hazard ratio: 0.53, 95% confidence interval: 0.36 to 0.79, p = 0.002). Similar effect was observed in the subgroup analysis. Safety assessments showed no difference between the two groups, for the incidence of need for blood transfusion, transferring to on-pump CABG, re-operation for postoperative bleeding, delayed epicardial effusion, critical arrhythmias other than atrial fibrillation and major adverse events in the 30-day follow up. The economic assessments showed that postoperative medical cost was reduced in the intervention group (p=0.050). Conclusions: Partial cardiac denervation through cutting off the LOM and resecting the fat pad along the Waterston groove, was an effective and safe procedure to reduce the occurrence of POAF after isolated CABG.
Abstract 4143758: Identifying High-Risk Patients with Pathogenic Variants in <i>LMNA</i> Gene: Genome-First Approach
Authors: Seth Krueger, Martin Matsumura, Eric Carruth, Melissa Kelly
Journal: Circulation (2024)

Background: Pathogenic variants in the LMNA gene are associated with highly penetrant cardiomyopathy (CM), with most patients expressing the phenotype by the fourth decade. Those with LMNA variants are at increased risk of conduction defects or arrhythmia regardless of ejection fraction. Increased availability of genome sequencing enables discovery of LMNA variants in apparently asymptomatic individuals, yet data are lacking regarding the phenotypic expression profile to guide clinical management in this genome-first scenario. Aims: Characterize the clinical spectrum of LMNA phenotypes following genome screening-based identification to inform management and risk stratification. Methods: We screened 175,500 patient-participants with exome sequencing data in the Geisinger MyCode cohort, a healthcare-based population biobank in Pennsylvania, and identified 24 participants with pathogenic LMNA variants. These results have been disclosed to eligible participants through the MyCode Genomic Screening and Counseling program and referrals to genetic counseling and cardiology were recommended. From manual chart review, we abstracted: age, sex, variant consequence, lifetime cardiovascular symptoms, prior TTE, EKG and Holter data, interventions (e.g. permanent pacemaker (PPM) or implantable cardioverter-defibrillator (ICD) placement), and family history. Malignant arrythmia risk was calculated using an online risk assessment tool. Results: Of the 24, 92% (n=22) were unaware of their variant. The median age at result disclosure was 57 years (IQR: 35-66) with 10/24 (42%) &gt; 60 years. The most common symptoms were presyncope (58%) and palpitations (50%). Of the 24 patients, 21 had EKG or Holter data. AV Block of any degree was seen in 12/21 (57%), and 9 of the 12 (75%) received a PPM or ICD. Of the 19 patients with a TTE, 7 (37%) had an LVEF &lt; 50%. Complete data for LMNA risk assessment was available for 17 patients, and 9 (53%) met ACC/AHA/HRS criteria for primary prevention of sudden cardiac death. Evaluation by a genetic counselor was completed in 15/24 (63%). Among the 21 patients with complete data, 10 (48%) showed a family of history of PPM/ICD, and 10 (48%) had a history of heart failure. Conclusions: Individuals with a LMNA variant identified through genome screening had high rates of cardiac dysfunction and arrhythmia consistent with clinically ascertained cohorts. These results emphasize the value of genomic screening for the identification of LMNA -associated CM.
Abstract 4143505: An Examination of Contextual and Self-Management Factors in Relation to Blood Pressure Control among Adults Managing Comorbid HIV and Hypertension in Malawi
Authors: Everlyne Ogugu, Julie Bidwell, Rita Butterfield, Allison Ruark, Torsten Neilands, Sheri Weiser, Nancy Mulauzi, James Mkandawire, Amy Conroy
Journal: Circulation (2024)

Introduction: Uncontrolled hypertension substantially increases the risk for cardiovascular disease and is a major cause of mortality among people living with HIV in many countries in sub-Saharan Africa, including Malawi. Despite previous studies showing low rates of blood pressure (BP) control among individuals with comorbid HIV and hypertension in these settings, few have focused on identifying potentially modifiable factors for improving BP control. This study examined contextual and self-management behaviors associated with BP control. Methods: This is a cross-sectional analysis of baseline data from participants in Healthy Hearts, a cohort study of persons with HIV and cardiometabolic conditions in Malawi. Participants were adults aged ≥18 years with HIV and hypertension (n=202), recruited from HIV care clinics at 3 hospitals. Multiple logistic regression was used to examine factors associated with BP control, defined as mean systolic BP &lt;140mmHg and diastolic BP &lt;90mmHg based on the 2020 International Society of Hypertension guidelines. Independent variables included age, gender, education level, access to healthcare, presence of comorbid conditions, body mass index, multimorbidity illness perceptions, hypertension-related knowledge, and self-management behaviors (self-reported physical activity, salt intake, fruit and vegetable intake, and antihypertensive medication adherence). Results: All participants were on antiretroviral therapy, 83.1% were on antihypertensive medication, and only 37.3% had controlled BP. Having a higher score in hypertension-related knowledge was positively associated with BP control (odds ratio [OR], 2.44; 95% CI 1.14–5.23). Factors negatively associated with BP control included increasing age (OR, 0.92; 95% CI 0.89–0.96), low antihypertensive medication adherence (OR, 0.32; 95% CI 0.11–0.89) or not being on antihypertensives (OR, 0.30; 95% CI 0.11–0.82), and perceiving multimorbidity as having greater negative impact on health (OR, 0.54; 95% CI 0.30–0.98). Conclusions: Age and potentially modifiable factors such as hypertension-related health literacy, medication adherence, and multimorbidity illness perceptions were independently associated with BP control at baseline in a cohort of Malawian adults with comorbid HIV and hypertension. These insights can help guide the development of tailored interventions for promoting BP control in persons with HIV at high risk for cardiovascular disease living in low-income countries.
Abstract 4143744: Cross-talk between oxidized LDL, oxidative stress and renin-angiotensin-aldosterone system: Impact on endothelial function and atherosclerosis
Authors: Rusan Catar, Julian Kamhieh-Milz, Claudia Goettsch, Lei Chen, Daniel Zickler, Ashraf Taye, Anja Hofmann, Coy Brunssen, Gregor Muller, Maria Cybularz, Clara Hengst, Maria de Leyre Villar Ballesteros, Susann Lehmann, Undine Schubert, Barbara Ludwig, Christian Ziegler, Stefan Bornstein, Alexander Krug, Thomas Walther, Guido Moll, Henning Morawietz
Journal: Circulation (2024)

Introduction/Background: Hypertension and hypercholesterolemia are important risk factors of endothelial dysfunction and atherosclerosis. Previous studies suggested a crosstalk between an activated renin-angiotensin-aldosterone system (RAAS), reactive oxygen species (ROS) and oxidized low-density lipoproteins (oxLDL) in atherosclerosis, but the underlying molecular mechanisms are not well understood. Research Question/Hypothesis: Can we identify novel signaling pathways controlling the molecular crosstalk of the RAAS with ROS and oxLDL in endothelial dysfunction and atherosclerosis? Methods/Approach: The impact of AT 1 R blockade on oxLDL-induced superoxide anion formation and endothelial dysfunction was studied in human umbilical artery endothelial cells and aortic rings of wild-type mice by chemiluminescence and Mulvany myograph. We cloned 5’-terminal deletions of the AT 1 R promoter and assessed the luciferase activity in human endothelial cells. Oct-1 binding to the human AT 1 R promoter region was studied by EMSA. Further assays included real-time PCR, confocal microscopy, Western blotting, G protein reporter assays, phospho-ERK1/2 antibodies and specific siRNAs. The data were validated in heart of obese C57BL/6 mice and cardiac and aortic tissue of AT 1a /AT 1b double knockout mice in vivo . Results/Data: AT 1 R promoter activation studies upon Ang II- and oxLDL-stimulation in endothelial cells revealed that Ang II and oxLDL activate AT 1 R signaling through G protein Gα 12/13 , followed by activation of ERK1/2 MAP kinases, and transcription and translation of Oct-1, resulting in up-regulation of AT 1 R, LOX-1 and NOX2 expression, which could be antagonized by specific inhibitors at each step of the identified signaling cascade. AT 1 R blockade improved oxLDL-induced endothelial dysfunction in aortic rings of wild-type mice. Male C57BL/6 mice fed a high-fat diet exhibited upregulation of Oct-1 levels in cardiac tissues, compared to normal controls, while AT 1a /AT 1b double knockout mice demonstrated downregulation of Oct-1, AT 1 R, LOX-1, and NOX2 on mRNA and protein level in cardiac and aorta tissue, thus confirming the identified signaling cascade in vivo . Conclusions: Oct-1 is an essential transcription factor for Ang II- and oxLDL-induced upregulation of AT 1 R and LOX-1 expression in endothelium, thus identifying a novel molecular cross-talk of oxLDL with ROS signaling and the RAAS contributing to development of endothelial dysfunction and atherosclerosis.
Abstract 4143749: Impact of SGLT2 Inhibitors on Cardiovascular Outcomes Following Acute Myocardial Infarction with Heart Failure with Preserved Ejection Fraction: A Propensity-Matched Registry Study
Authors: Tess Calcagno, Rochell Issa, GAURANGA MAHALWAR, Ryan Issa, Andrei Brateanu, David Kaelber, Venu Menon, Wai Hong Tang, Brian Griffin, Deborah Kwon, Tom Kai Ming Wang
Journal: Circulation (2024)

Background: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have effectively reduced cardiovascular mortality and hospitalizations in heart failure with preserved ejection fraction (HFpEF). This study investigates their effects on patients with HFpEF after an acute myocardial infarction (AMI), focusing on long-term outcomes. Aims: The study aims to determine whether an SGLT2 inhibitor (SGLT2i) can improve cardiovascular morbidity and mortality. Methods: Using TriNetX, a health research network accessing data from over 100 million patients globally, AMI patients with HFpEF (identified by NYHA Class 2-4, diagnosis code, and EF&gt;50%) treated with and without SGLT2i were identified. Equal cohorts of 1,675 patients were created, and propensity scores were matched for demographics, medical history, medications, and lab values. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Survival analysis was conducted at intervals ranging from 30 days to 5 years post-AMI to determine the efficacy of SGLT2i, examining MACE and its component outcomes. Results: The analysis included 3,350 post-AMI patients between 2014 and 2023, with a mean age of 69.7 ± 11.4 years, 46.1% female. Of the SGLT2i group, 90.8% had T2DM compared to 91% of the non-SGLT2i group. The SGLT2i group had significantly lower 30-day mortality (2.6% versus 7.4%, P&lt;0.0001) and MACE (58.6% versus 64.3%, P=0.002). Over a 5 year period, the SGLT2i group exhibited lower mortality (32.5% versus 55.8%, HR 0.767, P&lt;0.0001) and a lower rate of MACE (58.6% versus 64.3%, HR 0.818, P&lt;0.0001). Other outcomes, including MI, stroke, and bleeding events, also favored the SGLT2i group at both 30 days and 5 years (P&lt;0.0001). Conclusions: SGLT2i use post-AMI in HFpEF patients was associated with improved survival and reduced rates of MACE and further MI. These results support further investigation into the inclusion of SGLT2i in therapeutic strategies for HFpEF patients post-AMI.
Abstract 4143727: AI Integration Decreased Rural Documentation Burden by 40% in Medicare's Chronic Care Management Setting
Authors: Jered Miller, Garrett Jimmerson, Callie Miller, Ashley Dey, Caroline Wheeler, Samuel Miller, Ghaith Al Tibi, Nicolas Chronos
Journal: Circulation (2024)

Efforts to ameliorate rural healthcare burnout stemming from overwork have taken many approaches, including the increased usage of Artificial Intelligence (AI) to aid in generating electronic medical records (EMR). This new application of AI technology demands characterization of the possible benefits and efficacy of its new use. Using a commercially available AI software (Freed AI) designed for EMR production, we conducted a study to determine the quality of EMR generated by AI. Methods: This trial analyzed 248 patient-provider interactions within a rural setting of Medicare’s Chronic Care Management (CCM program), recorded by Freed AI and a human scribe. Three blinded readers with a clinical background were given 2 notes from the same patient-encounter. One note was written by a provider and one was generated by Freed AI. Each reader performed a binary, independent assessment of each note compared with the note generated by the human control. Readers were trained on definitions of the categories clarity, accuracy, completeness, and relevance. The time required per encounter was also recorded and analyzed. Discussion: As seen in Table 1, AI performed better than a human-generated EMR in the fields of clarity and relevance, suggesting effective formatting and a well calibrated understanding of what information is medically relevant. No significant difference in completeness was observed, suggesting AI was able to record as much valuable information as traditional charting. AI performed below the human standard in the category of accuracy. For example, AI sometimes misspelled names or misunderstood complex situations being discussed because it was not able to infer certain information which a human, using outside knowledge and past experiences, could. The reduction in time spent while utalizing AI demonstrates a highly significant decrease in workload and allows providers freedom to allocate more time interacting with each patient and hopefully reducing physician burnout.