tbuckley/cabot-search huggingface dataset:
Abstract 4134873: Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk - A Systematic Review and Meta Analysis
Authors: Sandesh Raja, Adarsh Raja, Muhammad Sohaib Asghar, Muhammad Ashir Shafique, Muhammmad Saqlain Mustafa, Hafsah Alim Ur Rahman, Muhammad Ahmed, Muhammad Ahmed Ali Fahim, Bazil Azeem, Madiha Salman
Journal: Circulation (2024)

Background: Hypertriglyceridemia, a common lipid disorder linked to increased risks of cardiovascular diseases and metabolic syndrome, remains a global health challenge. Traditional treatments, though widely used, often have limited efficacy and adverse effects. Olezarsen, a novel antisense oligonucleotide, targets apolipoprotein C-III and shows promise in significantly reducing triglyceride levels. Aim: To conduct a meta-analysis comparing Olezarsen with placebo in patients with hypertriglyceridemia. Methods: We performed an extensive literature search of PubMed, EMBASE, and Cochrane Library databases up to May 2024 to identify studies comparing Olezarsen and placebo in patients with hypertriglyceridemia, irrespective of comorbid cardiovascular disease. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs) for each. Results: Three randomized controlled trials (RCTs) with a total of 334 participants were included. Olezarsen significantly reduced triglyceride levels at 6 months (SMD: -1.69; 95% CI -2.22 to -1.17; P &lt; 0.00001; Figure ) and 12 months (SMD: -1.64; 95% CI -2.22 to -1.07; P &lt; 0.00001; Figure ). VLDL levels also decreased at 6 months (SMD: -1.95; 95% CI -2.38 to -1.51; P &lt; 0.00001) and 12 months (SMD: -0.83; 95% CI -1.13 to -0.53; P &lt; 0.00001). Lipid profile improvements included reductions in total cholesterol, non-HDL cholesterol, and apoB levels, with increases in HDL cholesterol and apoA-1. Adverse events were comparable between Olezarsen and placebo, although serious adverse events were significantly higher in the Olezarsen group (RR: 2.55; 95% CI 1.17 to 5.58; p = 0.02). Conclusion: Olezarsen demonstrates significant efficacy in reducing triglyceride and VLDL levels while improving overall lipid profiles in hypertriglyceridemia patients. Despite higher rates of serious adverse events, its overall safety profile remains acceptable.
Abstract 4134345: Diastolic Dysfunction And The Risk Of Stroke And Major Bleeding
Authors: John Kundrick, Karina Saba, Aditi Naniwadekar, Virginia Singla, Suresh Mulukutla, Floyd Thoma, Aditya Bhonsale, Krishna Kancharla, Andrew Voigt, Alaa Shalaby, Nathan Estes, Sandeep Jain, Samir Saba
Journal: Circulation (2024)

Background: Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident ischemic stroke/transient ischemic attack (TIA) and with bleeding events is not well established. Aims: To examine the association of presence and severity of DD with the risk of incident ischemic stroke/TIA and major bleeding. Methods: A total of 219,667 patients who underwent at least one echocardiogram between 2010 and 2022 at a large academic institution and were followed for at least 3 months were included. Patients with prior history of stroke or TIA (n=21,505, 10%) were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups, based on the most severe DD assessment: Normal (n=113,265), grade I (n=21,981), grade II (n=7,215), and grade III (n=1,627). Patients in whom the presence of DD could not be determined (n=54,074) were excluded. The final study cohort (n=144,088) was followed to the endpoint of hospital admission for ischemic stroke/TIA or for major bleeding. Results: Over a median follow-up of 3.4 years, 3482 (2.4%) patients were hospitalized for stroke/TIA and 6994 (4.9%) for major bleeding. After adjusting for several confounding variables (Table), DD remained a strong predictor of incident stroke/TIA (hazard ratio (HR)=1.34 per grade increase in DD, p&lt;0.001, Figure) and of major bleeding (HR=1.32 per grade increase in DD, p&lt;0.001, Figure). These results were similar in patients with (n=11,508, 8%) or without prior history of atrial fibrillation. Conclusions: Patients with DD have a heightened risk of ischemic cerebrovascular accidents and major bleeding independent of the presence of atrial fibrillation. These risks escalate with the severity of DD. DD should be considered when counseling patients regarding their risk profile and management options.
Abstract 4134594: More than One Way to Catch a Fish: Micra Extraction Case Series
Authors: Nathaniel Davis, Narut Prasitlumkum, Siva Mulpuru, Samuel Asirvatham, Nicholas Tan
Journal: Circulation (2024)

Description of Cases: Case 1: A 72 year old male with atrial fibrillation (AF) and tachy-brady syndrome underwent Micra implantation. On post-procedure day 2, pacing thresholds were unacceptably elevated. A new Micra device was deployed; subsequently, a microsnare was placed through the Micra delivery catheter and the docking button of the old Micra was successfully snared (Figure A). The old Micra was then captured over the delivery catheter and removed from the body. Case 2: A 76 year old male underwent Micra implantation and AV node ablation for AF with persistent tachycardia. One month later, he presented with heart failure and interval decrease in ejection fraction from 66% to 33%. After biventricular leads were implanted, an Agilis catheter was advanced towards the Micra. The docking button was successfully snared with a gooseneck snare (Figure B), and the Micra was extracted with gentle traction. Case 3: A 76 year old male with complete heart block and longstanding persistent AF received a Micra. Nine months later, he presented with heart failure and interval decrease in ejection fraction from 55% to 25%. A defibrillator lead was implanted but no suitable CS branch was identified. The Aveir retrieval catheter was advanced and the Micra docking button was captured with the triloop snare (Figure C). The protective sleeve was advanced over the Micra and it was successfully removed. Subsequently, a left bundle area lead was placed. Discussion: Although uncommon, extraction of the tined leadless pacemaker (Micra) may be indicated at times. As rates of implantation continue to increase, establishing uniform procedures for extraction becomes increasingly important. These three cases highlight unique options for Micra extraction, and the feasibility of each approach. However, a dedicated tool and protocol would be ideal for patient safety and consistency. No complications occurred with the above cases.
Abstract 4137820: Extreme heat and cardiovascular disease in a changing climate: An urgent need for risk management and health research
Authors: Xiaowen Wang, Liyun Wang, John S. Ji, Cunrui Huang
Journal: Circulation (2024)

Background: Extreme heat can trigger or exacerbate cardiovascular disease (CVD) through ischemia or thrombosis, and its deleterious impacts are inclined to worsen as increased heat exposure and heightened vulnerability from climate change interacted with natural and social environment. Research Questions: Previous studies have primarily focused on quantifying the increased risk of CVD due to heat exposure, while lacking a comprehensive understanding of the association, underlying mechanisms, and vulnerability in CVD patients. Consequently, there is a scarcity of clinical and public health interventions aimed at preventing the convergence of extreme heat exposure and the risk of CVD within the context of climate change. Methods: We conducted a systematic search in PubMed, Embase, and Web of Science from inception to December, 2023, and we retrieved articles which assessed the effects of extreme heat or climate change on CVD. Results: In this review, we outline the existing evidence on the epidemiology and pathophysiological mechanisms that elucidate how extreme heat affects the risk of CVD. Extreme heat is associated with increased risks for CVD morbidity and mortality, where older persons, low socioeconomic status, pre-existing medical conditions, and unfavorable living environments confer greater susceptibility to heat. The adverse effects of extreme heat on cardiovascular system involved a wide range of complex mechanisms between different organs and regulatory pathways (Figure 1). Additionally, we identify the factors that contribute to the vulnerability of CVD patients to heat exposure. The discrepancy in heat-related risk can be attributed to individual susceptibility, sociocultural factors, population temperature adaptations, and environmental factors. Future climate change is projected to exacerbate the burden of extreme heat, particularly due to the interaction of air pollution, population aging, and urbanization (Figure 2). Conclusions: Addressing extreme heat should be within the framework of the prevention of CVD. Health professionals and scientists are responsible for mitigating the cardiovascular effects mediated by extreme heat, with an emphasis on engaging in risk management tactics and health research to implement preventive strategies. As CVD is a climate sensitive disease, evidence-based interventions during heat extremes are urgently needed to cope with the cardiovascular risks associated with the inevitable trajectory of climate change.
Abstract 4137914: Eligibility for Semaglutide in US Adults with Diabetes and Potentially Preventable Cardiovascular Events Projected from the SUSTAIN-6 Trial
Authors: Nathan Wong, Hridhay Karthikeyan, WENJUN FAN
Journal: Circulation (2024)

Background: The Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6) trial showed cardiovascular disease (CVD) benefits of semaglutide therapy in patients with type 2 diabetes mellitus (T2DM). Purpose: To estimate the number of US adults with T2DM that may be eligible for semaglutide based on SUSTAIN-6 eligibility criteria and the number of preventable CVD events from semaglutide treatment based on observed CVD event reductions in SUSTAIN-6. Methods: We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2011– 2020 who had eligibility criteria from SUSTAIN-6. This included an HbA1c&gt;7.0%, age &gt; 50 with established CVD, heart failure, or chronic kidney disease or an age &gt; 60 with at least one CVD risk factor. We estimated the number of primary composite and secondary CVD endpoints that would occur based on SUSTAIN-6 treated and placebo published event rates, with the difference indicating the number of preventable events (and annualized based on median 2.1 year follow-up time). Results: Among 5002 (projected to 34.0 million [M]) adults we identified with T2DM, we estimated 1,132 (6.9 million) (20.3%) to fit SUSTAIN-6 eligibility criteria. Compared to SUSTAIN-6 trial participants, our sample was slightly older, had a higher proportion of Black participants, shorter duration of diabetes, lower HbA1c and diastolic blood pressure, but similar body mass index and systolic blood pressure. Prior history of ischemic heart disease, myocardial infarction, and stroke were also less common in our NHANES sample. From SUSTAIN-6 semaglutide and placebo primary composite CVD event rates of 6.6% and 8.9%, respectively, we estimated 456,060 and 614,990 events would occur, respectively, for a total of 159,930 preventable CVD events, or 75,681 on an annualized basis. We similarly estimated annualized preventable events for secondary outcomes as shown in the Figure. Conclusion: Semaglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting SUSTAIN-6 eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including semaglutide.
Abstract 4134878: Single Perclose Plus Angioseal Versus Double Perclose for Percutaneous Femoral Access: A Systematic Review and Meta-Analysis
Authors: Enrico Bertolino, Milena Monteiro Mastra Fontoura, Dilson Pimentel Junior, Miguel Fernandez, Cynthia Mesquita, Ivo Queiroz, Braiana Diaz, Lucas Barbosa, Grace Mulatti
Journal: Circulation (2024)

Background: Vascular Closure utilizing Suture Based Devices (SBD) is an established approach for large-bore arterial access in percutaneous procedure patients. Standard of care uses two devices when accessing the artery with 8 Fr sheaths and above. The bailout use of Plug-based devices (PBD) is well established, but little is known about the intentional combination of SBD with PBD and how this technique compares to the standard approach. We aimed to compare these different approaches in this meta-analysis. Methods: PubMed, Scopus, and Cochrane databases were searched for observational studies comparing the hybrid approach to the standard one utilizing exclusively SBDs for arterial closure in large bore vascular access and reported the outcomes of (1) Access-related complications (ARC); (2) Major bleeding; (3) All bleeding events; (4) Need for surgical intervention; (5) Need for endovascular intervention ; (6) Device failure; (7) Pseudoaneurysm. Heterogeneity was examined with I2 statistics. A random-effects model was used for all outcomes. Results: We included five observational studies with 1,586 patients, of whom 1,489 (93.8%) underwent TAVI and 97 (6.1%) EVAR. Sheath size had an average of 20.56 Fr in the EVAR patients. ARC (RR 0.48; 95% CI 0.28-0.81; p&lt;0.01), major bleeding (RR 0.29; 95% CI 0.19-0.44; p&lt;0.01), all bleeding events (RR 0.36; 95% CI 0.23-0.56; p&lt;0.01), surgical intervention (RR 0.28; 95% CI 0.10-0.78; p=0.01), or endovascular intervention (RR 0.53; 95 % CI 0.28-0.98; p=0.04), and device failure (RR 0.28; 95% CI 0.11-0.72; p&lt;0.01) were significantly less common in patients treated with the hybrid technique compared to standard care. Pseudoaneurysm (RR 1.13; 95% CI 0.57-2.25; p=0.71) was not significantly different between groups. Conclusion: These findings suggest the hybrid technique, was associated with fewer access complications compared to the standard double SBD as a closure strategy in patients with large bore arterial access.
Abstract 4134695: The Effect and Mechanism of Histone Lactylation In Pathological Cardiac Hypertrophy Induced by Pressure Overload
Authors: Miao Chen, Zhen Wang, Hongfei Xu
Journal: Circulation (2024)

Introduction: Cardiac hypertrophy is characterized by significant metabolic changes, notably an increase in glycolysis. Histone lactylation, a post-translational modification influenced by the glycolytic state of cells, plays a crucial role in regulating gene transcription. However, the relationship between histone lactylation and cardiac hypertrophy remains unclear. Research Questions: This study aims to elucidate the effects and underlying mechanisms of histone lactylation in the progression of cardiac hypertrophy induced by pressure overload. Methods and Results: We observed an increase in histone lactylation levels in hypertrophic hearts from both humans and mice. To investigate further, male mice underwent transverse aortic constriction (TAC) to induce cardiac hypertrophy, followed by either an intraperitoneal injection of Oxamate (an LDHA inhibitor) to reduce histone lactylation or sodium lactate to increase it. Reducing histone lactylation protected the hearts from TAC-induced hypertrophy and fibrosis, preserving cardiac function, while increased histone lactylation exacerbated cardiac hypertrophy and fibrosis, impairing cardiac function. Cardiomyocyte-specific deletion of LDHA also led to a reduction in cardiac hypertrophy. In vitro experiments showed that inhibiting histone lactylation reduced the expression of hypertrophic markers and the hypertrophic growth of cardiomyocytes stimulated by phenylephrine. Using co-immunoprecipitation, we confirmed that P300 and GCN5 are the transferases mediating histone lactylation in cardiomyocytes. Mechanistic studies using the CUT&amp;Tag technique revealed lactate-dependent histone modification was enriched at the promoter of TGFB2, activating its transcription. Inhibiting cardiac-specific TGFB2 expression through adeno-associated viral delivery of shRNA reduced TAC-induced cardiac hypertrophy. Furthermore, TGFB2 overexpression induced a hypertrophic phenotype in cardiomyocytes and activated the PI3K/AKT/mTOR pathways. This hypertrophic phenotype, induced by TGFB2 overexpression, was suppressed by inhibitors of PI3K or AKT. Conclusion: Our findings reveal a critical role for histone lactylation in the development of pathological cardiac hypertrophy by regulating TGFB2 expression and the PI3K/AKT/mTOR pathway.
Abstract 4137846: Smooth muscle expression of RNA editing enzyme <i>ADAR1</i> controls vascular integrity and progression of atherosclerosis
Authors: Chad Weldy, Qin Li, Joao Monteiro, Hongchao Guo, Drew Galls, Wenduo Gu, Paul Cheng, Markus Ramste, Daniel Li, Brian Palmisano, Disha Sharma, Matthew Worssam, Quanyi Zhao, Amruta Bhate, Ramendra Kundu, Trieu Nguyen, Jin Billy Li, Thomas Quertermous
Journal: Circulation (2024)

Mapping the genomic architecture of complex disease has been predicated on the understanding that genetic variants influence disease risk through modifying gene expression. However, recent discoveries have revealed that a significant burden of disease heritability in common autoinflammatory disorders and coronary artery disease is mediated through genetic variation modifying post-transcriptional modification of RNA through adenosine-to-inosine (A-to-I) RNA editing. This common RNA modification is catalyzed by ADAR enzymes, where ADAR1 edits specific immunogenic double stranded RNA (dsRNA) to prevent activation of the double strand RNA (dsRNA) sensor MDA5 ( IFIH1 ) and stimulation of an interferon stimulated gene (ISG) response. Multiple lines of human genetic data indicate impaired RNA editing and increased dsRNA sensing to be an important mechanism of coronary artery disease (CAD) risk. Here, we provide a crucial link between observations in human genetics and mechanistic cell biology leading to progression of CAD. Through analysis of human atherosclerotic plaque, we implicate the vascular smooth muscle cell (SMC) to have a unique requirement for RNA editing, and that ISG induction occurs in SMC phenotypic modulation, implicating MDA5 activation. Through culture of human coronary artery SMCs, generation of a conditional SMC specific Adar1 deletion mouse model on a pro-atherosclerosis background, and with incorporation of single cell RNA sequencing cellular profiling, we further show that Adar1 controls SMC phenotypic state, is required to maintain vascular integrity, and controls progression of atherosclerosis and vascular calcification. Our data implicates MDA5 activation to occur in SMC phenotypic modulation and accelerates formation of chondromyocytes in a distinct cellular lineage trajectory — indicating a cell type and context specific requirement of RNA editing. Through this work, we describe a fundamental new mechanism of CAD, where RNA editing and sensing of dsRNA in a cell type and context specific mechanism mediates disease progression, bridging our understanding of human genetics and disease causality.
Abstract 4137781: Relationship between Race, Predelivery Cardiology Care and Cardiovascular Outcomes in Pre-eclampsia/Eclampsia among a Commercially Insured Population
Authors: Ikeoluwapo Bolakale-Rufai, Shannon Knapp, Sadiya Khan, Brownsyne Tucker Edmonds, LaPrincess Brewer, Selma Mohammed, Amber Johnson, Sula Mazimba, Daniel Addison, Khadijah Breathett
Journal: Circulation (2024)

Background: Inequities in Preeclampsia/Eclampsia (PrE/E) persist. It is unknown if the receipt of cardiology care relates to future risk of major adverse cardiovascular events (MACE) in Black and White patients with PrE/E. We sought to determine the cumulative incidence of MACE by race and whether predelivery cardiology care was associated with the hazard of MACE up to 1-year post-delivery for Black and White patients with PrE/E. Methods: Using Optum’s Clinformatics® Data Mart Database (CDM), we identified Black and White patients with PrE/E who had a delivery between 2008 to 2019. MACE was defined as the composite of heart failure, acute myocardial infarction, stroke, and death. Cumulative incidence functions were used to compare the incidence of MACE by race. Cox regression models were used to assess the hazard of MACE by cardiology care for Black and White patients. Results: Among 29,336 patients (83.4% White, 16.6% Black, mean age of 30.9 years) with PrE/E, 11.2% received cardiology care (10.9% White, 13.0% Black). Black patients had a higher incidence of MACE than White patients at 1-yr post-delivery (2.7% vs 1.4%). After adjusting for age and clinical comorbidities, receipt of cardiology care was associated with lower hazard of MACE for White patients (HR= 0.68, 95%CI: 0.50-0.92 p=0.013) but not Black patients (HR: 1.22, 95% CI: 0.82-1.81; p= 0.328). The interaction effect between race and cardiology care was statistically significant (p=0.013) Conclusions: Among a well-insured population of patients with PrE/E, Black patients had a higher cumulative incidence of MACE up to a year post-delivery. However, cardiology care significantly lowered the hazard of MACE for only White women. This observation does not suggest that cardiology care is detrimental to Black individuals but underscores the necessity to investigate why outcomes are disparate among these racial groups.
Abstract 4137805: Loss to Follow-Up Among Adults with Congenital Heart Defects: A Report from Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE)
Authors: Andrew Dailey Schwartz, Caroline Shi, Osamah Aldoss, Michael Fundora, Mansi Gaitonde, Gurumurthy Hiremath, Anitha John, Kimberly McHugh, Geetha Raghuveer, Lazaros Kochilas, Matthew Oster
Journal: Circulation (2024)

Background: Many of the 1.4 million adults with congenital heart disease (CHD) are lost to follow up (LTF). We aimed to identify factors associated with LTF and compare to those who remained in care. Methods: In the Congenital Heart Disease Project to Understand Lifelong Survivor Experience (CHD PULSE), we performed a cross-sectional survey in 2021-2023 of CHD survivors with a history of intervention at 11 centers in the Pediatric Cardiac Care Consortium, a large US-based registry of CHD procedures. Participants reported their cardiac history, general health, education, income, health insurance, healthcare utilization, and marital status. LTF was defined as having seen a cardiologist three or more years ago. Results: Among the 3109 respondents with CHD (median age 33) there were 1157 (37%) LTF and 1952 (63%) in care. Age, sex, marital status, and household income were not risk factors for LTF; but lack of health insurance, lower severity of CHD, and increasing time since last heart surgery were. Notably, respondents who reported being told in adolescence about the lifelong need for a cardiologist were almost three times as likely to report being in care (79% vs 28%, p&lt;0.0001). Among women, most reported no LTF if counseled about concerns with pregnancy or told to avoid pregnancy. The most common reasons for being LTF for 5 years or more (N=857) included feeling well (60%), not thinking there was a need for lifelong care (49%), and a doctor told them they no longer needed to see a cardiologist (47%). Those LTF were more likely to report excellent or very good general health, physical health, and quality of life than those not LTF. There were no differences in self-assessment of mental health between groups. Conclusion: Adults with CHD and LTF were more likely to report less severe heart defects, a younger age at last surgery and a lack of counseling about the need for lifelong care.