tbuckley/cabot-search huggingface dataset:
Abstract 4144292: Attenuation of Black-White Disparities in Cardiovascular Disease Incidence and Total Mortality by Life’s Essential 8: Cardiovascular Lifetime Risk Pooling Project (LRPP)
Authors: Mariam Ardehali, Hongyan Ning, John Wilkins, Donald Lloyd-Jones
Journal: Circulation (2024)

Background: Higher cardiovascular health (CVH), as measured by Life’s Essential 8 (LE8) score, is associated with lower mortality and incident cardiovascular disease (CVD). It is unclear if having higher CVH attenuates racial disparities in CVD and total mortality. Methods: We used data from the LRPP, including the ARIC, CARDIA, MESA, and Framingham Offspring cohorts, for which LE8 scores (0-100 points, higher is better) could be calculated in participants (ppts) aged 20-59 years who self-identified as Black or White. We compared incidence rates and adjusted hazard ratios (aHR; adjusted for age, sex, and maximal education years) for incident CVD and total mortality between Black and White ppts. We estimated the quantitative reduction in Black-White hazards without vs. with adjustment for LE8 score by examining the proportional change in the beta coefficients. Results: Our sample included 20,618 ppts (28.6% Black; 54.8% women; mean age 45.9±11.6 years) followed for 499 000 person-years, of whom 4316 developed CVD events and 5660 died. Mean LE8 score was 66.4±14.3 for White and 61.5±14.7 for Black ppts. Among White ppts, 19.9% had a CVD event and 25.8% died, compared to 23.4% and 31.7% of Black ppts, respectively. Compared with White ppts, Black adults had higher hazards for incident CVD (aHR 1.55; 95% CI 1.54-1.56). Additional adjustment for LE8 score attenuated the HR to 1.20 (95% CI 1.12-1.29), representing a 58.1% reduction in the beta estimate for race (see Table ). Considering LE8 metrics individually, adjustment for blood pressure score was associated with the greatest proportional reduction in the Black-White beta estimate (47.7%). Findings were overall similar for associations and attenuation of racial disparities in total mortality, with a 39.9% reduction in the beta estimate for Black vs. White ppts. Conclusions: In young and middle-aged adults, adjustment for cardiovascular health score partially attenuated Black-White disparities in incident CVD events and mortality. It is likely that the observed disparities are based on social and structural determinants. Improving CVH from young adulthood could be an important strategy for reducing racial disparities in CVD events and mortality.
Abstract 4144488: 4-5 Years Outcomes of Left Atrial Appendage Closure vs. Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-Analysis:
Authors: Muhammad Aslam Khan, Anza Muhammad, Nouman Shafique, Hitesh Bhatia, Asna Aafreen, Abid Nawaz Khan Adil, Usman Akbar, Alamzaib Khan, Muhammad Adnan Haider, Taimoor Haider, Shraddha Bhattarai, Hafsa Afzal, Bilal Khan
Journal: Circulation (2024)

Background: Oral anticoagulants (OAC) including Vitamin K antagonists such as warfarin and direct oral anticoagulants like Apixaban, Rivaroxaban, and Edoxaban, have long been the standard treatment for stroke prevention in patients with atrial fibrillation (AF). However, they increase the risk of bleeding, making them unsuitable for certain patient populations, particularly those with a personal history of bleeding, elderly individuals prone to falls or those with high-risk occupation with safety hazards. In cases of non-valvular AF, where thrombi typically form in the left atrial appendage, mechanical left atrial appendage closure (LAAC) has come out as an alternative for selected patients. Numerous studies have shown that LAAC is comparable to OAC in preventing strokes while significantly reducing major bleeding events. This meta-analysis aims to compare the 4–5-year outcomes of these two treatment strategies in non-valvular AF. Methods: 4 studies (3 randomized controlled trials and 1 observational study) comparing the 4–5-year outcomes of LAAC versus OAC in patients with AF were included in this meta-analysis. These studies were identified after a thorough search of PUBMED, COCHRANE, and MEDLINE databases from inception till May 2024. The outcomes of interest were MACE (composite of stroke, embolism, and death), ischemic stroke, major bleeding episodes, cardiovascular (CV) deaths, and all-cause death. The results were reported as Risk Ratio (RR) with 95% confidence intervals (CI), using a random effects model. Results: 6,012 patients were identified from the 4 studies. After a median follow-up of 4–5 years, LAAC was associated with a clinically significant reduction in MACE (RR: 0.76, 95% CI: 0.61-0.94, p=0.01), all-cause mortality (RR: 0.77, 95% CI: 0.62-0.96, p=0.02), and CV mortality (RR: 0.64, 95% CI: 0.45-0.90, p=0.01). Additionally, a significant reduction in major bleeding episodes (RR: 0.63, 95% CI: 0.44-0.91, p=0.01) was also noted between the two treatment strategies favoring LAAC treatment group. There was no significant difference in the incidence of ischemic stroke (RR: 1.07, 95% CI: 0.62-1.85, p=0.80) between the two groups. Conclusion: Over a median follow-up of 4-5 years, LAAC was found to be as effective as OAC in preventing ischemic strokes, while also showing lower incidence of MACE, all-cause, CV mortality and major bleeding episodes. More RCTs are needed to further assess the long-term outcomes between the two strategies.
Abstract 4143955: Prevalence and Burden of Coronary Artery Calcium Across the Pooled Cohort Equation versus the American Heart Association PREVENT Risk Calculator
Authors: Gabrielle Gershon, Alexander Razavi, Yan Yang, Omar Dzaye, Seamus Whelton, Michael Blaha, Roger Blumenthal, Laurence Sperling, Carlo De Cecco, Marly van Assen
Journal: Circulation (2024)

Background: The 2013 Pooled Cohort Equation (PCE) has been a useful starting point to assess atherosclerotic cardiovascular disease (ASCVD) risk. In 2023, the PREVENT risk calculator was developed and validated as a contemporary calculator considering the cardiovascular-kidney-metabolic health paradigm. Coronary artery calcium (CAC), measured on non-contrast cardiac computed tomography (CT), improves ASCVD risk stratification beyond traditional risk factors. However, the prevalence of CAC burden across PCE versus PREVENT risk groups is unknown. Hypothesis: We hypothesized that there would be a higher CAC burden for PREVENT vs PCE calculated risk across low, borderline-intermediate, and high-risk groups. Methods: This retrospective study included 6,003 asymptomatic individuals who underwent CAC scoring for ASCVD risk stratification from 2010-2023 at Emory. The 10-year risk for ASCVD according to PCE and base PREVENT were retrospectively calculated. CAC was quantified using the Agatston method. CAC scores across PREVENT and PCE groups were compared using Chi-square tests, using CAC (0, 1-99, 100-299, ≥300) and PCE/PREVENT (low&lt;5, borderline-intermediate 5-19, high≥20%) 10-year risk categories. Concordant/discordant groups were created according to agreement between PCE and PREVENT ( &gt; 7.5 PCE/PREVENT &lt;7.5). Results: The mean age 57(9), 41% were women, and 11% were Black people. PCE classified 51.8% (n=3112) low, 41.5% (n=2490) borderline-intermediate, and 6.7% (n=401) high-risk participants, whereas PREVENT classified 72.1% (n=4329) low, 27.3% (n=1641) borderline-intermediate, and 0.6% (n=33) high-risk participants. Among participants, 41.2% (n= 2474) had CAC=0, 36.5% (n=2189) had 1-99, 11.4% (n=687) had 100-299, and 10.9% (n=653) had ≥300 CAC. For both PCE and PREVENT, higher risk groups had higher median CAC. CAC distribution was heterogeneous across risk categories within both PCE and PREVENT, and between PCE and PREVENT (p&lt;0.001). CAC prevalence was 72% and 81% for individuals with borderline-intermediate risk according to PCE and PREVENT, respectively. Median CAC scores were similar across discordant PCE/PREVENT risk groups (33 (1-201) vs 29 (1-201)). Conclusion: The prevalence of CAC was similar across calculated PCE and PREVENT risk groups, including individuals with borderline-intermediate risk. These results underline the continued utility of CAC at improving risk stratification beyond PCE and PREVENT.
Abstract 4143830: Clonal hematopoiesis portends worse mortality among individuals with ATTR cardiac amyloidosis
Authors: Aeron Small, Shilpa Vijayakumar, Sarah Cuddy, Peter Libby, Pradeep Natarajan, Hanna Gaggin, Sharmila Dorbala, Michael Honigberg
Journal: Circulation (2024)

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a restrictive cardiomyopathy characterized by deposition of misfolded transthyretin in the myocardium. Untreated individuals with ATTR-CM have a median survival of 2-4 years after diagnosis. Individuals with clonal hematopoiesis, including clonal hematopoiesis of indeterminate potential (CHIP), mosaic chromosomal alterations (mCAs), and loss of Y (LOY), have heightened risk of adverse cardiovascular outcomes. It is unknown whether the presence of clonal hematopoiesis is associated with mortality in ATTR-CM. Methods: We tested the association between clonal hematopoiesis and all-cause mortality among individuals with ATTR-CM in the Mass General Brigham Biobank (MGBB). ATTR-CM status was determined by pyrophosphate scintigraphy (PYP) scan. CHIP was called from whole exome sequencing; mCAs and LOY were called from genotype array data. Key exposures were the presence of any CHIP (defined as a variant allele fraction [VAF] ≥2%), large CHIP (VAF ≥10%), CHIP driver mutations (DNMT3A, TET2, and non-DNMT3A), mCA, and LOY. Cox models were used to generate hazard ratios (HRs) for all-cause mortality with adjustment for age at scan, sex, type 2 diabetes, and coronary artery disease. Results: Among 54 genotyped individuals in the MGBB with a positive PYP scan (mean [SD] age 79.1 [6.7], 48 [89%] male), any CHIP was identified in 16 (29%) individuals, large CHIP in 9 (17%), LOY in 11 (23% of males), and mCAs in 10 (19%). The most common CHIP clones were DNMT3A (11 [20%] individuals), TET2 (3 [6%] individuals), and ASXL1 (2 [4%] individuals). Over a median [interquartile range] follow-up of 2.89 [1.48-4.37] years, non-DNMT3A CHIP was significantly associated with risk of all-cause mortality (HR 5.97 [95% CI 1.13-31.55], P =0.036). TET2 CHIP had a suggestive association with all-cause mortality (HR 5.94 [0.79-44.68], p = 0.08). Neither any CHIP, large CHIP, nor DNMT3A CHIP was significantly associated with all-cause mortality, though effect estimates were directionally consistent with increased risk (any CHIP: HR 2.06 [0.60-7.12], P=0.25; large CHIP HR 2.57 [0.53-12.60], P=0.24; DNMT3A CHIP HR 1.76 [0.47-6.57], P=0.40). In addition, mCAs, but not LOY, were associated with mortality (mCA HR 4.75 [1.33-16.96], P=0.017; LOY HR 2.79 [0.74-10.59], P=0.13). Conclusions: In a small observational study of individuals with ATTR-CM, non-DNMT3A CHIP and mCAs were associated with increased risk of all-cause mortality.
Abstract 4144010: Digital Health Intervention Yields Modest Improvements in Diet and Blood Pressure Among Adults with Hypertension
Authors: Hailey Miller, Sandy Askew, Miriam Berger, Qing Yang, Dori Steinberg, Gary Bennett
Journal: Circulation (2024)

Background: The Dietary Approaches to Stop Hypertension (DASH) diet is an evidence-based treatment for adults with hypertension and has health benefits for other cardiovascular disease risk factors. Yet, DASH has not been fully disseminated. Digital health solutions offer a promising approach to disseminate DASH. However, the efficacy of these approaches is unknown. Aims: To evaluate the efficacy of a digital health intervention on DASH adherence and blood pressure (BP) among adults with hypertension. Methods: Nourish was a 2-arm RCT to evaluate the efficacy of a 12-month digital health intervention, compared to attention control, among adults with hypertension. The intervention, delivered virtually, included skills training, goal setting, self-monitoring, personalized feedback, and dietitian coaching. The primary and secondary outcomes were 6-month changes in DASH adherence and BP, respectively. DASH scores ranged from 1 (lowest) -9 (highest). Outcomes were also assessed at 12 months to evaluate long term effect. We used linear mixed models to test the efficacy of the intervention on change in DASH score and BP. BP models adjusted for change in BP medications. Results: . Nourish randomized 301 adults: 150 to the intervention and 151 to attention control. The mean age of participants was 54.4 (SD=13.4) years. Most participants identified as female (65%); over half identified as white (53%); and 31% identified as Black. Change in DASH score was not significantly different between arms at 6 months ( M diff =0.02, 95% CI=-0.37,0.41), yet the intervention arm had a greater increase in DASH score, relative to attention control, at 12 months ( M diff =0.64, 95% CI=0.17,1.11). Mean SBP and DBP were significantly reduced in the intervention arm at 6-months compared to baseline (mean SBP change=-4.4 mm Hg, 95% CI=-6.6,-2.1; mean DBP change=-2.9, 95% CI:-4.3,-1.5). However, no significant between-group differences were found. Findings were similar at 12 months ( Table 1 ). Conclusions: A 12-month digital health intervention led to modest improvements in DASH and BP among adults with hypertension. Further research is needed to elucidate the effectiveness of smartphone interventions to promote DASH. Trial registration: NCT03875768
Abstract 4143938: Transcription Factor EB (TFEB) Regulates Metabolic Exchange Between Cardiomyocytes and Epicardial Cells
Authors: Astanina Elena, Gabriella Doronzo, Chiara Riganti, Alessandra Ghigo, James Cimino, Sushant Parab, Andrea Ballabio, Federico Bussolino
Journal: Circulation (2024)

Introduction: Metabolic symbiosis has been discovered in several contexts between cells with a high energy demand and supporting cells. Recently, reports have highlighted the existing lactate shuttle between cardiomyocytes (CMs) and cardiac fibroblasts. Epicardium is the embryonic source of cardiac fibroblasts and an active player in ischemic heart repair, however, its contribution to heart metabolism is unstudied. TFEB is a known regulator of energy metabolism in different cell types. Previously, we demonstrated that in mouse embryonic epicardium TFEB modulates TGFβ-driven epithelial-to-mesenchymal transition. Methods and Results: In adult mice with epicardium-specific Tfeb knock-out, no morphological defects were observed in the hearts. However, echocardiography demonstrated impaired heart contractility, specifically, reduced fractional shortening. The analysis of lysates of mutant hearts revealed reduced activity of enzymes involved in glycolysis, oxidative phosphorylation, and ATP production. We developed in vitro co-cultures between CMs differentiated from H9C2 cells and mouse epicardial cells (MEC), silenced for Tfeb or control. Tfeb knockdown in MEC led to decreased glucose metabolism, as assessed by biochemical assays and Seahorse analysis, resulting in reduced lactate secretion. By measuring the activity of lactate dehydrogenase and C14 tracing, we showed that CMs consumed lactate produced by MEC utilizing it to fuel their metabolism. Knockdown of lactate transporters Mct1 and Mct4 in MEC led to the same inhibitory effect on the metabolism of CMs as Tfeb silencing, while the addition of lactate to the medium rescued CMs’ metabolic parameters. RNAseq and ChIPseq analyses in MEC pointed to TFEB targets, DUSP4 and DUSP6 phosphatases. They were upregulated in MEC si Tfeb, leading to dephosphorylation of AKT and ERK kinases, possibly deregulating glucose metabolism. To investigate whether the metabolic deficiency in CMs could cause functional impairment, we co-cultured primary rat CMs with MEC si Tfeb and analysed contraction dynamics in microscopy videos. CMs co-cultured with MEC siCtrl but not with MEC si Tfeb performed better in terms of contraction amplitude and frequency than CMs cultured alone, and the addition of lactate to the medium rescued the deficit. Conclusions: These data suggest a novel mechanism of lactate shuttle between epicardial cells and CMs with a potential role for TFEB in regulation of glucose metabolism in epicardial cells.
Abstract 4143899: cusp-overlap view versus three cusp coplanar view during transcatheter aortic valve replacement using self-expandable valves: A meta-analysis of 5947 patients.
Authors: Ahmed K. Awad, Basma Khalefa, Ahmed R. Gonnah, Mazen Negmeldin Aly Yassin, Nada G.Hamam, Mohamed Ramadan, Ali Dway, Karim Alsalhi, Mohamed T. Osman, Serge Sicouri, Ramlawi Basel
Journal: Circulation (2024)

Background &amp; Objectives: Transcatheter aortic valve replacement (TAVR) is currently the treatment of choice for most patients with symptomatic severe aortic stenosis. We conducted this systematic review, and meta-analysis to compare the efficacy and procedural outcomes of using the cusp overlap technique (COT) versus the standard three-cusp technique during self-expandable valves implantation for the management of aortic stenosis. Methodology: We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science (WOS) from inception to March 5, 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. To estimate the effect size, dichotomous outcomes were pooled as risk ratio (RR), and continuous outcomes were pooled as mean difference (MD) with their respective 95% confidence interval (CI). Results: We included seventeen studies in our systematic review and meta-analysis with a total of 3129 patients in cusp-overlap technique (COT) arm and 2818 patients in standard technique (ST) arm. The rate of 30-day mortality was significantly decreased in COT compared with ST (RR = 0.61; 95% CI: [0.37–1.00], P = 0.05). Regarding conduction abnormalities, COT was related to lower risk of complete atrioventricular (AV) block (RR = 0.51; 95% CI: [0.37–0.69], P &lt; 0.01), reduced likelihood of left bundle branch block (RR = 0.77; 95% CI: [0.61–0.97], P = 0.03) and permanent pacemaker implantation (PPI) (RR = 0.56; 95% CI: [0.46–0.70], P &lt; 0.01). There was also lower likelihood of major and life-threatening bleeding with the COT compared to ST (RR = 0.60; 95% CI: [0.46–0.79], P &lt; 0.01). Our analysis also showed that COT was associated with significantly lower implantation depth compared with ST (MD = -1.00; 95% Cl: [-1.83 to -0.17], P = 0.02). Procedural success was similar between COT and ST (RR = 1.01; 95% CI: [0.98–1.04], P = 0.42). Major vascular complications (RR = 0.90; 95% CI: [0.61–1.33], P = 0.61), and mild to severe paravalvular leak (RR = 1.00; 95% CI: [0.66–1.51], P = 1.00) were also comparable between COT and ST. Conclusion: Our study findings suggest that COT offers several advantages over ST, including reduced 30-day mortality and decreased bleeding complications, without compromising long-term outcomes or increasing procedural complications. The COT most importantly lower risk of conduction abnormalities, and hence permanent pacemaker implantation.
Abstract 4143855: Identifying the implementation potential for Mobile Integrated Health interventions for patients with heart failure
Authors: Meghan Reading, Victoria Puplampu, Leah Shafran Topaz, Stephanie Nino de Rivera, Melani Ellison, Erik Blutinger, Brock Daniels, Ruth Masterson Creber
Journal: Circulation (2024)

Introduction: Mobile Integrated Health (MIH) is a novel care delivery model utilizing community paramedics and telehealth to manage chronic illnesses such as heart failure (HF) outside hospital settings. Implementation of MIH is widely variable between institutions and stakeholder perspectives are poorly described in the literature. Objective: To identify stakeholder (e.g., MIH experts, HF clinicians, and caregivers of adults with HF) perspectives on predisposing, enabling, and reinforcing factors to the adoption, implementation, and maintenance of MIH. Methods: We used the RE-AIM (Reach Effectiveness Adoption Implementation Maintenance) framework to analyze MIH implementation. Stakeholders were recruited using a combination of convenience and snowball sampling nationally in the United States (U.S.). An interview guide based on the relevant domains of the RE-AIM framework was tailored to participant types. Interviews were conducted via phone or Zoom, with verbal consent obtained. Sessions were audio-recorded, transcribed verbatim, and qualitatively analyzed by four reviewers using directed content analysis. Results: Twenty-five stakeholders were recruited: six clinicians (four cardiologists, two nurses), eight MIH staff (four paramedics, one dispatcher, three nurse care coordinators), two caregivers, and nine MIH Program Directors. Predisposing factors included EMS skills and knowledge, the rising value of digital health, clinician beliefs about “phenotypes” of patients who benefit most from MIH, and alignment with the right outcome measures. Enabling factors included the comprehensiveness and quality of care provided during MIH visits, interdisciplinary team integration, patient trust in community paramedics, and telehealth functionality. Reinforcing factors included the ability of MIH programs to demonstrate value and financial sustainability, embrace future innovations and improvements, and show high patient satisfaction with MIH. Illustrative quotes are provided in Table 1 . Conclusions: This study highlighted unifying predisposing, enabling, and reinforcing factors across MIH programs nationally, which may guide future efforts for those launching or scaling these programs for adults with HF.
Abstract 4143813: Secular Trends and Mortality Rates in Percutaneous Coronary Intervention in Non-ST Elevation Acute Coronary Syndrome: 15-Year Nationwide Survey
Authors: Zaid Abood, Suhail Allaqaband, Balamrit Sokhal, Kirsten Tunink, Mohamed Hommeida, Tanvir Bajwa, M. Fuad Jan
Journal: Circulation (2024)

Background: Non-ST elevation acute coronary syndrome (NSTE-ACS) is a leading cause of cardiovascular morbidity, with variable mortality across age groups. Older patients exhibit higher in-hospital mortality and often experience delayed percutaneous coronary intervention (PCI) owing to comorbidities. Large-scale data on PCI and inpatient mortality trends are limited. Aim: To evaluate inpatient mortality rates of NSTE-ACS treated with PCI over a 15-year period, comparing trends based on age groups. Methods: We used the National Inpatient Sample from 2005 to 2019 to identify the study population using the International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification. The primary outcome was the PCI trend of NSTE-ACS among age groups. The secondary outcome was in-hospital mortality. Multivariate logistic regression and adjustment for sex, race, and Charlson comorbidity index score were used. Results: We evaluated 6,645,610 patients hospitalized in the United States for NSTE-ACS. Of these, 2,291,282 (34.4%) underwent PCI; mean age was 64.8 years, and 34.3% were female. PCI rates increased in all age groups during the study period; however, they remained significantly lower in patients above 80 years of age. The rate of PCI increased from 38% to 44.7% in the 18-64 years age group, from 29.1% to 43.1% in the 65-79 years age group, and from 15.6% to 31.7% in those 80 years and older during the study period (P&lt;.001) (Figure 1). Furthermore, inpatient mortality rates decreased significantly across all age groups. From 2005-2007 to 2017-2019, mortality rates declined from 1.1% to 0.8% in the 18-64 years age group (P&lt;.001), from 2.5% to 1.6% in the 65-79 years age group (P&lt;.001), and from 4.8% to 2.9% in those aged 80 years and older (P&lt;.001). Conclusion: From 2005 to 2019 (15 years), an increasing number of patients with NSTE-ACS underwent invasive treatment with PCI each year, most notably in those aged 80 years and older. This was associated with a decline in inpatient mortality across all age groups, greatest in those 80 years of age and older. These results are reassuring as people are living longer and NSTE-ACS is increasingly identified in an older population group.