tbuckley/cabot-search huggingface dataset:
Abstract 4145840: Hypertensive Cardiorenal Disease with Cardiorenal Failure vs. Hypertensive Renal Disease with Renal Failure: Racial Mortality Trends from 1999 to 2020 in the United States
Authors: Fatima Ashfaq, Ahmad Zain
Journal: Circulation (2024)

Introduction: High levels of blood pressure (BP) are responsible for 7.6 million deaths each year worldwide, more than any other risk factor. The diagnosis of hypertension is associated with a significant increase in the risk of kidney or cardiovascular events, with no prior history of these events. Our study aims to analyze trends in hypertensive heart disease and hypertensive heart and kidney disease-related mortality in the United States, focusing on different races. Method: We retrieved death certificate data from the CDC-WONDER database for adults aged ≥25 years. Crude mortality rates (CMRs) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated. Temporal trends were examined using the average annual percent change (AAPC) determined by joinpoint regression. Result: From 1999 to 2020, a total of 100,705 people died from hypertensive heart and renal disease in the USA. The overall AAMR of 1.4 per 100,000 displayed a trend during this period (AAPC: 4.8, 95% CI [3.3–6.2]). Total deaths from hypertensive heart disease and renal disease associated with heart failure were 5,274, showing an increasing trend from 1999 to 2020. The AAMR for hypertensive heart and renal disease with heart failure was 0.1 (AAPC: 5.2, 95% CI [3.8–6.7]). Black or African Americans have the highest AAMR (0.1, 95% CI [0.1–0.1]). Total deaths from hypertensive heart disease and renal disease associated with renal failure were 34,519, showing an increasing trend from 1999 to 2020. The AAMR for hypertensive heart and renal disease with renal failure was 0.4 (AAPC: 3.9, 95% CI [2.6–5.1]). Black or African American has the highest AAMR (1.6, 95% CI [1.5–1.6]), followed by American Indian or Alaska Native (0.5, 95% CI [0.4–0.5]), Asians and Pacific Islanders (0.4, 95% CI [0.4–0.4]), and White (0.4, 95% CI [0.3–0.4]). Conclusion: African Americans and other identified high-risk races should get targeted therapies to reduce the burden of hypertensive-related morbidity and mortality; those with renal impairment should receive special attention. The goals of these interventions ought to be to increase access to healthcare, raise public knowledge of hypertension, and support lifestyle changes.
Abstract 4135629: Grades and trends from the 2024 United States Report Card on Physical Activity for Children and Youth
Authors: Kashica Webber-Ritchey, Amanda Staiano, Yang Bai, Elizabeth Dodson, Erin Dooley, Bethany Forseth, Jayne Greenberg, amanda grimes, Rebecca Hasson, Paul Hibbing, Russell Pate, Natalicio Serrano, Heidi Stanish, Qianxia Jiang, Katherine Spring, Andrew Fox, Mallory Moon, Chelsea Steel, Jordan Carlson
Journal: Circulation (2024)

Background: Regular physical activity provides numerous health benefits including improved cardiovascular health. Population-level physical activity surveillance is critical for informing research, practice, and policy efforts for supporting population health and health disparities. The United States Report Card on Physical Activity for Children and Youth addresses physical activity surveillance needs by integrating data from numerous sources capturing levels of physical activity and related behaviors (e.g., sedentary behavior, sleep), and facilitators and barriers for physical activity among United States youth. The 2024 Report Card is the 5 th and decennial iteration in the series, released October 2024. Methods: A Report Card Working Group was assembled under the auspices of the Physical Activity Alliance and National Physical Activity Plan. Members reviewed the evidence for 11 indicators using data from nationally representative surveys and assigned grades. Data were examined for the overall population and, when possible, by age, sex, race/ethnicity, and disability subgroups. A standardized grading rubric was used to assign a letter grade to each indicator ranging from A to F. Trends in key benchmarks over time were examined since the first report card (2014) or earliest available data. Results: Sufficient data were available to assign grades for 8 of the 11 indicators. The assigned grades ranged from B- to F, with overall physical activity levels earning a D- (Table 1). No indicators improved since 2014. Five indicators - overall physical activity, organized sport participation, active transportation, sedentary behaviors, and school - worsened since 2014. Conclusions: The compiled surveillance report indicates generally poor grades and concerning trends over the recent decade. These findings highlight opportunities to improve physical activity levels and resources for supporting cardiovascular health among United States youth. Policy approaches are needed to combat societal factors that interfere with physical activity. Gaps in data availability, specificity, and quality point to needs for improved surveillance to track impacts. The 2024 Report Card can be a tool for supporting advocacy of regular physical activity at the national and local level.
Abstract 4144595: Real-World Outcomes of Impella 5.5 in Advanced Heart Failure Patients Undergoing Evaluation for Heart Transplant
Authors: Khush Patel, Erik Suarez, Ashrith Guha, Ngo Uy, Ju Kim, Mehmet Akay, Arvind Bhimaraj
Journal: Circulation (2024)

Background: Impella 5.5 provides robust support as temporary mechanical circulatory support (t-MCS) device in advanced heart failure patients in cardiogenic shock. Understanding short- and long-term outcomes is crucial. Hypothesis: Impella 5.5 supports advanced heart failure patients in cardiogenic shock and successfully bridges them to cardiac replacement without affecting long-term survival. Methods: From February 2020 to April 2024, all patients who received an Impella 5.5 and underwent evaluation for advanced therapies at Houston Methodist Hospital were identified. Implantation of Heartmate 3 (HM3) Left Ventricular Assist Device (LVAD), orthotopic heart transplantation (OHT), mortality, and device removal after Impella implantation were assessed. For HM3 LVAD patients, outcomes were categorized as death, transplantation, or survival. Survival after OHT was analyzed using Kaplan-Meier analysis and compared to patients who received OHT without Impella 5.5. Cumulative incidence rates was calculated using Competing risk regression. Results: 140 patients were identified, median age 59.4 years (50.4-66.5), majority Caucasian (54%) and Black (36%). 89 (63.6%) were either bridged to advanced therapies or recovered. 52 (37.1%) underwent OHT, 21 (15%) received an HM3 LVAD, and 51 (36.4%) died post-implantation. 3 (2.1%) died post-transplant. Post-LVAD, 6 (4.3%) died, 3 (2.1%) underwent OHT, and 12 (8.6%) were alive with LVAD. 10 (7.1%) survived after Impella 5.5 removal, 2 (1.4%) went to hospice, and 1 (0.7%) was transferred to another hospital. 3 (2.1%) are currently hospitalized. Fig1a shows outcomes. Fig1b indicates death within 90 days of Impella implantation. 3-year survival of patients bridged with Impella to OHT (N=55) was 94%, comparable (p=0.27) to patients receiving OHT without Impella (N=215)(Fig 1c). Conclusion: Mortality for cardiogenic shock patients remains high. Using Impella 5.5 with a cardiac replacement strategy can salvage some patients. Long-term outcomes for patients bridged to heart transplant with Impella 5.5 are similar to those without the device. Further studies on predictors of early adverse outcomes post-implant can help mitigate risks for advanced heart failure patients in cardiogenic shock.
Abstract 4122309: Prognostic implication and hemodynamic characteristics of modified SCAI class in comatose OHCA patients: data from the BOX trial.
Authors: Louise Linde, Rasmus Beske, Martin Meyer, Simon Molstrom, Johannes Grand, Ole Helgestad, Hanne Berg Ravn, henrik Schmidt, Jesper Kjaergaard, Christian Hassager, Jacob Moller
Journal: Circulation (2024)

Background: Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) is associated with high mortality. Transient myocardial stunning seen after out-of-hospital cardiac arrest (OHCA) often presents similar clinical characteristics as CS upon hospital arrival. OHCA involves a sudden cessation of circulation followed by a low-flow period during resuscitation, while CS involves prolonged myocardial dysfunction leading to hypoperfusion. The Society for Cardiovascular Angiography and Interventions (SCAI) proposed five distinct shock stages, further refined by the Cardiogenic Shock Working Group (CSWG). OHCA typically places patients in SCAI stage E, but this study abandoned that automatic classification. Methods: This post hoc analysis of the BOX trial data involved comatose OHCA patients with a presumed cardiac cause. Patients were classified using the CSWG-SCAI shock classification upon hospital admission without automatically assigning OHCA patients to stage E. Invasive arterial and pulmonary arterial measurements were taken within the first 72 hours of ICU admission. Cardiac Index (CI), cardiac power output (CPO), and perfusion pressure (mean arterial pressure minus central venous pressure) were calculated. Results: The results demonstrated that 31.6% of the 789 included patients were classified as SCAI class B/C, 29.9% as SCAI class D, and 38.5% as SCAI class E. One-year mortality for SCAI classes was as follows: B/C (21.3%), D (34.3%), and E (48.4%), with a p-value of &lt;0.001 (Figure 1). There was no difference in CI and CPO within the first 72 hours of the ICU stay between SCAI classes. The first recorded perfusion pressure differed between SCAI class B/C and E (63.4±14.3 mmHg vs. 60±14.1 mmHg and 60.9±14.2 mmHg, respectively, p=0.008). This difference was only found at the first measurement. As lactate levels are a variable of SCAI classification, it was anticipated that there would be a significant difference in lactate at arrival. This difference in lactate remained at 36 hours after admission (1.3±0.7 mmol/L vs. 1.6±0.8 mmol/L and 1.9±1.1 mmol/L, respectively, p&lt;0.001), but not thereafter. A higher proportion of patients developed acute kidney injury (AKI) as the SCAI classification increased (20%, 31% and 48%, respectively, p&lt;0.001). Conclusion: One-year mortality increased with increasing SCAI classes but hemodynamic parameters within the first 72 hours of treatment did not differ between groups.
Abstract 4136971: Prognostic Value of Late Gadolinium Enhancement to Predict Non-Sustained Ventricular Tachycardia in Patients with Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis
Authors: Ahmed Siddiqi, Muhammad Talha Maniya, ozlem bilen, Mahmoud Abdou, Carlo De Cecco, MUHAMMAD NAEEM
Journal: Circulation (2024)

Background: Non-sustained ventricular tachycardia (NSVT) has been shown to be independently associated with sudden cardiac death (SCD) among patients with hypertrophic cardiomyopathy (HCM). There is limited evidence regarding the efficacy of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging to predict the incidence of NSVT. Aims: To address this gap in knowledge, our meta-analysis aims to comprehensively evaluate the prognostic value of LGE on cardiac magnetic resonance in predicting the incidence of NSVT in HCM. Methods: PubMed, Embase and Cochrane CENTRAL databses were queried from inception until May 2024 for all studies assessing the prognostic value of LGE on CMR in patients with HCM and reported the incidence of NSVT. Data were combined using a random-effects model meta-analysis to determine the pooled sensitivity, specificity and accuracy of LGE in predicting NSVT in patients with HCM. The association between the LGE extent on CMR and NSVT incidence was also assessed, and weighted mean differences (WMDs) were reported with 95% condidence intervals (CIs). Heterogeneity across the studies was evaluated using the Higgins I 2 statistic. Results: A total of twenty studies were included in our analysis. The pooled senstivity, specificity, and accuracy of LGE in predicting the incidence of NSVT among HCM patients was 91.33%, 37.45%, and 52.86%, respectively. Moreover, we saw a significantly greater extent of LGE (5.95%, CI: 3.08-8.81, P&lt;0.0001) in patients who had NSVT, as compared to patients without NSVT ( Figure 1). Conclusion: Our meta-analysis underscores the significant prognostic value of LGE as a risk stratification tool on CMR imaging in predicting the incidence of NSVT in patients with HCM, by demonstrating a high sensitivity, and a notable association between the LGE extent and NSVT incidence. Nevertheless, the low to moderate Ispecificity and accuracy underscores the need for additional imaging biomarkers for risk stratification.
Abstract 4139115: Genomic, Phenomic, and Geographic Relationships with Leukocyte Telomere Length in the U.S. Yields New Insights for Neoplasms and Cardiometabolic Disease
Authors: Tetsushi Nakao, Satoshi Koyama, Buu Truong, Md Mesbah Uddin, Anika Misra, Aniruddh Patel, Caitlyn Vlasschaert, Alexander Bick, Veryan Codd, Nilesh Samani, Whitney Hornsby, Patrick Ellinor, Pradeep Natarajan
Journal: Circulation (2024)

Background: Leukocyte telomere length (LTL) is an age-related marker strongly associated with neoplasms and cardiometabolic disease. LTL is also intimately linked with clonal hematopoiesis of indeterminate potential (CHIP), a recently described risk factor for cardiovascular disease (CVD). However, population-scale investigations of LTL in diverse backgrounds are limited, and geolocational variance has not been studied. Method: LTL and CHIP were derived using blood-derived whole genome sequencing data from 244,819 diverse U.S. residents in the NIH All of Us Research Program (AoU). We performed association analyses of LTL with CHIP and other available health-related traits, Phecode, as well as geolocation data by ZIP code. Genome-wide association study (GWAS) of LTL in AoU and meta-analysis with UK Biobank were performed. All association tests were adjusted for age, sex, sequencing site, and the first 10 genetic principal components with multiple test corrections. Mediation analysis was adjusted for additional risk factors for CVD. Result: Among 244,819 AoU participants, 146,717 (59.9%) were female with mean (standard deviation) age 51.8 (±16) years. Estimated LTL correlated strongly with age, sex, and genetic ancestry in AoU. Socioeconomic status, lifestyle variables, anthropometry, blood biomarkers (e.g., lipids and glucose), and vital signs were associated with LTL in AoU. Phecode analysis showed LTL is associated with neoplasms and age-related conditions, including CVDs. LTL mediated some of the observed increased coronary artery disease risk among individuals with hematologic malignancies ( P &lt; 2 × 10 -16 ). Significantly longer LTL clustered in the West Coast and Central Midwest ( P = 0.001 and 0.033, respectively), while significantly shorter LTL clustered in the Southeast ( P = 0.001) (Figure). GWAS meta-analyses identified 197 loci, of which 36 (18%) were novel, including ancestry-specific loci. Rare variant aggregation test found 9 novel associated genes. Conclusions: LTL is a marker of biological age that is associated and interacts with neoplasms, CVDs, and its various risk factors, with notable geographic variability within the U.S. Germline genetic analyses of LTL yield new insights into drivers of LTL.
Abstract 4140191: ChREBP Drives Brown Adipocyte Differentiation and Lipid Utilization for Excess Energy Expenditure
Authors: Oto Inoue, Meghana Ginugu, archana Singh, Juan Sanchez-Gurmaches
Journal: Circulation (2024)

Introduction: Although several anti-obesity drugs have become recently available, they reduce patients’ appetite, which might worsen cardiovascular disease (CVD) prognosis by malnutrition/cachexia. Brown adipose tissue (BAT) oxidizes glucose and lipids for thermogenesis, a process that requires excess energy expenditure provided by uncoupling protein 1 (UCP1) + cells. Recently, critical roles of BAT in cardio-protection have been discovered. Taken together, boosting BAT activity can be a novel anti-obesity treatment suitable for CVD patients. In this study, we aimed to establish anti-obesity strategy by manipulation of the glucose-sensing lipid-storage transcription factor, ChREBP, with unexpected function of boosting lipid utilization in BAT. Methods and Results: Through mouse/human single-cell/nucleus RNA sequencing analyses, we identified ChREBP as specifically expressed in highly thermogenic UCP1 + brown adipocytes ( Fig.A ). To investigate the role of ChREBP in BAT formation, we generated human brown adipocyte-like model from induced pluripotent stem cells (iPSC-BAT, Fig.B ). The iPSC-BAT exhibited high UCP1 and ChREBP expression, multi-locular lipid droplets, and vigorous oxygen consumption. Knocking down ChREBP strongly blocked iPSC-BAT differentiation ( Fig.C ) and impaired lipid utilization ( Fig.D ). Consistently, in vitro deletion of ChREBP in mouse BAT progenitors impeded differentiation, lipid droplet accumulation, and oxygen consumption ( Fig.E-F ). In vivo, BAT-specific deletion of all ChREBP isoforms reduced lipid accumulation and BAT characteristics. Conversely, using a new mouse model for Cre-mediated ChREBPβ overexpression, we showed that ChREBPβ overexpression in BAT (Chβ BATOX) increased BAT cellularity and activated lipogenic machineries, with paradoxical decreased lipid content, suggesting excessively activated lipid consumption in BAT ( Fig.G ). More importantly, Chβ BATOX maintained UCP1 expression and reduced fat volume ( Fig.H ) even after strongly inhibiting BAT activity. Conclusion: In summary, ChREBP is essential for BAT development and thermogenic capacity by affecting lipid utilization. Our results suggest that ChREBPβ activation may be a novel anti-obesity avenue for CVD patients.
Abstract 4144528: The Polygenic Mechanisms of Dilated Cardiomyopathy Contribute to The Development of Tachycardia-Associated Cardiomyopathy in Patients With Atrial Tachyarrhythmias
Authors: Sina Safabakhsh, Paloma Jordà, Steffany Grondin, Jeremy Parker, Amir Fazeli, Ismael Castillo, Zachary Laksman, Jean-Claude Tardif, Rafik Tadros, Alexandre Raymond-Paquin
Journal: Circulation (2024)

Background Longstanding tachycardia can lead to reversible left ventricular (LV) systolic dysfunction called tachycardia-associated cardiomyopathy (TAC). It is unknown if there is a genetic predisposition to the development of TAC or whether there is overlap between the genetic pathways of TAC and dilated cardiomyopathy (DCM). Research Questions Is there a genetic predisposition towards the development of TAC in individuals with arrhythmia? If so, do these genetic pathways overlap with those of DCM? Methods/Approach The study is a single-center case control study performed at the Montreal Heart Institute (MHI). Inclusion criteria for TAC cases are shown in Table 1. All cases underwent array genotyping and exome sequencing. Previously genotyped controls with arrhythmia but no documented LV dysfunction were included from the MHI Biobank. Following imputation using the TOPMed imputation server, a polygenic score for DCM (PGS DCM ; PGS000666) was calculated for cases and controls. The rate of (likely) pathogenic variants in known cardiomyopathy genes was reported in cases. Results/Data (descriptive and inferential statistics) The study included 107 cases and 878 controls. Case characteristics are shown in Table 1. The average PGS DCM for cases was significantly higher than that of controls (p-value &lt;10 -10 ; Figure 1). Logistic regression with correction for age, sex, and ancestry (principal components) showed a strong association of PGS DCM with TAC (OR 1.99, 95% CI 1.54-2.58; p-value &lt;10 -6 ). Notably, among patients with atrial tachyarrhythmias, those with a PGS DCM above the 95 th percentile had a 3.53-fold increased risk of TAC (p-value 4.5 -4 ). Exome sequencing in TAC cases identified only 2/107 (2%) carriers of (likely) pathogenic variants (in cardiomyopathy genes TNNT2 and MYH7 ). Conclusions Pathogenic variants account for a small minority of TAC cases. In contrast, a significant association between PGS DCM and TAC is suggestive of a shared polygenic pathway between TAC and DCM.
Abstract 4140151: Network Analysis of Differentially Expressed Genes after Silencing Dynamin 2 in Pulmonary Arterial Hypertension
Authors: Danchen Wu, Asish Das Gupta, Kuang-Hueih Chen, Charles Hindmarch, Ting Hu, Stephen Archer
Journal: Circulation (2024)

Rationale: Pulmonary arterial hypertension (PAH) is a rare cardiopulmonary disease that can cause right heart failure and even death. In PAH, excessive mitochondrial fission is responsible for the hyperproliferation of pulmonary artery smooth muscle cells (PASMC), which is incompletely mediated by the large GTPase dynamin-related protein 1 (Drp1). We hypothesize that another GTPase, Dynamin 2 (DNM2), elevated in PASMC of PAH patients, is responsible for the final stage of mitochondrial fission. Objectives: 1. Identify the differentially expressed gene (DEG) signature in PAH PASMC after silencing DNM2 using small interfering RNA (siRNA) by means of RNA sequencing (RNA-seq); 2. Identify the biological processes or pathways associated with these DEGs. Methods: Human PAH PASMCs (n=5 cell line) were transfected with control siRNA or siRNA targeting DNM2. 3’RNA-seq was used to create libraries which we sequenced on the Illumina Nextseq550. Bioinformatic analysis revealed DEGs which we placed into context using the STRING: protein query database and visualized using Cytoscape 3.10.2. Network functional enrichment analysis was performed using STRING. Results: Inhibiting DNM2 significantly reduced mitochondrial fission and slowed PAH PASMC proliferation. RNA-seq identified 156 DEGs (80 down-regulated, 56 up-regulated). The top 5 down-regulated DEGs were DNM2 , RGCC , TICAM1 , RASSF3 , MRPL39 and the top 5 up-regulated DEGs were ITIF1 , ARL6IP1 , POLR3G , CBX1 , CMPK2 . We tested the biologic relevance of RGCC which encodes the Regulator of Cell Cycle using siRNA and showed inhibition of cell proliferation in human PAH PASMC. Network analysis identified 152 edges amongst all DEGs. The largest subnetwork contains 77 nodes and 151 edges. PXDN , which encodes Peroxidasin, a heme-containing peroxidase that is secreted into the extracellular matrix, has the highest degree of connectivity (15 connections), the highest betweenness centrality (0.266), and the highest closeness centrality (0.441). Enrichment analysis found that the p53 signaling pathway and the cytokine signaling in the immune system are the top KEGG and Reactome pathways affected by siDNM2, respectively. Conclusions: DNM2 appears to be an important regulator of the increased mitochondrial fission in PAH. Silencing DNM2 not only inhibits fission but also slows cell proliferation, apparently by reducing the expression of RGCC. Silencing DNM2 in human PAH PASMC results in the disruption of 136 genes.