tbuckley/cabot-search huggingface dataset:
Abstract 4141948: Direct and Indirect Relationships between Historic Redlining and Prevalence of Diabetes
Authors: Jennifer Campbell, Rebekah Walker, Sebastian Linde, Leonard Egede
Journal: Circulation (2024)

Background: Structural racism has emerged as an important contributor to poor health outcomes. Historic redlining, the previously legal practice of systematically denying credit access and insurance, resulted from Home Owners’ Loan Corporation (HOLC) residential security maps graded on a color coded scale (A (Green)=Best; B (Blue); C (Yellow); D (Red)=Hazardous), hence the term redlining. The goal of this study was to investigate the direct and indirect relationships between historic redlining and prevalence of diabetes in a national sample. Methods: We combined census tract level data across multiple sources: a) diabetes prevalence from CDC PLACES 2019 database, b) HOLC grade from Mapping Inequality project, and c) incarceration risk, poverty, housing, education, employment, job environment, economic mobility, and demographics, from Opportunity Insights database. The assignment of redlining to present-day census tract was done based on overlap with historically HOLC graded areas. The final analytic sample consisted of 9,590 US census tracts. Structural equation modeling was then used to investigate direct and indirect relationships between redlining and diabetes prevalence through possible mediators of health care access, community resources, social capital, and social risk. Stata v16 was used for the analysis and analyses were adjusted for population. Results: Higher prevalence of diabetes was directly associated with more redlining within a census tract (0.28, p&lt;0.001). All indirect paths were significant with the three strongest indicating diabetes prevalence is indirectly associated with redlining via health care access (0.48, p&lt;0.001); community resources measured via education level (-0.44, p&lt;0.001); and social risk measured via income (-0.23, p&lt;0.001). Figure 1 shows standardized coefficients to allow comparison with higher numbers indicating stronger relationships. Conclusions: Consistent with our conceptual framework, redlining has significant direct and indirect relationships with diabetes prevalence. Indirect relationships include health care access, community resources including employment and education, social capital, and social risk factors of low income and high incarceration.
Abstract 4141913: Feasibility and safety of ICE-guided electrical isolation of the superior vena cava using pulsed-field ablation in patients with atrial fibrillation
Authors: Sanghamitra Mohanty, Brandon Doty, Kirollos Gabrah, Vincenzo Mirco La Fazia, Marco Schiavone, PremGeeta Torlapati, Carola Gianni, John allison, G Gallinghouse, John Burkhardt, Rodney Horton, Amin Al-Ahmad, Claudio Tondo, Devi Nair, Andrea Natale
Journal: Circulation (2024)

Background: Earlier studies have documented the risk of sinoatrial node injury and phrenic nerve palsy as complications following radiofrequency catheter ablation for electrical isolation of superior vena cava (SVCI). Objective: We evaluated the safety and feasibility of SVCI in patients with atrial fibrillation (AF) undergoing pulsed-field ablation (PFA) Methods: Consecutive patients undergoing PFA procedure for SVCI were included in this multicenter analysis. SVC ablation was performed with the ablation catheter placed at the level of the pulmonary artery under the guidance of intracardiac echocardiography (ICE). A total of 4 applications were given; two in the flower and 2 in the basket configuration of the PFA catheter. In all patients, the procedure was performed under imaging with ICE; endpoint was complete electrical isolation of the vein. Mapping was done before and after ablation to verify the effect of PFA. Patients were asked to report symptoms compatible with phrenic nerve injury (cough, shortness of breath) at follow-up. They also underwent periodic clinical and 7-day holter monitoring to assess sinus node injury. Results: A total of 67 patients (age: 62.92±9.44 year, male: 20 (66.6%), BMI: 26.43±4.33) receiving SVCI were included in the analysis. Acute SVCI was achieved in all 67 (100%) patients (fig 1 and 2). After ablation, the PFA catheter placed in the SVC did not record any electrical activity (figure 2). No phrenic nerve palsy (normal diaphragmatic motion with fluoroscopy) or sinus node injury (no acceleration of the sinus rate) was observed during the procedure. Additionally, during the 3-month follow-up period, patients neither reported symptoms pertaining to phrenic nerve injury nor the Holter monitoring revealed sinus node dysfunction. Conclusion: ICE-guided PFA can effectively isolate SVC without causing phrenic nerve palsy or sinus node injury.
Abstract 4141874: Social Determinants Of Aging Speed Among Hispanic/Latino Adults From The Hispanic Community Health Study/Study Of Latinos (HCHS/SOL, 2008-2017)
Authors: Robert Mesa, Maria Llabre, David Lee, Tatjana Rundek, Adina Zeki Al Hazzouri, Katrina Kezios, Linda Gallo, Paola Filigrana, Martha Daviglus, Amber Pirzada, Tali Elfassy
Journal: Circulation (2024)

Background: From 2018 to 2060 the proportion of US seniors (age 65+) will increase from 16% to 23%, with much of this growth driven by Hispanic/Latino seniors. Adverse social determinants of health (SDoHs) are drivers of poor health outcomes and accelerated aging. Objective: To examine the association between SDoHs (education, income, and nativity) and aging speed among Hispanic/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos is a longitudinal cohort of Hispanic/Latino adults from four US urban communities. Participants completed questionnaires, underwent clinic examinations, and provided biospecimens at visit 1 (V1: 2008-2011) and visit 2 (V2: 2014-2017). Education, income, and nativity were self-reported at V1. The Klemera-Doubal Method, an algorithm consisting of equations using biomarkers from different organ systems (waist-to-hip ratio, pulse pressure, lipids, glycosylated hemoglobin, alanine aminotransferase, cystatin C, and albumin-to-creatinine ratio), was used to calculate biological age (BA) among 5,316 females and 3,087 males ages 30 to 75 at either V1 or V2. Aging speed was defined as the difference between change in BA from V1 to V2 and follow-up time from V1 to V2. We used multivariable linear regression models to determine the sex-specific association between each SDoH with aging speed. Results: At V1, mean chronological age was 47 years for females and 46 years for males. Over an average of six years, females aged biologically by 5 years and males aged biologically by 4 years. Compared with having more than a high school education, aging speed was greater by 0.69 years (95% CI: 0.45, 0.94) among females with less than a high school education but not among males (ß=0.57, 95% CI: -0.04, 1.17). Compared with an income ≥$50K, aging speed was greater by 0.67 years (95% CI: 0.30, 1.04) among females with an income &lt;$30K but not among males (ß=0.62, 95% CI: -0.08, 1.31). Compared to those born in the 50 US states/DC, being foreign born was associated with slower aging speed by 0.39 years (95% CI: -0.72, -0.06) among females but not among males (ß=0.52, 95% CI: -0.35, 1.39). Conclusion: Over six years, Hispanic/Latino males and females demonstrated slower biological aging compared with chronological aging. Lower income, lower educational attainment, and being born in the 50 US states/DC were associated with greater biological aging (faster aging speed) among Hispanic/Latino females.
Abstract 4141934: Psychosocial Stress Subgroups and Cardiovascular Disease (CVD) Events in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Tiwaloluwa Ajibewa, Laura Colangelo, Diana Chirinos, Kiarri Kershaw, Mercedes Carnethon, Norrina Allen
Journal: Circulation (2024)

Introduction: Heightened psychosocial stress is a CVD risk factor. While stressors are common and often co-occur, identifying sources and patterns of psychosocial stress exposure may provide insight into individual susceptibility to CVD. Therefore, we sought to identify and examine the longitudinal associations of baseline psychosocial stress subgroups with CVD events in MESA. Methods: Data from 6,349 adults (aged: 62.2±10.2 years; 52.9% women) from the MESA cohort with no prior CVD event at baseline (years 2000-2002) were used in this analysis. Latent class analysis (LCA) was used to specify distinct stress subgroups based on 6 variables: chronic burden, neighborhood safety, adequate food shopping, neighborhood noise, lifetime- and past-year discrimination. Five classes were determined after examining traditional fit indices. Adjudicated fatal and nonfatal CVD events were ascertained in annual follow-up visits through the year 2019. Cox proportional hazards models with sequential adjustment of baseline variables were used to examine the associations between subgroup membership and CVD events. Results: Five distinct stress subgroups were identified via LCA and were labeled “moderate neighborhood noise” (12.1%), “excessive noise/crime” (6.4%), “elevated on all” (6.3%), “high discrimination/safe neighborhood” (21.4%), “optimal” (53.8%) (see figure). By the year 2019, 1,121 participants had experienced a CVD event. Membership in the “elevated on all” and “high discrimination/safe neighborhood” subgroups (see table) were associated with higher risk of a CVD event when adjusted for sociodemographic characteristics and cardiovascular health metrics. However, when adjusted for measures of anxiety and depression, possible mediators, only membership in the “high discrimination/safe neighborhood” subgroup was associated with increased risk of a CVD event. Conclusions: Among 5 distinct stress subgroups those experiencing high discrimination had higher risk for CVD events.
Abstract 4141933: Supraventricular Tachycardia (SVT) Related Mortality Rates Among Adults (25 Years and Above) in The United States from 1999 to 2020; A CDC WONDER Database Study.
Authors: Rohab Sohail, Hafsa Mansoor
Journal: Circulation (2024)

Introduction: Supraventricular tachycardia (SVT) is known to affect children and teenagers predominantly but can also occur in adults. However, due to a presumed good disease outcome, fatality rates of SVT in adults (above 25 years) are yet to be explored. Aim: This study aims to shed light on the mortality trends of SVT in the adult population across the United States from 1999 to 2020. Methodology: The CDC WONDER database was used to identify SVT-related deaths using ICD-10 code I47.2 in adults (above 25 years) from 1999 to 2020. The reported data was in the form of crude rate and age-adjusted mortality rate (AAMR) per 100,000 individuals and was stratified by year, ten-year age groups, gender, races, census region, census division, states, and rural-urban division. The Joinpoint regression was then used to determine the changes in trends and annual percentage change (APC). Results: From1999 to 2020, 31,036 (AAMR=0.6) SVT-related deaths were reported. AAMR showed an initial steep decline from 0.9 in 1999 to 0.5 in 2011 (APC -5.11 [95% CI -6.08 to -4.14]), followed by a gradual increase till 2020 (0.8) (APC 5.14 [95% CI 3.41 to 6.90]). The crude death rates increased with age and were reported to be highest in ages greater than or equal to 85 (9.1); the trend showed a steep decrease from 1999 (12.4) to 2008 (7.9) (APC -4.35 [95% CI -5.36 to -3.33]), followed by a gradual decline till 2017 (7.8) (APC -0.66 [95% CI -2.04 to 0.73]), and ultimately rising sharply till 2020 (10.6) (APC 9.23 {95% CI 3.32 to 15.47]). Among races, Blacks and Whites displayed the highest mortality (0.7). Blacks showed an initial decrement from 1999 (1.0) to 2017 (0.6) (APC -2.71), followed by a rise back to 1.0(2020) (APC 19.58), while whites showed an initial fall (0.9 (1999) to 0.6 (2008), APC -4.91), followed by no change till 2017 (APC 0.18), and ultimately rise to 0.9 in 2020 (APC 13.66). Although no significant gender or geographical variations were observed, more deaths were seen in rural areas (1.0) than in Urban (0.6). Conclusion: Following an initial decline, the incidence of SVT-related mortality has been increasing over the years, pre-dominantly among the 85+ age group, Blacks, and rural populations. However, due to a limited understanding of the epidemiology of SVT in adult populations, more extensive research is needed to formulate better preventive and management strategies.
Abstract 4141912: Targeting NEK2 to Induce Senescence and DNA Damage in Pulmonary Arterial Hypertension
Authors: Sandra Martineau, Keiko Yamamoto, Alice Bourgeois, Sarah-Eve Lemay, Melanie Sauvaget, Sandra Breuils Bonnet, Francois Potus, Steeve Provencher, Olivier Boucherat, Sebastien Bonnet
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling of the distal pulmonary arteries (PAs) leading to progressive elevation of PA pressure, right heart failure and death. Extensive proliferation and resistance to apoptosis of PA smooth muscle cells (PASMCs) is perhaps the most prominent feature of PAH accounting for the histopathological changes seen in this disease. With the recognition of this, direct targeting of vascular remodeling may represent a promising strategy. Goal: To illuminate new actionable targets involved in pulmonary vascular remodeling in PAH. Methods: Molecular, biochemical and pharmacological approaches were used to identify Never In Mitosis A-Related Kinase 2 (NEK2) and study its role in pulmonary vascular remodeling in PAH Results: We performed a comparative RNA-sequencing analysis between control and PAH-PASMCs and then integrated our dataset with publicly available datasets conducted on comparable samples. Among the genes that were concordantly up-regulated in PAH-PASMCs, we identified NEK2, a kinase and druggable target implicated in the progression of mitosis. Using Western blot (WB) and immunofluorescence (IF), we confirmed that NEK2 is upregulated in PASMCs and distal PAs of PAH patients and animal models (Sugen/Hypoxia- and monocrotaline-exposed rats). Pharmacological (NCL0017509) and molecular (siNEK2) inhibition of NEK2 reduced PAH-PASMCs proliferation, as assessed by IF (Ki67 labeling, EdU incorporation, p&lt;0.05) and qPCR (MCM2, PLK1 and Survivin , p&lt;0.05). Further analysis revealed that pharmacological inhibition of NEK2 blocks cell cycle progression in the G2/M phase (flow cytometry, p&lt;0.01) and increases DNA damage (comet assay p&lt;0.001, WB of pDNAPK/DNAPK and RAD51, p&lt;0.05). Moreover, we found that PAH-PASMCs subjected to NEK2 inhibition acquire a senescent phenotype (WB of p16, p21 and p53, p&lt;0.05). Conclusion: Our results suggest that NEK2 contributes to the pro-proliferative phenotype of PAH-PASMC and may represent a new target in PAH.
Abstract 4141798: Empagliflozin dramatically reduced stroke size and cerebral edema in a rat model
Authors: Wangde Dai, Juan Carreno, Niema Pahlevan, Rashid Alavi, Robert Kloner
Journal: Circulation (2024)

Background: Ischemic stroke is associated with high mortality, morbidity and disability that significantly affects the quality of life of patients even in the current thrombolytic/thrombectomy era. The effect of empagliflozin (EMPA), a sodium glucose co-transporter 2 inhibitor on stroke is unknown. Methods: Male SD rats were randomized into three groups (n = 10 in each group): (1) Control group: rats received regular diet alone (without EMPA); (2) Acute treatment group: EMPA (10 mg/kg, IV) given at 10 minutes prior to middle cerebral artery occlusion (MCAO) and one minute prior to reperfusion; (3) Chronic treatment group: EMPA given by food (20 mg/kg) for 7 days before MCAO. A standard intraluminal filament MCAO was performed for one hour of MCA occlusion followed by 3 hours of reperfusion. The brain was harvested and sliced for 2,3,5-triphenyltetrazolium chloride (TTC) staining to measure the volume of cerebral infarction and edema using the technique of Regoldi. Results: The size of the cerebral infarction, expressed as percentage (%) of the infarct volume to the whole brain volume, was significantly smaller in the acute EMPA treatment group (2.8 ± 1.2%) and chronic EMPA group (7.3 ± 2.7%) compared with the control group (16.7 ± 3.2%; p = 0.002) (Figure). The edema of the ipsilateral hemisphere, expressed as percentage of the edema volume to the contralateral hemisphere volume (%), was significantly reduced in the acute EMPA group (4.6 ± 0.9%) and chronic EMPA group (5.2 ± 0.7%) compared to the control group (11.2 ± 1.5%; p = 0.001). Conclusion: Our data indicates that EMPA significantly reduced cerebral infarction and edema in a stroke model in rats. Acute IV EMPA reduced stroke size by 83%.
Abstract 4141915: Catheter Ablation for Atrial Fibrillation May Improve Mortality in Patients with Heart Failure with Preserved Ejection Fraction, Similar to Reduced Ejection Fraction
Authors: Patrick Benjamin, Olamide Oyenubi, EMMANUEL FOHLE, Vahe Shahmoradi, Dawlat khan, Andrii Maryniak
Journal: Circulation (2024)

Introduction: Atrial remodeling in HFpEF typically results in impaired ventricular diastolic function, and the maintenance of sinus rhythm would be key to improve clinical outcomes in these patients. The CABANA trial provides limited evidence for the benefits of AF ablation in HFpEF patients. While observational studies suggest otherwise, the results of upcoming RCTs like AMPERE and CABA-HFPEF may offer deeper insights. Objective: This study examines the inpatient outcomes of hospitalized HFpEF patients with AF who underwent catheter ablation Methods: A retrospective analysis of a nationwide inpatient database from 2017 to 2019 was conducted. The study included patients diagnosed with both HFpEF and AF. A propensity score-matched cohort compared HFpEF and AF patients who underwent catheter ablation with those who did not. Results: Among 8.2 million HFpEF patients, 2.6 million had AF, and 24,015 underwent catheter ablation. Mortality was significantly lower in the ablation group compared to the control group (4.6% vs. 1.7% in unmatched cohort, 3.8% vs. 1.7% in matched cohort). The adjusted hazard ratio for mortality was 0.43 (95% CI: 0.34-0.55, p&lt;0.00), indicating a 57% lower risk of death in the ablation group. Conclusion: Catheter ablation may offer mortality benefits for HFpEF patients with AF, as suggested by this study. This could foreshadow the findings of ongoing trials like AMPERE and CABA-HFPEF, indicating that ablation could be a valuable treatment option for this high-risk patient group not responding well to standard therapies.
Abstract 4141914: Fragmentation Analysis of Heart Rate Variability after Ischemic Stroke in Rats: A New Indicator of Heart-Brain Connection
Authors: Rashid Alavi, Wangde Dai, Niema Pahlevan, Xianghong Arakaki, Morteza Gharib, Robert Kloner
Journal: Circulation (2024)

Introduction: Fluctuations of heart rate, or heart rate variability (HRV), contain important information about autonomic functions and regulations of the cardiovascular system. Heart rate fragmentation (HRF) is an inter-beat interval dynamics approach (Front Physiol, 2017 PMID: 29184505) that enhances analysis of short-term HRV. HRF has shown consistency with breakdown of neuroautonomic-electrophysiologic control system of the sino-atrial node. Here, we evaluate alterations of HRF metrics prior to, during the ischemic stroke and after reperfusion. Methods: We used the standard ischemic stroke model (intraluminal suture middle cerebral artery (MCA) occlusion) in adult male/female Sprague Dawley rats (n=11, 2-3 months old, weight: 296 ± 47 g, 27% female). The common carotid artery (CCA) was temporarily occluded while a suture was introduced to the internal carotid artery and advanced until it interrupted blood supply to MCA. We occluded the MCA for 1 hour followed by 3 hours of reperfusion (Fig.1). Electrocardiogram (ECG) was continuously measured throughout the surgeries. Post-surgery, the presence of cerebral infarction was confirmed by incubating brain slices in triphenyl tetrazolium chloride (TTC staining). HRF metrics were computed using 1-minute recordings of ECG at 3 time-points: a) baseline; b) 1 hour after MCA occlusion (pre-reperfusion); and c) 3 hours after reperfusion. Results: Significant differences (p&lt;0.05) were found between the baseline and 3 hours after reperfusion (Fig.2) for two HRF metrics: PIP% (percentage of inflection points i.e., changes in heart rate acceleration sign) and W1% (percentage of only 1 inflection point in sequences of five consecutive heart rate intervals). Conclusions: Our results suggest that there are specific HRF metrics that alter significantly after ischemic stroke in rats. This study shows the possibility of developing noninvasive HRF-based techniques for detection or monitoring of ischemic stroke and treatment in future.
Abstract 4141882: The importance of adenine in the formation of coronary artery calcification and development of ischemic cardiomyopathy
Authors: Ian Tamayo, Aleksandra Gruslova, Marc Feldman, Esmeralda Trevino, Kenneth Bedi, Kenneth Margulies, Hak Joo Lee, Jean Chrisostome Bopassa, Kumar Sharma
Journal: Circulation (2024)

Introduction: Adenine has been demonstrated to be involved in the development of diabetic kidney disease. We postulate that adenine may play a similar role in the progression of cardiovascular disease. The underlying metabolic changes in ischemic cardiomyopathy (ICM) progression are not fully understood and may present novel targets to mitigate ischemic heart injury. This study aims to identify common metabolic targets based on adenine metabolism in both coronary artery calcification and ICM. Methods: Coronary arteries from human donor hearts with and without calcification were analyzed by mass spectrometry imaging (MSI) and serial section von Kossa’s staining for image co-registration with identified metabolites. Bulk tissue LC-MS of the same artery samples were measured for adenine pathway metabolites. Another cohort of human heart tissues from healthy donors and those with a history of ICM were analyzed for bulk left ventricle tissue LC-MS measurement of adenine pathway metabolites. Further, to evaluate a mechanistic role for adenine in the development of ICM, a rat model of MI was studied with and without pharmacologic inhibition of MTAP, the enzyme responsible for adenine production. Infarct size was used as the readout of heart injury. Results: An untargeted analysis by MSI reveals an increase in adenine highly localized to arterial calcification as well as other metabolites such as glycolytic intermediates and C16 ceramide-derived lipids. Bulk tissue LC-MS showed calcified arteries have an overall increase in adenine, 5’-methylthioadenosine (MTA), S- adenosylmethionine (SAM). Left ventricle tissue from human donors with a history of ICM showed a significant increase in adenine by bulk LC-MS compared to controls (t-Test, **p&lt;0.01). There was a negative correlation of heart adenine with LVEF (Pearson R = -0.6807, **p&lt;0.01). In a rat model of MI, inhibition of MTAP resulted in significantly reduced infarct size (from 50% to 10%, t-Test, *p&lt;0.05). Conclusion: Spatial metabolomics revealed increased adenine, several glycolytic intermediates, and C16 ceramide-derived lipids as highly co-localized to arterial calcification. Further, adenine was found to be increased in LV tissues with ICM and was negatively correlated with LVEF. Inhibition of adenine production reduced infarct size in a rat model of MI by &gt;80%. Taken together, multimodal metabolomics reveals adenine to be mechanistically involved in cardiovascular disease and presents as a novel therapeutic target.