tbuckley/cabot-search huggingface dataset:
Abstract 4139135: Trends in Stroke Related Mortality in Atrial Fibrillation Patients Aged 25 and Older in the United States: Insights from the CDC WONDER Database
Authors: Muhammad Abdullah Naveed, Muhammad Omer Rehan, Ahila Ali, Rabia Iqbal, Bazil Azeem, Usman Akbar, Karthik Gonuguntla, Muhammad Khan, yasar sattar, Zain Ul Abideen Asad, sudarshan balla, Bilal Munir
Journal: Circulation (2024)

Background: Stroke associated with atrial fibrillation (AF) is a significant cause of mortality. This CDC analysis delves into mortality trends due to stroke in AF patients aged ≥ 25 years, from 1999 to 2020. By analyzing extensive datasets we scrutinized how factors such as gender, race, region of residence, and level of urbanization intersect with mortality rates. Methods: Death data from 1999 to 2020 was analyzed using the Centers for Disease Control and Prevention database, employing ICD codes I48 for AF and I64 for stroke. Age-adjusted mortality rate (AAMR) per 100,000 people with 95% confidence intervals was calculated for the total population, stratified by gender, race, urban/rural status, and census region. The Joinpoint regression software was used to calculate annual percentage change (APC) trend for each stratification. Results: In the U.S. between 1999 and 2020, total of 331,106 deaths occurred among adults due to AF associated with stroke. Deaths occurred predominantly in medical facilities (43.2%). The overall AAMR for AF associated stroke decreased from 26.8 per 100,000 in 1999 to 18.4 in 2020, with an AAPC of -2.05 (p value &lt; 0.000001). Additionally, AAMR declined significantly from 1999 to 2018 (APC: -2.65, p value = 0.012398), followed by an increase from 2018 to 2020 (APC: 3.90, p value = 0.220356). Women had slightly higher AAMRs compared to men (men: 6.6; women: 7.1). The AAMR for women reduced substantially from 1999 to 2020 than for men. AAMRs varied among racial/ethnic groups, with White patients having the highest AAMR (7.4), followed by Blacks (5.4), American Indian or Alaska Natives (4.6), Asian or Pacific Islanders (4.5), and Hispanic population (4.1). AAMRs decreased for all races except for Black population. Geographically, AAMRs ranged from 4.3 in Nevada to 11.9 in Vermont, with the Western region showing the highest mortality (AAMR: 7.9). Nonmetropolitan areas had slightly higher AAMRs than metropolitan areas, with both experiencing a decrease over the study period. Conclusion: This analysis depicts significant disparities in mortality rates attributed to stroke associated with AF and underscores the need for larger population-based studies to further understand the primary factors influencing the observed geographical, racial, and gender differences. Targeted interventions and equitable healthcare access are crucial to mitigate these disparities and improve outcomes for this population.
Abstract 4142799: Central role of LIM domain binding 3 (LDB3) protein in Tetralogy of Fallot assessed by single-nuclei multiome profiling of paediatric right ventricular samples
Authors: Mariann Gyongyosi, Emilie Han, Dominika Lukovic, Ena Hasimbegovic, Benjamen White, Artur Gynter, Veronika Mancikova, Imre Pavo, Ina Michel-Behnke
Journal: Circulation (2024)

Background and aims: Tetralogy of Fallot (TOF; EC: 1565/2019) is the most common cyanotic congenital heart defect with a world-wide incidence of 0.02–0.04%. The pathophysiological mechanisms driven by variable genetic background are poorly understood. We applied the single-nuclei multiome profiling, composed of ATAC and RNA-seq from the same nuclei, of right ventricular samples of children with TOF. The final aim was to define cell types and characterize gene regulation states in different cell clusters including activation and maturation. Methods: Right ventricular samples were prospectively gathered during routinely performed cardiac surgery for TOF correction (EC: 1565/2019). In total, six paediatric patient samples were processed, and on average ~1,500 nuclei were sequenced per sample. Data was analysed using Scanpy to cluster and annotate cells, pycisTopic to identify cell stats and cis-regulatory topics, and SCENIC+ for enhancer-driven gene Regulatory network (eRegulon) construction. Results: Through manual annotation, using published markers, we identified cell types including cardiomyocyte, fibroblast, endothelial, pericyte, immune and neuronal cells. From this, we observed cell type specific expression, with overexpression of decorin in fibroblasts, PTPRC in immune cells, and neurexin genes in neuronal cells found. Differential expression analysis highlighted patient specific patterns of expression, of which gene set enrichment showed enrichment for genes associated with actomyosin structure organisation, dilated cardiomyopathy and cardiac muscle contraction. Integration of the gene expression data with the ATAC-seq data, across all patients, allowed for the construction of eRegulons networks. In detail, in the cardiomyocyte-annotated clusters, we identified enrichment of MEF2, MEIS2 and EPAS1 family enhancers with a central role of LIM domain binding 3 protein (LDB3, associated with cytoskeletal actin and muscle alpha-actin binding) (Fig. 1). Conclusion: Single nuclei multiome profiling of paediatric right ventricular TOF samples identified several patient specific patterns of expression and regulatory networks, related to the development of cyanotic congenital heart disease, and sheds light to the potential drivers of TOF.
Abstract 4140115: Comparison of Lipoprotein(a) and Other Apo B Containing Lipoproteins as Predictors of Major Adverse Cardiovascular Events in ODYSSEY OUTCOMES
Authors: Vera Bittner, Michael Szarek, Philippe Steg, J Jukema, Esther Reijnders, Deepak Bhatt, Rafael Diaz, Sergio Fazio, Genevieve Garon, Shaun Goodman, Robert Harrington, Harvey White, Andreas Zeiher, Christa Cobbaert, Gregory Schwartz
Journal: Circulation (2024)

Background: Lipoprotein(a) [Lp(a)] and other atherogenic lipoproteins each contain one molecule of apolipoprotein B (apoB) per particle. Recent studies have suggested that on a per particle basis, Lp(a) is more strongly associated with major adverse cardiovascular events (MACE) than low density lipoprotein. Hypothesis: In statin-treated patients with recent acute coronary syndrome (ACS), we tested the hypothesis that, on a per particle basis, Lp(a) and its change on treatment with alirocumab (ALI) are more strongly associated with MACE than other [non-Lp(a)] apoB-containing particles. Methods: Molar apolipoprotein(a) [corresponding to Lp(a)] and apo B were measured by mass spectrometry at baseline and month 4 (M4) in a subgroup of 11,957 patients who provided consent for use of stored samples in the ODYSSEY OUTCOMES trial. Non-Lp(a) apoB in nmol/L was calculated as total apo B – Lp(a). Lp(a) and non-Lp(a) apo B at baseline in the placebo group, and absolute changes in their levels on ALI, were related to risk of MACE using proportional hazards models. The latter analysis was adjusted for baseline Lp(a) and non-Lp(a) apo B and stratified by baseline Lp(a) (&lt;125 nmol/L and ≥125 nmol/L). Results: Baseline levels of Lp(a) and non-Lp(a) apoB are shown in the Table . In the placebo group, both baseline Lp(a) and non-Lp(a) apo B independently predicted MACE. At M4 in the ALI group, median Lp(a) change from baseline was -40.9 and -7.0 in those with baseline levels ≥ or &lt;125 nmol/L, respectively. Corresponding median changes in non-Lp(a) apoB were -739 and -776 nmol/L (all P&lt;0.001). In the ALI group with baseline Lp(a)&gt;125 nmol/L, the decrease from baseline in Lp(a), but not the decrease in non-Lp(a) apo B, was significantly related to risk of MACE. Among those with baseline Lp(a)≤125 nmol/L, the decrease from baseline in non-Lp(a) apo B, but not in Lp(a), with ALI was significantly related to risk of MACE. Conclusions: On a per particle basis, baseline Lp(a) and non-Lp(a) apo B both predicted MACE. Among those with high baseline Lp(a), reduction in MACE with ALI was predominantly associated with reduction of Lp(a); among those with lower baseline Lp(a) reduction in MACE with ALI was predominantly associated with reduction in non-Lp(a) apo-B. Lp(a) may be an important target of treatment with ALI in those with elevated levels after ACS.
Abstract 4141485: Liver Steatosis in Women with Coronary Microvascular Dysfunction
Authors: Amelie Paquin, Alan Kwan, Sachini Ranasinghe, Michael Nelson, Jenna Maughan, Marie Lauzon, Martha Gulati, C Noel Bairey Merz, Janet Wei
Journal: Circulation (2024)

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) has been previously associated with coronary microvascular dysfunction (CMD) and is closely related to metabolic syndrome among men and women. Data regarding the association of quantitative liver steatosis and CMD in women with ischemia and no obstructive coronary arteries (INOCA) are scarce. Aim: To evaluate the association of liver steatosis with myocardial perfusion in women with CMD and reference controls. Methods: Women with CMD and no obstructive coronary arteries (n=55) from 2 prospective cohort studies (R01HL146158, R01HL153500) and asymptomatic age- and sex-matched reference controls (n=10) underwent stress and rest cardiac magnetic resonance imaging (MRI), with a validated MRI quantification of liver fat by proton density fat fraction (PDFF), at a single center. CMD was confirmed by coronary function testing or prior diagnostic stress tests. Parameters of liver fat and LV structure, function and myocardial perfusion reserve index (MPRI, a measure of CMD) were compared between cases and controls. A threshold of PDFF ≥5.2% was used to define significant liver steatosis. Results: Other than higher prevalence of hypertension in the CMD group, age and cardiometabolic history were not significantly different between the groups, as were the PDFF and prevalence of liver steatosis (Table). PDFF directly correlated with body mass index (r=0.41, p&lt;0.01). There was no correlation between PDFF and MPRI (Figure). Conclusions: In this pilot study, our results suggest similar prevalence of liver steatosis between women with CMD and reference controls. Interestingly, MPRI did not correlate with PDFF, suggesting that mechanisms other than metabolic health may play a significant role in the pathophysiology of CMD among women with INOCA.
Abstract 4141442: The Feasibility and Adherence of Online Intensive Cardiac Rehabilitation Program for Coronary Artery Disease-A pilot Study
Authors: Kazuhisa Kaneda, Neiko Ozasa, Koichi Washida, Yoko Umeda, Sawako Yoshiuchi, Saeko Imai, Toshiko Yoshida, Takeshi Kimura, Koh Ono
Journal: Circulation (2024)

Introduction/Background: Remote cardiac rehabilitation is becoming more popular, but most are exercise-based cardiac rehabilitation programs, and online intensive cardiac rehabilitation (ICR) programs that include not only exercise training but also dietary guidance, stress management, and group support have not been widespread. Research Questions/Hypothesis: Whether high adherence and improvement of CAD risk factors demonstrated for the online ICR program. Goals/Aims: We assessed the program adherence by participation rate as the primary endpoint and physical findings, typical CAD risks and nutritional indices as the secondary endpoint. Methods/Approach: The J-ICR program provides online instruction using Zoom (San Jose, CA: Zoom Video Communications Inc.). The program consisted of four parts: aerobic exercise training, dietary education for the Japan diet, stress management training through mindfulness, and group support (10 participants per group) for 3 hours per session, once a week for 12 weeks (36 hours total). Twenty-two patients were enrolled and adherence to the program was examined. Changes in CAD risk factors were also analyzed. Results/Data: After excluding 3 patients who withdrew consent before the program, the current study population consisted of 19 male participants. The mean age was 66 years old, 95% had hypertension, 37% had diabetes mellites and all had hyperlipidemia. Eight patients had myocardial infarction and 15 cases of angina pectoris. The average participation rate of the program was 90.2% and there was no drop out during the program. As the secondary endpoint, body weight （69.2kg vs. 68.2kg; p=0.02), systolic and diastolic blood pressure (126.8mmHg vs. 121.4mmHg; p&lt;0.01 and 79.5mmHg vs. 77.6mmHg; p=0.18), LDL cholesterol (78.9mg/dl vs 77.6mg/dl; p=0.68), HbA1c (6.3% vs. 6.4%; p=0.39), and amount of sodium intake (9.5 g/day vs. 9.5g/day; p=0.68) and total energy intake (2,137kcal/day vs. 2,076kcal/day; p=0.25). Conclusion: The J-ICR program is feasible and may yield improvements in CAD risk factors such as body weight and systolic blood pressure. Since this is a pilot study to explore the feasibility of the online J-ICR, its secondary prevention effect should be verified with appropriately powered randomized trials at multiple centers.
Abstract 4139194: Predicting Cholesterol Screening Behavior After Age 50 Using Machine Learning: Insights from the Health and Retirement Study
Authors: Wan-Chin Kuo, Jingyu Chen, Anthony McDonald, Jui-Hung Chang, Heather Johnson
Journal: Circulation (2024)

Background: In the U.S., about 8% of adults never received cholesterol screening. Although machine learning (ML) has been used to develop decision tools for Atherosclerotic Cardiovascular Disease (ASCVD) risk prediction, its application in behavioral forecasting has not yet been explored in the context of cholesterol screening behaviors. This study aimed to examine the performance and accuracy of ML algorithms in forecasting cholesterol screening behaviors in adults after age 50. Methods: This analysis used deidentified data from the Health and Retirement Study (HRS) 2004-2018. HRS is a longitudinal survey among 23,000 households in the U.S. Participants were excluded from the current analysis if they passed away by 2019, ever had ASCVD or stroke, were under age 50 at baseline, or had missing data in self-reported cholesterol screening. In total, 7176 participants (mean age [SD]=62 [8]) met the inclusion criteria; participants were randomly split into a training set (80%) and a testing set (20%). The synthetic minority oversampling technique was used to solve the imbalance distribution of the rare event. Five ML algorithms were used: random forest, gradient boosting machine (GBM), XGBoost, Support Vector Machine (SVM), and logistic regression. Accuracy, AUROC, and positive predictive value (PPV) were used to compare model performance. The average gain was evaluated for feature importance in the demographic and health domains. Results: In total, 232 (3.2%) respondents did not receive any cholesterol screening from 2008 to 2018. Experiments with five ML algorithms suggested that XGBoost with deeper trees and learning rate performed better in classifying those who did not screen for cholesterol levels over 10 years. Adding prior cholesterol screening history (2004-2006) into the model significantly improved model performance. Hypertension, self-rated health, and smoking were the major health features, while insurance, poverty, and work status were the major demographic features in the predictive model (accuracy=0.97; AUROC=0.88; PPV=0.42). Conclusion: Findings underscore the potential utility of ML models in predicting cholesterol screening behaviors after age 50. This could be the basis for developing decision tools for clinicians to identify those with a lower chance of cholesterol screening or make reminders accordingly. The low-cost predictive model might improve the uptake of preventive screening behaviors in middle-aged and older adults.
Abstract 4147627: A Pharmacovigilance Study of Bempedoic Acid: Balancing Risks and Benefits
Authors: Sulochana Khadka, Bibek Timilsina, Pallavi Matai, Seema Sharma, Kripa Rajak, Gabriela Calderon Barahona, Seema Oli
Journal: Circulation (2024)

Introduction: Bempedoic acid has been approved by FDA since Feb 2020 as an adjunct to maximally tolerated statin therapy for the reduction of LDL-C, specifically in individuals afflicted by atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH). Bempedoic acid is also a viable alternative for patients intolerant to statins. Most recently, it has been approved to use for primary prevention of hyperlipidemia, alone or in combination with a statin. It is important to study its side effect profile as it is anticipated to be used more frequentlynin the future. Methods: We explored reported adverse events (AEs) of bempedoic acid using FDA Adverse Event Reporting System (FAERS). A total of 1202 adverse effects were reported until March 31, 2024. 69.97% AEs were reported by healthcare professionals (HCPs), which were further analyzed. AEs were analyzed in men (32.53%) vs women (53.24%) and in three age groups of 18-64, 65-85, and &gt;85 years. Results: A total of 586 (48.7%) events were serious adverse effects. Most common side effects were myalgia which included muscle pain, extremity pain and muscle spasm (25.04%), arthralgia including back pain and bone pain (18.47%), nausea (6.6%), headache(5.5%), gout (4.4%). Among the patients with adverse effects, 4.75% had cardiac side effects which included atrial fibrillation (12%), palpitation (29%), angina pectoris (18%), Myocardial Infarction (5%). Discussion: A thorough understanding of bempedoic acid's complex pharmacology empowers healthcare professionals to tailor treatment plans based on individual patient requirements. This enables informed decision-making in prescribing, optimizing dosage regimens, and mitigating potential adverse reactions. Most studies have been relatively short term in order to confirm the long term side effect profile. It would be beneficial to be cautious in using this medication for patients with above mentioned clinical conditions like myalgia, arthralgia, gout, rhabdomyolysis, atrial fibrillation, angina pectoris. Conclusion: Long term pharmacovigilance is needed to assess the safety profile of bempedoic acid over extended use. With the current increasing use of bempedoic acid, there is a need for more data on safety profiles. In future, further randomized trials are required to better assess the safety profile.
Abstract 4135636: Age- and Sex-Related Coronary Atherosclerosis by Artificial Intelligence Quantitative Coronary CT Angiography from the INVICTUS Registry
Authors: Hitoshi Matsuo, Yoshihiro Sobue, Umihiko Kaneko, Hideyuki Sato, Shinichiro Fujimoto, Yui Nozaki, Takashi Kajiya, Toru Miyoshi, Keishi Ichikawa, Mitsunori Abe, Toshiro Kitagawa, Hiroki Ikenaga, Kazuhiro Osawa, Mike Saji, Nobuo Iguchi, Gaku Nakazawa, Kuniaki Takahashi, Takeshi Ijichi, Hiroshi Mikamo, Akira Kurata, Masao Moroi, raisuke iijima, Tami Crabtree, James Min, James Earls, Rine Nakanishi
Journal: Circulation (2024)

Background: Coronary plaque analysis using artificial intelligence quantitative coronary CT (AI-QCT) is a promising tool to identify coronary atherosclerosis. However, there is insufficient data on coronary atherosclerosis volume and morphology using AI-QCT in patients who are at high risk of atherosclerosis. The purpose of this study is to clarify the differences in the volume and phenotypes of coronary atherosclerosis by age and gender using AI-QCT. Methods: The INVICTUS Registry is a multi-center registry enrolling patients who clinically underwent coronary CT angiography and invasive coronary angiography with invasive imaging modalities in Japan. Patients with a history of percutaneous coronary intervention or coronary artery bypass graft were excluded in this study. Using AI-QCT, the volume, and phenotypes (calcified, non-calcified, low-density non-calcified plaque [LD-NCP]) of coronary atherosclerosis were analyzed and assessed by age (&lt;55, 55-64, 65-74, and 75 and older) and gender. Results: A total of 982 patients were enrolled in the study. The mean age was 70.3 ± 10.8 years, 71.9% were male. Approximately two-thirds of patients had hypertension (73.3%) and dyslipidemia (71.5%), and 36.7% had diabetes. Mean total plaque volume (PV), calcified PV, non-calcified PV, and low-density PV were 745.5±529.8 mm 3 , 248.3±302.0 mm 3 , 482.2±340.6 mm 3 , and 15.0±29.4 mm 3 , respectively. The results of plaque volume and phenotypes by age are shown in the figure. Compared to those under 55 years of age, total PV increased gradually and significantly by about 10% for every 10 years of age (p=0.022). Though no significant difference was observed in non-calcified PV between the age groups (p=0.379), calcified PV progressively and significantly increases approximately 70% for every 10 years of age (p&lt;0.001). In contrast, the low-density plaque volume showed a trend toward a significant decrease with increasing age (p=0.073). These trends did not differ by gender. Conclusion: In a large cohort of patients at high risk for atherosclerosis analyzed by AI-QCT, total coronary PV increased with age, primarily calcified PV. While no change in non-calcified PV between the age groups, LD-NCPV was likely to decrease with increasing age. These findings may contribute to the guidance for the prevention of coronary artery diseases based on coronary atherosclerosis phenotype by age and gender.
Abstract 4140117: A novel risk score predicts the prevalence of left atrial low-voltage areas and rhythm outcome in patients undergoing long-standing persistent atrial fibrillation ablation
Authors: Hirotaka Ooka, Yasuhiro Matsuda, Masaharu Masuda, Shin Okamoto, Takayuki Ishihara, Kiyonori Nanto, Takuya Tsujimura, Yosuke Hata, Hiroyuki Uematsu, SHO NAKAO, Masaya Kusuda, Wataru Ariyasu, Satoshi Kudo, Subaru Fujii, Toshiaki Mano
Journal: Circulation (2024)

Background: Catheter ablation is a most common treatment for atrial fibrillation (AF), but rhythm outcome after AF ablation in long-standing persistent atrial fibrillation (LS-PerAF) is still poor. Left atrial low-voltage areas (LVAs) is associated with poor rhythm outcome after catheter ablation. However, the predictors of LVAs presence have not been fully elucidated in patients with LS-PerAF. Purpose: The purpose of this study was to establish a novel predictive score for the prevalence of LVAs in patients with LS-PerAF ablation. Methods: In total, 109 consecutive patients who underwent initial ablation for LS-PerAF were included. LS-PerAF was defined as AF whose duration was more than 1 year. LVA was defined as areas with bipolar peak-to-peak voltage of &lt; 0.50mV. A clinical risk score was obtained as the total number of independent predictors analyzed by multivariate logistic regression analysis. AF recurrence after the catheter ablation was followed for 24 months. Results: Of 109 patients with LS-PerAF, LVAs existed in 26 (24%) patients. A novel predictive score, named DESK score, consisted of diabetes mellitus (odds ratio [OR] 3.7, [95% confidence interval {CI} 2.2–11], p = 0.02), age ≥ 70 years (OR 3.8, [95% CI 1.4-10], p = 0.007), female sex (3.0 [95% CI 1.04-8.4], p = 0.04), AF duration ≥ 3.7 years (44 months) (OR 3.7, [95% CI 1.3-11], p =0.02). LVAs were more frequently found in patients with a higher DESK score (OR, 3.5 [95% CI, 1.9–6.5], p &lt; 0.001) (Figure 1A). On receiver operating characteristic curve analysis, DESK score was a moderate predictor of LVAs presence (area under the curve, 0.750; Figure 1B). The optimal cut-off of DESK score was 3 points, corresponding to a 38.5% sensitivity, 97.6% specificity, and 83.5% predictive accuracy. Freedom from AF recurrence was significantly lower in patients with DESK score ≥ 3 than in those with DESK score &lt; 3 (10.4% vs. 43.5%, p = 0.008). Conclusions: In patients who underwent LS-PerAF ablation, the DESK score correlated with the prevalence of LVAs, and associated with poor rhythm outcome.