tbuckley/cabot-search huggingface dataset:
Abstract 4136743: Current Oral Anticoagulation Use Among Patients With Atrial Fibrillation and Risk Factors Associated With Inadequate Treatments: A Report From a UK Population Cohort Study
Authors: Amiee Kang, Ellen O'Brien, Jenny Jiang, Alyshah Abdul Sultan, Merena Henderson, Vishnu Mandala, Gregory Lip
Journal: Circulation (2024)

Background: The worldwide prevalence of atrial fibrillation (AF) continues to grow with approximately 60 million cases each year. Aim: To understand demographic and clinical attributes of patients receiving adequate DOAC (direct oral anticoagulant) treatment, DOAC undertreatments, or no OAC (oral anticoagulant) treatments, thus providing valuable perspectives into the current landscape of stroke prevention in AF within the UK. Methods: We used the Clinical Practice Research Datalink (CPRD) Aurum database from January 2020 to March 2021 for this retrospective observational study. Patients’ characteristics from various cohorts (standard dose [SD], low dose [LD] per label, LD inconsistent per label prescribing, and untreated) were evaluated based on OAC treatment. Duration of index OAC treatment, time to discontinuation and incidence rates across OAC treated cohorts were assessed. A machine learning method (Elastic Net) identified factors associated with being undertreated or untreated. Results: The final sample included 13,341 patients (mean age 78.5 and female 47%). Within a 180-day timeframe post-diagnosis, 76% of patients received OAC treatment, while 24% did not receive any OAC therapy. Among those treated with DOAC (n=9947), 74% were administered SD (n=7238), 18% received LD per labels (n=1756) and 10% were inappropriately prescribed LD of DOACs (n=953). Both LD cohorts tended to have shorter duration of OAC therapy (figure) and higher discontinuation rates (per 100 person-years; LD per label: 42.97; LD not per label: 39.11) compared to the SD cohort (SD: 31.67). Patients who were untreated were associated with elevated bleeding risk factors such as renal disease and prior bleeding history; patients who received inappropriate LD were associated with age above 75, renal disease, GI conditions with PPI (proton pump inhibitor) concomitant treatments when compared to SD cohort. Conclusions: In our study, a considerable proportion of AF patients remained untreated/undertreated and were associated with bleeding risk factors, highlighting the unmet needs within this population. Exploring potential alternative treatment options with enhanced safety profiles could offer substantial benefits to patients in need.
Abstract 4136678: Detecting Myosteatosis-Related Low Physical Function in Heart Failure Patients Using Abdominal Computed Tomography and Plasma Amino Acid Profile
Authors: Wataru Kawaharata, Hidemichi Kouzu, Keishi Ogura, Toshiyuki Yano, Satoshi Katano, Ryohei Nagaoka, Ryo Numazawa, Kotaro Yamano, Katsuhiko Ohori, Ryo Nishikawa, Takefumi Fujito, Nagano Nobutaka, Masato Furuhashi
Journal: Circulation (2024)

Background: Evaluation of sarcopenia requires quantifying appendicular skeletal muscle mass and functional capacity, but resource constraints often limit feasibility. Alterations in muscle quality, especially intramuscular lipid infiltration (i.e., myosteatosis), and systemic metabolic derangements are associated with disability. Hypothesis: Opportunistic CT imaging and plasma amino acid profiling could identify low physical function in patients with heart failure (HF). Methods: We retrospectively examined 220 HF patients (74 ± 13 years old; 59% male) who underwent plasma amino acid profiling, abdominal CT imaging, and dual-energy X-ray absorptiometry (DXA) scan within two months. Myosteatosis was evaluated using single-slice CT imaging at the L3/4 level and quantified as mean muscle attenuation (MMA). Physical function was assessed by the short physical performance battery (SPPB), with low physical function defined as SPPB ≤9. Results: CT-derived single-slice areas of skeletal muscle and adipose tissue were highly correlated with DXA-derived appendicular skeletal muscle mass and total fat mass. Logistic regression analyses revealed that higher age and lower MMA, but not skeletal muscle area, were significantly associated with low physical function independently of NT-proBNP. Subjects with MMA below the median value (32.0 HU for males and 23.7 HU for females) had higher odds of low physical function (adjusted OR 2.04, 95% CI 1.04-3.96). Ten amino acids and the Fischer ratio were significantly correlated with MMA levels. Multivariate regression analyses, adjusted for potential confounders including age, gender, and body mass index, demonstrated that serum albumin and Fischer ratio were independent determinants of MMA levels. When serum albumin and Fischer ratio were dichotomized by their median values (3.6 mg/dL and 3.23, respectively), the prevalence of low physical function was significantly higher in subjects with low albumin and low Fischer ratio, but not in those with low levels of only either parameter, compared to those with high albumin and high Fischer ratio (adjusted OR 2.36, 95% CI 1.02-5.49). Conclusions: Myosteatosis assessed by single-slice abdominal CT imaging is an independent determinant of low physical function in HF patients. Combined with an assessment of serum albumin and Fischer ratio, these simple biomarkers could facilitate the early detection of patients at risk for developing frailty.
Abstract 4136727: The role of immune mechanism in Immune Checkpoint Inhibitor-Associated Myocarditis: seeking key genes
Authors: Junyi Zhang, Shenglin Qu, Yafeng Zhou
Journal: Circulation (2024)

Background: Immune checkpoint inhibitors (ICIs) are extensively employed in cancer treatment; however, the development of ICI-associated myocarditis (ICI-MC) introduces a severe and potentially fatal complication with elusive pathophysiological mechanisms. This study aimed to pinpoint pivotal immune-related genes in ICI-MC and unveil potential therapeutic targets using bioinformatics. Methods: Utilizing the GSE180045 dataset (comprising three groups: Group A - ICI patients without immune adverse events, Group B - ICI patients with non-myocarditis immune adverse events, Group C - ICI patients with myocarditis), we scrutinized differentially expressed genes (DEGs) between ICI-MC samples (Group C) and non-myocarditis controls (Group A&amp;B). These DEGs were cross-referenced with 1796 immune-related genes (IRGs) from the immPort database to derive IR-DEGs. We conducted functional enrichment analyses (GO, KEGG, GSEA), constructed a PPI network, and identified hub genes. Validation was performed using the GSE4172 dataset, and optimal feature genes (OFGs) were identified from the overlap of hub genes and validation DEGs. Predictions of target miRNAs were made, and a ceRNA network was constructed. Target drugs for hub genes were forecasted using the cMAP database. Results: We pinpointed 58 DEGs between ICI-MC and controls, leading to the identification of 32 IR-DEGs after intersecting with 1796 IRGs. Functional analyses revealed enrichment in cell lysis, CD8+ T cell receptor, natural killer cell-mediated cytotoxicity, and RAGE signaling. Up-regulated hub genes (IL7R, PRF1, GNLY, CD3G, NKG7, GZMH, GZMB, KLRB1, KLRK1, CD247) were highlighted. In the validation dataset, 407 DEGs were uncovered, resulting in the identification of 3 OFGs (KLRB1, NKG7, GZMH). Predicted target miRNAs, lincRNAs, and circRNAs formed a comprehensive ceRNA network. The top 10 drugs with elevated connectivity scores included acetohydroxamic-acid, suggesting caution in ICI treatment. Conclusion: NKG7, GZMH, and KLRB1 emerged as pivotal immune-related genes in ICI-MC. Biological enrichments encompassed cell lysis, CD8+ T cell receptor pathway, natural killer cell-mediated cytotoxicity, RAGE signaling, and proinflammatory pathways. The ceRNA network shed light on critical molecules, emphasizing the need to avoid drugs like acetohydroxamic-acid in ICI treatment.
Abstract 4135780: Predictors of Engagement in a Coaching Intervention for Heart Failure Caregivers
Authors: Sue Hyon Kim, Karen Hirschman, Quinn Ryan, Barbara Riegel
Journal: Circulation (2024)

Background: Even the best intervention will not be effective without engagement in the experience. We developed and tested a virtual health coaching intervention ("ViCCY”, Virtual Caregiver Coach for You) for informal caregivers of patients with HF in a RCT. Of the 125 caregivers in the intervention group, completion rates varied (mean 6 ± 4 sessions, median 9; 21% no sessions). The aim of this study was to identify factors associated with intervention engagement defined as receipt of ≥8 of 10 intervention sessions over a 6-month period based on core intervention content. Methods: This explanatory sequential mixed methods study was conducted in two phases. First quantitative data were analyzed with respect to number of completed sessions, sociodemographics, and the Credibility-Expectancy Questionnaire measuring expectations regarding intervention effectiveness. We used multivariable logistic regression to quantitatively identify salient predictors of caregivers’ intervention engagement. Then, based on the number of sessions completed, 24 caregivers assigned to ViCCY were interviewed to explore individual, family, community, and societal factors associated with intervention engagement. Transcribed interviews were coded using content analysis. Results: Each one hour increase in hours caregiving was associated with reduced odds of completing ≥8 sessions. Race other than White and income insufficient to make ends meet were associated with reduced odds of completing ≥8 sessions. Each unit increase in intervention credibility was associated with increased odds of completing ≥8 sessions. Interviews with participants who completed some sessions revealed common challenges such as the patient’s HF progression and life events including caregiver health issues, balancing multiple responsibilities, and interpersonal issues. Reluctance to accept help from an unfamiliar individual through a virtual network and perceiving additional resources as burdensome also hindered participation. Practical issues such as finding a suitable space for virtual meetings and scheduling conflicts interfered. In those who did not complete any sessions, the main reason for non-engagement was misunderstanding of what to expect in the intervention. Conclusions: The daily lives of HF caregivers are influenced by caregiving demands exacerbated by social determinants of health. These issues may reduce the capacity of caregivers to accept help and ultimately act as a barrier to program engagement.
Abstract 4136584: The Association of De Novo Niacin Use with Long-Term Mortality
Authors: Rina Takahashi, Thuy-Anh Bui, ibrahim Elali, Diana Tran, KEIICHI SUMIDA, Fridtjof Thomas, Ramanath Dukkipati, anjja shah, Connie Rhee, Csaba Kovesdy, Kamyar Kalantar-Zadeh
Journal: Circulation (2024)

Introduction: Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for cardiovascular diseases. However, previous studies have reported inconsistent effects of niacin on mortality, and its effect on long-term prognosis has not been well studied. Goals: The aim of this study is to examine the association of niacin therapy with long-term all-cause mortality. Methods: In a nationwide historical cohort of 1,139,630 US Veterans with normal baseline kidney function, we examined the association of de novo niacin prescription from 2004 to 2006 with all-cause mortality during a 14-year follow-up. Associations were examined in Cox proportional hazard models adjusted for demographics, major comorbidities, and laboratory measurements. Prescription time-distribution matching was used to control for survival bias. Results: We identified 133,450 new users of niacin. Overall, patients had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% White, 16% Black, and 6% Hispanic. Niacin users were more likely to be male, White, current, or former smokers and had higher frequencies of comorbidities. Niacin use (vs. non-use) was associated with a lower risk of death (Hazard ratio: 0.89, 95% confidential interval: 0.88-0.90) in the fully adjusted model (Model 4, Figure). Conclusion: In a large national cohort of US Veterans, niacin use was associated with a lower risk of death. Further studies are needed to corroborate the potential benefits of niacin on survival.
Abstract 4136754: Psychoactive medication use in pediatric heart transplant recipients: An assessment of prevalence, risk factors, and outcomes
Authors: Jenna Schauer, Othman Aljohani, Ryan Cantor, Anna Fraser, Firezer Haregu, Kyle Hope, James Kirklin, Consuela Thompson, Simon Urschel, Nadia Zaim, Hong Zhao, Micah Brosbe
Journal: Circulation (2024)

Background: There is increasing recognition of the mental health burden experienced by pediatric heart transplant (HTx) recipients. Mental health concerns can impact physical health and increase risk of poor health outcomes. Using the Pediatric Heart Transplant Society (PHTS) database, we assessed the use of psychoactive medications as a proxy for mental health issues. We assessed the prevalence of psychoactive medication usage, pre- and post HTx factors, and post HTx outcomes associated with psychoactive medication usage. Methods: We queried the PHTS database for patients &gt;5 years of age at time of follow-up who underwent HTx between January 2015 and June 2023. Patients with use of any psychoactive medication were identified. Sub-analyses were performed for use of antianxiety/antidepressant and attention-deficit/hyperactivity disorder (ADHD) medications. Multivariate logistic regression models were utilized to assess risk factors and impact on outcomes, including graft survival, coronary artery vasculopathy (CAV), and rejection at 1, 3, and 5 years post-HTx. Results: Among 1792 patients older than 5 at 1 year post HTx, 301 (16.8%) were prescribed at least one psychoactive medication; 246 (13.7%) were prescribed medication for antianxiety/antidepressant medications and 59 (3.3%) for ADHD. Utilization of psychoactive medication decreased at 3 years (14.8%, N= 240 of 1629) and 5 years post HTx (11.3%, N=230 of 2029). Patients on psychoactive medications at 1 year post HTx tended to be older (OR=2.1, p&lt;0.001), had higher priority listing status (OR=2.3, p&lt;0.05), and longer bypass time (OR=1.6, p&lt;0.05). Black patients were less likely to be prescribed psychoactive medication at 3-years post HTx than white patients (OR=0.57, p&lt;0.05) or other races (OR=0.43, P &lt;0.001). There was no association of psychoactive medication usage on graft survival, CAV, or rejection at 1 year post HTx. At 3 years post HTx psychoactive medication usage was associated with significantly higher prevalence of CAV (p&lt;0.05). At 5 years post HTx graft loss (p&lt;0.005) and CAV (p&lt;0.05) were significantly increased in patients on psychoactive medications. Conclusions: A significant proportion of pediatric HTx patients take psychoactive medications. This population may be at risk for worse long-term outcomes. There is a need to assess the mental health burden of pediatric HTx and to identify modifiable factors to improve assessment and treatment of mental health issues and its impact on outcomes.
Abstract 4135951: Single Nuclei RNA Sequencing Reveals Distinct Cellular Composition of Pericoronary Adipose Tissue
Authors: Jessica Regan, Lydia Kwee, Caroline de Calvacamp, Kristin Corey, Krish Dewan, Ryan Gross, Vaibhav Jain, Simon Gregory, Dawn Bowles, Svati Shah
Journal: Circulation (2024)

Introduction: Adipose tissue is a metabolically active organ with local paracrine interactions on adjacent tissues. Pericoronary adipose tissue (PcAT) is an emerging cardiovascular disease (CVD) risk factor and likely has paracrine effects on coronary vasculature that may promote coronary artery disease (CAD) development. PcAT may be functionally and clinically distinct from epicardial adipose tissue (EAT) given its proximity to the coronary artery adventitia. The cellular composition of PcAT and EAT and whether they have unique inflammatory cell signatures and functional expression at a single cell level has not been explored. Hypothesis: PcAT will have diverse cellular composition with heightened inflammatory cell content compared to EAT. Methods: Visual dissection of paired EAT not adjacent to an epicardial coronary artery and PcAT in direct apposition to an epicardial artery (left anterior descending artery) was performed from a single human heart immediately after explant (prior to heart transplantation). Nuclei were isolated using the Chromium Nuclei Isolation Kit (10x Genomics) with RNAse inhibitor. Cells were counted with a Cellometer K2 and Chromium Next GEM Single Cell libraries were prepared, followed by reverse transcription, PCR and NovaSeq 6000 platform sequencing. Raw sequence reads from single nuclei RNA-seq (snRNA-seq) were processed and after QC filtering, cells were clustered using Seurat. Clusters were annotated using singleR. Results: In PcAT and EAT, &gt;7000 cells were successfully extracted with 73755 and 48750 mean snRNA-seq reads per cell, respectively. snRNA-seq cellular composition analysis delineated a heightened inflammatory milieu and distinct cellular composition of human PcAT vs. EAT. A UMAP (Uniform Manifold Approximation and Projection) plot displays higher inflammatory cell infiltrate with a neutrophil predominance and lesser adipocyte composition in PcAT compared with EAT ( Figure 1) . Conclusions: We have generated snRNA-seq data from human PcAT and shown distinct cellular composition compared to EAT. Given the proximity of PcAT to coronary vasculature, these results are supportive of paracrine inflammatory effects and highlight adipose tissue biology in cardiovascular disease. Understanding this biology may identify novel therapeutic targets for CVD.
Abstract 4135993: Body Composition and Mortality Throughout the Reproductive Cycle: Findings from the Multi-Ethnic Study of Atherosclerosis
Authors: Icy Liang, Spencer Flynn, KAROL WATSON, Preethi Srikanthan, Tamara Horwich
Journal: Circulation (2024)

Introduction: Changes in body composition throughout the reproductive cycle accelerate during the 2 years following the final menstrual period (FMP), known as the menopausal transition (MT). During MT, an increase in fat mass (FM) and a decrease in fat free mass (FFM) are usually seen, but the relationship between these changes and cardiovascular events is not well understood. We aim to explore how FM and FFM are associated with cardiovascular events and total mortality across the reproductive cycle in participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: This study included 3439 women from exam 1 of MESA. Outcomes of interest were either MACE (heart failure, myocardial infarction, coronary revascularization, cardiac arrest, or stroke) or all-cause mortality. Equations to determine FM and FFM at exam 1 were validated with the NHANES 2003 population and derived from regression models based on bioelectrical impedance analysis results at exam 5 and anthropometric and demographic measures. Women were divided into 3 groups based on time since FMP: reproductive phase (before FMP), MT phase (&lt;2 years after FMP), and late menopause phase (&gt;2 years after FMP). Adjusted Cox multivariate models assessed the association between FM, FFM and MACE or all-cause mortality. Results: Median follow-up time was 14.1 years. FM was associated with MACE in the late menopause group, whereas FFM was not associated with MACE (Table). With respect to all-cause mortality, FM had a positive association (HR=1.19, P=0.03) while FFM had a negative association (HR=0.68, P=0.04) in the MT phase. The late menopause group showed similar relationships between FM, FFM, and all-cause mortality. The reproductive group showed no significant associations (Table). Conclusion: In this cohort, FM is associated with a higher risk of mortality whereas FFM is associated with a lower risk. We observed these associations to be more pronounced during the MT, a time of accelerated body composition change. Our results suggest and will need further investigation to confirm that the MT may be a critical time in the female lifespan to initiate interventions which positively impact muscle mass with a view to improving survival.
Abstract 4136203: Risk of Mortality and Heart Failure with Myosin Inhibition Among Hypertrophic Cardiomyopathy Patients
Authors: Nirav Patel, Naman Shetty, Mokshad Gaonkar, Girija Divekar, Nehal Vekariya, Li Peng, Garima Arora, Pankaj Arora
Journal: Circulation (2024)

Background: While prior studies have established that mavacamten therapy in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) leads to significant clinical and functional improvement, long-term data on the effect of mavacamten on mortality and heart failure with reduced ejection fraction (HFrEF) in these patients is lacking. Methods: In this retrospective cohort study utilizing electronic health record data from the TriNetX Network, we aimed to assess the association of mavacamten therapy with mortality and HFrEF compared to medical management among patients with oHCM between 04/2022 and 04/2024. The hazard ratio (HR) and 95% confidence interval (CI) for the study outcomes were estimated by comparing propensity-score matched groups. Results: Among 47,601 adults (45.4% females; mean age: 63.5±16.6 years), 701 and 46,900 patients were included in the mavacamten and medical management groups, respectively. ( Table ) In the propensity-matched analysis, mavacamten was associated with a lower risk of mortality (HR=0.40;95%CI:0.21-0.73,p=0.002), but a similar risk of incident HFrEF (HR=1.03;95%CI:0.56-1.88,p=0.93) compared with medical management. ( Figure ) Conclusions: The current study is among the first to report improved survival with mavacamten therapy among patients with oHCM utilizing real-world data. The similar risk of HFrEF between the mavacamten and medical management cohorts highlighted in this study indicates the efficacy of the Risk Evaluation and Mitigation Strategy (REMS) program in maintaining patient safety and offsetting any potential excess risk of HFrEF.