tbuckley/cabot-search huggingface dataset:
Abstract 4143306: Circulating Factors in Single-Ventricle Congenital Heart Disease Promote Pathological Metabolic Remodeling in Cardiac Myocytes, Which is Abrogated with Phosphodiesterase-5 Inhibitor Therapy
Authors: Ashley Pietra, Mary Turner, Genevieve Sparagna, Brian Stauffer, Carmen Sucharov, Shelley Miyamoto, Anastacia Garcia
Journal: Circulation (2024)

Introduction: While operative and perioperative care continues to improve for single ventricle heart disease (SVHF), the 10-year survival in this population is only 39-50%. Phosphodiesterase-5 inhibitors (PDE5i) are increasingly used in this population, however there are currently no proven medical therapies for SVHF. Our group has previously demonstrated that SVHF myocardium is characterized by increased PDE5 activity and impaired mitochondrial bioenergetics, however little is known regarding myocardial effects of PDE5i therapy. We hypothesize SVHF serum circulating factors are distinct from healthy controls and contribute to cardiomyocyte metabolic dysfunction, thereby promoting heart failure progression. Additionally, we hypothesize that PDE5i abrogates these pathologic metabolic alterations. Methods: Mass spectrometry-based proteomics and metabolomics were performed on healthy control and SVHF patient sera. Using an established novel in vitro model, primary cardiomyocytes (neonatal rat ventricular myocytes, NRVMs) were treated with serum +/- 1.5µM PDE5i for 72 hours. In NRVMs, the Seahorse Bioanalyzer was used to assess mitochondrial bioenergetics and mass-spectrometry was used to assess lipid and metabolite profiles. Results: Unbiased proteomic and metabolomic analysis suggests the serum circulating peptide and metabolite milieu in SVHF is significantly altered, including significant dysregulation of pathways involved in mitochondrial metabolism, glycolysis, amino acid metabolism, oxidative stress, and inflammation (Panel 1). Additionally, SVHF serum circulating factors pathologically remodel cardiomyocytes, including decreased cardiolipin and phosphatidylglycerol lipid species, and shifted metabolite profiles suggesting altered glycolysis, CoA biosynthesis, oxidative phosphorylation, and fatty-acid beta-oxidation (Panel 2). Importantly, PDE5i treatment abrogates the SVHF serum-induced changes in phosphatidylglycerol, and in various metabolites, including in glucose-6-phosphate, pyruvate, and L-carnitine (Panel 3). Conclusions: Together, these data suggest PDE5i therapy has direct myocardial effects, and likely contributes to beneficial cardiomyocyte metabolic remodeling in SVHF.
Abstract 4143206: Gender Disparities in Heart Transplant Outcomes for Heart Failure Patients: Insights from the National Inpatient Sample Dataset
Authors: Chinenye Odo, Oluwaremilekun Tolu-Akinnawo, Toluwalase Awoyemi, Kayode Ogunniyi, Anderson Anuforo, Rocio Barriga Guzman
Journal: Circulation (2024)

Background: Heart failure is a leading cause of morbidity and mortality globally, and heart transplantation remains a definitive treatment for end-stage heart failure. Previous studies have suggested potential gender disparities in access to and outcomes of heart transplantation, but comprehensive analyses using large datasets are limited. Objective: This study aims to investigate gender disparities in heart transplant outcomes among heart failure patients using the National Inpatient Sample (NIS) dataset. Methods: Using the National Inpatient Sample NIS dataset (2017-2020), we analyzed data from 11,025 heart failure patients who underwent heart transplantation, with 7,920 males and 3,105 females. Demographic characteristics, comorbidities, and clinical outcomes were compared between genders. Multivariate analyses were conducted to adjust for potential confounders. Results: In this study, females undergoing heart transplant were significantly younger than males (51.6 ± 29.8 vs. 55.0 ± 26.4 years, p &lt; 0.001). Males exhibited higher incidences of comorbid conditions including hypertension (80.7% vs. 69.7%), diabetes (37.3% vs. 24.8%), and ischemic heart disease (43.4% vs. 26.3%) (all p &lt; 0.001). Both genders had comparable odds of in-hospital mortality (OR 0.98, 95% CI 0.80-1.19, p = 0.842) and mechanical ventilation requirements (OR 1.04, 95% CI 0.93-1.17, p = 0.509). Additionally, the length of hospital stay (difference -2.09 days, 95% CI -3.81 to -0.37, p = 0.223) and hospital charges (difference $31,645, 95% CI -$15,309 to $78,599, p = 0.044) were similar between genders. However, females had significantly higher odds of post-transplant complications such as vasopressor requirements (OR 1.14, 95% CI 1.03-1.26, p = 0.014), stroke (OR 1.22, 95% CI 1.01-1.47, p = 0.044), and vascular complications (OR 1.35, 95% CI 1.17-1.57, p &lt; 0.001). Conclusion: These findings suggest that while age and pre-existing conditions vary by gender, in-hospital outcomes are largely similar, though females may face higher risks of specific post-transplant complications.
Abstract 4143372: Outcomes following the development and implementation of a multi-component, multidisciplinary cardiogenic shock program
Authors: Morgan Hill, Anthony Carnicelli, Jeffrey Yourshaw, Brian Houston, Lucas Witer, Jeffrey McMurray, Kaylen Dodson, Lindsey Bull, Jennifer Hajj, Mary Summer, Arman Kilic
Journal: Circulation (2024)

Background: Cardiogenic shock is associated with significant morbidity and mortality, necessitating a multidisciplinary approach to achieve optimal outcomes. Aims: This study evaluated the impact of a multi-component, multidisciplinary cardiogenic shock program on clinical outcomes. Methods: In 2021, we initiated a cardiogenic shock program incorporating several key components: monthly meetings within the entirety of the heart and vascular service line for patient review and dissemination of protocols and initiatives; formation of a core leadership group comprising representatives from cardiac surgery, heart failure, interventional cardiology, cardiac intensivists, and shock nursing coordinators; implementation of a shock paging system for real-time multidisciplinary discussions; appointment of two nursing coordinators for protocol development, education, and data tracking; development of a temporary MCS quality scorecard; and establishment of a program to transition Impella patients to a stepdown unit for bed optimization. Patient outcomes were compared between the inaugural year and the subsequent year of the shock program. Results: 143 patients in cardiogenic shock were activated through our shock paging system during the study period. Patient age averaged 54.5 years. 51.1% of patients were located at our institution and 48.9% were located at an outside hospital upon shock call initiation. The most common etiology for shock was decompensated HF (33.6%), followed by acute MI (25.2%), arrhythmia (14%), and other (27.3%). The majority of patients presented with a SCAI shock stage of C (41.3%), followed by D (25.9%) and E (20.3%). 78.3% of patients received an MCS device as a result of the shock call, with 33.6% receiving an Impella CP, 16.8% receiving an Impella 5.5, 29.4% receiving an IABP, and 27.3% requiring VA ECMO. Prior to the shock team initiation, historical hospital survival rates in cardiogenic shock patients approached 30% at our institution. After initiation of the shock program, survival to hospital discharge improved to 67.8% and 1-year survival was 53.2%. 30-day survival improved in the second year of the program compared to the inaugural year (70.1% vs. 53.6%, p=0.0447). Conclusion: Implementation of a multi-component multidisciplinary shock program facilitates a systematic approach to cardiogenic shock and is associated with improved hospital culture and collaboration and excellent outcomes in a challenging patient subset.
Abstract 4143332: Cross-Platform Variations in Transthoracic Echocardiography: Implications for Clinical Decision-Making
Authors: Mohammad Hashemi, Yasaman Farsiani, Gregg Pressman, MohammadReza Amini, Arash Kheradvar
Journal: Circulation (2024)

Background: Precise measurement of cardiac chamber size and function is crucial for clinical decision making, and these measurements should be consistent across different echocardiography systems. Despite the assumption that modern echocardiography machines have negligible cross-platform variations, few studies have rigorously compared them. This study evaluates the cross-platform variations between Philips EPIQ CVx (release 9.0.3) and Canon Aplio i900 (release 7.0) in assessing cardiac volumes, ventricular function, and valve structures. Hypothesis: Data acquired across various echocardiography platforms exhibit statistical equivalence. Aims: To study cross-platform variations in transthoracic echocardiography and their implications for clinical decision-making Methods: In this gender-balanced prospective study, 40 volunteers aged 40 and older were scanned sequentially by both systems. Each subject was scanned by the same sonographer using identical settings for both 2D and 4D acquisitions. Ventricular volumes were compared using Simpson’s biplane method. Data were analyzed by two board-certified cardiologists with respect to diagnostics. Results: Left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) showed no significant differences (p&gt;0.05) between platforms across both 2D and 4D methods. However, left ventricular end-diastolic volume (LVEDV) significantly differed (p&lt;0.03) between platforms. Right ventricular volumes and ejection fraction (RVESV, RVEDV, RVEF) from 4D imaging were consistent across platforms (p&gt;0.05), but 2D versus 4D volume measurements showed significant differences (p&lt;0.01) within each platform. Notable differences between platforms were observed in LV Systolic Dyssynchrony Index (p=0.03), LV Longitudinal Strain (p=0.04), LV Twist (p=0.004), and LV Torsion (p=0.005). cardiologists' assessments of aortic and mitral valve’s structure varied between platforms, with a notable increase in frequency of reported valvular abnormalities when using the Philips platform (Fig.1). Conclusions: While LV and RV volumetric measurements are largely consistent across platforms, LV strain metrics show significant variation. Differences in valve structure assessment between platforms suggest that interpretation may vary depending on the echocardiography system used. The study results suggest that patients should undergo follow-up examinations using the same echocardiography platform to ensure diagnostic consistency.
Abstract 4143321: Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction
Authors: Haoyu Sun, Florencia Schlamp, Sarah Liberow, Nathaniel Smilowitz, Judith Hochman, Harmony Reynolds, Tessa Barrett, Jeffrey Berger
Journal: Circulation (2024)

Background: Coronary endothelial dysfunction plays a key role in the pathogenesis of cardiovascular events. In the setting of myocardial infarction (MI), activated platelets release prothrombotic and proinflammatory factors, contributing to vascular injury and dysfunction. However, the effect of platelets on coronary endothelial function during MI is not fully understood. We investigated the effect of platelets from patients with MI on cultured coronary endothelial cells in vitro. Methods: Platelet RNA sequencing was performed and platelet releasates were obtained from patients with acute MI (n = 24) and control patients with stable coronary artery diseases (n = 22) who were referred to invasive coronary angiography. Human coronary artery endothelial cells (HCAECs) were treated with platelet releasates for 6 hours and collected for RNA sequencing. Mitochondrial function of treated HCAECs was evaluated by live cell imaging and JC-1 assay with flow cytometry. Results: Overall, 1832 genes were differentially expressed in the transcriptome of HCAECs treated with MI (vs control) platelets (p &lt; 0.05). Ingenuity pathway analysis found that mitochondrial dysfunction (up-regulated; p = 1.7 × 10 -8 ) and oxidative phosphorylation (down-regulated; p = 7.2 × 10 -8 ) were the top two altered pathways in HCAECs treated with MI platelets ( Figure A&amp;B ). Consistently, live cell imaging with MitoTracker Red staining and JC-1 assay by flow cytometry showed MI (vs. control) platelet releasate-treated HCAECs had reduced mitochondrial membrane potential. By correlating the differentially expressed platelet genes in MI vs controls, we identified the platelet gene cluster that induced endothelial cell mitochondrial dysfunction, which was enriched in coagulation, platelet activation, and platelet degranulation ( Figure C ). Conclusions: Platelets-derived mediators from patients with MI induce altered endothelial cell gene expression and mitochondrial dysfunction.
Abstract 4143445: Regardless of age or gender, diet quality, smoking status, and, exercise are key to cardiovascular health
Authors: Tsuey-yuan Huang, Ming-Fen Tsai, Debra Moser
Journal: Circulation (2024)

Introduction: Maintaining a heart-healthy lifestyle is crucial for good cardiovascular health. However, the moderating effects of age and gender on the relationship of diet quality, smoking status, and exercise to cardiovascular health are unknown. The purpose of this proposed study was to investigate the moderating effects of age and gender on the relationship of diet quality, smoking status, and exercise to cardiovascular health in community-dwelling adults in Taiwan. Methods: Cardiovascular health was defined using American Heart Association Life’s Simple 7 (LS7) scores, including cholesterol levels, blood pressure, blood sugar, body mass index, diet, smoking status, and physical activity levels, that were collected using a self-administered questionnaire and blood tests. Healthy lifestyle (diet quality, not smoking, and exercise) was also defined using a self-administered questionnaire. PROCESS macro model 3 was used to analyze the moderation effects of age between genders, the continuous independent variable (X) healthy lifestyle, the continuous dependent variable (Y) LS7, the categorical moderator (W) gender, and the continuous moderator (Z) age. Results: We recruited 484 participants (35.33±23.39 yrs., 86% female). The final model was significant (R2=51.19%, F=125.49, p=.000). Healthy lifestyle is a predictor of cardiovascular health (β=1.14, p=.000). However, the regression coefficient for XMW is not statistically significant, b7=0.0018, F (476) =0.1131, p=.7368, meaning that there is no three-way interaction between healthy lifestyle, age, and gender. Conclusion: The study findings elucidate that while gender and age can impact the prevalence rates of cardiovascular diseases, the effect of adopting a healthy lifestyle on cardiovascular health remains consistent across different age groups and genders. Consequently, regardless of age or gender, fostering a cardioprotective lifestyle is paramount.
Abstract 4142517: Reduced Global Longitudinal Strain Assessed by Echocardiogram is Associated with Higher Collateral Burden and Volume Overload in Fontan Patients
Authors: Andres Moreno, Meaghan Beattie, Sujatha Buddhe, Sharon Chen, Ali Syed, Shiraz Maskatia
Journal: Circulation (2024)

Background: In patients with Fontan palliation, ejection fraction (EF) and global longitudinal strain (GLS) are associated with exercise capacity and survival. We investigated the associations between EF and GLS on echo and 4-dimensional phase contrast (4DF) cardiac MRI (CMR) parameters, including percent collateral flow (%CF). Methods: Single-center, retrospective review of patients post-Fontan who underwent CMR in 2023 and echocardiogram within 1 year. GLS was measured on echo in the apical 4-chamber view. %CF and regurgitant fractions were measured using 4DF. Indexed ventricular end-diastolic (iEDV) and end-systolic (iESV) volumes and EF were also measured. Descriptive data are presented as median (Q1 – Q3). Spearman correlation was used to compare continuous variables. Linear regression analysis was performed to quantify the relationship between GLS and predictor variables. Results: Thirty-two patients met inclusion and exclusion criteria. Of the 32 patients in the study cohort, 40.6% were females and 75% had a systemic right ventricle. Median age at CMR was 16.6 (12.1 – 20.0) years, median duration between echo and CMR was 49.5 (2 – 95) days. There was moderate to high correlation between GLS and iEDV, GLS and iESV, and GLS and EF. There was no significant association between %CF and GLS, and %CF and EF (table). Moderate or severe valve regurgitation was present in 12 (38%) patients. When excluding these patients, GLS had a moderate correlation with %CF, EF, iEDV, and iESV (table). Multivariable linear regression analysis was performed to test if a combination of CMR parameters could best predict GLS. EF and %CF, remained associated with GLS. The overall regression was statistically significant (R2 = 0.5, F(2, 17) = 8.75, p = .002). Conclusion: In this pilot cohort of Fontan patients, worse (less negative) GLS% was associated with larger iEDV and iESV. There was also an association between GLS and higher %CF when excluding patients with more than mild valve regurgitation. This relationship may be mediated by volume load of collateral flow on the heart. These data may provide evidence of an early impact of %CF burden and resultant volume overload on ventricular contractility.
Abstract 4142273: Pharmacosurveillance study of FDA Adverse Event Reporting System (FAERS) events of Tirzepatide and Semaglutide
Authors: Ilana Logvinsky, Sait Barlas, Gautam Maddineni, Malissa Wood, Maja Delibasic
Journal: Circulation (2024)

Background: GLP-1 Receptor Agonists have become widely used for treating Diabetes Mellitus Type 2 and weight loss in patients across the United States. However, new data reports increasing cases of pancreatitis, acute kidney injury, increased Hba1c, and thyroid malignancy. Research question: Like many medications, GLP-1 receptor antagonists have a risk of side effects. The question is which medication, Semaglutide or Tirzepatide, has the highest risk of developing the above mentioned side effects. Goals: Using the FAERS database to calculate the reporting odds ratio (ROR) for the risk of pancreatitis, acute kidney injury, increased HgA1c, and thyroid malignancy. Methods: The FDA's FAERS system gathers information on adverse events and medication errors. The data shows that both Semaglutide and Tirzepatide have been linked to pancreatitis, acute kidney injury, elevation in HbA1c, and various types of thyroid malignancies. For consistent analysis, this data covers the period from 2022 to 2024 for both drugs. Results: January 2022- March 2024 data showed that Semaglutide and Tirzepatide had 11584 AE and 29453 AE, respectively. Semaglutide had a higher risk of developing pancreatitis, elevation of HbA1c, and thyroid malignancy compared to Tirzepatide (ROR 2.62, 95% CI 2.21-3.10) (ROR 1.72, 95% CI 1.38 to 2.15), (ROR 4.32, 95%CI 2.66 to 7.01) respectively. However, Semaglutide had 72% fewer reported cases of AKI than Semaglutide (ROR 0.28, 95% CI= 0.20 to 0.37). Conclusion: Lately, the popularity of GLP-1 Agonists is soaring mainly due to their role in facilitating weight loss and providing additional cardiovascular benefits. To the best of our knowledge, this is the first study comparing the likelihood of these four AEs with Semaglutideand Tirzepatide, using the FAERS Database. Being the newer agent, Tirzepatide is significantly less strongly associated with three AEs than AKI. Additional studies are needed to investigate further the epidemiology and pathophysiology of AKI with Tirzepatide use. In the meantime, Tirzepatide should be the drug of choice in patients who are at high risk for pancreatitis, thyroid cancer, and poorly controlled DM. Semaglutide might be considered in chronic kidney disease patients.
Abstract 4142520: Causal associations between age of menarche or sex hormones and the risk of cardiovascular mortality: A Mendelian randomization analysis
Authors: Myunghee Hong, Je-Wook Park, Oh-Seok Kwon, Hee Tae Yu, Tae-Hoon Kim, Jae-Sun Uhm, BOYOUNG JOUNG, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2024)

Background: Recently, observational studies have reported several sex-specific factors associated with risk of cardiovascular (CV) disease and mortality. In addition, endogenous sex hormone levels in both men and women are related to the risk of CV disease and mortality. We explored the causal relationships between several sex-specific factors or sex hormones and CV mortality. Methods: Among 219,320 women or 187,297 men registered in the UK biobank database, we investigated two-sample Mendelian randomization analyses for outcome data (CV mortality). Exposure data were extracted from published genome-wide association studies (GWAS) catalog database. We selected each SNP with sex-specific (age at menarche, age at menopause in women) factors and sex hormones (total testosterone, sex hormone-binding globulin adjusted for BMI, Estradiol, dehydroepiandrosterone sulfate (DHEAS), androsterone sulfate in both men and women), to use it as an instrumental variable. Mendelian randomization analysis was performed using the inverse variance weighted (IVW), MR-Egger regression, and weighted median methods. Results: Among the sex-specific factors, we found that genetically predicted age at menarche was causally associated (IVW, beta=−0.134, SE=0.062, P=0.031), but not the age at menopause (IVW, beta=-0.028; SE=0.019, P=0.131) with the risk of CV mortality in women. Among the several sex hormones, androsterone sulfate has a causal relationship with CV mortality (IVW, beta=0.272, SE=0.089, P=0.002), but not other sex hormones (IVW, P=0.498 for total testosterone; P=0.469 for sex hormone-binding globulin adjusted for BMI; P=0.441 for Estradiol (men); P=0.099 for DHEAS). Conclusions: These results provide evidence that the earlier age at menarche in women and higher androsterone sulfate levels are associated with increased CV mortality. Key words: sex specific factors, sex hormones, cardiovascular mortality, Mendelian randomization , genetic variants