tbuckley/cabot-search huggingface dataset:
Abstract 4147205: Characterization of plasma proteome perturbations to distinguish thrombotic myocardial infarction from non-thrombotic myocardial injury and chronic coronary artery disease.
Authors: Shubham Tomar, Patrick Trainor, Karita Lidani, Hossein Mousavi, Andrew DeFilippis
Journal: Circulation (2024)

Background: The distinction between thrombotic myocardial infarction (TMI) and non-thrombotic myocardial injury (nTMi) is crucial, given their varied etiologies, unique treatment approaches, and higher misclassification in clinical setting. In this study, we compared plasma proteome among individuals with TMI, nTMi, and chronic coronary artery disease (cCAD). Methods: Mass spectrometry-based proteomic analysis was conducted in 173 patients (84 with TMI, 36 with nTMi, and 51 with cCAD) who underwent coronary angiography (T 0 - acute time) and had an average 3-month post-procedure follow-up (T fu, quiescent state). Initially, we assessed temporal change from T 0 to T fu in proteomic profile in TMI group to identify proteins elevated during acute thrombosis. Subsequently, we compared these proteins’ levels at the acute phase across all groups to find differentially expressed proteins. We used hierarchical Bayesian models to analyze protein abundances, considering study group, time-point, and their interaction, with random effects for individual variability. Statistical significance was determined using Bayesian factor analysis with a threshold of BF &gt; 150. Results: Proteomic profiling of plasma samples quantified 1,756 proteins. In TMI, 141 proteins varied significantly between T 0 and T fu . Proteins related to platelet activation, hemostasis, cell adhesion, and tissue remodeling were elevated. In contrast, proteins associated with extracellular matrix remodeling, cell adhesion, receptor signaling, and growth factor binding were reduced. Notably, six proteins showed differences when comparing TMI to nTMi. Specifically, Decorin, Myoglobin, and C-reactive protein levels were elevated during T 0 , while the others were decreased in TMI group. Comparing TMI to cCAD, 47 proteins differed significantly ( Figure 1A ). Conclusion: Our unique study design, using patients as their own controls, helped us in identifying distinct proteomic signature that can offers a promising set of noninvasive biomarkers for differentiating between TMI from other myocardial injury events.
Abstract 4147732: Does Risk Stratification of Fetuses with d-Transposition of the Great Arteries Shorten Time to Transport and Cardiac Intervention?
Authors: JoAnn Nam, Erik Michelfelder, Andrew Jergel, Shanelle Clarke, Nikhil Chanani, Michael Wolf, Sanghee Ro
Journal: Circulation (2024)

Background: Newborns with d-transposition of the great arteries (d-TGA) often require an urgent balloon atrial septostomy (BAS) immediately after birth, which can be challenging to predict. As such, cardiac centers, especially those without in-house delivery, should plan for immediate transport and cardiac intervention. The objective of this study was to evaluate the impact of risk stratification on both transport times to the cardiac intensive care unit (CICU) and to BAS in the d-TGA population. Methods: A retrospective analysis was performed on all fetuses with d-TGA and an intact ventricular septum born between 1/1/2013 and 12/31/2023. Fetuses born before 2018 were not risk stratified or assigned a level of care (LOC) assignment. Fetuses born after 2018 were assigned either a moderate risk of hemodynamic instability (LOC 3) or high risk of hemodynamic instability (LOC 4), based on findings on fetal echocardiography (FE) associated with increased risk for urgent BAS. Primary outcomes were times from birth to CICU arrival and from birth to BAS. A BAS was considered urgent if completed within 2 hours of CICU arrival. A BAS was excluded if performed greater than 48 hours after birth. Statistical analyses compared time-based outcomes among pre-LOC and post-LOC fetuses (stratified as either LOC 3 or 4). Results: A total of 81 newborns with a prenatal diagnosis of d-TGA were analyzed. Fetuses assigned an LOC had a lower time between birth and CICU arrival compared to fetuses with d-TGA who were not risk stratified (p=0.012) (Table 1). There were no differences in times from birth to BAS or from CICU arrival to BAS for pre- or post-LOC groups. Conclusion: Implementation of risk stratification for d-TGA fetuses can help decrease time between birth and arrival to the CICU. Risk stratification and appropriate delivery planning should be considered, especially at centers without in-house delivery. Although risk stratification alone does not shorten time to cardiac intervention, further research is needed to determine if other prenatal characteristics may predict which patients will require an urgent BAS.
Abstract 4146840: Findings From Learning Collaborative Listening Sessions Assessing The Operationalization Of Community-Clinical Linkages
Authors: Diana Aguirre, Linda King, Kyna Shine
Journal: Circulation (2024)

Introduction/Background: The American Heart Association’s National Hypertension Control Initiative (NHCI) collaborated with health care professionals and public health advocates to facilitate listening sessions for learning collaboratives (LCs) to discuss ways to address hypertension (HTN) through Clinical-Community Linkages (CCL) in five regions. CCLs have been recognized as essential for effective HTN control. Research Questions/Hypothesis: LC knowledge exchange sessions can play a crucial role in strengthening CCL by fostering relationships to address social determinants of health (SDoH) and enhancing HTN control collaborations in health care. Methods/Approach: From October 2023 to April 2024, the NHCI participated in HTN-focused LC listening sessions in 5 regions, utilizing CDC’s CCL approach to identify key stakeholders' engagement level. LC listening sessions facilitated knowledge exchange identifying recommendations for improving HTN. NHCI developed a 10-item assessment for data collection and conducted a thematic analysis. Results/Data: An estimated 210 community and clinical stakeholders participated in six LC listening sessions, five virtual and one in-person, providing insights for optimizing CCL for better HTN control. Findings highlighted five major barriers to implementing CCLs. Barriers that hindered CCL optimization include staffing shortages, low health literacy, lack of funding, an absence of leadership buy-in, and low patient engagement. One consistent insight that emerged as integral was incorporating Community Health Workers. Self-Measured Blood Pressure (SMBP) monitoring tools and the AMA MAP™ framework, along with capacity-building resources were deemed effective approaches. Building stakeholder relationships and addressing SDoH were frequently highlighted as good practices. The top three SDoH factors identified as influencing HTN control were nutrition security, transportation, and income. Conclusion: LC listening sessions allow for knowledge exchange providing insights on advancing and sustaining CCLs to improve HTN control. Innovative pathways for sustainable improvement and advancement of CCL consist of staff and patient education tools, training, capacity building, bi-directional referrals, and solution-oriented advocacy efforts.
Abstract 4146787: Causal Association between Major Depressive Disorder and Cardiovascular Diseases: A Meta-Analysis of Mendelian Randomization Studies
Authors: Azra Kothawala, Bhaswanth Bollu, Nimra Shafi, Akshay Sharma, Naga Amrutha Sai Yalla, Sandeep Singh, Rupak Desai
Journal: Circulation (2024)

Background: Major depressive disorder (MDD) has been hypothesized to have a causal relationship with various cardiovascular diseases, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). Our meta-analysis of Mendelian Randomization (MR) studies aims to identify these associations by using genetic variants as instrumental variables and minimizing confounding factors and reverse causation. Methods: We systematically reviewed the Pubmed, Embase, and Scopus databases to find studies through May 2024 evaluating the association of MDD with the occurrence of Coronary Artery Disease (CAD), Heart Failure (HF), and Atrial Fibrillation (AF). Data sources included multiple genome-wide association studies (GWAS) involving European and mixed ancestries, the IEU Open GWAS Project, the Psychiatric Genomics Consortium (PGC), and combined data from 23andMe, PGC, and the UK Biobank. Random effects models and I 2 statistics were used for pooled odds ratios (OR) and heterogeneity assessments, respectively. The impact of individual studies on the overall estimate was assessed with Leave one-out sensitivity analysis. Results: MDD and CAD: Seven studies were included in the analysis. The overall Inverse Variance Weighted (IVW) estimate indicated odds of developing CAD were 17% higher in those with MDD than without (OR: 1.17, 95% CI: 1.08-1.28, P &lt; 0.01), with substantial heterogeneity (I 2 = 89.89%, P &lt; 0.01). Leave-one-out analysis confirmed equal results as the pooled estimate remained significant across all iterations (OR range: 1.14 to 1.20). MDD and AF: Three studies were included in the analysis. No significant association between MDD and AF was observed in the pooled IVW estimate (OR: 1.03, 95% CI: 0.98-1.08, P = 0.35). The heterogeneity was low (I 2 = 5.22%, P = 0.35). MDD and HF: Three studies were included in this analysis. MDD was associated with a significant risk of developing heart failure (OR: 1.11, 95% CI: 1.05-1.18, P &lt; 0.01), with no observed heterogeneity (I 2 = 0%, P = 0.49). Conclusion: MDD increases the risk of CAD by 17% and the risk of HF by 11% with no significant association between MDD and AF. The substantial heterogeneity in the MDD-CAD association suggests that further studies are warranted to explore potential sources of this variability. These findings highlight the importance of managing depressive symptoms as part of cardiovascular disease prevention strategies.
Abstract 4147238: Targeting Current Delivery During Atrial Fibrillation Ablation May Improve Ablation Success
Authors: Rachel Murphy, Joseph Adewumi, Lucasz Cerbin, Syed Rafay Ali Sabzwari, Carmel Ashur, Bilal Saqi, Daniel Varela, Alex Grubb, Kishan Padalia, Christopher Barrett, Lohit Garg, Alexis Tumolo, Johannes Von Alvensleben, Ryan Aleong, Paul Varosy, Michael Rosenberg, Wendy Tzou, Matthew Zipse, Amneet Sandhu
Journal: Circulation (2024)

Background: Contemporary power-controlled radiofrequency (RF) ablation prioritizes power, force, and time. However, variables such as impedance and current also greatly impact ablation lesion formation. The appropriate current values to target at various pulmonary vein (PV) regions are not well established. Objective: To characterize 1) the range of current (mA) delivery with standard ablation and impedance (ohms) values at PV ostia, and 2) the impact of maximum current achieved on freedom from atrial fibrillation (AF) at one year. Methods: One hundred fifteen consecutive paroxysmal AF patients at our institution between 2020-2021 undergoing first-time RF PV isolation were retrospectively analyzed. Baseline impedance (ohms), impedance drop, power, force, and time were compiled and separated by ostial PV site (CARTO®). Current was calculated based on Power=current x resistance. Calculated current was then compared in a small cohort of patients with the displayed current on the Smart Ablate® system. Results: Of all patients, 27 patients had atrial fibrillation recurrence within one year. Calculated current was lower than the displayed Smart Ablate® current but had reliable correlation. Baseline impedance was higher in the roof and posterior wall compared to anterior/inferior regions. There was a statistically significant difference in the mean maximum current achieved between patients with AF recurrence vs those without in the regions of the left posterior wall (543 mA vs 564 mA, p = 0.049), left roof (556 mA vs 575 mA, p = 0.043), and right roof (559 mA vs 578 mA, p = 0.042). Conclusion: Current delivery during RF ablation is dependent on baseline impedance and the impedance drop achieved. We noted significant differences in delivered current in those with and without AF recurrence at the left posterior wall/roof and right roof. Titrating ablation parameters to achieve effective current delivery may be a promising intraprocedural strategy for AF ablation success.
Abstract 4147667: Elevated Hsp70 Does Not Rescue BAG3 Levels After Hypoxia-Reperfusion Stress or Ischemia-Reperfusion Injury
Authors: Laura Sherer, Ahmed Zied, Thomas Martin, Michaela Door, Christine Delligatti, Jonathan Kirk
Journal: Circulation (2024)

The co-chaperone BAG3 is critical for protein quality control at the cardiac sarcomere. BAG3 binds to Hsp70 and coordinates the assembly of the CASA (chaperone-assisted selective autophagy) complex, thus supporting proteostasis and cardiomyocyte contractility. BAG3 mutations and/or decreased BAG3 levels are associated with cardiomyopathies, whereas BAG3 overexpression rescues ventricular function after myocardial infarction in mice. Despite BAG3’s promise as a therapeutic target, the mechanisms underlying BAG3 regulation are largely unresolved. Here, we investigate the mechanisms of BAG3 downregulation after stress. We found that BAG3 protein is reduced in human dilated cardiomyopathy hearts compared to non-failing hearts, yet there is an increase in bag3 mRNA transcript, suggesting BAG3’s downregulation in heart disease may be controlled post-transcriptionally. To identify these post-transcriptional pathways, we subjected neonatal rat ventricular myocytes (NRVMs) to prolonged hypoxia-reoxygenation (H/R) stress, which recapitulated the decrease in BAG3 levels observed in human heart disease. Notably, disrupting Hsp70 binding to BAG3 in NRVMs via the drug JG-98 decreases BAG3’s half-life by ~90%, suggesting that Hsp70 protects BAG3 from degradation. Loss of Hsp70-mediated protection could contribute to declining BAG3 levels, so we quantified Hsp70 abundance after H/R stress in NRVMs, finding no significant change. We also found that overexpressing inducible Hsp70 did not rescue BAG3 levels. To examine BAG3 regulation in vivo, we subjected wildtype mice to ischemia-reperfusion injury. After 24 hours, male mice had no change in Hsp70 abundance in the left ventricle, whereas Hsp70 was significantly upregulated in female mice. Despite this difference in Hsp70, BAG3 levels were decreased by ~20% in both sexes. Thus, our in vivo and in vitro data both suggest that BAG3 downregulation is not caused by loss of Hsp70 binding/protection. Interestingly, the decline in full-length BAG3 (85 kDa) was accompanied by an increase in a BAG3 cleavage product at 74 kDa. We analyzed this product via mass spectrometry, discovering that it lacks a third of the WW domain, which is involved in autophagy. In future experiments, BAG3 cleavage will be explored as a potential mechanism of BAG3 loss. Such mechanisms will provide insight into how to maintain BAG3 levels, and thus cardiac function, during stress.
Abstract 4147550: Evaluating the Clinical Reasoning of GPT-4, Grok, and Gemini in Different Fields of Cardiology
Authors: Jonathan Reyes-Rivera, Alberto Castro Molina, Marco Romero-Lorenzo, sajid ali, Charles Gibson, Jorge Saucedo, Matias Calandrelli, Edgar García Cruz, Cecilia Bahit, Gerald Chi, Stephanie Angulo, michelle moore, Juan M. Lopez-Quijano, Abdallah Samman, Antonio A. Gordillo-Moscoso, Asif Ali
Journal: Circulation (2024)

Introduction: The use of Large Language Models (LLMs) in clinical practice seems increasingly possible, although comparative studies are needed to achieve standardization. GPT-4, Grok and Gemini are three commonly used LLMs. While these LLMs may exhibit some level of clinical reasoning, their performance could differ between them and between areas of cardiology. Aim: To evaluate the clinical reasoning of GPT-4, Grok and Gemini in distinct fields of cardiology. Methods: A total of 12 cases were selected from the AHA Circulation Journal, representing six cardiology areas: General Cardiology (GC), Interventional Cardiology (IC), Cardiac Imaging (CI), Electrophysiology (EP), Heart Failure (HF) and Congenital Heart Disease (CHD). Each area included two cases. We only provided the case presentation to the LLMs, ensuring they were unaware of the diagnosis and management. Four questions were asked with the following prompts: 1. What are the diagnostic steps?, 2. What is the most likely diagnosis?, 3. What is the differential diagnosis?, 4. What is the appropriate management?. The responses were systematically evaluated with a digital rubric through an international collaboration of 12 cardiologists from various institutions. Each cardiologist evaluated two cases in their area of expertise and was aware of the diagnosis and management. One-way ANOVA was used for analysis. Results: GPT-4 had a slightly best overall performance (Table 1) and the highest score in GC and CHD; Grok excelled in determining the management and was superior in CI, HF and IC; Gemini had the highest performance in EP, although these findings were not statistically significant (Table 2). Conclusions: This is one of the first studies comparing the clinical reasoning of LLMs in cardiology. Our results propose that GPT-4 has the best overall performance and Grok is superior indicating the management. More studies comparing LLMs are required for further standardization of their use.
Abstract 4147111: Correlation between Plasma Adiponectin, Leptin Levels, and Adverse Outcomes in Hypertrophic Cardiomyopathy Patients
Authors: Shifa Younus, Muhammad Hassan Cheema, Muhammad Hussnain Cheema, Alamdar Hussain, Noor Fatima, Aeman Zafar, Aamir Ali, Hamza Saleem, Tauseef Hussain, Humais Choudhary
Journal: Circulation (2024)

Introduction: Hypertrophic cardiomyopathy (HCM) stands as a significant cause of sudden cardiac death in the younger population. Adipokines, originating from adipose tissue, regulate processes such as heart inflammation, fibrosis, and hypertrophy. Among these adipokines, adiponectin and leptin are particularly linked to cardiac remodeling in HCM. This study aimed to examine the association between plasma levels of adiponectin and leptin and the occurrence of all-cause mortality as well as ventricular tachycardia/fibrillation (VT/VF) in individuals with HCM. Methods and Materials: In a multicenter prospective cohort study involving individuals diagnosed with HCM, we assessed plasma adiponectin and leptin concentrations upon enrollment. We examined the combined occurrence of all-cause mortality and new-onset VT/VF. Subsequently, the cohort was stratified into four categories based on adiponectin and leptin levels. Using the Cox proportional hazards model, we compared the likelihood of experiencing the outcome event across these groups, adjusting for age, body mass index, left atrial diameter, and maximum left ventricular wall thickness, with the largest group serving as the reference. Results: The endpoint event occurred in 48 of 384 individuals throughout a 2.8-year median follow-up period. The four groups based on adiponectin and leptin levels exhibited varying risks of the outcome event (log-rank P &lt; 0.001). The Cox proportional hazards model showed that the High-Adiponectin, Low-Leptin group had a considerably higher risk (adjusted HR 7.34, 95% CI 1.12-14.25, P &lt; 0.005) than the reference (Low-Adiponectin, High-Leptin) group. Conclusion: High plasma adiponectin and low leptin levels are independently linked with mortality and new-onset VT/VF in HCM patients. These adipokines can potentially be novel biomarkers for risk stratification in HCM, improving current prediction models.
Abstract 4147589: Heart Rate Variability as a Predictor of Postoperative Outcomes in Congenital Heart Surgery
Authors: Mia Vaida, Eric Feins, John Kheir, John Triedman, Jane Newburger, Audrey Dionne
Journal: Circulation (2024)

Background: Reduced heart rate variability (HRV) reflects sympatho-vagal imbalance and is associated with cardiovascular mortality in adults. Literature is limited in pediatrics, but reduced HRV has been observed in congenital heart disease (CHD) and is associated with prolonged postoperative hospitalization. Objective: To investigate the effect of HRV metrics on outcomes after surgery for CHD. Methods: This single-center retrospective cohort study included children aged 0-18 years who underwent surgery for CHD (2010-2018). Preoperative 12-lead ECGs (within 10 days) and the first postoperative ECGs were analyzed. ECGs with atrial or ventricular pacing were excluded. Ultra-short term HRV metrics were calculated, including standard deviation of interbeat intervals (SDNN) and the root mean square of successive RR interval differences (RMSSD). SNDD and RMSSD were classified as low if &lt;25 th percentile. Post-operative complication was defined as CPR, unplanned open chest, unplanned reoperation, low cardiac output, bleeding, extracorporal membrane oxygenation (ECMO) or death prior to hospital discharge. Major adverse cardiac event (MACE) was defined as CPR, ECMO and/or death. All analysis were adjusted for age and gender. Results: Among 7,192 children undergoing surgery (55% male, age 0.9 [0.2, 4.5] years), 2,413 (34%) experienced postop complications, 344 (5%) MACE, and 270 (4%) died prior to hospital discharge. HRV metrics could be calculated in 3347 (47%) patients pre-operatively and 3392 (47%) post-operatively. SDNN and RMSS were 0.012 [0.005, 0.028] ms and 0.010 [IQR 0.005, 0.029] ms pre-operatively, and 0.002 [0.002, 0.005] ms and 0.003 [IQR 0.002, 0.005] ms post-operatively. Pre-operative low SDNN and RMSSD were associated with increased risk of post-operative complications, MACE, and death prior to hospital discharge (Figure). Low post-operative RMSS was associated with MACE and death prior to hospital discharge. Low pre- and post-operative SDNN and RMSSD were associated with prolonged CICU and hospital length of stay. Conclusion: Low HRV metrics were associated with worse post-operative outcomes. Pre-operative HRV metrics were most predictive of post-operative complications and mortality.