tbuckley/cabot-search huggingface dataset:
Abstract 4143634: Macrophage MST4 Exacerbates Cardiac Microvascular Ischemia/reperfusion Injury by Phosphorylating ACLY
Authors: Ao Chen, Yan Xia, Xinyu Che, Zhangwei Chen, Juying Qian, Junbo Ge
Journal: Circulation (2024)

Background: Cardiac microvascular dysfunction is a contributing factor to cardiac ischemia/reperfusion (I/R) injury. The impact of mammalian Ste20-like kinase 4 (MST4) on cardiac microvascular I/R injury remains unknown. Aims: To decipher the role of MST4 in cardiac microvascular I/R injury and the underlying mechanisms. Methods: Single-cell RNA sequencing was performed to explore the expression changes of MST4 in different cardiac cell types. Myeloid-specific MST4 knockout mice (MST4 CKO) and bone marrow transplantation were used to testify to the role of myeloid-derived MST4 in cardiac microvascular I/R injury. Bone-marrow-derived macrophage (BMDM) and cardiac microvascular endothelial cells (CMEC) were used to dissect molecular mechanisms. Adeno-associated virus and adenovirus were constructed to overexpress ATP Citrate Lyase (ACLY) with mutation of serine 455 (S455A) in vivo and in vitro, respectively. Results: MST4 was dominantly upregulated in CCR2+ monocyte-derived macrophages. Myeloid-specific deficiency of MST4 or wild type mice that were transplanted with BMDM from MST4 CKO mice improves cardiac performance in the I/R mouse model. Metabolomics showed that the primary bile acid biosynthesis pathway was upregulated in BMDM overexpressing MST4. The level of 7α-hydroxyl3-oxo-4-cholestenoic acid (7-HOCA), an intermediate of bile acid, was dramatically increased in I/R mice or BMDM overexpressing MST4, which can be reversed by knocking down MST4. Phosphoproteomics and LC-MS/MS analysis discovered that ACLY was one of the most important substrates of MST4 in the process of I/R injury. ACLY was directly phosphorylated by MST4 at serine 455, which increased ACLY enzyme activity. Mechanistically, ACLY promoted cholesterol catabolism through the bile acid synthesis pathway, leading to the accumulation of 7-HOCA in the macrophage-endothelial cell microenvironment. A high level of 7-HOCA was able to promote endothelial cell mtDNA release, leading to endothelial cell pyroptosis through the inflammasome pathway. However, mutation of serine 455 of ACLY blocked the role of MST4. Conclusions: Our data defined a previously unrecognized role of the MST4/ACLY pathway in cardiac microvascular I/R injury. MST4 led to the accumulation of 7-HOCA by phosphorylating ACLY, furthermore, 7-HOCA promoted endothelial cell injury. Targeting the MST4/ACLY pathway ameliorated cardiac microvascular I/R injury, which may provide a novel therapeutic strategy for I/R injury.
Abstract 4143686: Unipolar and omnipolar voltage mapping of the pediatric sino-atrial node
Authors: Mathijs van Schie, Roxanne Zwijnenburg, Manouk Linderhof, LIXIA DAI, Can Zhang, Yannick Taverne, Annemien van den Bosch, Natasja de Groot
Journal: Circulation (2024)

Introduction: Sinus node dysfunction (SND) commonly occurs in pediatric patients with congenital heart disease (CHD). It includes disturbances in sino-atrial node (SAN) impulse generation and/or its propagation from SAN exit sites towards the atrial myocardium. Various voltage mapping techniques i.e., unipolar, bipolar and omnipolar, are available to explore the degree of electrical remodeling. However, the interrelationship between unipolar and omnipolar voltages and the added value of either technique with respect to SAN mapping is unknown. Therefore, we performed epicardial high-resolution voltage mapping of the SAN area in pediatric CHD patients. Methods: Intra-operative mapping (128 electrodes; interelectrode distance 2mm) was performed in 45 patients (0.6[0.4-3.1] years). Unipolar morphology characteristics were computed, including peak-to-peak voltages and R/S ratios. Bipolar potentials were constructed from unipolar potentials in both horizontal and vertical directions. Omnipolar potentials were constructed from each orthogonal bipolar pair. Omnipolar peak-to-peak voltages were compared to the corresponding unipolar voltages. Low-voltage areas were defined as unipolar voltage &lt;1 mV (U-LVA) and omnipolar voltage &lt;0.5 mV (O-LVA). Results: In total, 2313 unipolar electrograms were recorded from which 7831 omnipolar electrograms were derived. Omnipolar voltages surrounding the SAN area were larger than unipolar voltages (6.2[4.8-7.6] vs 5.2[3.6-6.3]mV,p&lt;0.001). There was also a strong linear correlation between omnipolar and unipolar voltages (r=0.890,p&lt;0.001). O-LVAs near the SAN were identified in only 9 patients (20%), while U-LVAs were present in 34 patients (76%); 8 patients had combined U/O-LVAs. U-LVAs were larger than O-LVAs (6.5[4.6-10.5] vs 0.7[0.5-2.2]%,p&lt;0.001). At the SAN exit site, there were no differences between unipolar and omnipolar voltages (4.1[2.8-5.7] vs 3.7[2.6-5.5]mV,p=0.453). However, unipolar potentials at the SAN exit site consistently consisted of full S-waves (R/S ratio: 0.99[0.94-1]), while omnipolar potential morphology was highly variable. Conclusions: At the SAN area, a considerable amount of U-LVAs could be identified. These unipolar potentials typically consisted of full S-waves, which were easily recognizable but probably led to an overidentification of U-LVAs. By utilizing combined omnipolar voltage mapping, LVAs near the SAN may be more accurately identified and used to identify patients at risk for developing SND.
Abstract 4143663: Quantifying the Coronary Artery Slow Flow Phenomenon: Insight from Dynamic Angiography and Deep Learning
Authors: Loc Vu, Minh Mai, Thuan Huynh, Duc Chinh Nguyen, Thanh Tam Pham, Huan Pham, Hien Nguyen, THIEN TAN TRI TAI TRUYEN, Khiem Ngo, Pham Thao Vy Le, Hieu Nguyen, Vinh Sieu Lam, Dung Ho, Thach Nguyen
Journal: Circulation (2024)

Background: The coronary slow-flow phenomenon is frequently seen in patients with coronary stenosis, coronary endothelium dysfunction, microvascular dysfunction, etc. It is diagnosed as TIMI-2 flow grade (requiring ≥ 3 cardiac cycles to opacify the vessel) or a corrected TIMI frame count (TFC) greater than 27 frames. However, the TFC has variability due to its dependence on injection force. In cases without autonomic injection, how could to quantify frame count with minimal bias? Methods: All patients underwent the angiogram included, and the exclusive criteria were patients with heart failure, cardiomyopathy, congenital heart disease, valvular disease, and multivessel disease. The angiographic recording began with the injection of contrast into the coronary artery and continued with the white-colored blood moving until all the contrast had been washed out from the arteries. The review of coronary was 15 frames per second and focused on the white-colored blood flow against a black contrast background. The arterial phase (AP) calculation started when the blood began moving and ended when all the contrast was washed out of the distal arterial vasculature. The artificial intelligence program was built based on U-net and Densenet-121. At first, a segmentation model and a Convolutional neural network (CNN) model are responsible for detecting the starting frame of AP with a full index of contrast. In the end, the CNN model will detect the ending frame of AP. Results: 151 patients met the inclusion criteria, and 76.8% were males. Subgroup analysis of patients with patent coronary arteries showed that the AP of the group with slow flow at the distal segment was 32.3 ± 4.4 frames. There was a statistically significant difference compared to the no-slow-flow group (p&lt;0.001). The AP of patients with patent coronary artery was 25.8 ± 4.4 frames, compared with the AP of the group with a significant lesion, which was 32.2 ± 4.0 frames (p&lt;0.001). The cut-off value of the AP frame count in diagnosing coronary slow flow was 27.5 frames, with a sensitivity of 91% and a specificity of 67%. Moreover, the Deep Learning model for calculating AP frames was successfully trained, achieving a root mean square error of 5.1 frames. Conclusion: In addition to TIMI frame count, AP frame count analysis is feasible for cath labs without autonomic injection. The preliminary results suggest AP is a potential marker for diagnosing the slow flow phenomenon.
Abstract 4143450: Strong correlation between preoperative CT-reconstructions and postoperative samples in the assessment of mitral annular calcification: Validation of Calcium scores and MAC scores
Authors: Jagdip Kang, Andre Luppi, Svitlana Bielichenko, Michael Borger, Thoralf Sundt, Brian Ghoshhajra, Serguei Melnitchouk
Journal: Circulation (2024)

Background: The surgical management of severe mitral annular calcification (MAC) has become an increasingly common challenge. Accurate preoperative prediction of the extent and location of calcification is crucial for preoperative planning, informed consent, and safe surgical management. Hypothesis: CT-derived calcium scores correlate with the Guerrero classification of MAC severity. Furthermore, CT reconstructions provide an accurate representation of calcifications observed in postoperative macroscopic specimens. Methods: Patients with preoperative CT imaging and MAC resection were included. Preoperative CT assessed MAC using Aquarius, TeraRecon software (V.4.7). Severity was graded based on calcium thickness, distribution, and involvement of leaflets and trigones according to the Guerrero classification. Calcium scores were quantified using the Agatston method, and MAC was 3D reconstructed. The relationship between calcium and MAC scores was assessed using Spearman's ρ. Additionally, qualitative comparisons were made between CT reconstructions and postoperative samples. Results: A total of 31 patients were analyzed, with a median age of 74. Two patients had mild MAC (mean calcium score: 2996), 14 had moderate MAC (mean calcium score: 6105), and 15 had severe MAC (mean calcium score: 9271). There was a strong positive correlation between preoperative calcium scores and Guerrero classification grades (Spearman's ρ = 0.65, p &lt; 0.01). Qualitative assessment showed a high degree of similarity between preoperative CT reconstructions and postoperative macroscopic findings. Conclusions: The study demonstrates a strong correlation between preoperative CT-derived calcium scores and the Guerrero classification of MAC severity. However, the high degree of similarity between preoperative CT reconstructions and postoperative samples carries a higher informational value than the MAC score itself. Preoperative CT reconstructions of MAC, coupled with the calcium score as a surrogate for MAC volume and severity, provide the most accurate assessment of MAC for surgical planning and evaluation of alternatives. Further studies are required to determine preoperative criteria that predict safe MAC resections.
Abstract 4143756: Demographic Characteristics and Geographic Patterns of Atrial Fibrillation-Associated Mortality among Older Adults with Heart Failure in the United States (1999-2020)
Authors: Hafsah Alim Ur Rahman, Abdul Moeed, Priya Hotwani, Farah Yasmin, Rohan Kumar Ochani, Muhammad Hanif, Aman Goyal, M Chadi Alraies
Journal: Circulation (2024)

Background: Heart failure (HF) continues to pose a substantial threat to global mortality, exacerbated by the increasing prevalence of atrial fibrillation (AF) among the elderly population in the United States (US). Despite this, AF-related mortality in HF patients aged 65 and above remains understudied. This study aims to analyze the demographic and regional trends of AF-related mortality in the older adults with HF in the US. Methods: Utilizing death certificates from the CDC WONDER (Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research) database spanning 1999 to 2020, AF-related mortality in HF patients aged ≥65 years was examined using ICD-10 (International Classification of Diseases 10th Revision) codes. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and annual percentage change (APCs) with 95% confidence intervals (CI) were calculated. Mortality trends were analyzed by year, sex, race/ethnicity, and geographic region. Results: Between 1999 and 2020, 822,358 AF-related deaths occurred in HF patients aged ≥65 years. The overall AAMR was 88.4 (95% CI: 88.2 to 88.6). Males had higher AAMRs than females (overall AAMRs: 100 vs 80.6). Non-Hispanic (NH) white individuals exhibited the highest AAMR (96.3), followed by NH American Indian or Alaska Native (66.2), NH black or African American (54.2), Hispanic or Latino (46.9), and NH Asian or Pacific Islander (39.4). By census region, the highest AAMRs were in the West (100.8), Midwest (95.7), and Northeast (80.6), with the lowest in the South (80.5). Non-metropolitan areas showed higher AAMRs than metropolitan areas (103 vs 85.2). The top 90th percentile states included Washington, Vermont, Oregon, and Minnesota, with AAMRs nearly double those in the bottom 10th percentile states such as the District of Columbia, Florida, Nevada, and Hawaii. Conclusion: AF-related mortality trends among older HF patients increased from 1999-2020, with higher AAMRs observed in men, NH White individuals, Non-Metropolitan areas, and the Western region. Targeted strategies addressing precipitating events and further investigations are needed to overcome these trend disparities.
Abstract 4143465: Aortic Root Pressure for Detecting Aortic Stenosis using Machine Learning
Authors: Michael Dunn, David Lalush, Sterling Wheaten, George Stouffer, Faisal Syed
Journal: Circulation (2024)

Background: Aortic stenosis (AS) is a progressive, deteriorative valvular condition that is associated with significant morbidity and mortality. The best method to diagnose the severity of AS is controversial as all of the current modalities have multiple potential sources of error. As severity of AS increases, the time from aortic valve opening to peak systolic pressure increases. We hypothesized that machine learning applied to pressure measured in the aortic root via a fluid filled catheter at the time of cardiac catheterization would accurately diagnose aortic stenosis. Aims: Use a long-short term memory (LSTM) neural network to identify AS using aortic root pressure. Methods: We assessed aortic root pressure recordings in 102 consecutive patients undergoing transcatheter aortic valve replacement (TAVR) at our institution between 2014 and 2017. A LSTM was trained, validated, and tested using pre- and post- TAVR aortic root pressure 1 Hz digital recordings of 3.5 seconds duration. Recordings were selected to be artifact-free and in sinus rhythm. A 10-fold cross-validation structure was used (170 training, 17 validation, 17 testing tracings). The model was assessed using area under the receiver operating curve (AUROC) and F1 score. Results: The LSTM was able to distinguish between pre-TAVR (severe AS) and post-TAVR (no AS) tracings with sensitivity of 0.764, specificity of 0.703, AUROC of 0.792, and F1 score of 0.741. In comparison, when pressure tracings of the left ventricle were added to the model, the LSTM performance improved to sensitivity of 0.956, specificity of 0.950, AUROC of 0.977, and F1 score of 0.954. Conclusion: This proof-of-concept study demonstrated that aortic pressure alone can be used to detect severe AS. A larger analysis is needed to validate these findings across gradients of severity. This study has implications for using automatic AS severity assessments during cardiac catheterization to accurately diagnose AS.
Abstract 4143638: Donation After Circulatory Death in Pediatric Heart Transplant Recipients: A Lost Opportunity for Donor Pool Expansion
Authors: Anuja Shikhare, Gaurang Vaidya, Liliam Aquino, Mark Cocalis, Othman Aljohani
Journal: Circulation (2024)

Background: Donation after circulatory death (DCD) is underutilized in pediatric heart transplant (HTx). Methods: UNOS database was analyzed for HTx with reported DCD donors (1/2020-4/2024). Data is reported as median (interquartile range). Multiorgan and retransplant recipients were excluded from outcome analysis. Results: The youngest DCD heart donor was &lt;1 year old and the median age was 15 years. During the study period, 86 (4%) pediatric donors were DCD. However, in terms of pediatric recipients, DCD accounted for only 12 (0.9%) of the total pediatric HTx. The remaining pediatric DCD donors (74) were assigned to adult recipients. In the same period, all DCD donors accounted for 10% of adult HTx. The pediatric donor cohort was subdivided into 4 categories based on the recipient's age-group and whether the donor was DCD or not (table 1). Pediatric DCD hearts were allocated to lower priority listed recipients and those with blood group O (in both pediatric and adult recipients). Despite this, the total waitlist time was shorter among DCD recipients, suggesting the potential role of DCD to lower wait times. Distance travelled between donor to transplant center can be longer with DCD due to the use of a different organ care system. Table 1 summarizes the findings. Few UNOS regions (4, 5, 10, 11) are using pediatric DCD hearts for pediatric recipients (figure A). For outcome analysis, adult recipients who received pediatric DCD hearts were compared to those who received pediatric non-DCD hearts. No difference was noted in the one-year survival (figure B). Conclusion: Pediatric DCD heart for pediatric recipients represents an unexplored strategy for donor pool expansion.
Abstract 4143565: <i>Outstanding Research Award in Pediatric Cardiology:</i> Prevalence, evaluation, and treatment of neurodevelopmental disorders in publicly insured children with critical congenital heart disease in the first 5 years after infant heart surgery
Authors: Daniel O'Meara, Brandi Henson, Caitlin Rollins, Kimberlee Gauvreau, Jay Berry, Matthew Hall, Jane Newburger
Journal: Circulation (2024)

Background: Survivors of infant heart surgery are at greater risk for neurodevelopmental (ND) disorders. Rates of ND diagnoses (dx) and resource utilization are derived from referral centers or single-state studies, with few multi-state data on diagnosis and utilization across inpatient and outpatient settings. Methods: We characterized ND dx, medications, screening/evaluation, and non-medical therapies up to 5 years of life among children born in 2016-2020 in the Merative MarketScan Medicaid Claims database from 12 anonymized states. Surgical complexity was assessed with RACHS-2 category. Cox proportional hazards regression was used to identify risk factors for time to 1) first ND dx and 2) first ND evaluation/intervention. Results/Data: Among 3,147 patients enrolled for a mean 30.5 months, surgery was neonatal in 48%; 23% had a genetic dx; and highest RACHS-2 category was 1= 30%, 2=29%, 3=13%, 4=18%, and 5=10%. Brain imaging was performed in 13%, most commonly MRI (8%). Without adjusting for variable follow-up, the proportion with ≥1 ND dx was 41%, most commonly Communication Disorder (25%), Global Developmental Delay (15%), and Motor Disorder (19%). At latest follow-up, 85% had received ≥1 ND service and 78%, ≥1 direct intervention (ST, OT, and/or PT). Brief ND screening was completed in &gt;58%, but few had psychological/neuropsychological (6.6%) or comprehensive developmental (8.5%) evaluation. Use of stimulants (0.5%), anti-depressants (0.1%) and antipsychotics (0.2%) were uncommon, but anticonvulsants had been used in 7.3%. Independent risk factors for earlier time to any ND dx were Black (p=0.043) or Hispanic (p=0.032) vs. White race/ethnicity, and RACHS-2 Category 4 (p=0.002) or 5 (p=0.007) vs. 1. Independent risk factors for shorter time to first ND evaluation or intervention included RACHS-2 Classes 2 (p=0.012), 4 (p&lt;.001), and 5 (p&lt;.001). Birth sex and genetic abnormalities were not significant predictors of ND dx or utilization. Data for center and region were not available. Conclusions: The prevalence of ND dx and utilization of ND services was high up to age 5 years in this population-based sample of publicly insured children who underwent infant heart surgery. Rates of developmental screening were comparable to those in general pediatric samples, but few children received formal ND evaluations, falling short of AHA recommendations for universal developmental evaluation.
Abstract 4143723: Thrombocytosis is Prevalent and Associated with Greater Inflammation and Coronary Artery Involvement in Both Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Associated with COVID-19
Authors: Ashraf Harahsheh, Melissa Wehrmann, michelle grcic, Todd Nowlen, Nagib Dahdah, Supriya Jain, Luis Garrido, Michael Khoury, Jacqueline Szmuszkovicz, Pei-Ni Jone, Benjamin Barnes, Kevin Harris, Mark Hicar, Nicolas Hidalgo Corral, nadine choueiter, Jean Ballweg, Tapas Mondal, Cedric Manlhiot, Brian McCrindle
Journal: Circulation (2024)

Introduction: Thrombocytosis, sometimes extreme, after acute Kawasaki disease (KD) is common and felt to be pathognomonic of this diagnosis, although has also been reported after multisystem inflammatory syndrome in children (MIS-C), a clinically similar condition. We sought to determine differences in factors associated with thrombocytosis for each condition. Methods: From 01/2020 to 10/2023 across 41 sites in 8 countries from the International KD Registry, 1674 MIS-C and 1290 contemporaneous KD patients with adequate laboratory data were included in the analysis. Age-related cutpoints (derived from the CALIPER Study of normal children/adolescents; AJCP 2020; 154:342) were applied to peak platelet counts to define thrombocytosis (age &lt;1 year, &gt;647 x10 9 /L; age 1 to &lt;12 years, &gt;434; age 12 to &lt;21 years, &gt;371). Associations of demographic, clinical, laboratory and outcome factors with thrombocytosis were determined for each diagnosis group. Results: Thrombocytosis was more prevalent after KD (57%) than MIS-C (49%; p&lt;0.001), with higher median peak platelet count (492 vs. 413 x10 9 /L; p&lt;0.001). The difference remained significant after adjustment for age. Thrombocytosis was significantly associated with greater total days of fever for both KD (median 8 vs. 7 days; p=0.005) and MIS-C (median 7 vs. 6 days; p&lt;0.001), but not with any symptoms/signs or presentation with shock in either group. For both groups, thrombocytosis was associated with significantly greater laboratory abnormalities, specifically higher markers of inflammation, lower hemoglobin and lower albumin. Cardiac biomarkers (peak NTproBNP, peak troponin I) were significantly lower for KD patients with thrombocytosis. While there was no significant association of thrombocytosis with ventricular function in either group (FIGURE A), coronary artery involvement was worse for both groups if thrombocytosis occurred (FIGURE B), with an overall lower prevalence and severity for patients with MIS-C, despite more severe clinical presentation and greater laboratory abnormalities. Conclusions: Thrombocytosis has a high prevalence for both KD and MIS-C, and is associated with both more severe inflammation and greater coronary artery involvement for both diagnoses.