tbuckley/cabot-search huggingface dataset:
Abstract 14192: Accuracy Improvement In The Fully Automated Assessment Of Right Ventricular Function Using Artificial Intelligence
Authors: Shuo Wang, Daksh Chauhan, Hena Patel, Alborz Amir-Khalili, Alireza Sojoudi, Keigo Kawaji, Amita Singh, Lius Landeras, Victor Mor-Avi, Patel R Amit
Journal: Circulation (2021)

Introduction: The use of deep learning (DL) contouring algorithms to automatically calculate right ventricular ejection fraction (RVEF) is challenging due to the highly variable right ventricular (RV) geometry. The robustness of a DL algorithm to quantify RVEF using cardiac magnetic resonance (CMR) is highly dependent on the quality of the dataset used to train and cross-validate the algorithm. Using an insufficiently heterogeneous dataset to cross-validate a DL algorithm during development may poorly affect its performance when deployed in a clinical environment with diverse disease states and variable image quality. This study was designed to test the hypothesis that using a heterogeneous CMR dataset with a wide range of RV pathology during the cross-validation phase of DL algorithm development would result in more accurate quantification of RV function. Methods: We identified 100 CMR exams in which the RV function could not be accurately quantified using a commercially available DL algorithm (DL1), resulting in errors &gt;5%. We then used a new algorithm that was developed while including images from a greater diversity of disease states and acquisition techniques during the cross-validation phase (DL2). RVEF was measured automatically using both DL1 and DL2 (Figure A) and compared to measurements made in a core laboratory (Core). Results: DL2-RVEF correlated highly with Core-RVEF (r=0.87), whereas DL1-RVEF correlated only modestly (r=0.42) (Figure B). DL2 also resulted in a smaller RVEF error than DL1 when compared to Core-RVEF (Figure C). For DL1, the percentages of smaller errors were considerably lower with no cases with &lt;5% error, while errors &gt;10% were noted in 35% of cases. In contrast, for DL2, 70% of cases were within 5% error, while only 10% of cases showed errors &gt;10%. Conclusions: The use of a diverse dataset during the cross-validation phase of DL algorithm development resulted in a considerable improvement in the accuracy of the automated analysis of RVEF.
<i>Laboratory Prognostic Index (LaPI)</i>: Three Laboratory Variables Are Able to Stratify Diffuse Large B-Cell Lymphoma <i>NOS</i> Patients in Prognostic Clusters at Diagnosis
Authors: Fernando Martin Moro, Juan Marquet Palomanes, Jesus Villarrubia, Ana Lario Arribas, Alberto Gonzalez Rodriguez, Beatriz Astibia Mahillo, Maria Isabel Delgado Trillo, Claudia Lopez Prieto, Federico Santiago Herrera, Gemma Moreno Jiménez, Valentín Garcia Gutierrez, Jose Antonio Garcia Vela, Javier Lopez Jimenez
Journal: Blood (2021)
Abstract 12548: Temporal Strain Data Reconstruction From Echocardiographic Strain Graphs
Authors: Rahul A Devathu, Ramsey M Wehbe, Lauren Nelson, Sanjiv J Shah, James D Thomas
Journal: Circulation (2021)

Introduction: Myocardial strain imaging provides a complex dataset that is often reduced to a single parameter, global longitudinal peak strain (GLPS). Raw temporal strain data is largely unexplored and restricted as studies often only save images of graphs lacking numerical data. While certain strain imaging packages do allow for the prospective export of raw data, the task is slow, rarely done, and cannot be done retrospectively. The troves of retrospective strain studies saved as images can be unlocked by reconstructing the numerical values contained in strain graphs. Such a dataset would be critical to future artificial intelligence strain analysis and morphological detection of disease modalities. This study aims to investigate the methods of extracting and reconstructing strain curve graphs to raw numerical outputs. Methods: By using vendor-specific color recognition algorithms, individual curves can be isolated as scattergram type plots of pixels. These pixel locations are converted to temporal strain values by defining scale factors for the graph. Intelligence-guided filtering, interpolation, and curve overlap filling can convert the pixel scattergrams into clean and complete temporal strain data. Using a set of 21 studies each containing 3 views (2Ch, 4Ch, APLAx) with each view containing 6 regional curves, 378 unique curves were reconstructed and compared to prospectively exported temporal strain data. Results: Results demonstrate that this method reconstructs the numerical data with high accuracy and precision. The reconstructed data was compared with the exported numerical data, yielding an average R 2 of .996 with an average runtime per study of 7.32s. The minute deviation from fidelity can be attributed to the finite resolution of the pixels in the analyzed graph. Discussion: Highly accurate temporal data can be extracted from routine strain graphs in clinical studies, which may allow for more nuanced assessment and deep learning of strain.
Abstract 12410: The Critical Role of Mitochondrial Dysfunction in the Impaired Angiogenesis Associated With the Pulmonary Hypertensive Phenotype
Authors: Maki Niihori, Joel James, Rohit C Philip, Ruslan Rafikov, Olga Rafikova
Journal: Circulation (2021)

Introduction: Mitochondrial dysfunction (MD) is known to be tightly associated with the pathobiology of pulmonary arterial hypertension (PAH). Recently, we discovered that rats reproducing a human mutation in NFU1 (NFU1 G206C ) have a severely altered mitochondrial function and spontaneously develop PAH characterized by increased right ventricle (RV) systolic pressure, RV hypertrophy, and severe obliterative disease of small pulmonary arteries. Hypothesis: In this study, we investigated whether MD induced by NFU1 mutation is sufficient to impair pulmonary angiogenesis contributing to PAH pathogenesis. Methods: Angiogenesis was assessed by micro-computed tomography of the pulmonary vasculature, microangiography of small pulmonary arteries (PAs), and histological evaluation of pulmonary capillary density. The angiogenic capacity was also investigated in vitro using cell migration and tube formation assays and analysis of EC tip cell population by flow cytometry. Results: MD significantly reduced the complexity of the pulmonary vascular network and prevented its further advancement (PA density (mean intensity/pxl) in WT vs. NFU1 G206C at 6 and 10 wks of age is 0.07±0.004 vs. 0.03±0.002 and 0.1±0.004 vs. 0.04±0.003; p&lt;0.0001; N=5). NFU1 G206C rats had a reduced number of PA branches and junctions and impaired PA capillary density. PA endothelial cells isolated from NFU1 G206C rats demonstrated a strongly attenuated cell migration (~30% of WT) and tube formation capacity and a ~2.2 fold decrease in the number of CD-304 positive EC tip cells. Supplementation of NFU1 G206C rats with lipoic acid (LA, 1.70 mM in drinking water) aimed to attenuate the LA-synthase insufficiency secondary to NFU1 mutation, restored mitochondrial function, preserved the complexity of PA vascular network at WT level, and averted the PAH phenotype. Conclusions: We conclude that MD plays a causative role in the impaired pulmonary angiogenesis. Indeed, the lungs of NFU1 G206C rats fully reproduced the “dead-tree” picture of pulmonary vasculature described in PAH patients. At the same time, normalized mitochondrial function was sufficient to preserve pulmonary angiogenesis and prevent the PAH, suggesting the protective role of MD ameliorative approaches.
Abstract 13317: Optimization of Left Ventricular Assist Device Therapy: A Combined in vitro and in silico Strategy to Reduce Thromboembolic Adverse Events via Evidence-Based Surgical Configuration and Medical Management
Authors: Alberto Aliseda, Venkat Keshav Chivukula, Fanette Chassagne, Song Li, Jennifer Beckman, Claudius Mahr
Journal: Circulation (2021)

Introduction: Left Ventricular Assist Devices are growing in frequency and importance in the treatment of medical-refractory heart failure. The incidence of thromboembolic events is a principal cause of mortality and morbidity for these patients, despite third generation pumps greatly reducing in-pump thrombosis. Hypothesis: To understand this problem, we hypothesize that LVAD-induced hemodynamics precondition platelets to activate and aggregate, leading to incipient thrombus formation which may propagate throughout the circulation, explaining the high incidence of thromboembolic events in the absence of in-pump thrombosis. Methods: A combined computational and in vitro modeling approach is used to simulate blood flow in the left ventricle, LVAD inflow cannula, outflow graft and aortic arch, with the goal of understanding the role of LVAD therapy in hemodynamics. Results: A systematic optimization of surgical parameters (inflow cannula angle, inflow cannula insertion depth, outflow graft anastomosis angle, outflow graft diameter) and medical management (LVAD speed, blood pressure, aortic valve opening frequency) based on Lagrangian metrics confirmed that the thrombogenicity of LVAD therapy can be potentially be significantly reduced. These metrics allow for quantitative comparisons of device management. Guidelines of optimum ranges of therapy configurations, and definition of “high risk” surgical configurations to avoid have been proposed. Conclusions: Reducing thrombogenicity and improving hemocompatibility is the next frontier in durable LVAD therapy for advanced heart failure. Risk-benefit analysis of many surgical configurations and medical management strategies can be quantitatively analyzed. Systematic analysis can serve as the rationale for future clinical trials that will optimize patient outcomes and reduce complications.
A Healthy Volunteer-Derived, Factor VIII-Neutralized, Acquired Hemophilia a-Mimetic Plasma Produces Similar Pharmacodynamic Responses of Emicizumab to Those in Patients with Congenital Hemophilia a with or without Inhibitors
Authors: Koichiro Yoneyama, Kazuo Tokuda, Tetsuhiro Soeda, Tomohisa Saito, Midori Shima
Journal: Blood (2021)
An Unusual Wide Complex Rhythm—What Is the Diagnosis?
Authors: Qinghua Chang, Yuanzhe Jin
Journal: JAMA Internal Medicine (2021)

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Abstract 13743: Prevalence of Cardiac Rhythm Disturbances in Heart Failure Patients With and Without Cardiac Amyloidosis: A National Inpatient Sample Analysis
Authors: Ramtej Atluri, Sreeram Yalamanchili, Mouna Kodali, Prajwal Shrestha, Cyra Kang
Journal: Circulation (2021)

Background: Cardiac amyloidosis (CA) is well-known to affect electrocardiographic findings. However, the impact of CA on the prevalence of cardiac arrhythmias, particularly in heart failure (HF) patients, is unknown. Our aim was to assess the prevalence of arrhythmias in HF patients with and without CA. Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2017. About 5,074,059 patients who had acute, acute on chronic and chronic HF as primary or secondary diagnosis were identified and stratified based on the presence or absence of CA using ICD-10 codes. Both univariate regression and literature review were used to determine the covariates. Multivariate logistic regression analysis was used to adjust for confounders and analyze the variables. Results: Out of the 5,074,059 hospitalized patients with a primary and secondary diagnosis of HF, 7,980 individuals had CA. HF patients with CA had a higher prevalence of Atrial Fibrillation (AF) (52.6% vs 39.3%), Atrial Flutter (AFL) (9.4% vs 3.89%), Ventricular tachycardia (VT) (9.6% vs 4%), Supraventricular tachycardia (SVT) (3.9% vs 2.1%), right bundle branch block (RBBB) (2.9% vs 1.6%), 1st degree AV block (1AVB) (3.07% vs 1%), 2nd degree AV block (2AVB) (1.4% vs 0.4%), and 3rd degree AV block (3AVB) (1.25% vs 0.7%) than without. When adjusted to patient demographics, comorbidities, and hospital characteristics, HF patients with CA had higher risk of AF (aOR= 1.67, p&lt;0.0001), AFL (aOR=2.9, p&lt;0.0001), VT (aOR=2.08, p&lt;0.0001), SVT (aOR=1.63, p&lt;0.0001), RBBB (aOR=1.62, p=0.002), 1AVB (aOR=2.27, p&lt;0.0001), and 2AVB (aOR=2.86, p&lt;0.0001) compared to those without. However, there was no significant difference in the prevalence of Ventricular Fibrillation (VF) (aOR=0.92, p=0.82) in the same population. Conclusion: HF patients with CA are 67%, 190%, 108%, 63%, 62%, 127%, and 186% more likely to develop AF, AFL, VT, SVT, RBBB, 1AVB, and 2AVB respectively, than those without. However, HF patients with CA did not have a significant difference in the prevalence of VF, 3AVB, and LBBB. CA is an infiltrative disease process that is known to cause cardiac conduction disturbances. Limitations include the underdiagnosis of CA in our society as well as the non-specificity of ICD codes for CA.
Abstract 11093: Patients with Post-Acute Sequelae of Sars-cov-2 Syndrome Exhibit No Significant Abnormalities in Cardiac Energetics, Structure, Function, Blood Flow or Tissue Characteristics
Authors: Mira Gorecka, Sharmaine Thirunavukarasu, Nicholas Jex, Amrit Chowdhary, Noor Sharrack, Hui Xue, Peter Kellman, Sven Plein, Alexander D Simms, John P GREENWOOD, Eylem Levelt
Journal: Circulation (2021)

Introduction: Despite the initial recovery from the acute COVID-19 infection, an increasing number of patients are experiencing a wide spectrum of symptoms more than 12 weeks after the index diagnosis. The underlying pathophysiology of post-acute sequelae of SARS-CoV-2 (PASC) syndrome remains unknown. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease. The relative concentration of phosphocreatine to ATP (PCr/ATP) measured non-invasively by 31-phosphorus magnetic resonance spectroscopy (31P-MRS) is a sensitive index of the myocardial energetic state. It is currently unknown whether PASC is associated with abnormalities of myocardial structure, function, perfusion and tissue characteristics or energetic derangement. Methods: A total of 13 patients with a clinical diagnosis of PASC syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and ten matching controls underwent 31P-MRS and CMR at 3T at a single time point. Results: Clinical characteristics and imaging results are provided in Table-1. Between the PASC syndrome patients and controls there were no differences in myocardial energetics (PCr/ATP), in cardiac structure (left ventricular volumes, mass), function (ejection fraction, global longitudinal strain), tissue characterization (T1 and extracellular volume fraction mapping, late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). Conclusion: Patients with a clinical PASC syndrome with no prior CVD exhibit no significant abnormalities in cardiac energetics, structure, function, myocardial blood flow or tissue characteristics.
Abstract 12420: Interleukin-38 Inhibits Nod-Like Receptor Protein 3 Inflammasomes to Suppress Aortic Valve Calcification
Authors: Erlinda The, Dennis M de Graaf, Yufeng Zhai, Qingzhou Yao, Zichao Luo, Lihua Ao, David A. Fullerton, Charles A. Dinarello, Xianzhong Meng
Journal: Circulation (2021)

Calcific aortic valve disease (CAVD) is common in the elderly. Progressive valvular calcification is a characteristic pathobiology in CAVD, and chronic valvular inflammation is known to promote CAVD progression. Matrilin-2 is an extracellular matrix (ECM) protein. Soluble matrilin-2 can function as a damage - associated molecular pattern to induce the inflammatory and osteogenic responses in aortic valve interstitial cells (AVICs). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine. Lower IL-38 levels are associated with several chronic inflammatory diseases. Recent studies found that IL-38 limits skin inflammation and nephritis by reducing the inflammatory activity of immune cells. We hypothesized that IL-38 is capable of suppressing AVIC osteogenic activity. Methods and Results: We performed immunoblotting and ELISA to assess IL-38 protein levels in AVICs isolated from normal human aortic valves (normal AVICs) and diseased human aortic valves (diseased AVICs). Diseased AVICs had lower levels of IL-38 compared to normal AVICs. Interestingly, recombinant IL-38 inhibited spontaneous deposition of calcium in diseased AVICs. To determine the effect of recombinant IL-38 on AVIC osteogenic response to soluble matrilin-2, we treated normal AVICs with recombinant IL-38 (0, 1, 5 and 10 ng/ml) prior to an exposure to matrilin-2 for 24-72 hour. IL-38 at 10 ng/ml markedly reduced the expression of RUNX-2 and ALP in normal AVICs exposed to matrilin-2. Further, IL-38 suppressed calcium deposition in normal AVICs exposed to matrilin-2 for a prolonged period. Knockdown of IL-38 by shRNA enhanced the osteogenic responses and exaggerated the calcification deposit formation in normal AVICs exposed to matrilin-2. The anti-osteogenic effect of IL-38 is associated with down-regulation of Nod-like receptor protein 3 (NLRP3) inflammasomes, and inhibition of the NLRP3 inflammasomes also suppresses the osteogenic activity in normal AVICs exposed to matrilin-2. Conclusions: IL-38 suppresses the osteogenic activity in human AVICs by inhibiting NLRP3 inflammasomes. The novel findings of this study suggest that IL-38 may have therapeutic potential for prevention of CAVD progression.
Abstract 14154: Genome-Wide Association Study of Dilated Cardiomyopathy in the VA Million Veteran Program
Authors: Krishna G Aragam, Brian Charest, J M Gaziano, Peter Wilson, Lawrence Phillips, Jacob Joseph, Yan Sun, Jennifer E Huffman
Journal: Circulation (2021)

Introduction: Rare, Mendelian drivers of dilated cardiomyopathy (DCM) are well-established, but the contribution of common genetic variation to DCM risk has emerged more recently. As common variant discovery has largely relied on genome wide association studies (GWAS) of prospectively recruited DCM cases, we sought to conduct a GWAS of retrospectively-defined DCM from a large biobank. Methods: We used electronic health record-based phenotyping to define DCM in the VA Million Veteran Program (MVP), performed ancestry-specific GWAS in MVP participants of European and African genetic ancestry, and then conducted a trans-ethnic meta-analysis. We pursued replication of sentinel DCM single nucleotide polymorphisms (SNPs) in the UK Biobank. We further assessed the association of sentinel DCM SNPs with subclinical cardiac magnetic resonance imaging measures of left ventricular (LV) structure and function in UK Biobank, and with hypertrophic cardiomyopathy (HCM) in MVP. Results: Among 459,937 MVP study participants, mean age was 61.5, 43,971 (9.6%) were female, and 5,597 had DCM (N=3,786 European ancestry, N=1,811 African ancestry). In trans-ethnic meta-analysis, we identified eight genomic regions associated with DCM at genome-wide significance (P &lt; 5x10 -8 ). These included three of four known DCM associations near HSPB7 , LSM3 , and BAG3 ; and five novel genomic regions near SLC39A8 , CDKN1A , CD36 , NEDD4L , and MAP3K7CL . Three of the novel regions (at CDKN1A , NEDD4L , and MAP3K7CL ) were replicated in UK Biobank (all p&lt;8.0E-4; N=899 DCM cases, 449,574 controls). SNPs associated with increased DCM risk also associated with increased LV end-diastolic and end-systolic volumes and lower LV ejection fraction in UK Biobank participants without clinical heart failure or cardiomyopathy (N &gt; 31,614; all p &lt; 0.01). Sentinel SNPs for DCM also showed a trend towards an opposite direction of association with HCM in MVP (N=1,533 HCM cases, 465,877 controls). Conclusions: We conducted the largest GWAS of DCM to date, and identified five novel, common genetic loci associated with DCM with replication of three novel loci in an external cohort. Our findings highlight the potential to leverage emerging biobank populations to scale common variant discovery for DCM.
A growth factor–expressing macrophage subpopulation orchestrates regenerative inflammation via GDF-15
Authors: Andreas Patsalos, Laszlo Halasz, Miguel A. Medina-Serpas, Wilhelm K. Berger, Bence Daniel, Petros Tzerpos, Máté Kiss, Gergely Nagy, Cornelius Fischer, Zoltan Simandi, Tamas Varga, Laszlo Nagy
Journal: The Journal of Experimental Medicine (2021)

Muscle regeneration is the result of the concerted action of multiple cell types driven by the temporarily controlled phenotype switches of infiltrating monocyte-derived macrophages. Pro-inflammatory macrophages transition into a phenotype that drives tissue repair through the production of effectors such as growth factors. This orchestrated sequence of regenerative inflammatory events, which we termed regeneration-promoting program (RPP), is essential for proper repair. However, it is not well understood how specialized repair-macrophage identity develops in the RPP at the transcriptional level and how induced macrophage-derived factors coordinate tissue repair. Gene expression kinetics-based clustering of blood circulating Ly6Chigh, infiltrating inflammatory Ly6Chigh, and reparative Ly6Clow macrophages, isolated from injured muscle, identified the TGF-β superfamily member, GDF-15, as a component of the RPP. Myeloid GDF-15 is required for proper muscle regeneration following acute sterile injury, as revealed by gain- and loss-of-function studies. Mechanistically, GDF-15 acts both on proliferating myoblasts and on muscle-infiltrating myeloid cells. Epigenomic analyses of upstream regulators of Gdf15 expression identified that it is under the control of nuclear receptors RXR/PPARγ. Finally, immune single-cell RNA-seq profiling revealed that Gdf15 is coexpressed with other known muscle regeneration-associated growth factors, and their expression is limited to a unique subpopulation of repair-type macrophages (growth factor-expressing macrophages [GFEMs]).