tbuckley/cabot-search huggingface dataset:
Abstract 10497: Predictors of Poor Prognosis in Stable Coronary Artery Disease with and without N-Terminal Probnp Elevation
Authors: Juan Martinez-milla, Alvaro Acena, Hans P Gaebelt, Ana M Pello-Lazaro, Marta Lopez-Castillo, Carlos Gutierrez-Landaluce, Tarin Nieves, Ana Huelmos, Carmen Cristobal, Maria L Gonzalez-Casaus, oscar lorenzo, Andrea Kallmeyer, Ester Canovas, Joaquin Alonso, Jose tunon
Journal: Circulation (2021)

Background: Mineral Metabolism (MM) system and N-terminal probrain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in SCAD has not been shown yet Methods: We analyzed the prognostic value of MM markers (parathormone [PTH], klotho, phosphate, calcidiol [25-hydroxyvitamin D3], and fibroblast growth factor-23) in 964 pts. with SCAD and NT-ProBNP&gt;125 pg/ml vs pts. with NT-ProBNP≤125 pg/ml included in five hospitals of Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: 622 pts. had NT-proBNP&gt;125 pg/ml and 342 pts. had NT-ProBNP≤125 pg/ml. Median follow-up was 5.1 years. In the group of NT-proBNP&gt;125 pg/ml patients were older, and there were more females and smokers than in pts. with normal NT-proBNP.In high NT-proBNP pts., the predictors of poor prognosis were PTH [HR=1.00 (1.00-1.00) p&lt;0.001] and NT-proBNP [HR=1.006 (1.00-1.01) p=0.011], along with age [HR=1.039 (1.02-1.06) p&lt;0.001], prior coronary artery by-pass graft [HR=1.624 (1.02-2.59) p=0.041], treatment with statins [HR= 0.315 (0.19-0.53) p&lt;0.001], insulin [HR=2.490 (1.59-4.09) p&lt;0.001], angiotensin receptor blockers [HR= 1.726 (1.16-2.56) p=0.007], nitrates [HR= 1.645 (1.10-2.45) p=0.014], and proton pump inhbitors [HR= 2.754 (1.74-4.36) p&lt;0.001]. In the NT-proBNP≤125 pg/ml subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol [HR=1.01 (1.00-1.02) p=0.014] and calcidiol [HR= 0.96 (0.92-0.99) p=0.045], as well as treatment with verapamil [HR=11.28 (2.54-50.00) p=0.001], and dihydropyridines [HR= 3.16 (1.63-6.13) p=0.001], Conclusion: In pts. with SCAD and NT-ProBNP&gt;125 pg/ml, PTH and NT-ProBNP, that are markers related with ventricular damage, are predictors of poor outcome. In the subgroup of pts. with NT-ProBNP≤125 pgm/l, calcidiol and non-HDL cholesterol, more related to vascular damage, are the independent predictors of poor outcome. Then, in pts. with SCAD, baseline NT-ProBNP may influence the type of biomarker that should be used for risk prediction.
Abstract 10249: Association of Eligibility for a Sodium-Glucose Co-Transporter 2 Inhibitor and Cardiovascular Outcomes in Patients with Atrial Fibrillation
Authors: Alireza Oraii, Jeff S Healey, Sylvanus Fonguh, Jia Wang, Arjun K Pandey, David Conen, Stuart J Connolly, William F McIntyre
Journal: Circulation (2021)

Introduction: Heart failure (HF) is the leading cause of death in patients with atrial fibrillation (AF). Although sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce HF in a broad range of populations, they have not been studied specifically in patients with AF. Objective: We aimed to determine the proportion of AF patients who are eligible for an SGLT2i based on co-morbidities, and compare their risk of cardiovascular outcomes to ineligible patients. Methods: We pooled data from two randomized controlled trials (RCTs) of AF patients (RE-LY and ACTIVE-W). Among patients assigned to the anticoagulation arms, those meeting the inclusion criteria from at least one of the large Phase 3 SGLT2i RCTs were included in the “SGLT2i-eligible” and the others in the “SGLT2i-ineligible” group. Eligibility indications were diabetes mellitus + cardiovascular disease (DM+CVD), HF with reduced ejection fraction (HFrEF), and renal disease. We examined a primary outcome of cardiovascular death and hospitalization for HF, and compared study outcomes between SGLT2i-eligible and ineligible groups. Results: A total of 21485 AF patients (mean age: 71.2±8.8, 36.1% women, Median CHA 2 DS 2 -VASc Score = 3, IQR 2-4) met inclusion. The proportion of AF patients eligible for treatment with an SGLT2i was 23.6%, with 8.9%, 22.6%, 9.1% being eligible for Empagliflozin, Dapagliflozin, and Canagliflozin, respectively. Renal disease (17.6%) was the most common eligibility indication, followed by DM+CVD (9.0%) and HFrEF (5.3%). After a median follow-up of 1.9 years, the incidence of cardiovascular death/hospitalization for HF (10.9% vs. 6.3%, p&lt;0.001), cardiovascular death (5.2% vs. 2.4%, p&lt;0.001), hospitalization for HF (6.8% vs. 4.2%, p&lt;0.001), hospitalization for AF (6.7% vs. 5.4%, p&lt;0.001), and thromboembolic events (4.9% vs. 3.9%, p=0.003) was significantly higher in the SGLT2i-eligible than the ineligible group. Conclusion: The majority of AF patients are not eligible for an SGLT2i. Although these patients are lower-risk than eligible patients, they still have high rates of cardiovascular events. RCTs are needed to test the efficacy of SGLT2is in AF patients.
Abstract 12528: Intima Thickening, Adenosine Reduction and Calcification in CD73-Deficient Mice
Authors: Song Gao, Tingting Mills, Harnath S Shelat, Yong-jian Geng
Journal: Circulation (2021)

Introduction and Hypothesis: The 5' exonucleotidase, CD73, is a key enzyme for extracellular adenosine production. Mutations of the CD73 gene NT5E have been recently reported to cause a rare arterial disease named Arterial Calcification due to Deficiency of CD73 (ACDC). Using a murine model of ACDC, we tested the hypothesis that CD73 protects the arterial wall from hyperplasia and inhibits calcification of vascular smooth muscle cells (SMC). Methods and Results: Echocardiography showed that CD73 deficient mice ( CD73 -/- , n=11) (1.5 yr old, both sexes) had significantly increased aortic intima thickness than C57BL/6J wild type mice (WT, n=8). In culture with inorganic phosphate (Pi, 3.6mM) for 9 days CD73 -/- aortic SMC exhibited elevation of intracellular calcium contents than WT cells (Fig. 1a). HPLC analysis revealed more than 50% reduction of extracellular adenosine in CD73 -/- SMC compared to that in WT SMC (Fig. 1b). Addition of recombinant apolipoprotein-J (Apo-J, 6μg/mL) diminished Pi-induced calcification and restored extracellular adenosine levels in both CD73 -/- - and WT SMC. Conclusions: CD73 plays a key role in maintaining arterial intimal normality, adenosine production and de-calcification. Apo-J serves a regulator of vascular adenosine production and calcification in CD73 -/- mice.
Liver cancer risk after HCV cure in patients with advanced liver disease without non-characterized nodules
Authors: Marco Sanduzzi-Zamparelli, Zoe Mariño, Sabela Lens, Victor Sapena, Gemma Iserte, Anna Pla, Núria Granel, Concepció Bartres, Neus Llarch, Ramón Vilana, Isabel Nuñez, Anna Darnell, Ernest Belmonte, Angeles García-Criado, Alba Díaz, Sergio Muñoz-Martinez, Carmen Ayuso, Luis Bianchi, Carla Fuster-Anglada, Jordi Rimola, Alejandro Forner, Ferran Torres, Jordi Bruix, Xavier Forns, Maria Reig
Journal: Journal of Hepatology (2021)
Impaired RAS Proteolysis Drives Clonal Hematopoietic Transformation
Authors: Sisi Chen, Rahul S. Vedula, Pau Castel, Antonio Cuevas Navarro, Simon J. Hogg, Eric Wang, Xiaoli Mi, Salima Benbarche, Katherine Knorr, Won Jun Kim, Hana Cho, Caroline Erickson, Michael E Singer, Daniel Cui, Benjamin H. Durham, Daichi Inoue, Sebastien Monette, Neal Rosen, Frank McCormick, R. Coleman Lindsley, Omar Abdel-Wahab
Journal: Blood (2021)
Genome-Wide Analysis of Allele-Specific Expression Genes in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Minjun Yang, Rebeqa Gunnarsson, Linda Olsson, Andrea Biloglav, Henrik Lilljebjörn, Eleanor L Woodward, Thoas Fioretos, Bertil Johansson, Kajsa Paulsson
Journal: Blood (2021)
Abstract 10648: The Presence of Iatrogenic Atrial Septal Defect Does Not Affect the Right Ventricular Strain Function in Patients with More Than Moderate Tricuspid Regurgitation
Authors: Chiehju Chao, Amith Seri, Evelyn Fennellly, Megan Campany, Courtney Kenyon, Ayman Fath, Sean Smith, Skye Buckner-Petty, Corbin Rayfield, David Fortuin, John Sweeney, Eleid Mackram, Mohamad Alkhouli, Charanjit S RIHAL, Peter Pollak, Abdallah El Sabbagh, Reza Arsanjani
Journal: Circulation (2021)

Background/Introduction: More than moderate tricuspid regurgitation (TR) at baseline is associated with worse outcome in MitraClip patients. The presence of iatrogenic ASD (iASD) may cause right-sided volume overload and lead to adverse events. However, the real effects of iASD are not well-investigated in these patients who are vulnerable to right-sided volume overload. Methods: Patients with more than moderate TR who underwent a successful MitraClip procedure in the period from June 2014 to September 2020 were identified from the Mayo institutional NCDR database. Follow-up transthoracic echocardiography (TTE) at about 1 year after the procedure was used to determine the presence of iASD, and speckle-tracking strain analysis was done. Patients were grouped according to the presence of iASD (iASD+ group vs. iASD- group) for statistical analysis. Results: A total of 141 consecutive patients were included for the final analysis (iASD+ group n=44 and iASD- group n=97). The mean age was 79.3 ± 8.8 years, and 72.3% were male. Follow-up echocardiography and speckle-tracking strain data did not show a significant difference in either left or right ventricular function in conventional echocardiographic parameters and strain. LA reservoir strain (13.7 ± 6.9 vs 11.5±7.5, P=0.0418) was the only parameter with significant difference among the two groups. Details are summarized in Table 1 . Conclusion: The presence of iASD can decompress the left atrium, but does not affect left or right ventricular strain function in MitraClip patients with more than moderate baseline TR.
Patient, Caregiver, and Healthcare Provider Priorities for Future Multiple Myeloma Research: Results of a James Lind Alliance Priority Setting Partnership
Authors: Anthony Reiman, Samantha Fowler, Lauren McLaughlin, Sarah Bridges, Marc Robichaud, Barbara Ridgway, Donna E. Reece, Kevin W Song, Lorelei Dalrymple, Robin Sully, Sharon Nason, Suzanne Rowland, Trish MacDonald, William Paine
Journal: Blood (2021)
Abstract 12957: Determining Disease Co-Occurrence Architecture of Hypertensive Heart Disease in Penn Medicine Biobank Using Longitudinal EHR Data Linked With PMBB Participants
Authors: Pankhuri Singhal, Marie A Guerraty, Dokyoon Kim, Daniel J Rader, Marylyn D Ritchie, Anurag Verma
Journal: Circulation (2021)

An estimated 1.2 billion individuals worldwide suffer from hypertension. Hypertensive heart disease (HHD) refers to structural alterations, such as left ventricular hypertrophy in the heart due to prolonged hypertension and can lead to ischemic heart disease, heart failure, and arrhythmias. HHD represents a transitory subclinical condition between the onset of hypertension and cardiovascular disease, typically remaining asymptomatic until the time of adverse cardiac event. The risk of HHD-related diseases is heightened due to hypertension-associated comorbidities such as dyslipidemia and renal failure. The complex etiology underlying HHD makes it challenging to predict outcomes in patients. The goal of this study is to leverage longitudinal electronic health record (EHR) data to identify the conditions and comorbidities that influence HHD outcomes for prognostication. We defined an HHD patient cohort (n = 4,268) in the Penn Medicine BioBank dataset using diagnosis code ICD-10: I11* for HHD. We constructed a disease-disease map of HHD comorbidities using the Ising model, a type of Markov Random Field undirected probabilistic graphical model. We estimated the co-occurrence of disease pairs by calculating pairwise similarities between diseases as relative risk and conducting network analyses. Our results reflect clusters of known disease-disease connections, including interactions between endocrine and nervous system diseases, as well as novel pairwise disease interactions between genitourinary and musculoskeletal diseases. Our findings shed light on the effect of comorbid conditions on the trajectory of HHD adverse outcomes. Using the probabilistic model of disease co-occurrence from these results, we can identify key comorbidities that predict adverse outcomes among HHD patients. This work lays the foundation to integrate rare and common genetic variants into the Ising model using a gene-based binning approach. Incorporating rare loss-of-function variants will enable us to evaluate shared genetic connections between HHD comorbidities. In conclusion, we used EHR data to identify the genetic and non-genetic connections between comorbidities of HHD to develop a predictive metric for the prevention and clinical monitoring of HHD.
Abstract 13789: Identification of a Proteomic Signature Showing Ongoing Inflammation in Severe Rheumatic Heart Disease
Authors: Taariq M Salie, Jing Yang, Carlos R Medina, Nophar Geifman, Liesl J Zuhlke, Simon Frain, Anthony Whetton, Bernard Keavney, Mark E Engel
Journal: Circulation (2021)

Introduction: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. Methods: We conducted a proteomic study in 215 African patients with severe RHD and 230 controls, using the SWATH-MS technique. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to AUC of the ROC for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. Results: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were each higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top 6 biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. Conclusions: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may in turn be related to prognostic severity.
Abstract 12779: Up-Regulation of the Renal Sodium Transporters is Associated With Increased CD81 in Preeclampsia Rats and Patients
Authors: Yanting Yu, Gangyi Zhu, Ping Wang, Zhiyin Wang, Dan Liu, Zhiyun Ren, yali hu, Xiaoyan Wang
Journal: Circulation (2021)

Introduction: the abnormalities of placental CD81 play an important role in preeclampsia (PE), a disorder that links to the impaired placentation in the early stages of pregnancy and the subsequent systemic endothelial cell activation. Hypothesis: up-regulation of the renal sodium transporters is associated with increased CD81 in preeclampsia rats and patients Methods: we examined the renal protein abundance of CD81 and sodium transporters, channels and pump along nephron in rat model with lipopolysaccharide (LPS) -induced PE. A single ultra-low dose of LPS (0.5ug/kg) (PE) or vehicle(control group,CTL) were applied to female SD rats( age: 8-12 wks, n=4/group) on gestational day 5 (GD5) by intraperitoneal injection. Results: The SBP (101±1.6 vs 116±0.8 mmHg, p&lt;0.001, tail-cuff, BP-98A, Softron, Japan) and urine albumin (1885±35 vs 3550±157.8 ug, p&lt;0.001) were higher in PE than CTL while there were no differences in BW, fetus number/weight and serum creatinine and cholesterol concentrations (GD18) between the 2 groups. The renal protein abundances of NKCC2 (168±14 vs 100±13, % of control,P=0.02,immunoblotting) and NCC (161±16 vs 100±13, P=0.04) , among the 8 sodium transport proteins checked, were greater in PE group than in CTL group along with the increase in renal protein abundances of CD81 in PE group relative to CTL group. The protein expressions of MCP-1, IL-6, TNF-a were similar between the 2 groups. CD81 were located in thick ascending limbs of Henle’s loop and distal convoluted tubules and co-immunoprecipitated with NKCC2 and NCC in rat homogenates. CD81 was not altered in placenta, serum, liver in the LPS-PE model indicated that the increase of CD81 is kidney-specific. In PE patients , urinary exosome CD81 was also increased along with increases of NKCC2 and NCC. Furthermore, the increases of CD81 and NCC were confirmed in cultured mouse distal convoluted tubule cells (DCT) stimulated by LPS for 24 hrs at different concentrations. The knockdown of CD81 by siRNA for 48 hrs had no effects on NCC but blocked the increase of NCC induced by LPS for 24 hr. Conclusions: inhibition and decrease of renal CD81 may reverse the increases of renal sodium transporters, therefore improve the hypertension in preeclampsia.
Abstract 12456: Apelin Expressing Endothelial Stem-Like Cells Orchestrate Lung Microvascular Repair in a Model of Lung-Targeted Endothelial Cell Ablation
Authors: Rafael Soares Godoy, Nicholas D Cober, Yupu Deng, David Cook, Ananya Chakravarti, Liyuan Wang, Duncan J Stewart
Journal: Circulation (2021)

Introduction: Endothelial damage plays a central role in acute lung injury (ALI) contributing to alveolar leak and inflammatory cell trafficking. In preclinical models of ALI, repair and regeneration of lung vascular endothelium is required for its resolution. Therefore, we sought to define the cellular and molecular mechanisms underlying lung microvascular regeneration in acute lung injury induced by lung endothelial cell (EC) ablation. Methods and Results: Transgenic mice were created expressing endothelial-targeted human diphtheria toxin receptor. Intratracheal instillation of diphtheria toxin (DT) resulted in the ablation of ~70% of lung endothelial cells, producing severe acute lung injury, with complete resolution by 7 days. Changes in global lung cell populations and gene expression profiles were determined using single-cell RNA sequencing of dissociated lung cells (10x Genomics) at baseline (day 0), 3, 5 and 7 days after lung EC ablation. Single cell analysis revealed 8 distinct EC clusters, including type-A capillary ECs which were characterized by the unique expression of apelin at baseline. DT-induced EC ablation resulted in the emergence of novel endothelial stem-like cells within a transient population of ‘general’ capillary ECs, characterized by the de novo expression of apelin at day 3 post injury. As well, this population exhibited unique expression of the vascular endothelial stem cell marker, protein C receptor, together with the progenitor cell marker, CD34. This was followed by the appearance of proliferative ECs at day 5 expressing apelin receptor and the transcription factor, FoxM1, and these cells were responsible for replenishment of all depleted EC populations. Finally, treatment with an apelin receptor antagonist, ML221, prevented lung microvascular recovery and resulted in death at 4-5 days post DT. Conclusion: Targeted EC ablation revealed a remarkable regenerative capacity of the lung microvasculature. Using single cell transcriptomics, we have demonstrated that lung microvascular repair was orchestrated by newly emergent apelin-expressing endothelial stem-like cells.
Abstract 10843: P2Y12 Inhibitor Adherence Patterns in Patients with Acute Coronary Syndrome
Authors: Aya Ozaki, Dennis T Ko, Alice Chong, Jiming Fang, Peter Austin, Maneesh Sud, Cynthia A Jackevicius
Journal: Circulation (2021)

Introduction: Dual antiplatelet therapy with P2Y12 inhibitors (P2Y12i) and ASA reduce cardiac events after acute coronary syndrome (ACS). Use has shifted from clopidogrel to ticagrelor, a more potent P2Y12i with higher bleeding risk, dosed twice rather than once daily. As these factors may impact adherence, a better understanding of adherence patterns by agent is needed. Methods: We conducted a population-based cohort study using administrative claims data in Ontario, Canada between 4/2014-3/2018. We identified individuals ≥65 years of age who were admitted for myocardial infarction or unstable angina and had filled a P2Y12i prescription within 7 days of discharge. We excluded patients who died within 1 year after discharge. We calculated “good” adherence [proportion of days covered (PDC) 1 year post-ACS ≥80%, and also used group-based trajectory models to characterize longitudinal patterns of good adherence by time over 1 year. Results: We included 21,680 ACS patients with 45.0% (n=9,763) prescribed ticagrelor and 55.0% (n=11,917) prescribed clopidogrel [mean age±SD: 73.6±6.8/77.3±8.3 years, 65.4%/56.2% male, PCI during index admission 87.4%/48.5%, respectively]. Overall, the good adherence rate was 73.0% for ticagrelor and 78.9% for clopidogrel. We identified 3 adherence patterns in the year post-ACS: 67.8% of ticagrelor and 75.0% of clopidogrel patients were in the adherent group (PDC≥80%), while 17.1 %/13.4% were in the gradually non-adherent, and 15.1%/11.6% were in the rapidly non-adherent groups, respectively. (Figure) Conclusions: Adherence rates and trajectories appeared more favorable for clopidogrel in the first year post-ACS. However, patient characteristics differed between the clopidogrel and ticagrelor populations and these may be associated with the observed adherence patterns. Identification of nonadherence risk factors and barriers specific to each trajectory group is needed to improve adherence and clinical outcomes.