tbuckley/cabot-search huggingface dataset:
Abstract 13407: Validation of the MIRACLE2 Score for Prognostication After Out of Hospital Cardiac Arrest
Authors: Francine Cheese, Zoe Leadbetter, Nicholas Sunderland, Thomas Johnson
Journal: Circulation (2021)

Background: Early prediction of long-term outcomes after out-of-hospital cardiac arrest (OOHCA) remains a diagnostic challenge. MIRACLE2 is a points-based risk score that has been derived as a simple tool to aid clinicians in prognosticating those at high risk of poor neurological outcomes. To date, the score has been validated in two independent cohorts in the MIRACLE2 study. The aim of this study was to validate the MIRACLE2 score in a further independent cohort, with the primary outcome poor neurological outcome at 6 months (Cerebral Performance Category (CPC) 3-5). Methods: We retrospectively identified all patients treated at the Bristol Royal Infirmary from January 2019 to July 2020 with a primary or secondary ICD-10 diagnosis code for cardiac arrest. Patients were screened against the inclusion and exclusion criteria used in the MIRACLE2 study and the data required to calculate the MIRACLE2 and CPC scores were extracted from medical records. Results: 198 patients met the OOHCA inclusion criteria and were included for analysis. Multivariable logistical regression confirmed 6 out of the 7 MIRACLE2 components as independent predictors of poor neurological outcome at 6 months: age category (60-80 years, OR 6.4, p=0.005; &gt;80 years, OR 148.1, p&lt;0.001), initial non-shockable rhythm (OR 36.9, p&lt;0.001), non-reactivity of pupils (OR 13.7, p=0.002), low pH &lt;7.20 (OR 5.1, p=0.014), adrenaline administration (OR 4.1, p=0.024), changing intra-arrest rhythms (OR 3.4, p=0.048). The MIRACLE2 score had an area under the curve of 0.89. The risk of poor neurological outcome in this cohort, across the previously described MIRACLE2 score risk groups (low &lt;=2, intermediate 3-4, and high &gt;=5), was comparable to that in the MIRACLE2 study (low: 15% vs. 6%; intermediate: 54% vs. 55%; and high: 93% vs. 92%, respectively). Conclusion: The MIRACLE2 score has been externally validated in an independent cohort as an accurate predictor of poor neurological outcome following OOHCA.
Abstract 14439: Complications With Medtronic’s SelectSecure 3830 Leads When Used for Atrial and Ventricular Pacing versus Conduction System Pacing in the United States
Authors: Keerthish C Jaisingh, Sania Jiwani, Sahith Reddy Thotamgari, Pramod Kumar Ponna, Paari Dominic
Journal: Circulation (2021)

Introduction: Conduction system pacing is physiological and is therefore gaining interest. The Medtronic SelectSecure 3830 lead was officially approved by the FDA for His-bundle pacing (HBP) in 2018. However, prior to 2017-2018, this lead was mainly used for atrial pacing, ventricular pacing, or both. We evaluated and compared nationwide adverse events and complications associated with this lead prior to and after 2017. Hypothesis: Compare adverse events and complications associated with Medtronic’s SelectSecure 3830 leads before 2017 when it was mainly used for atrial, ventricular, or atrial and ventricular pacing to events after 2017 when it was mainly used for HBP. Methods: We collected adverse event reports from the FDA’s Manufacturer and User Facility Device Experience (MAUDE) on SelectSecure 3830 leads between 2008 and 2020. We searched the data base with key words “selectsecure” and “select secure” along with the model number “3830” to aggregate the data. Duplicate entries were screened and removed, and the location the leads were used was classified. Results: Total number of adverse events reported before 2017 was 393 (90.5%) when compared to after 2017, 41 (9.5%). The percentage of adverse events reported when the lead was used for atrial, ventricular, or atrial and ventricular pacing was 95.3%, when compared to 4.7% when the lead was used for HBP. The most common adverse events reported were capture and threshold issues (16.8%; PRR for atrial/ventricular lead location 0.76 [95% CI: 0.32-1.78] vs. 1.30 [95% CI: 0.55-3.06] for His-bundle lead location) and lead dislodgement (15.6%; PRR for atrial/ventricular lead location 1.03 [95% CI: 0.27-3.81] vs. 0.96 [95% CI: 0.26-3.58] for His-bundle lead location); which were comparable. Conclusion: Medtronic’s SelectSecure 3830 leads had comparable capture/threshold and lead dislodgement issues regardless of the atrial, ventricular, or His-bundle location.
Abstract 10693: Noninvasive Assessment of Contractility and Compliance of the Left Ventricle in Children: Myocardial Stiffness Measured Throughout the Cardiac Cycle by Shear Wave Imaging
Authors: olivier villemain, Jerome Baranger, Dariusz Mroczek, Luc L Mertens, Minh Nguyen, Rajiv Chaturvedi
Journal: Circulation (2021)

Background: Intrinsic myocardial stiffness (MS) is load-independent, unlike most parameters to assess LV systolic and diastolic function. Pre-clinical studies have found good correlation between 1) peak-systolic MS and contractility (or ESPVR); 2) end-diastolic MS and compliance (or EDPVR). Shear wave imaging (SWI) by ultrafast ultrasound imaging allows MS measurement throughout the cardiac cycle. Methods (Fig 1): Five children with LV pressure-overload (LV-PO; 2 aortic stenosis, 3 coarctation) were studied during cardiac catheterization and there were 5 age-matched controls. Interventricular septal MS was measured by SWI every 100ms during the cardiac cycle, pre- and post-balloon dilation. ESPVR and EDPVR were assessed by pressure-volume loops by a pressure catheter and real-time 3D-echo volumes. Results (Fig 2): Peak-systolic MS was higher in LV-PO (22.7±6.7 kPa) than controls (8.4±2.8 kPa; p&lt;0.01) and compared to end-diastolic MS (LV-PO 4.8±1.7 kPa, control 1.3±0.8 kPa; p&lt;0.01). End-diastolic MS was correlated with LV end-diastolic pressure (r=0.74). Relief of PO did not change the peak MS in the LV-PO (p=0.88). Correlations between peak-systolic MS and ESPVR (r=0.72), and between end-diastolic MS and EDPVR (r=0.79) were confirmed. Conclusions: Non-invasive MS is a load-independent measure of LV systolic contractility and diastolic compliance in children.
Challenges in optimising patient participation in research: do patients participating in meetings represent the actual patient population with Behçet’s syndrome?
Authors: Sıtkı Safa Taflan, Sinem Nihal Esatoglu, Yesim Ozguler, Berna Yurttas, Melike Melikoglu, Gulen Hatemi
Journal: Annals of the Rheumatic Diseases (2021)

The importance of patient involvement in healthcare research is increasingly emphasised. Patients participate as research partners in designing studies and development of management recommendations, measurement tools and outcome measures.1 Both Outcome Measures in Rheumatology (OMERACT) and the British Medical Journal encourage patient involvement in various aspects of research.2 3 However, ensuring representation of the general patient population by specific patient groups may be challenging for multisystem diseases with heterogeneous phenotype. This is important for ensuring a successful structural involvement of patients in research, without over/underrepresentation of certain groups based on demographic or clinical features. Behcet’s syndrome (BS) is a multisystem variable vessel vasculitis that shows substantial heterogeneity in clinical findings and disease course.

We aimed to evaluate whether patients with BS participating in a patient convention represent the actual patient population attending the clinic. A questionnaire was applied to 104 patients with BS (Meeting group) attending the patient convention, which was held during the Cerrahpasa Behcet’s Disease Symposium in Istanbul in February 2020. Patients had been invited to …
Abstract 9715: Feasibility of Using Machine Learning to Establish a Risk Prediction Model for Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy
Authors: Jie Liu, Guixin Wu, Xinxing Feng, Shuai Zhang, Dong Wang, Lianjun Xu, Wen Jiang, xiaolu sun, Lianming Kang, Xin Huang, Jizheng Wang, lei song
Journal: Circulation (2021)

Introduction: Risk stratification for sudden cardiac death (SCD) is a great challenge in managing hypertrophic cardiomyopathy (HCM). Hypothesis: This study attempted for the first time to build a machine learning (ML) model for SCD risk prediction. Methods: The present study consisted of 1631 consecutive adult HCM patients without a history of SCD events. Extreme gradient boosting (XGBoost) was applied for ML model construction. We compared the predictive performance of the ML model with that of conventional models by calculating C-statistics and interpreted the ML model output using the SHapley Additive exPlanation (SHAP) value. Results: Fifty patients reached SCD endpoints during a median follow-up of 4.6 years. The C-statistic of the ML model was 0.745 [95% confidence interval (CI), 0.723-0.766], which was significantly higher than that of the model recommended in the 2014 European Society of Cardiology guidelines (C-statistics =0.609; 95% CI 0.585-0.623) and the model recommended in the 2020 American College of Cardiology/American Heart Association guidelines (C-statistics =0.628; 95% CI 0.604-0.652). The ML model incorporated 12 features as predictors, including 5 conventional SCD risk markers (NSVT, quantification of LGE, family history of SCD, LVEF 50%, unexplained syncope), WBC, creatine, uric acid, TBIL and cholesterol, NT-proBNP and family history of HCM. Using SHAP values, we quantified the contribution of each feature within the ML model to the final prediction and visualized the relationship between features and SCD risk. Conclusion: Our study constructed an ML model for the prediction of SCD risk in patients with HCM and provided a clinically intuitive interpretation. The ML model showed better discrimination performance than conventional models, demonstrating the feasibility of ML in SCD risk prediction for patients with HCM.
Abstract 11504: Socioeconomic Factors Including Neighborhood SES Leading to Gaps in Care for Patients with Significant Congenital Heart Disease
Authors: Abbas H Zaidi, Kimberlee Gauvreau, Emily M Bucholz, Susan F Saleeb, Kathy J Jenkins, Sarah Deferranti
Journal: Circulation (2021)

Introduction: Lifelong continuity of care is crucial for patients with significant congenital heart disease (CHD). Unfortunately, gaps in care (GIC) are common and may be attributed to vulnerable developmental periods, changes in insurance status, lack of symptoms or knowledge regarding follow-up, and inability to access specialty care. There is limited understanding of socioeconomic and demographic factors that contribute to GIC in CHD. Hypothesis: Socioeconomic factors including U.S. neighborhood socioeconomic score(SES) are associated with GIC in patients with significant CHD. Methods and Results: A total of 8674 patients followed at Boston Children's Hospital (BCH) with moderate to severe CHD(as defined by AHA/ACC 2008 guidelines) were seen in clinic between January 2013 and December 2015. Socioeconomic characteristics including language, race, ethnicity, and U.S. neighborhood socioeconomic score (SES) were analyzed. GIC of &gt; 3.25-years were identified in 33% (2829) of patients. GIC were associated with being an adolescent or young adult (13-23 years) (P&lt;0.001), non-English speaking (P&lt;0.002), non-white (P&lt;0.001), Hispanic ethnicity (P = 0.02), and a low SES (P &lt;0.001). Conclusions: A third of patients with significant CHD experienced a substantial GIC (&gt;3.25 years). Adolescent young adult age and socioeconomic factors, including race, ethnicity, language, and a low SES were associated with GIC in patients with significant CHD. Interventions to identify and support these vulnerable populations could improve patient continuity of care and overall outcomes. Further studies are needed to understand the reasons for such GIC in vulnerable populations.
CBIO-02. IN VITRO TUMOR TREATING FIELDS (TTFields) REDUCE PROLIFERATION AND ALTER MLH1 EXPRESSION IN TEMOZOLOMIDE RESISTANT (TMZR) PATIENT-DERIVED GLIOBLASTOMA (GBM) CELLS
Authors: Sharon Michelhaugh, Katherine Degen, Blake Walker, Sandeep Mittal
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND TTFields therapy is approved as a monotherapy for the treatment of recurrent GBM, tumors that often have acquired resistance to TMZ. To examine TTFields efficacy in the context of TMZR in vitro, TTFields were applied to TMZR GBM cells to assess proliferation, clonogenicity, and changes in expression of O6-methylguanine-DNA methyltransferase (MGMT) that confers TMZ resistance and DNA Mismatch Repair Protein Mlh1 (MLH1) that may confer TMZ sensitivity. METHODS 15-037 GBM cells were isolated from a newly-diagnosed patient tumor (IDH-WT, unmethylated MGMT promoter. Cells were grown in DMEM/F12 media with 10% FBS and gentamicin. U-251 MG cells and 15-037 cells were incubated with 100 µM TMZ for three 5-day cycles to establish TMZR. TMZR cells were plated on coverslips (1×104cells/coverslip) and incubated overnight prior to TTFields application. TTFields were applied at 200 kHz (field intensity of ~1.6 V/cm) for 14 days. Then coverslips (n=3/group) were harvested, counted, and replated for clonogenic assay at 1000 cells/35mm2 well. Clonogenic assay plates were stained with crystal violet, imaged, and colonies counted. Additional coverslips (n=3/group) were harvested and MGMT and MLH1 expression were assessed by qRT-PCR with the delta-delta Ct method using GAPDH as housekeeping control. Cell counts and colony counts were compared with two-tailed t-test with significance at p&amp;lt; 0.05. RESULTS In U-251 MG and 15-037 TMZR cells, TTFields application significantly reduced both cell counts and clonogenic assay colony counts compared to untreated controls (U-251 MG: 45.4% and 26.5%; 15-037: 96.2% and 60.9%, respectively, p&amp;lt; 0.05). In both TMZR cell lines, MGMT expression was unchanged by TTFields, but MLH1 expression increased 2.2 fold in U-251 MG cells and 7.1 fold in 15-037 cells after TTFields application. CONCLUSIONS Not only are TMZR GBM cells sensitive to TTFields in vitro, but TTFields increased expression of MLH1 which may be able to reduce resistance to TMZ.
Abstract 11701: Ultrasound Acceleration Does Not Provide Detectable Benefit During Catheter-Directed Thrombolysis for Massive or Submassive Pulmonary Embolism: A Meta-Analysis of the Available Evidence
Authors: Adam M Combiths, Feng Gao, Mahboob Alam
Journal: Circulation (2021)

Introduction: Compared with systemic thrombolysis, catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) reduces the risk of mortality and major bleeding due to lower thrombolytic doses. The only FDA-approved device for CDT is a more expensive ultrasound-accelerated CDT (USAT) device, which uses high frequency ultrasound waves to disrupt the fibrin mesh of the thrombus. No trials comparing CDT vs USAT exist. We conducted a meta-analysis of all published studies that employed CDT and/or USAT for acute PE, stratified by PE severity. Hypothesis: Ultrasound acceleration will improve mortality, bleeding risk, and right heart strain in acute PE over standard CDT. Methods: We performed a retrospective non-time-limited literature search of PubMed for all studies of either catheter-directed thrombolysis technique. Outcome measures (30-day mortality, major bleeding, RV/LV ratio, pulmonary artery systolic pressure) were extracted. Meta-analyses were performed using RevMan Review Manager 5.3 (Cochrane Collaboration). Random Effects Model was used to calculate proportion, mean difference, and Chi-square with 95% confidence intervals. Results: Of 1260 patients in the 34 identified studies, 311 had massive PE, and 928 underwent USAT. There was no difference between CDT and USAT in 30-day mortality in massive PE (27% [7, 48] vs 30% [-2, 62], Chi2=0.02, p=0.90, I2=40%) or submassive PE (5% [-5, 15] vs 3% [0, 7], Chi2=0.16, p=0.69, I2=0%), in major bleeding in massive PE (21% [0, 43] vs 16% [2, 31], Chi2=0.15, p=0.70, I2=58%), in pulmonary artery systolic pressure in massive PE (md 25.73 [16.06, 35.40] vs 19.75 [5.38, 34.12], Chi2=0.46, p=0.50, I2=89%) or submassive PE (15.71 [10.31, 21.89] vs 15.62 [9.77, 21.47] Chi2=0.01, p=0.91, I2=85%). Conclusions: Both techniques are efficacious in improving mortality, bleeding, and right heart strain. However, few studies report outcomes for standard CDT, and between-study heterogeneity is high. Differences in 30-day mortality, major bleeding events, and markers of right heart strain were not detected between techniques in our met-analysis. Practitioners are left without evidence of benefit for ultrasound acceleration, pending the results of the ongoing randomized-controlled trial .
Abstract 10140: Atrial Natriuretic Peptide Deficiency Associated with Greater Cardiometabolic Disease in Males
Authors: Tomoko Ichiki, Seethalakshmi R Iyer, Christopher Scott, Valentina CANNONE, Jeson Sangaralingham, Kent Bailey, Jens P Goetze, Yoshihisa Tsuji, Richard J Rodeheffer, John C Burnett
Journal: Circulation (2021)

Introduction: The cardiac hormone atrial natriuretic peptide (ANP) plays a key role in blood pressure (BP) and metabolic homeostasis through guanylyl cyclase receptor-A. While the role of ANP in cardiovascular disease (CVD) has been extensively investigated, its role in metabolic regulation has only recently emerged. A genetic variant of the ANP gene (rs5068), which increases production of ANP and NT-proANP, is associated with lower blood pressure (BP), reduced risk for hypertension and a decreased prevalence of obesity and metabolic syndrome. Hypothesis: We hypothesized that sex differences in ANP may have an important role in cardiometabolic disease together with cardiovascular (CV) morbidity and mortality. Methods: We studied 1176 subjects (age &gt; 45 years) in the general population from Olmsted County MN. Plasma ANP molecular forms were quantified. Metabolic and cardiorenal parameters, and detailed medical records were reviewed. The cardiometabolic protective action of the ANP gene variant rs5068 was also assessed. Subjects were followed for all-cause mortality and morbidity for 12 years. Results: Plasma ANP molecular forms were significantly lower in males compared to females. Males had higher BMI and greater incidence of myocardial infarction (MI), coronary artery disease and heart failure (HF). Males also had lower EF and HDL cholesterol and higher LA volume and LV mass, serum glucose, insulin and diastolic pressure. The presence of the rs5068 minor allele improved the cardiometabolic phenotype including BP and widespread metabolic parameters in males but not females. After adjustment by age, males had increased risk of all-cause mortality, HF, MI, and stroke. Conclusions: Males are characterized by a relative ANP deficiency compared to females and widespread prevalence of cardiometabolic disease and increased CV morbidity and mortality in the general population. We demonstrate that the cardiometabolic protective action of the ANP gene variant rs5068 minor allele is sex dependent and protective in males. These findings have diagnostic and therapeutic implications, particularly in males.
Abstract 13336: Investigating the Effects of Physiological Shear Stress on Monocyte Phenotype for Therapeutic Development in Atherosclerosis
Authors: Dasia Aldarondo, Chris Huynh, Elizabeth Wayne
Journal: Circulation (2021)

Introduction: Monocytes are highly plastic immune cells which play a significant role in atherosclerosis development and progression. Monocyte phenotype is modulated by stimuli including physical parameters like the shear stress induced by blood flow. Atherosclerotic plaque formation impedes blood flow thereby impacting the shear stress applied to monocytes. The altered shear stress could contribute to the abnormal monocyte phenotype populations in atherosclerotic patients. Aim: To understand the relationship between monocyte phenotypic response to varying physiological shear stresses. Methods: To investigate the dynamics of monocytes under inflammatory stresses, THP-1wt cells were exposed to 40 dyne/cm 2 and 5 dyne/cm 2 which represent above normal and below-normal, atherosclerotic shear stress conditions respectively. Monocytes were either untreated or stimulated with lipopolysaccharide (LPS) to simulate low-grade inflammation. To evaluate the phenotypic response, ELISA and qPCR measurements of pro-inflammatory (TNF-α IL-12, NOS2, MAC-1, CCL2, CD40), anti-inflammatory (IL-10), and adhesion molecules (ICAM-1, VCAM-1, CCR2) were taken directly after, and four hours post shearing. Results: Shear stresses of 5 dyne/cm 2 or 40 dyne/cm 2 show differential response profiles in monocytes. At both stresses, THP-1wt cells downregulated expression of inflammatory and adhesion molecules after 4hrs. However, pre-stimulation with LPS resulted in either maintained or increased levels of expression. Notably, LPS stimulation for both shear stresses saw a 40-fold or greater increase in TNF-α, CCL2, CD40, and VCAM-1 after 4-hour incubation. In all conditions angiotensin converting enzyme 2 (ACE2), a molecule important for blood pressure regulation, was downregulated. Conclusion: The data concludes that shear stress has an impact on the activation of monocytes in both unstimulated and stimulated conditions. LPS data suggests that monocytes which are already in proinflammatory conditions are more susceptible to sustained activation from shear stress.
Abstract P455: Acetylated Cyclophilin D Regulates Mitochondrial Electron Transport Chain Activity In The Developing Heart
Authors: Gisela Beutner, Jonathan Burris, George A Porter
Journal: Circulation Research (2021)

Background: Mitochondria generate energy in form of ATP in mature eukaryotic cells. The components of the electron transport chain (ETC) are expressed at embryonic (E) day 9.5 in mouse hearts, but ETC activity and oxidative phosphorylation (OXPHOS) are uncoupled, because the permeability transition pore (PTP) is open. In mouse hearts the mPTP closes around E11.5. Opening and closing of the PTP is regulated by cyclophilin D (CypD), but the regulatory mechanism are not understood. Hypothesis: Maturation of ETC activity is regulated by acetylated CypD. Methods: Cardiac tissue homogenates or isolated heart mitochondria from mice, ranging in age from E 9.5 to adult, were used to measure oxygen consumption and the calcium retention capacity. The expression of proteins of the ETC and their assembly into supercomplexes was followed by denaturing and native electrophoresis. The expression of CypD and its acetylation status were assessed by western blotting and densitometry. The enzymatic activity of the ETC complexes and CypD was measured using spectrophotometry. Results: In the heart of mouse embryos at E 9.5 mitochondrial ETC activity and OXPHOS are not coupled (respiratory control ratio (RCR) 1.48 ± 0.17, n=9). Addition of 1 μM cyclosporin A, an inhibitor of CypD and the PTP acutely increases the RCR to 3.69 ± 0.59 (n=5). At E13.5, the end of the embryonic period in the mouse, OXPHOS is coupled and not significantly different from the adult heart. The enzymatic activity of the ETC complexes I, II, III and V increases significantly from E9.5 to the adult heart and the assembly of mitochondrial supercomplexes begins at about E13.5. The total expression of CypD increases as the mouse heart matures, but the enzymatic activity of CypD decreases. In addition, the ratio of acetylated CypD to the total expressed CypD decreased from 1.1 ± 0.16 (n=3) at E9.5 to 0.54 ± 0.06 (n=3) in the adult heart. Conclusion: The activity of acetylated CypD regulates maturation of mitochondrial ETC activity in the developing mouse heart.