tbuckley/cabot-search huggingface dataset:
Exercise Stress Real-Time Cardiac Magnetic Resonance Imaging for Noninvasive Characterization of Heart Failure With Preserved Ejection Fraction
Authors: Sören J. Backhaus, Torben Lange, Elisabeth F. George, Kristian Hellenkamp, Roman J. Gertz, Marcus Billing, Rolf Wachter, Michael Steinmetz, Shelby Kutty, Uwe Raaz, Joachim Lotz, Tim Friede, Martin Uecker, Gerd Hasenfuß, Tim Seidler, Andreas Schuster
Journal: Circulation (2021)

Right heart catheterization using exercise stress is the reference standard for the diagnosis of heart failure with preserved ejection fraction (HFpEF) but carries the risk of the invasive procedure. We hypothesized that real-time cardiac magnetic resonance (RT-CMR) exercise imaging with pathophysiologic data at excellent temporal and spatial resolution may represent a contemporary noninvasive alternative for diagnosing HFpEF.The HFpEF-Stress trial (CMR Exercise Stress Testing in HFpEF; URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621. URL: https://dzhk.de/; Unique identifier: DZHK-17) prospectively recruited 75 patients with echocardiographic signs of diastolic dysfunction and dyspnea on exertion (E/e'>8, New York Heart Association class ≥II) to undergo echocardiography, right heart catheterization, and RT-CMR at rest and during exercise stress. HFpEF was defined according to pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during exercise stress). RT-CMR functional assessments included time-volume curves for total and early (1/3) diastolic left ventricular filling, left atrial (LA) emptying, and left ventricular/LA long axis strain.Patients with HFpEF (n=34; median pulmonary capillary wedge pressure at rest, 13 mm Hg; at stress, 27 mm Hg) had higher E/e' (12.5 versus 9.15), NT-proBNP (N-terminal pro-B-type natriuretic peptide; 255 versus 75 ng/L), and LA volume index (43.8 versus 36.2 mL/m2) compared with patients with noncardiac dyspnea (n=34; rest, 8 mm Hg; stress, 18 mm Hg; P≤0.001 for all). Seven patients were excluded because of the presence of non-HFpEF cardiac disease causing dyspnea on imaging. There were no differences in RT-CMR left ventricular total and early diastolic filling at rest and during exercise stress (P≥0.164) between patients with HFpEF and noncardiac dyspnea. RT-CMR revealed significantly impaired LA total and early (P<0.001) diastolic emptying in patients with HFpEF during exercise stress. RT-CMR exercise stress LA long axis strain was independently associated with HFpEF (adjusted odds ratio, 0.657 [95% CI, 0.516-0.838]; P=0.001) after adjustment for clinical and imaging measures and emerged as the best predictor for HFpEF (area under the curve at rest 0.82 versus exercise stress 0.93; P=0.029).RT-CMR allows highly accurate identification of HFpEF during physiologic exercise and qualifies as a suitable noninvasive diagnostic alternative. These results will need to be confirmed in multicenter prospective research studies to establish widespread routine clinical use. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03260621. URL: https://dzhk.de/; Unique identifier: DZHK-17.
Prediction of mortality from 12-lead electrocardiogram voltage data using a deep neural network
Authors: Sushravya Raghunath, Alvaro E. Ulloa Cerna, Linyuan Jing, David P. vanMaanen, Joshua Stough, Dustin N. Hartzel, Joseph B. Leader, H. Lester Kirchner, Martin C. Stumpe, Ashraf Hafez, Arun Nemani, Tanner Carbonati, Kipp W. Johnson, Katelyn Young, Christopher W. Good, John M. Pfeifer, Aalpen A. Patel, Brian P. Delisle, Amro Alsaid, Dominik Beer, Christopher M. Haggerty, Brandon K. Fornwalt
Journal: Nature Medicine (2020)
Abstract 14044: Engineering Bioactive Nanoparticles to Rejuvenate Vascular Progenitor Cells
Authors: Loan T Bui, Shanique Edwards, Laura Alderfer, Laura Haneline, Donny Hanjaya-putra
Journal: Circulation (2020)

Introduction: Fetal exposure to gestational diabetes mellitus (GDM) predisposes children to future health complications including hypertension and cardiovascular disease. A key mechanism by which these complications occur is through stress-induced dysfunction of vascular progenitor cells, including endothelial colony-forming cells (ECFCs). In particular, overexpression of transgelin (TAGLN), also known as SM22α, in GDM-ECFCs is associated with actin cytoskeletal rearrangement, which results in reduced cell migration and impaired vasculogenesis. We hypothesized that bioactive nanoparticles (NPs) conjugated on the surface of GDM-ECFCs can provide a sustained pseudo-autocrine stimulation to improve in vitro and in vivo vasculogenesis. Methods &amp; Results: We designed multilamellar lipid NPs with an average size of 147±63 nm in diameter to deliver small molecules SB-431542 (TGF-β inhibitor) directly to the surface of GDM-ECFCs. Bioactive NPs can be robustly conjugated to the surface of ECFCs using thiol-maleimide coupling without altering cell viability and key progenitor phenotypes. By controlling the release kinetic of TGF-β inhibitor from the NPs, we can normalize TAGLN expression and improve cell migration, a critical key step in establishing functional vascular networks. Moreover, bioactive NPs can restore the vasculogenic potential of GDM-ECFCs in both 2D Matrigel and 3D collagen assays. Finally, when transplanted into immunodeficient mice, GDM-ECFCs conjugated with bioactive NPs exhibit robust de novo blood vessel formation with high engraftment rate, comparable to normal ECFCs. Conclusions: Collectively, these findings highlight a simple, yet promising strategy to rejuvenate GDM-ECFCs and improve their therapeutic potentials, which can be clinically-translated to address various cardiovascular complications, as well as toward a range of approaches in tissue repair and regenerative medicine.
Abstract 15097: Covid-19 and Cardiovascular Complications: Pooled Analysis of Observational Studies
Authors: Vikramaditya Reddy Samala Venkata, Rahul Gupta, Surya Kiran Aedma, Bruce W Andrus
Journal: Circulation (2020)

Introduction: The pandemic of COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection. Studies published so far raise concerns for cardiac complications in the infected individuals.The aim of our study is to determine the prevalence of cardiac complications in COVID-19. Methods: A systematic electronic search was performed in PubMed, Embase, Google Scholar. Retrospective studies having original hospitalized patient data were included in our study; while studies focussed only on intensive care unit (ICU) patients were excluded to prevent selection bias. Pooled analysis using a random effects model (Mantel-Haenszel test) was performed to look at the incidence of troponin elevation and association between elevated troponin levels, admission to the ICU and associated mortality. Results: 18 studies from 6 countries with over 9,500 patients were included in our analysis. Troponin elevation was reported in 16% (1123/7130) of patients. Heart failure was reported in 1 study and cardiac arrhythmia was reported in 2 studies. Elevated troponin levels were associated with higher rates of ICU admission (OR 26.17, 7.06-96.94; p&lt;0.01) and mortality (OR 27.22, 10.24-72.33; P&lt;0.01) (Figure 1). Information regarding the degree of troponin elevation and etiology associated with it (myocarditis vs acute coronary syndrome vs stress induced from critical illness) was not reported. Conclusion: Heart failure was reported in around 20% of the patients in 1 study, while troponin elevation was seen in 16% of the patients in 10 different studies. This is similar to the rate of cardiac complications reported in severe community acquired pneumonia. Troponin elevation in itself was associated with higher rates of ICU admission and mortality. This should alert the clinicians to check for troponin levels in these patients and triage them accordingly. More studies are needed to better understand specific mechanisms of cardiac injury in COVID-19 patients.
Abstract 14713: Renal Denervation: Impact on Non-ST Segment Elevation Myocardial Infarction Rates in Patients With Hypertensive Heart Disease
Authors: Siyolise S Sibeko, Marshall J Heradien, Pieter Van Der Bijl, Rene Janse van Rensburg, Warren Stilwaney, Dale Peterson, Andre A Saaiman, Christeman J Greyling, Paul A Brink
Journal: Circulation (2020)

Introduction: Catheter-based renal denervation (RDN) is an emerging therapy for hypertension, with potential ancillary benefits, e.g. a decrease in atrial fibrillation. Little is known about its effects on coronary artery disease (CAD) and acute coronary syndromes (ACS), e.g. non-ST segment elevation myocardial infarction (NSTEMI). Hypothesis: RDN reduces the incidence of NSTEMI in patients with hypertension and CAD. Methods: Data were retrospectively analyzed from the Renal Sympathetic Denervation Prevents Atrial Fibrillation in Patients with Hypertensive Heart Disease (RDPAF) trial (NCT01990911), which prospectively randomized individuals with uncontrolled hypertension and hypertensive heart disease to RDN or sham procedure groups in a 1:1 fashion. All patients required an indication for invasive coronary angiography. The impact of RDN on incident NSTEMI was evaluated with a log-rank test. Results: A total of 80 patients (mean age 65±8 years, 73% male) were analyzed: 42 (53%) patients underwent RDN, while 38 (47%) received sham-RDN. Baseline characteristics did not differ between groups: 54% of the total study population had diabetes mellitus, 88% took statins, 13% were current smokers and 68% had established CAD. After a mean follow-up of 38±23 months, 9 (11%) patients experienced a NSTEMI: 1 RDN (2.38%) vs 8 sham patients (21%) (OR: 0.092; 95% CI: 0.01 to 0.77; p=0.009; figure). Office systolic blood pressures decrease after six months’ follow-up did not differ between groups (-12.88mmHg in RDN vs. -9.13 mmHg in sham group; p= 0.49). Conclusions: Hypertensive patients who underwent RDN experienced a lower rate of NSTEMI during long term follow-up, compared to a sham-RDN control group. This may signal a novel benefit of RDN, i.e. a reduction in the incidence of ACS. Larger, prospective studies are needed to test this hypothesis and unravel potential protective mechanisms of RDN.
Macrophage-Based Approaches for Cancer Immunotherapy
Authors: Nicholas R. Anderson, Nicholas G. Minutolo, Saar Gill, Michael Klichinsky
Journal: Cancer Research (2020)

Adoptive cell therapy with genetically modified T cells has generated exciting outcomes in hematologic malignancies, but its application to solid tumors has proven challenging. This gap has spurred the investigation of alternative immune cells as therapeutics. Macrophages are potent immune effector cells whose functional plasticity leads to antitumor as well as protumor function in different settings, and this plasticity has led to notable efforts to deplete or repolarize tumor-associated macrophages. Alternatively, macrophages could be adoptively transferred after ex vivo genetic modification. In this review, we highlight the role of macrophages in solid tumors, the progress made with macrophage-focused immunotherapeutic modalities, and the emergence of chimeric antigen receptor macrophage cell therapy.
Reporting Genetic Markers and the Social Determinants of Health in Clinical Cardiovascular Research<i>—</i>It Is Time to Recalibrate the Use of Race
Authors: Clyde W. Yancy, Elizabeth McNally
Journal: JAMA Cardiology (2020)

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Abstract 16998: Gender and Age Specific Baseline Predictors of MACE in PEACE Trial Identified by Machine Learning
Authors: Victoria Xin, Scout Hayashi, Anwar Husain, Ahmed A Hasan, Amit Dey, Avantika Banerjee, Ian Atkinson, Gauri Dandi, Khizar Qureshi, Natalie Lewis, Nayab Mahmood, Noah Hasan, Nowreen Haq, Nuha Gani, Zyannah Mallick, Yves D Rosenberg
Journal: Circulation (2020)

Introduction: The NHLBI supported Prevention of Events with Angiotensin-Converting Enzyme (ACE) Therapy trial (PEACE) (NCT00000558) found that the addition of ACE inhibitor trandolapril to conventional therapy in 8290 patients with stable coronary artery disease and preserved ejection fraction provided no benefit against MACE (cardiovascular death, nonfatal myocardial infarction, or the need for coronary revascularization), the composite primary endpoint. We reused publicly available individual patient-level PEACE data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF) to identify gender and age group specific predictors for MACE. Methods: RSF was performed on 50 baseline variables for the MACE outcome in male and female and in age group (&lt;60, 60-69, &gt;69) cohorts. The top ten predictors identified in each cohort were included in a multivariate analysis using a Cox proportional hazards model with a multiple regression approach. Results: The top 10 predictors for the MACE selected by RSF are shown in Figure 1. Expected cardiovascular (CV) risk predictors like blood pressure, Canadian CV Society angina classification (CCS), age, and a history of various CV procedures consistently emerge amongst the top ten predictors of the primary MACE outcome across all gender and age specific subgroups. Interestingly, RSF also identified renal function biomarkers like serum potassium and glomerular filtration rate as common top ten predictors. Conclusion: Using ML, we uncovered in an unbiased fashion, gender and age groups specific unanticipated top predictors for MACE in PEACE trial. This underscores the value of gender and age specific predictors to examine the efficacy and outcomes of therapeutic interventions in advancing precision and personalized medicine.
Abstract 16734: Oral Nitrite Supplementation Improves Skeletal Muscle Mitochondrial Respiration and Cardiorespiratory Fitness in Older Adults With Heart Failure With Preserved Ejection Fraction
Authors: Rohan Shah, Paul Coen, Mark T Gladwin, Daniel E Forman
Journal: Circulation (2020)

Introduction: Prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, especially among older adults. HFpEF is commonly associated with exercise intolerance and skeletal muscle weakening which likely contribute to functional decline. We studied the utility of nitrite (NO 2 ) supplementation with the aim to augment skeletal muscle mitochondrial respiration. Hypothesis: NO 2 administered via oral supplements would be associated with improved mitochondrial respiration. Whereas prior studies with other oral and inhaled nitrate and NO 2 therapy in HFpEF patients have been inconsistent, we used novel NO 2 capsules that we hypothesized would achieve higher serum levels of nitrite and nitrate, and greater cellular and clinical benefits. Methods: A randomized, placebo-controlled pilot trial to study the utility of oral sodium (Na) NO 2 over 4 weeks in an older population (≥70 years) was done. Participants received 20 or 40 mg Na-NO 2 supplements 3 times daily based on their hemodynamic responses. Pre- and post-NO 2 intervention participants underwent biopsies of the vastus lateralis muscle with associated assessments of mitochondrial respiration in permeabilized fibers and also completed cardiopulmonary exercise test. Results: 15 participants were randomized and 13 completed the interventions (n=6 on NO 2 , n=7 on placebo, 69% men, mean age 75.7 years, range 70-91). Post-intervention serum NO 2 level increased (+0.61±0.67 μmol on NO 2, +0.25±0.15 on placebo). Ex-vivo analysis of mitochondrial respiration showed increased O 2 consumption in muscle (+27.1±27.4 pmol/(s*mg) on NO 2 , -11.7±11.3 on placebo). Rated perceived exertion during steady-state walking decreased (-1.2±2.0 on NO 2, +0.2±1.6 on placebo). Peak oxygen uptake (VO 2 ) increased (+1.4±5.2 ml/kg/min on NO2, -3.4±5.2 on placebo). Conclusion: Our study demonstrated efficacy and potential clinical utility of oral NO 2 supplementation in older HFpEF patients with an internally consistent physiologic composite of improved skeletal muscle mitochondrial respiration in association with improved cardiorespiratory fitness and diminished perceived exertion during steady-state walking. Clinical implications are auspicious and further research is indicated.
Abstract 17241: The Impact of Overweight and Obesity on End-Organ Function in Fontan Patients
Authors: Stephanie S Gaydos, Shahryar M Chowdhury, Nagraj Kasi, Lanier Jackson, Frances K Woodard, Andrew M ATZ, Kimberly E McHugh
Journal: Circulation (2020)

Introduction: Patients with Fontan circulation often develop multiorgan dysfunction. Obesity is a risk factor for systemic complications in the general population, but the impact of obesity in Fontan circulation is unclear. This study investigates the impact of increased BMI on end-organ function in Fontan survivors. Methods: Single center data from patients 13 years and older with Fontan circulation were retrospectively collected from June 2018 to May 2020. Weight at clinic visit was categorized as normal or overweight/obese by WHO BMI-for-age classifications. End-organ function between normal and overweight patients was assessed. The relationship between overweight and measures of end-organ function were modeled via multivariable regression analyses controlling for age, sex, race, heterotaxy, time since Fontan, ventricular function, and atrioventricular valve (AVV) regurgitation. Results: Among 75 patients (median age 18 [15, 26] years), 24 (32%) were overweight or obese. Age, race, duration since Fontan, oxygen saturation, and dominant ventricle did not differ between groups. There were significantly more overweight females (p= 0.02). Overweight patients had significantly lower GFR (p= 0.01), lower predicted peak VO2 (p= 0.02), and higher systemic vascular resistance (SVR) (p= 0.02) than normal weight patients. Duration since Fontan (β= 0.38, p = 0.02) and overweight (β= -0.35, p = 0.03) were independently associated with GFR. Female sex (β= -0.42, p &lt; 0.01) and overweight were independently associated with lower predicted peak VO2. Overweight was independently associated with presence of high SVR (OR = 7.5, p= 0.03). Other tested variables for hepatic (MELD-XI score, liver stiffness), cardiovascular (cardiac index, Fontan pressure, ventricular and AVV function), pulmonary, bone, and hematologic function did not significantly differ between groups. Conclusions: Overweight/obese BMI is common in aging Fontan patients and is significantly associated with worse renal function, exercise capacity, and elevated SVR. These findings suggest a possible relationship between weight, vascular changes, and renal perfusion. Further studies are needed to investigate this mechanism and the impact on Fontan patient outcome.
Identification of Myeloperoxidase As a Leukemia-Associated Antigen and Therapeutic Target for Acute Myeloid Leukemia
Authors: Eran Tallis, Sijie Lu, Xiaoling Ding, Dan Li, Kathryn Ruisaard, M. James You, Lisa St. John, Gheath Alatrash, Qing Ma, Jeffrey J. Molldrem
Journal: Blood (2017)
Abstract 356: Skill Retention in Medical Students Trained in Cardiac Arrest Care
Authors: Miguel A Moretti, Adriana O Camboim, Caroline A Ferrandez, Isabela C Etcheverria, Iaggo B Costa, Juliana S Canonaco, Vanessa L Mathia, Roberto R Giraldez, Joao Fernando M Ferreira, Antonio C Chagas
Journal: Circulation (2020)

Background: Morbidity and mortality reduction in cardiac arrest depends upon early and effective care. Basic life support (BLS) measures encompass a series of procedures to be started outside the hospital usually by trained lay people. Therefore, it is key that lay caregivers retain knowledge and skills late after instruction. However, studies demonstrate loss of cardiopulmonary resuscitation (CPR) skills as early as 30 days after training, pending mostly on the caregiver professional background. In this study, we evaluated medical students’ retention skills at 6 months. Methods: Prospective case-control observational study. Medical students underwent a 40-hour BLS training program. CPR skills were evaluated immediately and 6 months after the course based on individual scores before and after training as well as on categorical stratification as excellent, good or poor. Data were compared using F-test, paired t-test and chi-square for categorical variables. A 95% confidence interval was used with a level of significance of 0.05. Results: Fifty first-year medical students (54% female) aged between 18 and 24 years were enrolled in the BLS training program. Total number of CPR steps accurately performed decreased after 6 months of training (10.8 vs . 12.5; p&lt;0.001). Sex and age were not associated with performance. Categorical evaluation was considered excellent in 78% of the students immediately after training but decreased to 40% in 6 months (p&lt;0.01). Hands-on basic skills were mostly lost within the period. Conclusion: First-year medical students lost hands-on skills after 6 months of training decreasing the efficacy of CPR measures which might affect outcomes of patients in cardiac arrest.
Pre-symptomatic detection of COVID-19 from smartwatch data
Authors: Tejaswini Mishra, Meng Wang, Ahmed A. Metwally, Gireesh K. Bogu, Andrew W. Brooks, Amir Bahmani, Arash Alavi, Alessandra Celli, Emily Higgs, Orit Dagan-Rosenfeld, Bethany Fay, Susan Kirkpatrick, Ryan Kellogg, Michelle Gibson, Tao Wang, Erika M. Hunting, Petra Mamic, Ariel B. Ganz, Benjamin Rolnik, Xiao Li, Michael P. Snyder
Journal: Nature Biomedical Engineering (2020)