tbuckley/cabot-search huggingface dataset:
Abstract 11482: A Neural Network-Based Model Detects Low Ejection Fraction from Electrocardiograms Without Overt Rhythm or Conduction-System Abnormalities
Authors: Ryuichiro Yagi, Shinichi Goto, Calum Macrae, Rahul C Deo
Journal: Circulation (2021)

Introduction: While detection of asymptomatic left ventricular dysfunction (LVD) is important given the effectiveness of preventive medical treatments, the gold standard method using echocardiograms requires trained experts and thus is less suitable for widespread screening. Previous studies have found that convolutional neural network (CNN) models could detect patients with LVD from 12-lead electrocardiogram (ECG). However, they were developed in an unselected population which included an unknown number of patients with overt rhythm and conduction system abnormalities, which frequently coexist with LVD. It is unclear to what extent these models relied on such obvious features to detect LVD from ECGs. Herein, we aimed to assess the ability of a CNN-based model to detect LVD using ECGs having no apparent rhythm or conduction abnormalities. Methods: 56,985 ECGs with an echocardiogram within a 2-week interval were identified from the BWH ECG database. The dataset was split into 28,465, 11,306 and 17,214 ECGs for derivation, validation and test, respectively, with no overlap of patients across groups. A CNN model was trained as a binary classifier to detect LVD, defined as LV ejection fraction &lt; 35 %. The final model was selected as that with the best area under the receiver operating characteristics curve (AUROC) on the validation set and performance assessed on the test set. The model was further tested after excluding ECGs with overt rhythm and conduction system abnormalities defined as the presence of atrial fibrillation, premature atrial complexes, premature ventricular complexes, electronically paced rhythms, left or right bundle branch block. Results: The mean patient age in the test set was 69.8 years, and 57.3% of patients were male. prevalence of low LVEF was 9.7%. The test dataset contained 7,633 ECGs with overt rhythm and conduction system abnormalities. The model yielded good accuracy with an AUROC of 0.91 (95% CI:0.90-0.91) to identify patients with LVD in the test data set. The model performed similarly in the presence or absence of rhythm or conduction-system abnormalities (AUROC 0.90 95% CI:0.89-0.92 and 0.89 95% CI:0.88-0.90 respectively). Conclusion: The model detected low LVEF from ECG without overt rhythm and conduction system abnormalities.
Abstract 13998: Predicting Atrial and Ventricular Tachyarrhythmias by Monitoring Intra-Thoracic Impedance, an Updated Meta-Analysis
Authors: Hossam Alzu'bi, Ahmad Al-abdouh, Ikram-Ul Haq, Anan AbuRmilah, Abhishek Deshmukh
Journal: Circulation (2021)

Background: Many cardiac implantable devices have the capability of monitoring the volume status in patients with heart failure by tracking the intra-thoracic impedance changes over time measured by OptiVol fluid index. Objective: The aim of this study is to evaluate the association between the intra-thoracic impedance measured by OptiVol fluid index and the onset of tachyarrhythmias. Methods: We searched Medline and EMBASE databases through January 2021 looking for studies evaluating intra-thoracic impedance measured by OptiVol with either ventricular tachycardia/ventricular fibrillation (VT/VF) or atrial tachycardia/atrial fibrillation (AT/AF). After extracting the data from each study, we calculated the odds ratio with 95% confidence intervals using RevMan 5 software. Results: Ten studies met our inclusion criteria with a total of 118,504 patients were included in our analysis. Seven studies measured VT/VF included 94,816 patients and 5 studies measured AT/AF included 23,688 patients. Two studies measured both AT/AF and VT/VF. The odds ratio for developing VT/VF with OptiVol fluid index crossing a threshold of 60 Ω-days was 1.55 (95% CI 1.35, 1.78) (P&lt;0.00001) and for developing AT/AF was 1.79 (95% CI 1.43, 2.24) (P&lt;0.00001) {Figure1} Conclusion: The decrease in intra-thoracic impedance measured by OptiVol fluid index threshold crossing of 60 Ω-days is associated with higher risk for developing new onset AT/AF and VT/VF. Key Words: intra-thoracic impedance; OptiVol; tachyarrhythmia Figure1: Forest Plot for risk of developing VT/VF Figure: Forest Plot for risk of developing AT/AF
Abstract 9085: Phenome-Wide Association Study (phewas) Identifies Clinical Factors Associated With Plasma Ketones from Four Large Studies
Authors: Senthil Selvaraj, Stephanie Giamberardino, Jawan Abdulrahim, Kenneth B Margulies, Daniel P Kelly, CAROL HAYNES, Robert J Mentz, Adrian F Hernandez, Rury Holman, Eric D Peterson, Svati H Shah
Journal: Circulation (2021)

Background: Ketosis is an adaptive mechanism to the stress imposed by cardiovascular disease, including heart failure (HF), with ketones constituting a more efficient myocardial fuel. Contributing factors to the development of ketosis and its association with adverse events have not been well studied. Methods: We performed a phenome-wide association study (PHeWAS) for serum ketone (beta-hydroxybutyrate [BHB]) levels in four cohorts with a total of 6,508 participants across a broad array of cardiovascular health, including CATHGEN (N=4,374), RELAX (N=161), TECOS (N=995), and EXSCEL(N=978). On cross-sectional analysis, we performed a random effects meta-analysis relating clinical and echocardiographic predictor variables to log transformed BHB using linear regression (with false discovery rate adjusted p-values). The relationship between BHB and HF metrics (HF history, ejection fraction, right ventricular systolic pressure [RSVP]) with markers of insulin resistance was assessed in each cohort. The association between BHB and death or HF hospitalization was assessed using Cox regression. Results: The mean age was 62 years, 36% female, and 75% white. Log BHB was associated with higher heart rate (beta-coefficient 0.009, p=0.001), HF (0.188, p=0.02), ejection fraction &lt; 55% (-0.138, p=0.008), RVSP (0.010, p=0.02), ischemic heart disease (-0.094, p=0.002), and statin use (-0.13, p=0.002). The association between HF phenotypes and BHB was not explained by markers of insulin resistance. Higher BHB levels were associated with increased risk for death and HF hospitalization ( Figure ), driven primarily by death. Conclusions: We identified several novel non-diabetic associations between ketosis and clinical measures in patients with cardiovascular disease. The link between ketosis and HF was independent of insulin resistance. BHB is a powerful predictor of outcomes, particularly death, across a spectrum of cardiovascular disease, including HF.
Abstract 12137: Common Metabolic Determinants of Cardiac and Pulmonary Function in the General Population
Authors: Nilanjana Ghosh, Sandra Wibom, Tomasz Czuba, Maya l Landenhed Smith, Gunnar Engstrom, Gustav Smith
Journal: Circulation (2021)

Background: Heart failure is associated with a restrictive spirometry pattern, but limited data is available on the relation of subclinical measures of pulmonary function to cardiac function. We sought to explore such associations in a population-based cohort study as well as metabolic factors commonly associated with such measures. Methods: Participants of the population-based Swedish cohort study SCAPIS-Malmö (age 50-64) underwent spirometry (n=6251), of which random subsets also underwent echocardiograpy (n=1885) and untargeted plasma metabolite profiling (n=3,986). The association of spirometric (FEV1, FVC, DLCO) and echocardiographic parameters (E/E', stroke volume [SV], systolic pulmonary arterial pressure [sPAP]) were examined using multivariable-adjusted regression models and cubic spline functions.Metabolites were tested for association with spirometric and echocardiographic parameters with adjustment for age, sex, bmi, smoking, eGFR, diabetes, hypertension, COPD, asthma, and heart failure. Results: After adjustment for smoking and other established risk factors, lower FEV1, FVC and DLCO remained associated with higher E/E', sPAP, and lower SV (p&lt;0.001). Spline analyses were consistent with linear effects. Profiling of 1318 metabolites identified associations with lower FEV1, FVC, DLCO and higher E/E' for lower levels of 6 correlated lipid molecules including plasmalogens, lysophospholipids and a phosphatidylcholine, all of which also correlated with the main constituent of pulmonary surfactant (dipalmitoylphosphatidylcholine), and with higher levels of an amino acid and its deaminated product. Lower levels of bilirubin were associated with lower FEV1, FVC, DLCO, and lower SV. Discussion: In this contemporary, middle-aged cohort with low prevalence of manifest cardiac or pulmonary disease we observed associations between lower lung volumes and CO diffusion capacity with restrictive cardiac filling. Furthermore, our findings nominate metabolic factors that associate with both cardiac and pulmonary function, suggestive of shared pathophysiological processes.
Abstract 14174: Utilization of a Standardized Aseptic Technique to Prevent Cardiovascular Implantable Electronic Device Infections
Authors: Rana Al-zakhari, Safa Aljammali, Arismendy Nunez Garcia, Chandra Rednam, Ryan Isber, Nidal Isber
Journal: Circulation (2021)

Introduction: The use of cardiovascular implantable electronic devices (CIED) (pacemaker, implantable cardiac defibrillators (ICD) and cardiac resynchronization therapy (CRT) systems) has had a significant impact in reducing mobility and mortality. However, these devices can be associated with a significant risk of infections. We present our experience showing a low incidence of infection and describe a standardized aseptic technique during CIED implantation that explains its effectiveness in the prevention of infection. Methods: A retrospective observational cohort study, with a concomitant cross-sectional cohort conducted at Richmond University Hospital in Staten Island New York. The department of electrophysiology has utilized a standardized aseptic technique for CIED implantations. We reviewed all data by a single operator at a single center from July 2006 to July 2016. Skin and pocket cultures were taken from fifty patients in a pilot study to determine its effectiveness at achieving complete sterilization of the surgical site which is consisted of the sequential use of antiseptics at all stages of the device implant. Tyrx Antibiotic pouch was not used during the procedure. Results: χ 2 test was used and a p-value of &lt;0.05 was considered statistically significant. 1811 cases were identified and included in the analysis. There were 612(34%) generator changes and 1198 primary implants (66%), 47% of the devices were pacemakers, whereas 33% and 17% were ICD and Biventricular Defibrillators, respectively. There was only one infection identified with a rate of 0.05 within one week of the procedure. Fifty patients underwent wound cultures at the time of the procedure, all revealed no growth after 5 days. Conclusion: The rate of CIED infection in our population was 0.05% and it remained low across all high-risk groups. Our technique that was used on all patients, proved its ability to achieve complete surgical site sterility. This result suggests that the use of a standardized asepsis strategy can potentially decrease the risk of CIED infections without the use of Tyrx antibiotic pouch. However, given the lack of a control group our results should be validated on a randomized control study.
Induction Mortality in Acute Myeloid Leukemia: A 9 Year Retrospective Study from a Tertiary Care Centre in a Low-Middle Income Country Setting
Authors: Vivek S Radhakrishnan, Sandeep A Pattnaik, Arunima Bhadhuri, Vasundhara Raina, Payal Mandal, Saurabh J Bhave, Jeevan Kumar Garg, Arijit Nag, Sushant Vinarkar, Mayur Parihar, Deepak K Mishra, Reena Nair, Mammen Chandy
Journal: Blood (2021)
Abstract 9792: Improvements in Disease-Specific and Generic Quality of Life After Coronary Artery Bypass Grafting Surgery: A Meta-Analysis of Randomized Trials
Authors: Ruth M Masterson Creber, Arnaldo Dimagli, Cristiano Spadaccio, Annie Myers, Marco Moscarelli, Michelle Demetres, Stephen E Fremes, Mario F Gaudino
Journal: Circulation (2021)

Background: We conducted a systematic review and meta-analysis to evaluate the short and long-term effects of coronary artery bypass grafting (CABG) on disease-specific and generic quality of life (QOL) and a quantitative comparison from before surgery to up to five years after surgery across contemporary randomized clinical trials. Methods: We searched four databases from 2010-2020 to identify all randomized clinical trials that included the measurement of QOL in patients undergoing CABG. The QOL assessments included the primary outcome, Seattle Angina Questionnaire (SAQ), and secondary outcomes included Short Form Health Surveys (SF-36 Physical Component (PC) and Mental Component (MC)) and EQ-5D. A random-effects model with an inverse variance method to pool the means and the weighted mean differences was used. We used meta-regression to assess the effects of covariates (sex, age, diabetes, and trial publication date) on changes in QOL over time. Results: A total of 2,533 studies were screened and 17 full-text studies were included in the meta-analysis. There were significantly higher scores at 1-year postoperatively for the SAQ-AF, SAQ-QOL, SF-36 PC, and EQ-5D (Figure). The weighted mean differences from before surgery to the 1-year after was 24 (95% CI: 21.6-26.4) for the SAQ AF; 31 (95% CI: 27.5-34.6) for the SAQ QOL; 9.8 (95% CI: 7.1-12.8) for the SF-36 PC; and 0.1 (95% CI: 0.03-0.2) for the EQ-5D. The SF-36 MC did not improve significantly. In the meta-regression, mean age was associated with higher SAQ AF scores at five years and SAQ QOL scores at one year. There was no evidence of publication bias or small study effect. Conclusions: CABG is associated with short and long-term improvements for both disease-specific QOL and generic QOL, with the largest improvement in angina frequency from before surgery to 1-year.
Rationale and Design of a Phase 3b Multicenter, Randomized, Double-Blind Placebo-Controlled, Parallel-Group Trial with an Open-Label Extension Phase to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Pediatric Patients with Immune Thrombocytopenia
Authors: Rachael F. Grace, Xiaoqiang Xue, Brian Jamieson
Journal: Blood (2021)
BIOM-42. IMMUNOHISTOCHEMICAL ASSESSMENT OF MEMBRANOUS SOMATOSTATIN TYPE 2A RECEPTOR (SST2A) EXPRESSION ACROSS HIGH-RISK PEDIATRIC CENTRAL NERVOUS SYSTEM (CNS) TUMORS
Authors: Margot Lazow, Andrew Trout, Christine Fuller, Jaime Reuss, Brian Turpin, Joseph Stanek, Sara Szabo, Ralph Salloum
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION 77Lu-DOTATATE, a radionuclide therapy which binds SST2A, has demonstrated efficacy in neuroendocrine tumors and evidence of CNS penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A. METHODS SST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by two experienced pathologists (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (&amp;lt; 10%), 2 (10-50%), 3 (51-80%), or 4 (&amp;gt;80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (range=0-12). RESULTS A total of 117 tumor samples from 113 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean±SD=7.6±3.6 [n=36]) and meningioma (5.7±3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3±0.6 [n=3]), ETMR (1.0±0 [n=3]), ependymoma (grades I-III; 0.2±0.7 [n=26]), and high-grade glioma (grades III-IV; 0.4±0.7 [n=22]). Pineoblastoma (3.8±1.5 [n=4]) and other embryonal tumors (2.3±3.8 [n=8]) exhibited intermediate, variable expression. Among expressors, there was no association between SST2A IHC score and patient age, sex, presence of metastases, likelihood of relapse, or prior treatment. In a subset of paired primary and recurrent specimens from 3 patients, SST2A IHC scores remained largely unchanged. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.6±3.2) than SHH (5.0±3.3) molecular subgroups (p=0.033). CONCLUSIONS High membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors.
Abstract 11357: Sleep Modulates Heartbeat Waveform in Humans During a Predatory Virtual Competition
Authors: Jonathan A Araujo Queiroz, Daniel S Brandao, Sidarta Ribeiro, Allan Kardec Barros
Journal: Circulation (2021)

Introduction: Psychological stress modulates cardiac activity as a self-defense mechanism established across animal evolution and known as fight or flight response. However, the fact that our everyday fears differ from the ones that motivated this evolution represent a difficulty to the study of this response in humans. In this work, we are particularly interested in finding morphological cardiac markers that demonstrate the modulation of sleep to the human response of feeling like prey or predator. Methodology: Twelve individuals (10 men and 2 women) were recruited in pairs to attend to the laboratory, where they were randomly assigned in two groups: preys and predators. They played for 45 minutes a first person shooter electronic game against each other with close-combat weapons, but the predator had the advantage of being able to use a medium-range shotgun. After the match, they slept for 2 hours, followed by another 45 minutes match. We evaluated the ECG of the first 20 minutes of each of these 3 blocks in windows of 1 minute. We measured each cardiac cycle using variance, then estimated each resulting signal with Shannon entropy. Result: We verified that the Shannon entropy applied to the variance of cardiac cycles (H(V)) is larger in preys than in predators during the second game (Figure), with a p-value of 0.028 by the paired Wilcoxon signed-rank test. No statistical differences were found for the first game or sleep blocks. Conclusion: We hypothesized that prey and predator cardiac signals have their own characteristics and, therefore, have unique parameters for each of the different blocks. Thus, we believe that this tendency towards a standardization of roles (predator x prey) over time is due to the fact that in the first game, predators and prey are arbitrarily instituted and not biologically established, and that during sleep the memory of game events is consolidated towards their role goals, which modulates heartbeat waveform in the second game.
Abstract 12054: Evinacumab Reduces Atherogenic Lipids and Apolipoprotein B in Patients With Severe Hypertriglyceridemia
Authors: Robert S Rosenson, Poulabi Banerjee, Claudia Gonzaga-Jauregui, Jennifer McGinniss, Cecilia Vitali, Robert Pordy, Jian Zhao, Manish P Ponda, Daniel J Rader
Journal: Circulation (2021)

Background: Hypertriglyceridemia (HTG) is the consequence of elevated triglyceride-rich lipoproteins (TGRLs) containing apolipoprotein B (apoB), such as VLDL and chylomicrons. Epidemiological and genetic studies indicate that triglycerides (TGs) and the cholesterol within TGRLs causally contribute to coronary heart disease risk (CHD). Evinacumab (EVIN), an angiopoietin-like 3 inhibitor, lowers TGs by derepressing lipoprotein lipase (LPL) and endothelial lipase activity. In a Phase 2 trial in patients (pts) with severe HTG (sHTG, fasting TGs ≥500 mg/dL), EVIN was previously shown to reduce TGs in patients (pts) without familial chylomicronemia syndrome (FCS) and to be generally well tolerated (NCT03452228). This post-hoc analysis reports further details on the efficacy of EVIN in reducing atherogenic lipids/lipoproteins. Methods: Pts (N=51) were treated and assigned to cohorts based on genotype: Cohort 1 (n=17), FCS pts with bi-allelic loss-of-function (LOF) LPL pathway mutations; Cohort 2 (n=15), multifactorial chylomicronemia syndrome (MCS) pts with heterozygous LOF LPL pathway mutations; Cohort 3 (n=19), MCS pts without LPL pathway mutations. Pts were randomized (2:1) to IV EVIN 15 mg/kg or placebo every 4 weeks over a 12-week double-blind treatment (tx) period (DBTP), followed by a 12-week single-blind tx period where all pts received EVIN. Results: Of 51 pts with sHTG treated in the DBTP, 70.6% were categorized as high cardiovascular risk, and 21.6% had a history of CHD. In non-FCS pts (Cohorts 2 and 3), in addition to reducing TGs, EVIN reduced atherogenic lipids and apolipoproteins at Week (W) 12 compared with baseline (Table), including non-HDL-C, remnant cholesterol, and apoB (including apoB100 and apoB48). Overall, reductions observed at W12 were maintained through W24. Conclusions: In this post-hoc analysis, EVIN reduced atherogenic lipids and apoB, indicating it may have the potential to reduce CHD risk in pts with sHTG without genetic FCS.
Abstract 9675: Right Ventricular and Right Atrial Function in Pulmonary Hypertension Secondary to Heart Failure With Preserved Ejection Fraction: A Comparison With Pulmonary Arterial Hypertension
Authors: Jessie Van Wezenbeek, Azar Kianzad, Arno Van De Bovenkamp, Jeroen Wessels, Sophia-Anastasia Mouratoglou, Natalia Braams, Samara Jansen, Eva Meulblok, Lilian J Meijboom, J. Tim T Marcus, anton vonk noordegraaf, Marie Jose Goumans, Harm J Bogaard, M L Handoko, Frances S De Man
Journal: Circulation (2021)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a prevalent condition for which no treatment exists. Pulmonary hypertension (PH) and right atrial (RA) and right ventricular (RV) dysfunction are frequently observed. The question remains whether PH and the associated RV/RA dysfunction in HFpEF are treatment targets or a mere reflection of disease severity. Methods: To study the relative contribution of pressure-overload and left-to-right interaction, we compared RA/RV function in three groups: 1. HFpEF (n=13); 2. HFpEF-PH (n=33), and; 3. pulmonary arterial hypertension (PAH) matched to pulmonary artery pressures of HFpEF-PH (n=47). Patients underwent right heart catheterization and cardiac magnetic resonance imaging. Groups were compared using one-way ANOVA, after which post-hoc analysis with unpaired t-test and Bonferroni correction was performed. Results: The right ventricle in HFpEF-PH was less dilated and hypertrophied than in PAH and RV ejection fraction was more preserved (HFpEF-PH: 52±11 vs. PAH: 36±12%). RV filling patterns were altered: vena cava backflow during RA contraction was observed in PAH only. In HFpEF-PH, RA pressure was elevated throughout the cardiac cycle (HFpEF-PH: 10[8-14] vs. PAH: 7[5-10] mmHg), while RA volume was smaller, reflecting excessive RA stiffness (HFpEF-PH: 0.14[0.10-0.17] vs. PAH: 0.08[0.06-0.11]mmHg/mL). RA stiffness was associated with an increased RA eccentricity index (HFpEF-PH: 1.3±0.2 vs PAH: 1.2±0.1) and transmural pressure gradient (9[5-12] vs 2[-2-5] mmHg). Conclusions: Despite similar pressure-overload, RV/RA function was less compromised in HFpEF-PH than in PAH. Increased RA pressure and stiffness in HFpEF-PH were explained by left atrial/RA-interaction. Our results indicate that increased RA pressure is not a sign of overt RV failure, but rather a reflection of HFpEF-severity.