tbuckley/cabot-search huggingface dataset:
Abstract 9572: Changes of the Incidence of Cardiovascular Risk Factors in General Population During the Covid-19 Pandemic
Authors: Hisako Tsuji, Ichiro Shiojima
Journal: Circulation (2021)

Background: To examine influence of COVID-19 pandemic on cardiovascular risk factors in general population, incidence of newly diagnosed hypertension, diabetes mellitus, hypercholesterolemia and excess body weight during the COVID-19 pandemic period was compared with that of those before the pandemic period. Methods: Annual incidence of hypertension, diabetes mellitus, hypercholesterolemia and excess body weight was evaluated in subjects who had annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan in 2019 and 2020. Those with history of cardiovascular disease were excluded. The incidence was compared with that of those who received the checkup in 2018 and 2019 as the control value. The incidence of each risk factor was evaluated in separate models in which subjects with the risk factor of interest at baseline were excluded. Multivariate logistic regression analyses were performed adjusted for clinical valuables including age, sex, hypertension, diabetes, current smoking, drinking habit and excess body weight in each model. Results: Characteristics of the subjects at baseline and incidence of the risk factor next year in each model were presented in the table. The incidence of hypertension (odds ratio (OR)=1.45, 95% confidence interval (CI)=1.29 to 1.64, p&lt;0.0001), hypercholesterolemia (OR=1.55, 95% CI=1.37 to 1.76, p&lt;0.0001), and excess body weight (OR=1.50, 95% CI=1.23 to 1.82, p&lt;0.0001) from 2019 to 2020 was significantly higher compared to that from 2018 to 2019 but that of diabetes was not increased (OR=0.94, 95% CI=0.71 to 1.24, p=0.6648). Conclusions: Increased incidence of hypertension, hypercholesterolemia, and excess body weight was observed during the COVID-19 pandemic period.
Abstract 9585: Impaired Renal Function Pre- and Post- MitraClip Implantation is an Independent Predictor of Late All-Cause Mortality: A Systematic Review and Meta-Analysis
Authors: ISRAEL SAFIRIYU, Sanjana Nagraj, Leonidas Palaiodimos, Robert Faillace
Journal: Circulation (2021)

Background: Impaired renal function, a well-recognized complication of severe heart failure, is associated with adverse outcomes following cardiovascular interventions. There are conflicting data reported about its impact on late all-cause mortality following transcatheter mitral valve repair with MitraClip (MC) implantation in patients with grade 3 or 4 mitral regurgitation. Hypothesis: We hypothesized that pre- and post- procedural renal dysfunction negatively impacts late (≥ 1 year) all-cause mortality following MitraClip implantation. Methods: Electronic databases PubMed, Embase, and Web of Science were systematically reviewed from inception to February 2021 for studies evaluating outcomes after MC implantation, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model meta-analysis was performed and heterogeneity of the included studies was assessed by using I-squared test. Result: Out of 2606 articles, 16 studies with 19,503 patients were included. Pre-procedural renal dysfunction i.e. chronic kidney disease (CKD) was independently associated with higher late all-cause mortality (Hazard ratio [HR] 1.59, 95% CI 1.25 - 2.02, I 2 = 60%) after MC implantation (fig 1). On subgroup analysis, late all-cause mortality rates were higher with CKD ≥stage 4 compared to CKD stage 3 (HR 2.86, 95% CI 1.87 - 4.39, I 2 = 26% VS HR 1.55 95% CI 1.19 - 2.01, I 2 = 0%). Development of post procedural acute kidney injury was also independently associated with higher late all-cause mortality (HR= 2.32, 95% CI 1.71 - 3.15, I 2 = 42%) after MC implantation (fig 2). Conclusion: Impaired renal function pre- and post-MC implantation is a strong independent predictor of late all-cause mortality. This should be considered during the clinical decision-making process of patients undergoing the MC procedure.
Covid-19: Build on success of vaccination programme in reaching ethnic minority groups, report recommends
Authors: Jacqui Wise
Journal: BMJ (2021)

Covid-19: Build on success of vaccination programme in reaching ethnic minority groups, report recommends Jacqui WiseLessons learnt in relation to increasing uptake of the covid-19 vaccine among ethnic minority groups should now be applied to the booster programme, a government progress report recommends.
Stratification of Intermediate-Risk Acute Myeloid Leukemia According to the Expression Level of WT1 mRNA at Diagnosis
Authors: Kyoko Fuse, Kaihatsu Akane, Toshiki Kitajima, Akihito Momoi, Takuya Kasami, Takayuki Katagiri, Yasuhiko Shibasaki, Tatsuo Furukawa, Miwako Narita, Hirohito Sone, Masayoshi Masuko
Journal: Blood (2021)
EXTH-79. TRIAL WORKING GROUPS TO EXPEDITE PRECLINICAL TRANSLATION FOR PAEDIATRIC BRAIN TUMOURS
Authors: Ruman Rahman, David Walker, Emma Campbell, Kristian Aquilina
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as intra-arterial and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate these. The science and technology underlying these developments is not traditionally embedded within the paediatric neuro-oncology network. In addition, custom-built hardware, novel surgical procedures, and the testing and licensing of implantable devices, add difficulty at the regulatory level. METHODS In early 2021, we launched the ‘Clinical Trials Working Group for Central Nervous System Drug Delivery’. This aims to accelerate clinical trials to assess the safety and effectiveness of drug delivery devices for treating paediatric brain tumours. On March 1st, we hosted the first virtual meeting of this group, involving 38 leading brain tumour scientists and clinicians from the UK, EU and US. RESULTS A pre-meeting survey identified the main challenges to acceleration of this preclinical to clinical research pathway as: (1) a lack of specific funding for prototype development and/or scale up for clinical trials; (2) difficulties in navigation of the regulatory landscape; (3) lack of accurate preclinical models; and (4) increased need for multicentric working. Discussion at the meeting echoed the survey responses, and there was agreed consensus that a ‘Roadmap’ document for preclinical to clinical translation should be created. Following the meeting, we launched a pump prime funding call for projects that will address challenges along the preclinical to clinical pathway to move trial proposals into an ‘advanced state of readiness’. CONCLUSION The ideas generated during the initial meeting will help form the basis of a ‘Clinical Trials’ workshop in the autumn of 2021.
Update on CAR T-Cell Therapies for Relapsed/Refractory B-Cell Lymphomas
Authors: Stephen J. Schuster
Journal: Journal of the National Comprehensive Cancer Network (2021)

CAR T cells are genetically engineered to produce an artificial receptor on the T-cell surface for use in immunotherapy, which immediately engages its target, results in CAR T-cell proliferation, and effects target cell cytotoxicity. Prior to CAR T-cell therapy, approximately 30% of patients with diffuse large B-cell lymphoma (DLBCL) had an unmet need for a new treatment approach. There are now 3 commercially available CAR T-cell products capable of achieving long-term, disease-free survival in the third line of therapy for patients with relapsed or refractory DLBCL, transformed follicular lymphoma, or primary mediastinal large B-cell lymphoma: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.
Abstract MP223: CCR2 <sup>+</sup> Macrophages And T-cells Infiltrate The Murine Heart Following Immune Regulator Treatment With CD40
Authors: Jesus Jimenez, Pan Ma, Jing Jing, Andrea Bredemeyer, Inessa Lokshina, Kory J Lavine
Journal: Circulation Research (2021)

Immune checkpoint inhibitors have revolutionized cancer treatment but have been associated with severe adverse cardiac events including myocarditis. CD40 agonist (CD40ag) antibodies are immune regulators that have emerged as promising candidates with remarkable efficacy across tumors including those thought to be resistant to established ICIs. To investigate CD40 signaling and its potential for adverse cardiac events, C57BL/6J, CCR2-GFP, and CCR2-knockout mice were injected with CD40ag or isotype antibodies for 7 days. Flow cytometry showed a specific increase in CCR2 + macrophages that was independent of monocyte recruitment. There was no change in neutrophil recruitment and only a modest increase in dendritic cells was evident. We also observed a significant expansion of CD4 and CD8 T-cells that displayed an effector memory phenotype. Bulk cardiac tissue gene expression analysis (Figure A) revealed that CD40 activation upregulates multiple inflammatory cytokines (Ifng, Tnf, Il-12β) and chemokines (Ccl3, Ccl5, Ccl7, Cxcl9, Cxcl10), which are regulated by interferon gamma and coordinate the activation of APCs and T-cells. Finally, RNA in situ hybridization (Figure B-C) demonstrated increased levels of Cxcl9 (red) expression in cells consistent with CCR2 + (white) macrophages when comparing isotype control to treatment with CD40ag. These findings reveal that CD40 activation results in a robust expansion of CCR2 + macrophages and activation of T-cells within the heart, initiating a feed forward loop of activation that is mediated by interferon gamma and generates inflammatory cytotoxic mediators that may lead to myocardial injury.
Abstract 13905: Radial vs Femoral Approach for Cardiac Catheterization With or Without Percutaneous Coronary Intervention in Patients With Prior Coronary Artery Bypass Grafting
Authors: Ayan Nasir, Melissa Dasalla, Shahyar M Gharacholou, Unnati Bhatia, Gurpreet S Sandhu, Dilip Pillai
Journal: Circulation (2021)

Background: Owing to reduced bleeding risks, radial is favored over femoral for access site selection in patients referred for coronary angiography, with specific benefits in patients presenting with acute coronary syndrome. However, studies were often limited to patients without coronary artery bypass grafts (CABG), given the technical challenges of the radial approach in these patients. Methods: We evaluated patients with prior CABG undergoing coronary angiography with or without percutaneous coronary intervention (PCI) from 2015-2020 at our institution. We reviewed access site and bleeding outcomes as defined in the NCDR CathPCI registry. Additional outcomes included procedural duration, fluoroscopy time, contrast volume, and clinical events. Results: Of the 1,546 patients studied, 280 (18%) patients had radial access while 1,266 (82%) patients had femoral access. Over the study time period, frequency of radial access for post CABG catheterization procedures increased from 0% in 2015 to 45% in 2020. There were no statistically significant differences in comorbidities, bleeding events, complications, or mortality between radial vs femoral (Table). Fluoroscopy time was higher for radial vs femoral (14.9 mins vs 13.3 mins, p=0.04). Conclusion: Over time, radial access choice in post CABG patients increased, without significant differences with respect to bleeding events or complications as compared to femoral, though at increased fluoroscopy times.
Abstract 12654: Direct Oral Anticoagulants (DOAC) versus Warfarin for the Treatment of Left Ventricular Thrombus (LVT) in Patients With or Without Cardiorenal Comorbidities, Including CKD (Chronic Kidney Disease) and Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Nso Nso, KELECHI EMMANUEL, Hakeem Ayinde, Adedapo Iluyomade
Journal: Circulation (2021)

Background: The medical management of left ventricular thrombus (LVT) is very challenging due to the risk of embolic events. The current body of evidence supports the use of DOACs (direct oral anticoagulants) as safe substitutes to vitamin K antagonists/warfarin. We aim to identify the credibility of the evidence-based claims that advocate the safety/efficacy of DOACs in comparison to warfarin therapy for LVT patients. Methods: We systematically explored PubMed/Medline, JSTOR, Google Scholar, and Cochrane Library to identify relevant studies published between January 2006 and April 2021. The included studies categorically compared various clinical endpoints related to the safety/efficacy of DOACs versus warfarin in LVT scenarios. Results: We extracted 23 studies on 172,038 adult patients who received treatment for LVT and/or cardiorenal comorbidities via DOACs or warfarin. The odds ratios for all-cause mortality (OR: 1.08, 95% CI 0.69, 1.71), arterial thrombus (OR: 0.74 [95% CI 0.03, 18.76]), bleeding complications (OR: 1.16 [95% CI 0.67, 2.02]), composite of deep venous thrombosis or pulmonary embolism (OR: 0.95 [95% CI 0.10, 8.99]), hemorrhagic stroke (OR: 0.53 [95% CI 0.02, 13.30]), composite of stroke or systemic embolism (OR: 1.08, 95% CI 0.64, 1.83), systemic embolism (OR: 0.53 [95% CI 0.02, 13.30]), and rate of thrombus resolution for DOACs (versus warfarin) (OR: 1.32 [95% CI 0.66, 2.62]) supported their safety/efficacy in LVT treatment. The subgroup analysis affirmed the safety/efficacy of betrixaban and rivaroxaban (as compared to warfarin) in minimizing the episodes of stroke/ischemic stroke and clinically relevant/intracranial hemorrhage in patients with/without cardiorenal comorbidities. Conclusion: We found no difference in therapeutic efficacy and safety of DOACs as compared to warfarin in managing the clinical complications of left ventricular thrombus. The findings advocate the need for prospective randomized controlled trials to validate the safe replacement of warfarin with DOACs in LVT patients.
Abstract 11900: Quinidine as Salvage Therapy in Recurrent Monomorphic Ventricular Tachycardia
Authors: John D Larson, Amrish Deshmukh, Michael Ghannam, Ryan Cunnane, Hamid Ghanbari, Rakesh Latchamsetty, Thomas Crawford, Krit Jongnarangsin, Hakan Oral, Fred Morady, Frank Bogun, Jackson Liang
Journal: Circulation (2021)

Introduction: Quinidine is an effective therapy for a subset of polymorphic ventricular tachycardias and ventricular fibrillation (VF), however the efficacy of quinidine on scar related monomorphic ventricular tachycardia (MMVT) is unclear. Hypothesis: We sought to assess the efficacy and adverse effects of quinidine in scar related MMVT. Methods: All patients with MMVT treated with quinidine from 2009-2020 at a single VT referral center were reviewed. Results: A total of 22 patients with MMVT and structural heart disease (age 66.7 ± 10.9, 20 males, 15 with ischemic cardiomyopathy, mean LVEF 22.2 ± 12.3%, 9 with left ventricular assist device (LVAD)) were treated with quinidine (14 patients on Gluconate formulation average dose 996mg±321, 8 patients on Sulfate formulation with average dose 1062mg±588). Quinidine was used in combination with other antiarrhythmics (AAD) in 18 (13 also on amiodarone). All patients previously failed &gt;1 AAD (Amiodarone 100%, mexiletine 73%, sotalol 32%, other 32%) and 8 had prior ablations (median of 1.5). Quinidine was initiated in the setting of VT storm despite other AADs (6), inability to tolerate other AADs (4), or recurrent VT despite prior therapies (12). Ventricular arrhythmias requiring ICD or external shock occurred despite quinidine in 13 (59%) patients at a median of 26 (4-240) days after quinidine initiation. In patients with recurrent MMVT, VT cycle length increased from 359ms to 434ms (p=0.02). Treatment with quinidine was associated with an increase in QTc from 527ms (413-619) to 554ms (425-725) (p=0.004). Only 6 patients remained on quinidine at 1 year with recurrence of ventricular arrhythmias in all. Of the 6 patients on long term quinidine therapy, 3 patients had no shocks but did receive successful ATP within the first year. The following adverse effects were seen: GI side effects (6), QT prolongation (2), rash (1), thrombocytopenia (1), neurologic side effects (1). One patient discontinued due to cost. Conclusions: Quinidine therapy has limited tolerability and efficacy when used in the management of amiodarone-refractory scar related MMVT. When possible, more effective therapies should be offered in patients with VT refractory to standard pharmacologic therapies.
Abstract 12851: Prognostic Value Of Late Gadolinium Enhancement In Patients With Idiopathic Dilated Cardiomyopathy
Authors: Robert S Zhang, Yulei Cao, Peter T Evans, Yuchi Han
Journal: Circulation (2021)

Introduction: The aim of this study was to investigate the association between the extent and pattern of late gadolinium enhancement (LGE) and outcomes in a large idiopathic dilated cardiomyopathy (DCM) cohort Hypothesis: LGE is associated with worse outcomes in patient with idiopathic dilated cardiomyopathy Methods: In this study, we retrospectively identified all patients with idiopathic DCM who underwent cardiac MRI (CMR) from 2015 to 2020 at a single large academic center. The association between the pattern of LGE and event free survival from transplantation and mechanical circulatory support was analyzed using Kaplan Meier analysis and the log-rank test. Results: Of a total of 286 patients (64% male, 62% Caucasian) with idiopathic DCM who underwent CMR, LGE was detected in 59 (21%) patients. Of the patients with LGE, 7 (3%) patients had free-wall LGE, 40 (14%) had septal LGE and 12 (4%) had both septal and free wall LGE. All patients had linear mid-wall LGE and two patients had both linear-mid wall and sub-epicardial involvement. The presence of septal LGE was associated with older age (58 ± 12 vs 47 ± 16 years, p&lt;0.001), a lower LV ejection fraction (EF) (30% ± 12 vs 37% ± 12, p&lt;0.001), higher LV end-diastolic volume index (146 ± 47 vs 126 ± 36 ml/m 2 , p&lt;0.001), lower right ventricular EF (37% ± 13 vs 42% ± 13, p=0.013), higher LV mass index (82 ± 25 vs 73 ± 24 g/m 2 , p=0.013), higher incidence of LBBB (29% ± 16 vs 16% ± 29) and atrial fibrillation (31% vs 17%, p=0.021). Over a mean follow-up time of 26 ± 19 months, patients with septal LGE were less likely to experience event free survival from heart transplant or durable mechanical circulatory support (Figure 1, p=0.009). Conclusions: The presence of septal LGE in this large idiopathic DCM cohort is associated with worse outcomes. Additional research is needed to determine whether these findings will aid clinical management of these patients.
Abstract 11669: “Hearing the Heart” - Validation of a Novel Digital Health Earbud Technology to Measure Cardiac Time Intervals Through Infrasonic Hemodynography
Authors: Carmen M Wheeler, Siddarth Patel, Carly E Waldman, Jal Panchal, Rajbir S Sidhu, Monika Krol, Runyu Ye, Tomasz Szepieniec, Pratistha Shakya, Saumya Gupta, Karlen Shahinyan, Anna Barnacka, Hayley Engstrom, Kayla Southard, Misty Daniel, Curtiss Stinis, Steven Romero, Charles Bridges, Sanjeev Bhavnani
Journal: Circulation (2021)

Introduction: The cardiovascular (CV) system produces low frequency, ‘infrasonic’, auditory vibrations during the cardiac cycle. Herein, we report the first-in-person validation of a novel earbud sensor to capture CV time intervals and the feasibility of non-invasive infrasonic hemodynography (IH) using the MindMics ® wireless earbuds for long term in-ear CV monitoring. Methods: Infrasonic waveforms were captured during cardiac catheterization (CC) among 5 study subjects wearing the IH ear-buds (Figure A) who underwent CC for the evaluation of coronary artery disease. Simultaneous IH and CC waveforms were acquired and time synchronized at 1000Hz sampling rate as time-series datasets. Each subject underwent echocardiography to identify aortic valve opening/closure (AVO/AVC) and left ventricular (LV) outflow tract flow measurements with hemodynamic waveforms during CC measuring LV ejection time (LVET). Validation of the IH waveform (in-ear acoustic pressure measured in Pascals) was compared to echocardiography (AVO/AVC) and hemodynamic waveforms (LVET) with concordance and Bland-Altman analysis, and with overlaid data visualizations to CV time intervals. Results: 5 study subjects comprised 257 CV cycles with a total data set of &gt;450,000 time-series data points. IH signals collected simultaneously with the pulsed wave Doppler demonstrated alignment with AVO/AVC (Figure B) and were synchronized to CC waveforms in the aorta (Figure C). A high correlation between LVET measured from IH and CC was observed (R=0.87, p&lt;0.0001, Figure D), with a mean absolute error of 14.7ms and a bias of 7.2ms (Figure E) (mean±SEM of 342.3±2.1ms for CC and 349.5±2.1ms for IH). Conclusions: In a first-in-person study, we report high accuracy between IH, echocardiography, and CC hemodynamic waveforms to capture CV time intervals including CV performance measures. Further studies are underway to validate IH and the earbud sensor towards non-invasive hemodynamic monitoring.
Abstract 11402: Targeting RyR2 to Suppress Ventricular Arrhythmias and Improve Left Ventricular Function in Chronic Ischemic Heart Disease
Authors: Jeffrey Schmeckpeper, Kyungsoo Kim, Daniel J Blackwell, Kaylen Woodall, Bjorn C Knollmann
Journal: Circulation (2021)

Introduction: Sarcoplasmic reticulum Ca +2 leak from RyR2 is a common finding in chronic ischemic heart disease (CIHD) and may be a key driver for ventricular arrhythmias and reduced excitation-contraction coupling in failingm myocytes. Here, we test the hypothesis that targeting Ca +2 leak using the non-selective RyR inhibitor, Dantrolene, suppresses ventricular arrhythmias and improves left ventricular contractile function in CIDH. Methods: CHID was induced in 24 C57BL/6J mice by left coronary artery ligation. Four weeks after myocardial infarction (MI), subcutaneous osmotic pumps were placed to deliver continuous dantrolene (20 mg/kg/day) or vehicle (0.9% Saline). Left ventricular (LV) function was assessed by echocardiogram at 4-, 7- and 10-weeks post-MI. Peripheral muscle strength was assessed by provoked electromyogram at 6 weeks. Inducibility of ventricular tachycardia (VT) was assessed by rapid transesophageal pacing with isoproterenol at 10 weeks. Results: Dantrolene reduced the peripheral muscle strength in mice (0.014±0.001 vs 0.010±0.001 N, P&lt;0.05), but had no adverse effects on weight loss or mortality. Dantrolene increased fractional shortening (18.7±1.3% vs 22.1±1.6%, P&lt;0.001) and mean velocity fiber shortening (mVcfc 1.37±0.09 vs 1.74±0.1 circ/sec, P&lt;0.002) in non-infarcted regions at 10 weeks. This prevented the progression in LV ejection fraction reduction from 4 to 10 weeks (Saline: 35.6±3.4% to 30.6%±3.4%; Dantrolene 34.6±2.4% to 38.1±1.9% vs, P&lt;0.01). Dantrolene reduced VT frequency per animal (0.083±0.04 vs 0.028±0.02 VT/pacing train, P&lt;0.02) and the total duration of inducible VT per animal (59.2±24 secs vs 1.2±0.6 sec, P&lt;0.04). Dantrolene significantly prolonged the ventricular effective refractory period (VERP) (35.1±1.6 msec vs 42.0±0.9 msec, P&lt;0.005). Conclusion: Dantrolene suppression of RyR2 diastolic Ca +2 leak in chronic ischemic heart failure improves the systolic function of surviving myocardium and reduces VT burden by prolonging the VERP, preventing the re-entry circuit for VT in this model. RyR2 inhibition may represent a new therapeutic target for the treatment of CIDH with ventricular arrhythmias.