tbuckley/cabot-search huggingface dataset:
Abstract 9605: The Six Minute Walk Test: Right Test, Wrong Interpretation!
Authors: Mark Doyle, Geetha Rayarao, Roger Lacson, Nasir Hussain, Robert W Biederman
Journal: Circulation (2021)

Introduction: In patients with pulmonary hypertension (PHTN), after initial hemodynamic assessment, it is common practice to perform the six minute walk test (6MWT). The absolute distance walked represents an integration of pulmonary artery pressure (PAP) and right heart function. Thus, the initial distance walked for each patient is generally used as the benchmark to compare to future 6MWT to assess therapy/prognosis. Here we show that the absolute 6MWT distance (6MWD) is less ambiguously interpreted as the measured impedance between the LV and the aorta. Methods: Patients (n=33, 82% F), age 51± 12yrs) with PHTN (&gt;80% WHO I) underwent CMR to assess phasic blood flow through the aorta at the interface to the LV. CMR- phase velocity mapping flow data at single plane (acquisition time: 2min) was used to calculate the previously described and validated LV impedance (IMP LV ). IMP LV was calculated using the formula: IMP LV = (cardiac beat interval; CL) x (mean blood velocity) / (aortic diameter). Systolic PAP was measured during a right heart cath performed within one week of CMR and at the time of 6MWT. Multiple linear regression models were generated to predict the 6MWT distance. Results: A model predicting 6MWT was generated: systolic PAP, RVEF and age (r= 0.41, with PAP and RVEF not attaining significance). A second model entering IMP LV and age attained significance (r = 0.68, p&lt;0.01). Fig 1. Conclusions: This is the first demonstration of the utility of the 6MWT distance to reflect a uniform measure of the status of the PH patient, less so PAP, even at baseline. The impedance between the LV and the aorta incorporates the dual components of RV and the LV integrated ventricular/arterial function along with the systolic PAP, making it a more fundamental measure of PHTN health status. Thus, despite &gt;50 years of 6MWT used as the cornerstone for PHTN/PAH patients, we now show that this common application is really a predictor of impedance, and in turn, 6MWT was the right test for the wrong reason.
Abstract 10884: B-Cell-Mediated Sodium and Water Retention Contributes to Heart Failure Pathogenesis
Authors: Luke S Dingwell, Faisal Alibhai, Felix Chiu, Saad Khan, Tao Wang, Abdul Momen, Annie Zhou, Daniel A Winer, Clint S Robbins, Renke Li, Mansoor Husain
Journal: Circulation (2021)

Background: B-cells have been shown to serve pathogenic roles in heart failure through cardiac-specific monocyte mobilization and autoantibody deposition. Beyond this, we recently showed that mice with hypomorphic c-Myb activity ( c-myb h/h ) have reduced B-cells and that B-cell deficiency is associated with increased sodium- and water-excretion and reduced blood pressure. Here, we determine the relevance of these responses in an experimental model of heart failure. Methods &amp; Results: C57BL/6J wild-type (WT) and B-cell deficient c-myb h/h mice (male and female; aged 10-12 weeks) underwent either: (i) permanent LAD ligation to induce myocardial infarction (MI); or (ii) sham surgery. Echocardiography showed that B-cell deficiency preserved ejection fraction (53±2 vs. 44±2 %; N=6-7/group; P&lt;0.01) and limited pathologic remodeling with reduced LVID (end-diastolic: 4.9±0.1 vs. 5.5±0.1 mm; N=6-7/group; P&lt;0.01; end-systolic: 3.8±0.2 vs. 4.5±0.1 mm; N=6-7/group; P&lt;0.001) at 4-weeks post-MI compared to WT. Heart weight/tibia length and right lung weight/tibia length ratios (g/mm; P&lt;0.01), as well as pleural effusion volumes (μl; P&lt;0.05) were increased post-MI in WT, rather than c-myb h/h mice. Indeed, mice with B-cell deficiency manifest reduced right lung weight/tibia length ratio (0.005±0.000 vs. 0.009±0.001 g/mm; N=5-6/group; P&lt;0.01) and pleural effusion volume (17±6 vs. 55±18 μl; N=6-7/group; P&lt;0.06) post-MI compared to WT. Underlying this decongestion, metabolic cage studies revealed that B-cell deficient mice had sustained increases in 24-h urine volume/body weight and 24-h sodium excretion/body weight ratios, which correlated with ejection fraction 4-weeks post-MI (r=0.53; N=13 pairs; P&lt;0.05; and r=0.50; N=13 pairs; P&lt;0.05, respectively). Conclusion: Together, these data show that B-cells play a role in sodium- and water-retention, and consequently, extracellular fluid volume expansion and congestion post-MI, and suggest that B-cells may represent a therapeutic target in heart failure.
Abstract 14177: Gender Disparities in Failure to Rescue After Cardiac Surgeries
Authors: Sundos Alabbadi, Georgina Rowe, George Gill, Joanna Chikwe, Natalia Egorova
Journal: Circulation (2021)

Introduction: Women have a higher risk of mortality than men after cardiac surgery, independent of other risk factors. Death after postoperative complications, known as “failure to rescue (FTR)”, is a nationally endorsed quality care metric. This study was designed to evaluate differences in FTR after cardiac surgery in women and men. Methods: In this retrospective analysis, post-operative outcomes of 30,973 men (70.4%) and 13,033 women (29.6%) aged over 18 years undergoing coronary bypass or valve surgery identified from statewide administrative data from New York (2016-2019) and California (2016-2018) who experienced at least one serious postoperative complication, were compared according to gender. The primary outcome was FTR. Multivariable logistic regression was used to identify independent predictors of death after complication. Propensity matching was used to adjust for baseline differences between genders and yielded 12,608 pairs. Results: Women were older (mean age 67.8 vs 66.6, P&lt;0.001), more frail (median frailty score 0.1 vs 0.07, P&lt;0.001) and had more comorbidities (median Charlson score 2.5 vs 2.3, p&lt;0.001) than men. The overall FTR rate was 5.7% (2,524 of 44,006). Men were less likely to die after a complication than women (4.8% vs 8%, P&lt;0.001). Independent predictors of FTR included female gender, age≥75 years, higher Charlson comorbidity score, and higher number of postoperative complications (Figure). In the propensity matched cohort, FTR was significantly lower among men than women (5.7% vs 7.9%, P&lt;0.001). This difference in FTR was mainly driven by the difference in FTR after respiratory failure, bleeding, myocardial infarction, shock, and acute kidney failure. Conclusion: Women are more likely to die following complications after cardiac surgery, independent of clinical and socioeconomic characteristics, than men. Clinical practices contributing to this disparity may be an appropriate target for quality improvement.
TMOD-30. NTRK2 SPLICE VARIANT, TRKB.T1, LINKS NEUROBIOLOGY, EMBRYONIC DEVELOPMENT, AND ONCOGENESIS
Authors: Siobhan Pattwell, Sonali Arora, Nicholas Nuechterlein, Michael Zager, Keith Loeb, Patrick Cimino, Nikolas Holland, Hamid Bolouri, Tatsuya Ozawa, Michael Haffner, Junyue Cao, Jay Shendure, Eric Holland
Journal: Neuro-Oncology (2021)

Abstract Temporally regulated alternative splicing choices are vital for proper development yet the wrong splice choice may be detrimental. Here we highlight a novel role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis across multiple tumor types in both humans and mice. TrkB.T1 is the predominant NTRK2 isoform across embryonic organogenesis and is highly expressed in a wide range of adult and pediatric tumors. Further, forced expression of TrkB.T1 causes multiple solid and non-solid tumors in mice in the context of tumor suppressor loss. These results highlight a unique role for the neurotrophin receptor splicing in development and oncogenesis and underscore the need for considering alternative splicing and transcript level data in neuroscience, developmental biology, and oncology research.
QOLP-16. PATIENT-REPORTED SELECTION FOR INCIDENTAL FINDINGS IN A COMPREHENSIVE GENOMIC TRIAL: A DANISH SINGLE INSTITUTION EXPERIENCE FROM THE COPENHAGEN GLIOBLASTOMA COHORT
Authors: Dorte Schou Nørøxe, Hans Poulsen, Ulrik Lassen
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Participation in clinical trials is a high priority in the neuro oncology community and requires an informed, signed consent. However, patient information is increasingly complex as many trials include comprehensive molecular analyses and, according to Danish legislation, must include a statement about incidental findings. Incidental findings can range from variants of unknown significance to pathogenic variants in the mismatch repair-genes (MMR) and BRCA1-2. Pathogenic variants have been reported in 1-18% of cancers and can have significant influence for the patient and family. Patients with glioblastoma (GBM) can have impaired cognitive function, both due to GBM and due to morbidity after surgery. This can limit access to clinical trials as some patients might not understand the study information. We investigated whether patients were interested in participating in a comprehensive genomic trial and where they marked their preference of information for incidental findings. PATIENTS AND METHODS 108 consents from a published study from the Copenhagen Glioblastoma Cohort were examined. The study period was 2016-2019 and included whole exome- and RNA sequencing. The consent included three alternatives to receive information about incidental findings; 1) none, 2) if incidental findings could be treated or future disease be prevented or 3) full information even though no treatment or prevention existed. RESULTS A total of 108/111 (97.3%) patients consented to participate. Each category was marked as follows: 33 (30.6%) marked 1), 24 (22.2%) marked 2) and 45 patients (41.7%) marked 3), respectively. Six consents were N/A as either two or no boxes were marked. No pathogenic incidental findings were identified. CONCLUSION We found a high interest in trial participation despite of complex study information. Information about incidental findings was spread between groups with majority of patients interested in receiving full information, suggesting that complex information does not hinder participation in molecular-based trials for GBM patients.
Mass Cytometric Analysis Revealed Dynamic Alteration of the Tumor Immune Environment in Bone Marrow from Children with Recurrent B Cell Precursor Acute Lymphoblastic Leukemia
Authors: Takashi Mikami, Itaru Kato, James Badger Wing, Hiroo Ueno, Keiji Tasaka, Kuniaki Tanaka, Hirohito Kubota, Satoshi Saida, Katsutsugu Umeda, Hidefumi Hiramatsu, Tomoya Isobe, Ai Okada, Kenichi Chiba, Yuichi Shiraishi, Hiroko Tanaka, Satoru Miyano, Soichi Adachi, Keiko Iwaisako, Seishi Ogawa, Shimon Sakaguchi, Junko Takita
Journal: Blood (2021)
Abstract 11965: Association of Ticagrelor versus Clopidogrel With Bleeding, Dyspnea, and Premature Discontinuation in Patients With Acute Coronary Syndrome
Authors: Min Kang, Kyehwan Kim, Jong-Hwa Ahn, Hyun Woong Park, Jin-Sin Koh, Yongwhi Park, Seok-Jae Hwang, Jin-Yong Hwang, Young-hoon Jeong
Journal: Circulation (2021)

Introduction: Current clinical data have raised the issues regarding the risk of adverse events (e.g. bleeding and dyspnea) and the limited clinical benefit during ticagrelor vs. clopidogrel treatment in patients with acute coronary syndrome (ACS). Hypothesis: Association between bleeding and dyspnea during dual antiplatelet therapy (DAPT), and it would be related with drug switch or discontinuation. Methods: East Asian patients presented with ACS were undergoing percutaneous coronary intervention, and were treated with DPAT with ticagrelor (n=270) or clopidogrel (n=674). At 30-day follow-up, we evaluated platelet function with VerifyNow, and incidence of bleeding (BARC criteria) and dyspnea (MMRC scale) using the dedicated questionnaire. Results: During 30-day follow-up, ACS patients on ticagrelor showed the higher rates of bleeding (45.6% vs. 23.6%; HR, 2.71) and dyspnea (26.3% vs. 13.6%; HR, 2.25) compared with those on clopidogrel. In terms of low platelet reactivity (LPR), ticagrelor showed the lower cutoff (‘PRU≤20’) compared with clopidogrel (‘PRU≤110’). In multivariate analysis, LPR phenotype (OR, 2.70), not type of P2Y 12 inhibitor (OR, 1.34), was significantly associated with the risk of bleeding (Figure) . In addition, type of P2Y 12 inhibitor (OR, 2.14) and bleeding episode (OR, 2.83) increased the risk of dyspnea (Figure) . At 12-month follow-up, ticagrelor treatment showed a higher risk of drug discontinuation than clopidogrel treatment (27.8% vs. 4.7%; HR, 7.71). During ticagrelor administration, patients with both dyspnea and bleeding had a higher rate of drug discontinuation compared to those without both dyspnea and bleeding (adjusted HR, 3.05). Conclusions: This study suggests that incidence of bleeding and dyspnea was frequent during ticagrelor treatment in East Asian patients with ACS. A close association between bleeding and dyspnea increased the risk of drug discontinuation during ticagrelor treatment.
Abstract 11828: Productivity Targets and Performance Reviews for Cardiology Practices in the Veterans Health Administration: Do They Work?
Authors: Neil M Kalwani, Paul A Heidenreich
Journal: Circulation (2021)

Introduction: The optimal mode of promoting physician productivity in integrated healthcare systems is unknown. In 2013, the Veterans Health Administration (VHA) introduced a program setting productivity targets for specialty practices based on the ratio of total work Relative Value Units (wRVUs) to clinical full-time equivalents (FTEs). Practices with productivity less than 1.25 SDs below the mean for their complexity group were required to undergo annual performance reviews and develop remediation plans. Hypothesis: We hypothesized that performance reviews were associated with increased cardiology practice productivity and clinical volume. Methods: We extracted productivity metrics for 125 cardiology practices from fiscal year 2012-2019 reports. We used linear regression to assess the association of reviews with changes in productivity, clinical volume, and access measures, controlling for practice-level trends. Results: Performance reviews were associated with a 38% (95% CI 29 to 47%) relative increase in cardiology practice productivity in the year following review. In the year before review, these practices experienced a relative productivity decrease of 24% (95% CI -35 to -14%), suggesting the observed effect was not due to regression to the mean alone. Reviews were associated with a relative annual increase in practice wRVUs of 29% (95% CI 15 to 44%), a decrease in reported clinical FTEs of 12% (95% CI -24 to -1%), an increase in clinical encounters of 32% (95% CI 16 to 49%), and an increase in the total number of patients receiving care of 23% (95% CI 9 to 36%). There was no significant association between reviews and the annual change in the percentage of new or established patients waiting more than 30 days for an appointment. Conclusions: A program of productivity targets and reviews of low-performing practices was associated with increased cardiologist productivity and total wRVUs, clinical encounters, and number of patients receiving care at reviewed practices. Programs setting productivity targets for groups of specialist physicians may be an effective way to increase care efficiency in integrated healthcare systems. Future research should investigate the impact of these programs on care utilization, appropriateness, and quality.
Abstract 12104: Treatment With Exogenous Atrial Natriuretic Peptide Ameliorates Myocardial Insulin Resistance and Protects Against Ischemia-Reperfusion Injury in Diet-Induced Obesity
Authors: Yuhei Oi, Tomohisa Nagoshi, Haruka Kimura, Yoshiro Tanaka, Hirotake Takahashi, Rei Yasutake, Yusuke Kashiwagi, Toshikazu D Tanaka, Akira Yoshii, Michihiro Yoshimura
Journal: Circulation (2021)

Increasing evidence suggests natriuretic peptide (NP) coordinate inter-organ metabolic crosstalk in addition to its classical actions on hemodynamic regulation. We recently reported exogenous atrial NP (ANP) treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and by attenuating hepatic steatosis in diet-induced obesity. We herein hypothesized that exogenous ANP treatment also ameliorates insulin resistance of the myocardium in which endogenous NP is produced, leading to the cardioprotection during ischemia-reperfusion injury (IRI) in diet-induced obesity. The mice fed a high fat diet (HFD) or normal fat diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously via osmotic pump for another 3 weeks (0.5 μg/kg/min). Intraperitoneal administration of insulin induced Akt phosphorylation in NFD hearts, which was reduced in HFD. ANP treatment restored the impaired insulin-induced Akt phosphorylation in HFD hearts, suggesting that exogenous ANP ameliorated myocardial insulin resistance. To test the functional significance of this, hearts were exposed to IRI using Langendorff model. After IRI, HFD resulted in an impaired left ventricular developed pressure (LVDP) recovery with corresponding increase in infarct size. However, ANP treatment improved functional recovery and reduced injury along with restoration of the impaired IRI-induced Akt phosphorylation in HFD hearts. (% LVDP recovery of baseline: NFD 62.9%±3.6 &lt;n=8&gt;, NFD+ANP 64.5%±4.2% &lt;n=8&gt;, HFD 20.8%±3.3 &lt;n=9&gt;, HFD+ANP 31.4%±2.8% &lt;n=9&gt;, p&lt;0.05) Myocardial ultrastructural analyses by electron microscopy showed number of peri-mitochondrial lipid droplets was increased in HFD treated with ANP, suggesting that ANP protects mitochondria from lipid overload. Of note, ANP treatment substantially attenuated mitochondria cristae disruption after IRI in HFD hearts. In conclusion, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with restoration of disrupted mitochondrial structure in diet-induced obesity. The findings that exogenous NP has significant impact on the NP-rich failing myocardium provide new insight into the biological properties and dynamics of NP.
Abstract 13439: Long-Term Outcomes From Continuous Rhythm Monitoring After Hybrid Convergent Procedure in Longstanding Persistent Atrial Fibrillation Patients
Authors: Faraz Kerendi, David Tschopp, Alexandra Maningat, Brannon Hyde, Paul Coffeen, Bonnie B Punske
Journal: Circulation (2021)

Introduction: Endocardial catheter ablation has suboptimal effectiveness and durability in patients with longstanding persistent atrial fibrillation (LSPAF). Hybrid convergent ablation combines epicardial and endocardial ablation to create a transmural lesion set that isolates the left atrial posterior wall and pulmonary veins. The study objective was to evaluate long-term outcomes assessed by continuous rhythm monitoring in LSPAF patients who received hybrid convergent ablation. Methods: This was a single-center IRB-approved, observational study. Eligible patients were identified by retrospective chart review and included patients who received hybrid convergent procedures between September 2011 and November 2017. Patients were consented for prospective long-term follow-up visits and continuous cardiac monitoring (7-day ePatch). Baseline characteristics, procedural outcomes, and follow-up data were entered into the TRAC-AF registry. This analysis focused on the patient subgroup with pre-operative LSPAF (AF duration &gt;1 year). Results: Of 77 consented patients, 60 had pre-operative LSPAF. Mean age was 66.1 ± 7.9 years, 70% were male, and duration of AF was 6.8 ± 4.8 years. Mean CHA2DS2-VASc score was 2.6 ± 1.4; mean BMI was 32.1 ± 5.9, and 55% (33/60) of patients had previous catheter ablation. Thirty-day major adverse event rate was 5% (3/60) and included 2 inflammatory pericardial effusions and one major bleeding. On continuous monitoring, 71% (41/58) of patients had 0% AF burden at mean follow-up of 61.7 ± 18.9 months. Eight patients (13%) had repeat catheter ablation at mean 21.6 ± 16.3 months since index procedure. Comparison of baseline and follow-up left ventricular ejection fraction (LVEF) from echocardiography revealed a trend of 12.4 ± 13.0 units improvement at mean follow-up of 18.2 ± 23.7 months since baseline in 5 patients with severely reduced (&lt;40%) baseline ejection fraction (p=0.063). Conclusions: Long-term follow-up with continuous monitoring revealed a majority of patients with pre-operative LSPAF had 0% AF burden after a mean 61.7 months since the hybrid convergent procedure. These results are aligned with published studies and the CONVERGE trial on the effectiveness of hybrid convergent ablation in LSPAF.
Abstract 9740: Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Patients with Venous Thromboembolism or Nonvalvular Atrial Fibrillation and Chronic Kidney Disease a Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Maha Alharbi, Afrah Alkazemi, Joanne Doucette, Tewodros Eguale
Journal: Circulation (2021)

Background: Direct oral anticoagulants (DOAC) have proven to be safe and effective alternatives to warfarin for stroke prevention in non-valvular atrial fibrillation (NVAF) as well as treatment of venous thromboembolism (VTE). Chronic kidney disease (CKD) is associated with increased risk of thromboembolism as well as bleeding. The objective of this research is to evaluate the efficacy and safety of DOAC compared to warfarin in patients with either VTE or NVAF across varying renal function. Methods: A systematic literature search using PubMed, Embase (1996 -November 2020), and Cochrane CENTRAL databases was conducted. Randomized controlled trials published in English between 1996 and November, 2020 evaluating the safety and efficacy of DOAC versus warfarin in patients with VTE or NVAF and CKD were included. Outcomes of interest were stroke or thromboembolic events, all-cause mortality, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB). Random effects-model was used for meta-analysis. Risk of bias was assessed by utilizing the Revised Cochrane risk-of-bias tool for randomized trials. Results: After screening and review, a total of 9 randomized controlled trials with 96,103 participants were included. Of those, 81.5% (n=78,361) had a specific classification of renal function throughout the study. Majority of participants had mild to normal (48.5%) renal function, and 35% had mild impairment and moderate and severe renal impairment accounted for 16% and &lt;1%, respectively. DOAC reduced risk of stroke or thromboembolic events compared to warfarin (RR 0.83, CI 95%: 0.77-0.89; p -value&lt;0.01), as well as all-cause mortality (RR 0.91, CI 95%: 0.85-0.97; p -value&lt;0.01). For safety outcomes, MB events were less likely to occur in DOAC group (RR 0.76, CI 95%: 0.69-0.84; p -value&lt;0.01). Whereas, no significant difference was found between DOAC and warfarin in CRNMB events (RR 0.90, CI 95%: 0.73-1.12; p- value 0.36). Conclusion: DOAC demonstrated better efficacy in preventing stroke or thromboembolic events and in decreasing all-cause mortality. DOAC also caused less MB events compared to warfarin. No difference in CRNMB events was detected between these agents.