tbuckley/cabot-search huggingface dataset:
Abstract 16371: Clinical Outcomes of Early Ventricular Arrhythmias and Severe Right Ventricular Failure After Left Ventricular Assist Device Implantation
Authors: Kieun Seok, Dae Hyun Lee, Richard A Vautier, Fahad Hawk, Deepika Kulkarni, Yuan Yuan Lu, Benjamin Mackie, Ricardo Restrepo-Jaramillo, Zachary Stachura, Guilherme Oliveira, Xavier Prida, Jason Feliberti, Dennis Cassidy, Bengt Herweg
Journal: Circulation (2020)

Introduction: Right ventricular failure (RVF) and ventricular tachyarrhythmias (VA) are common causes of poor outcome and mortality in patients with left ventricular assist device (LVAD). VA can precipitate RVF and inotropic therapy can further exacerbate VA. The purpose of this observational study was to investigate the individual and combined impact of RVF and VA on mortality in the early postoperative period after LVAD. Methods: We performed a retrospective analysis of patients undergoing implantation of an LVAD between 2014 to 2017 (N=110). Telemetry tracings and device interrogations were reviewed. Early VA was defined as any ventricular tachycardia and ventricular fibrillation within the first month after LVAD associated with hemodynamic compromise that required device therapy, catheter ablation, and/or antiarrhythmic therapy. Kaplan-Meier statistics with the Mantel-Cox log-rank test was used to analyze survival. Results: We identified 110 LVAD patients, age 57±13 years, 80 males (73%), ischemic cardiomyopathy n=54 (49%), (HeartWare (n=44), HeartMate II (n=44), and HeartMate III (n=22)). Patients were categorized into group A - early VA and severe RVF (n=14); group B - early VA without RVF (n=16); group C - severe RVF without early VA (n=33); and group D - neither VA nor RVF (n=47). The 1-year survival of group A, B, C, and D was 50%, 69%, 73%, and 89%, respectively (p=0.001 comparing each group to the other groups, enclosed figure). The presence of early VA did not relate to RVF (p=0.7). Pre-operative VA was related to post-LVAD VA (RR 9.4, p=0.003). Conclusions: Patients without early VA or severe RVF demonstrated the best survival. Both, VA and severe RVF decreased survival. The presence of both, VA and RVF appears to potentiate mortality. Pre-operative VA is related to post-LVAD VA. These data raise the question if intra-operative ablative therapy in patients undergoing LVAD implantation could improve post-operative mortality, VA, and RVF.
Abstract 16277: Evaluation of Left Peri Atrial Cardiac Sympathetic Activity Using Mibg Scintigraphy Before and After Cryoballoon Ablation of Paroxysmal Atrial Fibrillation
Authors: Hiroshi Fukunaga, Nobuo Iguchi, Sou Asano, Nagase Takahiko, Junichi Nitta, Mitsuaki Isobe
Journal: Circulation (2020)

Introduction: Accelerated cardiac sympathetic activity has been implicated in the development of atrial fibrillation. Ablation or excision of atrial epicardial ganglia for the treatment of atrial fibrillation has been reported. However, visualization of the atrial neural network is considered difficult. We attempted to image the sympathetic innervation with 123 I-metaiodobenzylguanidine (MIBG) using a novel solid-state whole-body scanner (VERITON). Methods: We performed pulmonary vein isolation using a cryoballoon in 10 patients with paroxysmal atrial fibrillation. MIBG images using specific processing were evaluated before and 3 months after ablation to evaluate the neural network of the left peri-atrial cardiac sympathetic activity and its response to ablation. Discrete epicardial accumulation of MIBG was identified using MIBG images fused with atrial computed tomography images. We quantitatively calculated the discrete MIBG accumulation in each pulmonary vein within 2 cm from its ostium, which may have been modified by balloon ablation. Results: Discrete MIBG accumulation was generally reproducible in the pre- and postoperative evaluations. The discrete MIBG accumulation value was 2.8 per case, with an average count of 4.15х10 5 PROPCNTS. Of the overall 28 accumulations, 15 had disappeared and three had changed in accumulation level and location after ablation. There was no specific pattern of sympathetic image modification. However, the group in which accumulation disappeared had a significantly smaller cross-sectional area of the pulmonary vein than the group in which it did not (17.2±3.4 mm vs 19.7±1.7 mm, p=0.0056). For reference, the average cryoballoon size was 28 mm. Conclusions: The sympathetic innervation of the left atrium was visualized using MIBG imaging, and the image was modified by cryoballoon ablation. The ability to image sympathetic nerve modification by catheter ablation will be clinically useful.
Abstract 14471: Prognostic Impact of Sarcopenia in Men versus Women With Acute Decompensated Heart Failure and Preserved Left Ventricular Ejection Fraction
Authors: Takanari Kimura, Shungo Hikoso, Nakatani Daisaku, Shunsuke Tamaki, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Yoshio Yasumura, Takahisa Yamada, Yasushi Sakata
Journal: Circulation (2020)

Background: Sarcopenia is associated with poor prognosis in chronic heart failure. Fat-free mass index (FFMI) is an indicator of resting energy expenditure and has been used for the clinical diagnosis of sarcopenia. However, the prognostic impact of sarcopenia diagnosed by FFMI remains to be elucidated in patients admitted with acute decompensated heart failure (ADHF) and preserved LVEF (HFpEF), relating to gender. Methods: Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka. We studied 621 patients who survived to discharge (men, n=281 and women, n=340). Fat-free mass (FFM) was estimated by the formula [FFM (kg) = 7.38 + 0.02908 х urinary creatinine (mg/day)] and normalized by the square of the patient’s height in meters to calculate FFMI at discharge. Sarcopenia was defined as FFMI &lt;17 kg/m2 in men and &lt;15 kg/m2 in women. The endpoint was all-cause death. Results: During a follow-up period of 1.5±0.8 yrs, 102 patients died (men, n=46 and women, n=56). At multivariate Cox analysis, FFMI was significantly associated with the mortality independently of age, estimated glomerular filtration rate, NT-proBNP and LVEF in both men (p=0.0155) and women (p=0.0223). Patients with sarcopenia had a significantly higher risk of all-cause death than those without sarcopenia in both genders (Figure). Conclusions: In this multicenter study, sarcopenia diagnosed by FFMI was shown to be associated with poor clinical outcome in HFpEF patients admitted with ADHF in both genders.
Abstract 14554: Angiogenic Agent Ono-1301 Enhanced Cardiac Contractile Proteins in Hipsc Derived Cardiac Tissue-like Construct With Functional Angiogenesis
Authors: Xiang Qu, Junjun Li, Kota Suzuki, Akima Harada, Shigeru Miyagawa, Li Liu, yoshiki sakai, Yoshiki Sawa
Journal: Circulation (2020)

Introduction: Transplantation of human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) into myocardial infarcted areas has shown potential in healing myocardial infarction (MI). However, the survival rate of transplanted cells is yet considered limited, restricting the therapeutic effects of the transplantation. We assumed that adding angiogenic agent ONO-1301 could promote early stage angiogenesis between host and graft, and benefit the therapeutic effects of hiPSC-CM transplantation. Methods: This study is based on our former study of Cardiac Tissue-Like Construct (CTLC), where 5 x10e6 of hiPSC-CM was seeded on a 1x1cm poly(lactic-co-glycolic acid) (PLGA) nano fiber (Figure A). In addition, angiogenic agent ONO-1301 was mixed into the fibers. After 24h culture in vitro, 3 layers of CTLCs were transplanted into Nude rat MI models with or without ONO-1301. The rats were raised for another 4 or 8 weeks before sacrifice. Results: In vitro experiments have shown that supernatant of iPS-CM with ONO-1301 underwent a rise in VEGF during a 3 to 6 day culture (Figure B). The VEGF concentration in ONO-1301 positive group is much higer than ONO-1301 negative group (P=0.022) on day3. This difference narrows down over time. In vivo experiments on nude rat have shown that capillary density on MI border zone of ONO fiber+iPS-CM group is 29.95% higher than that of PLGA fiber+iPS-CM group (P=0.004) (figure C). HE and immunofluorescence staining shows remaining transplanted hiPSC-CMs in ONO fiber+iPS-CM group shows more significant TNT2 and human nuclear antigen(HNA) expression than that of PLGA fiber+iPS-CM group (Figure D and E). Also ONO fiber+iPS-CM group showed functional recovery compared to the sham.
Abstract 15450: Colchicine Therapy in Patients With Coronary Artery Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Ahmad Al-Abdouh, mahmoud Barbarawi, Safi U Khan, Mohammed Osman, Sireesha Upadhrasta, Vinod Kumar Reddy Solipuram, Waiel Abusnina, Qais Radaideh, Di Zhao, Erin D Michos
Journal: Circulation (2020)

Introduction: Inflammation is a substantial mediator of atherosclerosis. Colchicine has anti-inflammatory effects and has been investigated in many randomized controlled trials (RCTs) in patients with coronary artery disease (CAD). Methods: We searched PubMed/MEDLINE, Cochrane library, and Embase databases (inception through February 28 th , 2020) for RCTs evaluating colchicine in CAD patients. The outcomes of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), all-cause mortality, cardiovascular mortality, and stroke. Estimates were pooled using inverse variance random-effects model. We reported effect sizes as risk difference (RD) with 95% confidence interval (CI). Results: A total of 6 RCTs with 6,154 patients were included. The mean age ± SD for the patients in the colchicine group was 61.6±10.8 and control group was 61.5±10.7 years. At the median follow-up of 3.5 months, use of colchicine in patients with CAD was not associated with statistically significant reduction of MACE (RD -0.032; 95% CI, -0.083-0.018; p = 0.15; I 2 = 75%; low level of evidence) [ Figure ]; MI (RD -0.011; 95% CI, -0.030-0.007; p = 0.16; I 2 = 11.3%; low level of evidence); all-cause mortality (RD -0.001; 95% CI, -0.009-0.006; p = 0.65; I 2 = 0%; low level of evidence); cardiovascular mortality (RD -0.003; 95% CI, -0.010-0.004; p = 0.34; I 2 = 0%; low level of evidence); and stroke (RD -0.001, 95% CI, -0.005-0.004; p = 0.69; I 2 = 0%; very low level of evidence). Conclusion: This meta-analysis suggests that colchicine was not associated with a significant decrease in cardiovascular endpoints and mortality in patients with CAD.
Abstract 14125: An in vitro Pulmonary Vascular Platform From Endothelialized Whole Lung Scaffolds
Authors: Yifan Yuan, Katherine L Leiby, Allison M Greaney, Micha Sam B Raredon, Hong Qian, Pavlina Baevova, Taylor S Admas, Alexander J Engler, Mehmet H Kural, Jonas C Schupp, Young Hong, Naftali Kaminski, Laura E Niklason
Journal: Circulation (2020)

Introduction: The development of an in vitro system is critical to studying human diseases including the novel coronavirus disease-19 (COVID-19), and is typically centered on recapitulating native physiology. In the case of the pulmonary vasculature, the endothelium is critical for establishing the fluid-tight barrier in the alveolar compartment, and displays significant phenotypic and functional heterogeneity along vascular tree. Objective: Here, we developed an experimental platform that could mimic physiological functions and cellular phenotypes of pulmonary vasculature, during homeostatic and diseased states. Methods and Results: Lymphatic low pulmonary microvascular endothelial cells (Lymph low PMECs) were isolated from Prox1-GFP rodent lungs from regions of having low amounts of lymphatic tissue. Single-cell RNA-sequencing (scRNAseq) data revealed that these cells were becoming phenotypically homogenous over several passages while losing some markers of native differentiation during passaging. Intriguingly, after culturing in decellularized lung scaffolds, the phenotype of the lymph low PMEC changed back toward native lung endothelium. Vascular barrier function was partially restored in engineered lungs repopulated with endothelium, while small capillaries with patent lumens were appreciable. To evaluate the ability of the engineered endothelium to modulate permeability in response to exogenous stimuli, lipopolysaccharide (LPS) was introduced into repopulated lungs to simulate acute lung injury. After LPS treatment, the pro-inflammatory signal was significantly increased and the vascular barrier was severely impaired in the repopulated lung. Conclusions: Taken together, these results show a novel platform that recapitulates some pulmonary microvascular functions and phenotypes at a whole organ level. This development may help pave the way for using the whole organ engineering approach to model vascular diseases.
Abstract PO-021: Targeting glutamine dependencies in pancreatic cancers
Authors: Alec Kimmelman, Joel Encarnacion-Rosado
Journal: Cancer Research (2020)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with a 5-year survival rate of less than 10%. PDAC cells activate a non-canonical glutamine metabolic pathway essential to increase the level of NADPH, an important metabolite for redox balance, promoting tumor growth. Targeting glutamine metabolism using CB-839, a small molecule that targets glutaminase, the first step of glutaminolysis failed in PDAC. CB839 treatment only blocks the carbon utilization of glutamine and not the nitrogen portion which is critical for anabolic processes. We have previously shown that PDAC cells can rewire their metabolism and overcome GLS inhibition within days. We hypothesize that using a glutamine analog, such as 6-Diazo-5-oxo-L-norleucine (DON), which broadly inhibits all of the metabolic reactions that require glutamine, will provide a new therapeutic avenue for PDAC. Here, we investigate the role of DON in PDAC metabolism and progression. DON treatment leads to a profound decrease in proliferation, TCA cycle metabolites, and mitochondrial basal respiration in a panel of PDAC cells. In vivo studies using a syngeneic, orthotopically transplantation model in the pancreas demonstrated a significant decrease in tumor growth. Bulk RNA-seq studies demonstrated a decrease in the transcriptional signature of ECM and hypoxia, which was confirm by histology, suggesting the role of the TME in the response to glutamine blockage. Currently, we are testing the role of this drug and potential mechanisms of resistance using an autochthonous PDAC mouse model. Citation Format: Alec Kimmelman, Joel Encarnacion-Rosado. Targeting glutamine dependencies in pancreatic cancers [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-021.
Covid-19: Critically ill patients treated with arthritis drug tocilizumab show improved outcomes, researchers report
Authors: Jacqui Wise
Journal: BMJ (2020)

Covid-19: Critically ill patients treated with arthritis drug tocilizumab show improved outcomes, researchers report Jacqui WiseThe rheumatoid arthritis drug tocilizumab seems to improve outcomes in patients with covid-19 who are the most severely ill, show early results released from the Remap-Cap international platform trial.The researchers reported that critically ill patients receiving tocilizumab were more likely to improve than patients who received no immune modulator (odds ratio 1.87)."These are very exciting and encouraging results," said the chief investigator, Anthony Gordon, consultant in intensive care medicine at Imperial College Healthcare NHS Trust, at a Science Media Centre briefing on 19 November. 1 O'Hare R. Arthritis drug effective in treating sickest covid-19 patients.Imperial College London.19 Nov 2020.
Abstract 12717: Enhance Negative Modulation of Beta <sub>3</sub> -Adrenergic Stimulation on Cardiomyocyte Functional Performance, [Ca <sup>2+</sup> ] <sub>i</sub> Regulation and β-Adrenergic Reserve in Rats Expressing Human Angiotensinogen Gene
Authors: Jing Cao, Xiaoqiang Sun, Heng Jie Cheng, Tiankai Li, Yixi Liu, Jessica L VonCannon, Carlos M Ferrario, Che Cheng
Journal: Circulation (2020)

Background: Transgenic rats expressing the human angiotensinogen gene [TGR (hAogen) 1623] (hAogen) exhibit sustained hypertension and systolic dysfunction associated with altered cardiac renin-angiotensin system and β- adrenergic receptor (AR) signal transduction systems. We have shown previously, in contrast to β 1 - and β 2 -ARs, β 3 -ARs are linked to G i proteins, and stimulation of β 3 -ARs inhibits cardiac contraction and relaxation. Hypertension is associated with increased cardiac expression of G i proteins. This may alter β 3 -AR stimulation and play an important role in the cardiac functional impairment of this humanized model of hypertension. However, the alteration and functional effect of β 3 -AR activation in this model are unknown. We tested the hypothesis that high cardiac tissue Ang II content in hAogen may cause an up-regulation of cardiac β 3 -AR, which exacerbates myocyte dysfunction and impairs calcium regulation, thereby directly contributing to the cardiac dysfunction. Methods: We compared LV myocyte β 3 -AR expression and myocyte functional and [Ca 2+ ] i transient ([Ca 2+ ] iT ) responses to β- and β 3 -AR stimulation in myocytes obtained from 8 Sprague Dawley (SD) control and 8 hAogen male adult rats. Results: Versus SD, in hAGT rats, basal myocyte contraction (dL/dt max , 107.1 vs 138.8 μm/s), relaxation (dR/dt max , 94.0 vs 103.9 μm/s) and [Ca 2+ ] iT (0.15 vs 0.21) were depressed. A non-selective β-AR agonist, isoproterenol (ISO) (10 -8 M) produced significantly smaller increases in dL/dt max , (42% vs. 61%), dR / dtmax (35% vs. 51%), and [Ca 2+ ] iT (20% vs. 30%). Moreover, versus SD, in hAogen rats, LV myocyte β 3 -AR protein level increased by 32% (0.29 vs 0.22) with resulted significantly altered myocyte functional response to β 3 -AR stimulation. Compared with the changes in SD myocytes, in hAogen myocytes, BRL (10 -8 M) produced a significantly greater decreases in dL/dt max , (27% vs 12%), dR/dt max (28% vs 11%), and [Ca 2+ ] iT (17% vs 10%). Conclusions: TGR (hAogen) 1623, this humanized model of hypertension is associated with an up-regulation of LV myocyte β 3 -AR, which enhances β 3 -AR-caused inhibition of myocyte contractile, relaxation and [Ca 2+ ] iT and exacerbates β-AR desensitization, thereby directly contributing to the cardiac dysfunction.
Abstract 14948: Comparative Effectiveness of CRT in Older Patients With Heart Failure: Systematic Review and Meta-Analysis
Authors: Saeed Juggan, Clifford A Reilly, Praveen K Ponnamreddy, Lauren Gilstrap, Emily Zeitler
Journal: Circulation (2020)

Background: The pivotal cardiac resynchronization therapy (CRT) trials enrolled patients significantly younger than the typical contemporary heart failure with reduced ejection fraction (HFrEF) patients. Benefits of CRT in older HFrEF patients is largely unknown and may be less due to higher comorbidity burdens and higher procedural risk. We sought to address this evidentiary gap through meta-analysis. Hypothesis: Compared to patients &lt;70 years old (”younger”), patients ≥ 70 years old (“older”) have similar mortality rates, rates of complications and changes in ejection fraction (EF) following CRT. Methods: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older HFrEF patients. Differences in mortality and mean difference (MD) in EF were calculated between groups. Random effects meta-analysis of MD in EF (older minus younger) and relative risk (RR) of death and complications are reported along with estimates of heterogeneity. Results: Seven studies [n= 4381 younger, 1203 older] were included in LVEF meta-analysis. Compared to younger patients, there was greater EF improvement in older patients [MD 1.20; 95% CI 0.13 - 2.28, p=0.03, I 2 =46%]. RR of mortality was analyzed for 11 studies [n=5038 younger, 1653 older] (Figure). Survival was better in younger patients [RR 1.06; 95% CI 1.04 - 1.09, p&lt;0.01, I 2 =0%]. No significant differences in complication rates were observed between younger and older patients. Conclusions: CRT in older patients was associated with greater improvement in EF than younger patients. Mortality is greater in older patients which may reflect greater underlying risk of death from competing causes. Figures:
Effectiveness of progressive tendon-loading exercise therapy in patients with patellar tendinopathy: a randomised clinical trial
Authors: Stephan J Breda, Edwin H G Oei, Johannes Zwerver, Edwin Visser, Erwin Waarsing, Gabriel P Krestin, Robert-Jan de Vos
Journal: British Journal of Sports Medicine (2020)

To compare the effectiveness of progressive tendon-loading exercises (PTLE) with eccentric exercise therapy (EET) in patients with patellar tendinopathy (PT).In a stratified, investigator-blinded, block-randomised trial, 76 patients with clinically diagnosed and ultrasound-confirmed PT were randomly assigned in a 1:1 ratio to receive either PTLE or EET. The primary end point was clinical outcome after 24 weeks following an intention-to-treat analysis, as assessed with the validated Victorian Institute of Sports Assessment for patellar tendons (VISA-P) questionnaire measuring pain, function and ability to play sports. Secondary outcomes included the return to sports rate, subjective patient satisfaction and exercise adherence.Patients were randomised between January 2017 and July 2019. The intention-to-treat population (mean age, 24 years, SD 4); 58 (76%) male) consisted of patients with mostly chronic PT (median symptom duration 2 years). Most patients (82%) underwent prior treatment for PT but failed to recover fully. 38 patients were randomised to the PTLE group and 38 patients to the EET group. The improvement in VISA-P score was significantly better for PTLE than for EET after 24 weeks (28 vs 18 points, adjusted mean between-group difference, 9 (95% CI 1 to 16); p=0.023). There was a trend towards a higher return to sports rate in the PTLE group (43% vs 27%, p=0.13). No significant between-group difference was found for subjective patient satisfaction (81% vs 83%, p=0.54) and exercise adherence between the PTLE group and EET group after 24 weeks (40% vs 49%, p=0.33).In patients with PT, PTLE resulted in a significantly better clinical outcome after 24 weeks than EET. PTLE are superior to EET and are therefore recommended as initial conservative treatment for PT.