tbuckley/cabot-search huggingface dataset:
Abstract 10971: Prevalence and Risk Factors of Silent Brain Microbleeds in Patients with Severe Valvular Heart Disease
Authors: Tomohiko Watanabe, Yumiko Kanzaki, Ryo Yokoyama, Masaaki Hoshiga
Journal: Circulation (2021)

Introduction: The presence of cerebral microbleeds (CMBs) has been described using MRI in patients with cardiovascular risk factors or prior stroke and could predict future cognitive dysfunction or cardiovascular mortality. CMBs are highly frequent (&gt; 50%) in patients with infective endocarditis (IE). However, the association of CMBs and clinical factors in patients' valvular disease without IE remains unclear. Hypothesis: Valvular heart disease without IE confers a risk factor for microbleeds. Methods: We retrospectively examined data from the consecutive 96 patients ( 72 ± 9 years, 49 men) with severe valvular disease who underwent T2*-weighted brain MRI before cardiac surgery. The patients with neurological abnormalities or IE were excluded. Conventional echocardiography was performed to evaluate the left ventricular volume and valvular abnormalities. CMBs were coded by researchers blind to clinical details, who independently assessed the presence and location of CMBs using a standardized form. The study population consisted of 59 patients with severe aortic stenosis (AS) (group A) and 40 patients with severe aortic or mitral regurgitation (group B). Results: CMBs were found in 26 patients (27%), 14 (15%) had multiple CMBs. CMBs were most frequently seen in the lobar locations (69%), followed by deep or infratentorial locations (62%). No significant relationship was found between CMBs in dyslipidemia, diabetes mellitus, smoking status, anticoagulant, and antiplatelet therapy in both groups. In group A, the HAS-BLED score was higher in patients with CMBs, and the presence of CMBs was associated with hypertension (P&lt;0.05); however, no significant differences were observed in the left ventricular mass index (LVMI), LV end-diastolic volume (LVEDV), any aortic valve severity parameters. In group B, there were significant differences in LVMI and LVEDV between patients with CMBs and those without (154 ± 40 g/m 2 vs 125 ± 32 g/m 2 , P &lt; 0.01 ; 150 ± 39 ml vs 111 ± 38 ml, P&lt;0.01). Conclusion: CMBs were frequently observed in severe valvular heart disease without IE. The presence of CMBs was independent of antiplatelet or anticoagulant therapy. In aortic or mitral regurgitation patients, LV remodeling may contribute to the development of CMBs.
Abstract 14228: Mechanism of Atrial Fibrillation in an Animal Model of Inflammatory Bowel Disease
Authors: Andres F Pelaez, Disha Varma, Carlos H Pereira, Jonathas F Almeida, Jeremiah Wasserlauf, Ali Keshavarzian, Kathrin Banach
Journal: Circulation (2021)

Introduction: Ulcerative colitis (UC) is an i nflammatory bowel disease with a relapsing and remitting course. UC has extraintestinal manifestations and UC patients exhibit twice the risk for atrial fibrillation (AF) during acute disease activity. The mechanism of AF due to UC remains to be determined. Hypothesis: During acute UC a dysregulation of vagal signaling increases a patients propensity for AF. Methods: Mice (male, C57BL/6) were treated with Dextran Sulfate Sodium (DSS: 3%) supplemented drinking water for 7days that disrupts intestinal barrier function and mimics the disease phenotype of acute UC. Changes in atrial electrophysiology were quantified in vivo (EKG), on the whole heart (Langendorff configuration) and the cellular level (Fluo-4AM) during peak inflammation (DSS A ) and remission (DSS R ). Results: DSS A mice exhibited an attenuated heart rate (HR) in vivo (CTL: 491 ± 11 bpm, n=10; DSS A : 448 ± 11 bpm, n=16; p&lt;0.05) and in excised perfused hearts (Langendorff configuration: CTL: 321 ± 15 bpm, n = 3; DSS A : 256 ± 17 bpm, n = 4; p &lt; 0.05). The P-wave duration was prolonged (in vivo, CTL: 25.5 ± 0.6 ms, n=10; DSS A : 30.2 ± 0.5 ms, n=16; p &lt; 0.0001) and HR variability time-domain measure RR-corrected SDNN was attenuated (CTL: 11.3 ± 1.1 ms, n=10; DSS A : 8.2 ± 0.7 ms, n=16; p &lt; 0.05). The latter is an indicator for an attenuated vagal tone in DSS A mice and coincided with an increased sensitivity to the vagal agonist Carbachol in-vivo (CCh 150 ng/g, change in HR: CTL: -3.8 ± 4.4 %, n=6; DSS A : -42.2 ± 4.8 %, n=10; p &lt; 0.0001). After burst pacing DSS A hearts exhibited a prolonged RR-corrected sinus node recovery time (CTL: 11.2 ± 1.4 ms, n=3; DSS A : 25.5 ± 2.1 ms, n=4; p &lt; 0.0001), an increased AF propensity, and prolonged duration of AF episodes (CTL: 0.8 ± 0.17 s, n=3; DSS A : 2.4 ± 0.31 s, n=4; p &lt; 0.05) even in the absence of CCh. No changes in atrial myocyte Ca handling properties were determined. After remission HR, P-wave duration, and HRV in DSS R returned to control values. Conclusions: The data suggests that acute UC increases the risk for AF likely as a consequence of an attenuated sinus rhythm and atrial conduction velocity where vagal stimuli could exacerbate the risk for reentry of excitation. If these changes are the direct consequence of the attenuated vagal tone remains to be determined.
Abstract 10107: Adherence to a Comprehensive History, Physical Exam and AHA Target HF Checklist-A Quality Improvement Study of Heart Failure Readmissions
Authors: Kavin raj, Sanya Chandna, Sunayna Gurnani, Abi Watts, Monarch Shah, Christian Toquica, Sandesh Dewan
Journal: Circulation (2021)

Introduction: We planned to study the adherence to the AHA Target HF checklist and the adequacy of history and physical exam (HPE) in a community hospital. Methodology: Fifty-one patients readmitted within 30 days with index diagnosis coded as CHF in the year 2019 were included. Data was collected manually. Results: A significant proportion of patients (27-86%) did not have documentation of NYHA class, exertional dyspnea, PND/orthopnea, weight gain, S3, JVD, dietary compliance, and smoking status. The exacerbating factor was not identified in 54% (27 of 51) of patients, and reasons for not discharging on GDMT (Goal-directed medical therapy) were not documented in 25% (12 of 51). ACE/ARB was not given on discharge to 47% (24 of 51) of HFrEF patients, likely because of abnormal renal function. Only 19% (10 of 51) of patients received MRA (Mineralocorticoid receptor antagonist) (Table 1). Discussion: In our study, we found suboptimal usage of ACE/ARB, MRA, and the lack of a comprehensive HPE. HF patients need a comprehensive HPE and the identification of key exacerbating factors for decompensation to prevent readmissions.AHA Target-HF checklist can improve quality of care and prevent readmissions and hence should be used routinely in all CHF patients. Often the clinicians are not aware of the updated guidelines and the presence of AHA target HF checklists. Although ours was a single-center study, we hypothesize that this may be a major issue in other community hospitals as well. We have designed a comprehensive physician education program, standardized admission notes, discharge notes, order sets, and checklists to be used for the year 2021. We planned to track the readmission rates once these interventions are implemented.
EPCO-15. SPATIAL-TRANSCRIPTOMICS REVEALS UNIQUE MOLECULAR FEATURES OF FLUORESCENCE-SORTED 5-AMINOLEVULINIC ACID+ INFILTRATIVE TUMOR CELLS ASSOCIATED WITH RECURRENCE AND POOR SURVIVAL IN GLIOBLASTOMA
Authors: Geoffroy Andrieux, Tonmoy Das, Stuart Smith, Ruman Rahman, Sajib Chakraborty
Journal: Neuro-Oncology (2021)

Abstract Spatiotemporal heterogeneity of glioblastoma (GBM) originating from genomic and transcriptional variation in spatially distinct sites, may contribute to subtype switching in GBM prior to and upon recurrence. Fluorescence-guided neurosurgical resection utilizing 5-aminolevulinic acid (5ALA) has enabled the isolation of infiltrative margin tumor cells (5ALA+ cells) from a background of non-neoplastic cells. To falsify the hypothesis that the 5ALA+ subpopulation(s) is defined by a unique cellular state, we have explored the spatial-transcriptomic (ST) landscape to interrogate molecular signatures unique to infiltrating 5ALA+ cells in comparison to GBM core, rim, and invasive margin non-neoplastic cells. ST analysis reveals that GBM molecular subtype plasticity is not restricted to recurrence, but manifests regionally in a cell-type-specific manner. Whilst GBM core and rim are highly enriched with Classical and Proneural subtypes, 5ALA+ cells are uniquely enriched with the Mesenchymal subtype (MES). Upregulation of the wound response pathway in 5ALA+ cells implicate hijacking of the wound healing pathway of neural cells to promote tumor growth. Exon-intron split analysis revealed an upregulation of exonic counts for MES and wound-response genes in 5ALA+ cells, implying that these genes are under active post-transcriptional control. Network analysis suggests that wound response genes, including chemokine CCL2 that recruits regulatory T-cells and monocytic myeloid-derived suppressor cells, are controlled by an IRF8-mediated transcriptional program in 5ALA+ cells. A higher stemness signature both in 5ALA+ cells and non-neoplastic cells of the invasive margin emphasizes the role of this microenvironment in stemness acquisition and defines 5ALA+ cells as a rare sub-population of GBM stem cells. Finally, we establish a link between the unique molecular-signatures of 5ALA+ cells, and poor survival and GBM recurrence. Characterization of the 5ALA+ infiltrative sub-population offers an opportunity to develop more effective GBM treatments and urges focus away from the GBM proliferative core, upon which failed targeted therapies have been predicated.
Abstract 6979: Thromboembolic Risk of Movable Ball Type Left Atrial Appendage Thrombi in Patients with Atrial Fibrillation Under Widespread Use of Anticoagulant Therapy
Authors: Miho Sugitani, Takanao Mine, Masaharu Ishihara
Journal: Circulation (2021)

Background: Left atrial appendage thrombi (LAAT), especially movable ball type LAAT, have been reported to be high-risk for thromboembolic events in patients with atrial fibrillation (AF). However, thromboembolic risk of the movable ball type LAAT under widespread use of anticoagulant therapy remains unclear. Methods: We retrospectively studied 71 LAAT patients taking anticoagulants out of 1508 consecutive patients who underwent t transesophageal echocardiography (TEE) prior to cardioversion or catheter ablation for AF. Patients with significant valvular disease and coagulation disorder were excluded. Clinical data, blood sample, and transthoracic echocardiography were evaluated at the time of TEE. The LAAT were classified into movable ball, fixed ball and mountain type LAAT by three independent observers. Results: Ten of 71 LAAT patients showed movable ball type LAAT and 14 patients had fixed ball type LAAT. During follow-up (39±33 months), one patient underwent emergency thrombectomy, 5 patients developed thromboembolic event, and 12 patients died. There were no differences in clinical data, blood sample data, transthoracic echocardiographic parameters, thrombectomy/thromboembolic event rate, and survival rate among types of LAAT (Figure). Conclusion: Thromboembolic risk of the movable ball type LAAT is the same as fixed type LAAT, in patients with atrial fibrillation under widespread use of anticoagulant therapy.
Abstract 11688: Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer
Authors: Samuel A Shabtaie, Nicholas Y Tan, Robert C Ward, Joerg Herrmann
Journal: Circulation (2021)

Introduction: Prevention of stroke in patients with atrial fibrillation and cancer is challenging as patients are at increased bleeding and thrombotic risk. Left atrial appendage occlusion (LAAO) has evolved as a promising strategy for stroke prevention with protentional to reduce bleeding risk, though no data exists on its efficacy in patients with cancer. Hypothesis: LAAO is a safe and effective strategy for reducing stroke and bleeding risk in cancer patients with atrial fibrillation. Methods: We retrospectively reviewed all patients with nonvalvular atrial fibrillation who underwent LAAO at all Mayo Clinic sites from 2017-2020 and identified those who had undergone prior or current treatment for cancer. Baseline demographics, malignancy history, atrial fibrillation parameters, procedural success/complications, stroke and bleeding incidence and major adverse cardiac events were ascertained. Results: 55 patients were included in the study; 44 (80.0%) were male and mean age was 79.0 ± 6.1 years. Most common primary malignancies included prostate cancer (29.1%), oropharyngeal cancer (12.7%), and melanoma (10.9%) with 15 (27.3%) having metastatic disease and 14 (25.5%) patients having active malignancy at device implant. Mean CHA2DS2-Vasc score was 4.9 ± 1.3, with 47 (85.5%) patients having a prior bleeding event. Acute procedural success was achieved in all patients with 30-day complications including 4 (7.3%) with vascular access site bleeding, 1 (1.8%) with pericarditis and 1 (1.8%) with a seizure. At a follow up of 1.8 ± 1.1 years, ischemic stroke occurred in 2 (3.6%) patients with bleeding complications in 5 (9.1%) patients. Device related complications occurred in 6 (10.9%) patients with 4 (7.3%) with device thrombosis and 2 (3.6%) with a peri-device leak. Death occurred in 14 (25.5%) patients most commonly due to malignancy progression (9.1%) and infection (7.3%). Conclusions: In our study cohort, LAAO in patients with cancer was achieved with excellent procedural success and offered reasonable reduction in stroke and bleeding risk. Mortality was high likely due to the age of the patients studied, underlying malignancy and comorbidities. Further studies are needed to investigate the prevalence of device thrombosis in cancer patients.
Abstract 11390: Exercise Intensity, Minutes Walked for Exercise, and Improved Walk Performance in Peripheral Artery Disease: The Lite Randomized Clinical Trial
Authors: Joshua Slysz, Bonnie Spring, W. Jack Rejeski, Todd Manini, Jack Guralnik, Daniel E Forman, Lu Tian, Lihui Zhao, Dongxue Zhang, Mary M McDermott
Journal: Circulation (2021)

Introduction: Recent evidence showed that among people with peripheral artery disease (PAD), walking exercise conducted at a pace inducing ischemic leg symptoms improved six-minute walk distance (6MW), while walking exercise conducted at a pace without ischemic leg symptoms had no effect on 6MW. This report describes associations of walking exercise intensity and minutes walked for exercise among participants with PAD with the change in 6MW. Method &amp; Results: In the LITE clinical trial, 305 participants with PAD (69±4 years, 181 (59%) Black, 146 (48%) female) were randomized to: 1) walking exercise conducted at a pace without ischemic leg symptoms (low-intensity: LI), 2) walking exercise conducted at a pace eliciting ischemic leg symptoms (high-intensity: HI), or 3) an attention-control group for 12-months. Participants in both exercise groups were asked to walk in or around the home for up to five days/week for up to 50 minutes/session. Measurements of walking intensity and exercise minutes per week were determined individually for each participant in each exercise group using an Accelerometer. Participants in each exercise group were categorized into quartiles according to exercise minutes per week and exercise intensity, respectively (4 th quartile indicated greatest minutes or intensity). Within the LI and HI groups, more minutes of exercise per week were associated with greater 6MW improvement [(LI: 4 th vs 1 st Q: +54 m, 95%CI:16, 92; P=0.018), (HI: 4 th vs 1 st Q: +54 m, 95% CI: 12, 96; P=0.010), Table 1]. Within the LI group, but not the HI group, greater exercise intensity was associated with greater 6MW improvement [(LI: 4 th vs 1 st Q: +80 m, 95% CI: 31, 128; P=0.002), Table 1]. Conclusion: While high intensity exercise improves 6MW in PAD, exercising for a greater duration offers greater benefit. Additionally, there is benefit in exercising at low intensity, focusing on increased duration of exercise, if patients are unable to exercise at high intensity.
Abstract 12027: Low-Density Lipoprotein Cholesterol in Patients With Homozygous Familial Hypercholesterolemia Who Participated in Sequential Studies of Alirocumab and Evinacumab
Authors: Frederick J Raal, Robert S Rosenson, Genovefa Kolovou, Mariko Harada-shiba, Olena Mitchenko, Paolo Rubba, shazia ali, Poulabi Banerjee, Nagwa Khilla, Jennifer McGinniss, robert pordy, Dirk J Blom
Journal: Circulation (2021)

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by markedly elevated levels of low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. This analysis evaluated LDL-C changes in patients with HoFH who sequentially participated in interventional trials with alirocumab (NCT03156621) and evinacumab (NCT03399786). Methods: A total of 25 patients completed the alirocumab trial and entered the evinacumab trial and were randomized to intravenous evinacumab 15 mg/kg (n=16) or placebo (n=9) every 4 weeks. The primary outcome for the evinacumab trial was percent change in LDL-C from baseline to week 24. Results: Baseline characteristics were generally well balanced. Among patients who participated in the alirocumab trial, a reduction in LDL-C of –44.6% and –1.1% was observed at week 24 in patients treated with evinacumab versus placebo, respectively. Overall, mean total reductions in LDL-C (Figure) and apolipoprotein B of -62.9% and -54.9%, respectively, were observed in patients treated with the combination of alirocumab and evinacumab; and triglycerides were lowered by -54.5%. The absolute LDL-C reduction from their baseline in patients treated with the combination of alirocumab and evinacumab was -216.3 mg/dL. No new safety signals were observed when treated with alirocumab and evinacumab, and were consistent with the respective trial results. Conclusions: Combination therapy with alirocumab and evinacumab reduced LDL-C by more than 60% in patients with HoFH and was well tolerated.
Combination of Melphalan Flufenamide and Anti-PD-L1 or Anti-CD38 Antibodies Enhances Anti-Myeloma Immunity
Authors: Arghya Ray, Ting DU, Nina N. Nupponen, Fredrik Lehmann, Jakob Lindberg, Joachim Gullbo, Paul G. Richardson, Dharminder Chauhan, Kenneth C. Anderson
Journal: Blood (2021)
Abstract P452: Stem Cells Defect And Alarmins S100A8/A9 Overexpression Associate With Early-stage Frailty And Poor Cardiovascular Health In Older Adults
Authors: Benedetta Maria Bonora, Maria Teresa Palano, Gianluca Testa, Gian Paolo Fadini, Elena Sangalli, Fabiana Madotto, Giuseppe Persico, Francesca Casciaro, Rosa Vono, Ornella Colpani, Francesco Scavello, Roberta Cappellari, Patrizia Orlando, Franco Carnelli, Andrea Berardi, Stefano De Servi, Angela Raucci, PASQUALE ABETE, Marco Giorgio, Paolo Madeddu, Gaia Spinetti
Journal: Circulation Research (2021)

Importance: Frailty affects the physical, cognitive, and social domains exposing older adults to an increased risk of cardiovascular diseases and death. The mechanisms linking frailty and cardiovascular outcomes are mostly unknown. Objective: Here, we studied the association of hematopoietic stem/progenitor cells (HSPCs) and molecular markers of inflammaging with the cardiopulmonary phenotype and prospective adverse events of individuals classified according to levels of frailty. Methods: We conducted one observational study on two patients’ cohorts of older adults characterized for their frailty status examining the abundance (flow cytometry) and gene expression profile (RNAseq) of HSPCs, and the levels of cardiac dysfunction-associated alarmins S100A8/A9 and inflammatory cytokines (ELISA). Results: In a cohort of pre-frail 35 individuals (average age: 75 years), a physical frailty score above the median identified subjects with initial alterations in cardiorespiratory function and increased alarmins S100A8/A9 and inflammatory cytokines in peripheral blood. RNA sequencing revealed S100A8/A9 upregulation in HSPCs from the bone marrow (&gt;10-fold) and peripheral blood (&gt;200-fold) of individuals with greater physical frailty. We then interrogated the biomarkers in a cohort of 104 frail individuals (average age: 81 years) with multi-domain health deficits. Reduced levels of circulating HSPCs and increased S100A8/A9 concentrations were independently associated with the frailty index. Remarkably, low HSPCs and high S100A8/A9 simultaneously predicted major adverse cardiovascular events at 1-year follow-up after adjustment for age and frailty index. Conclusions and Relevance: Inflammaging resulting from alarmin and pro-inflammatory cytokines in pre-frail individuals is followed by pauperization of HSPCs in frail older people with comorbidities. S100A8/A9 upregulation is activated within HSPCs, identifying a phenotype that drives poor cardiovascular outcomes.
Abstract 9674: Stroke, Migraine, and Cervical Arterial Dissection: Shared Genetics Reveals Concordant and Opposing Risk Mechanisms
Authors: Daniel Chasman, Iyas Daghlas, Muralidharan Sargurupremraj, Rebecca Danning, Padhraig Gormley, Rainer Malik, Philipe Amouyel, Tiina Metso, alessandro pezzini, Tobias Kurth, Stephanie Debette
Journal: Circulation (2021)

Introduction: Migraine, stroke, and cervical artery dissection (CeAD) represent a triad of cerebrovascular disorders with pairwise comorbid relationships and vascular involvement. Systematic exploration of their shared genetics may inform shared and divergent etiology. Methods: The largest available GWASs for all three disorders were used, including for subtypes of stroke (ischemic stroke [IS], large artery stroke [LAS], small vessel stroke [SVS], cardioembolic stroke [CE]) and migraine (with aura [MA] and without aura [MO]). For each pair of disorders, genetic correlation was assessed both on a genome-wide basis and within candidate loci for each disorder. Cross-trait meta-analysis was used to identify shared novel candidate loci. Causality of migraine susceptibility on stroke and CeAD was evaluated by Mendelian randomization (MR). Results: Among all pairs of disorders, genome-wide genetic correlation was only observed for CeAD and migraine, particularly MO. Local genetic correlations were more extensive between migraine and CeAD than migraine and stroke or CeAD and stroke, identifying novel CeAD associations at rs6693567 ( ADAMTSL4/ECM1 ), rs11187838 ( PLCE1 ), and rs7940646 ( MRVI1 ), while strengthening prior subthreshold evidence at rs9486725 ( FHL5 ) and rs650724 ( LRP1 ). At known migraine loci, novel associations with stroke had concordant risk alleles for SVS at rs191602009 ( CARF ), and for CE at rs55884259 ( NKX2-5 ). However, at other migraine loci, there were novel associations with opposite risk alleles for all stroke, IS, and SVS at rs55928386 ( HTRA1 ), for LAS at rs11172113 ( LRP1 ), and for all stroke and IS, respectively, at rs1535791 and rs4942561 (both LRCH1 ). rs182923402 (near PTCH1 ) was a novel locus for both migraine and CE with concordant effects. MR supported causal influence of migraine on CeAD (OR [95%CI] per doubling migraine prevalence=1.69 [1.24-2.3], p=0.0009) with concordant risk, but with opposite risk on LAS (0.86 [0.76 - 0.96], p=0.0067). Conclusions: Genetic effects between migraine and CeAD had concordant effects on risk, highlighting vascular functions in migraine and novel CeAD loci. Most shared loci for migraine and stroke subtypes had opposite effects on risk. The LRP1 locus was common to all three disorders.