tbuckley/cabot-search huggingface dataset:
Abstract 10607: Evaluating Diastolic Function by Echocardiography in a Prospective Cohort of Patients with Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL) Who Received Anthracycline-Based Chemotherapy
Authors: Reema Tawfiq, Nicholas Boddicker, Juan Quintero Martinez, Sandra Cordova, Md Mashiul Alam, James Cerhan, Joerg Herrmann, Carrie A Thompson, Hector R Villarraga
Journal: Circulation (2021)

Introduction: Anthracyclines are a first-line chemotherapeutic agent used in the treatment of lymphoma. Myocardial injury can occur with cumulative doses of 250 to 350 mg/m 2 . Echocardiography is the imaging modality for identifying cardiac dysfunction; however, identifying diastolic changes in patients who received anthracyclines is not well represented in the literature. Variables used to identify diastolic dysfunction include lateral e’, medial e’, mitral E velocity, mitral A velocity, E/A, E/e’, and left atrial volume index (LAVI). This study aims to identify if diastolic abnormalities develop in a prospective cohort of patients with HL or NHL who received anthracycline-based chemotherapy. Methods: Lymphoma patients treated with anthracyclines from 2013 to 2020 were prospectively enrolled. Echocardiography was obtained at 3-time points: before the start of chemotherapy (T1), at 3-6 months (T2), and 9-12 months (T3). Diastolic variables were measured and analyzed based on the total cumulative dose of Doxorubicin per body surface area. Those that received greater than 250 mg/m 2 and greater than 300 mg/m 2 of Doxorubicin were compared to those that did not. Statistical analysis was done using one-way ANOVA, adjusting for age and gender. Results: 151 total patients (90 males, mean age 61 + 16 years); 21 (14%) HL, 130 (85%) NHL. 114 and 66 patients received a total cumulative dose of Doxorubicin greater than 250 mg/m 2 and 300 mg/m 2 , respectively. There was no significant association with 250 mg/m2. Lateral e’ at T3 vs. T1, was lower in those that received greater than 300 mg/ m 2 compared to those received less (0.09 vs 0.10, p &lt; 0.02) (Table 1). Conclusions: Lateral e’ decreased at 1-year follow-up in those that received higher doses of Doxorubicin. These changes in the lateral e’ could reflect early relaxation abnormalities related to anthracycline-based chemotherapy and suggest that changes in lateral e’ should be considered by itself since E/e’ was normal.
Trial in Progress: Phase 1b/2 Open-Label Study of Lisaftoclax (APG-2575) Monotherapy or in Combination with Lenalidomide/Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma (R/R MM)
Authors: Chengcheng Fu, Zi Chen, Wensi Li, Lichuang Men, Depei Wu, Dajun Yang, Yifan Zhai
Journal: Blood (2021)
Progression of Knee Osteoarthritis With Use of Intraarticular Glucocorticoids Versus Hyaluronic Acid
Authors: Justin Bucci, Xiaoyang Chen, Michael LaValley, Michael Nevitt, James Torner, Cora E. Lewis, David T. Felson
Journal: Arthritis & Rheumatology (2021)

Objective To determine whether intraarticular glucocorticoid (GC) injections are associated with increased knee osteoarthritis (OA) progression compared to hyaluronic acid (HA) injections, which have been reported to delay OA progression and knee replacement. Methods We identified participants from 2 large cohort studies, the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study. Study visits were performed at regular intervals and included questionnaires about intraarticular GC or HA injection use in the previous 6 months and incident total knee replacement (TKR). Knee radiographs were obtained at each study visit and interpreted in a similar manner. Outcome measures were radiographic progression based on Kellgren/Lawrence (K/L) grade and joint space narrowing (JSN) for both cohorts and based on medial joint space width for OAI participants, and incident TKR. We compared preinjection and postinjection radiographs to generate rate ratios of progression comparing GC injection with HA injection. A Cox proportional hazards model was used to estimate the rate of TKR for both groups. Results We studied 791 participants (980 knees) with knee OA, of whom 629 reported GC injection use and 162 HA injection use. Rate ratios of progression were similar between those receiving GCs and those receiving HA for JSN (1.00 [95% confidence interval (95% CI) 0.83–1.21]), K/L grade (1.03 [95% CI 0.83–1.29]), and medial joint space width (1.03 [95% CI 0.72–1.48]). Hazard of TKR was slightly lower for those receiving intraarticular GC compared to those receiving HA (hazard ratio 0.75 [95% CI 0.51–1.09]). Conclusion Intraarticular GC injections are not associated with an increased risk of knee OA progression compared to HA.
Abstract 11872: Use of Dronedarone and Periprocedural Stroke Risk in Patients Undergoing Catheter Ablation for Atrial Fibrillation
Authors: Nertila Poci Saglam, Diona Gjermeni, Volker Kuehlkamp
Journal: Circulation (2021)

Introduction: Dronedarone was introduced as a promising Amiodarone-analogue with a good safety profile and comparing efficacy. Because of a two-fold increase in all-cause death, stroke, myocardial infarction, and hospitalization in permanent AF, recommendations regarding the use of dronedarone therapy are limited. We aimed to evaluate the risk of periprocedural thromboembolic events (TE) in a group of patients who underwent catheter ablation for AF under on-going dronedarone therapy. Methods: We retrospectively studied 2254 AF cases who underwent catheter ablation between Jan 2011 and May 2017. A group of 145 cases out of the above cohort (mean age 65 yrs; male 54%; CHADSVASc &gt;2 on 51% of the cases; Persistent AF 21%) was under dronedarone at the time of catheter ablation. We compared the dronedarone (DG) vs non-dronedarone group (nDG) in terms of periprocedural TE, specifically transient ischemic attack and stroke. To assess the impact of other possible explanatory variables we performed a multivariate regression analysis with interaction terms. All patients were under optimal oral anticoagulation at the time of catheter ablation. Results: DG showed a significantly higher frequency of 2,06 % periprocedural TE compared to 0.5% in nDG (p=0,024). Significant predictors of TE in DG were found to be age (OR 2,7 p=0,036), persistent AF (OR 3,6 p=0,036), NYHA class at the time of catheter ablation (OR 2,35 p=0,006) and left ventricular systolic function (OR 1,37 p= 0,05).Intraprocedural median ACT (OR 1,04 p=0,024) and electrical cardioversion (OR 10,3 p= 0,003) were the two significant intraprocedural predictors for stroke among patients on Dronedarone at the time of pulmonary vein isolation. Not predictive for periprocedural stroke were the type of catheter ablation technique, gender, HASBLEED score and spontaneous echo contras in left atrium. There was a significantly higher risk of stroke in DG patients under Phenprocoumon vs the ones on NOACs (OR 6, p= 0,047). CHADSVasc &gt; 2 showed a trend in increasing the risk for stroke among DG patients (OR 3,1 p=0,07). Conclusions: Dronedarone therapy is associated with an increased risk for stroke in patients undergoing catheter ablation, with higher risk among the elderly, persistent AF, and heart failure patients.
TAMI-15. PROSTATE SPECIFIC MEMBRANE ANTIGEN EXPRESSION IN GLIOBLASTOMA TUMOR AND ENDOTHELIAL CELLS
Authors: Brittany Stopa, Katherine Degen, Sharon Michelhaugh, Csaba Juhasz, Sandeep Mittal
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Prostate specific membrane antigen (PSMA) has emerged in recent years as a potential target for PET imaging of CNS tumors. Originally studied for imaging in prostate cancer, it was incidentally found to have selective uptake in some CNS tumors. Early studies have shown promise for PSMA tracer use in glioblastoma (GBM), but more research is needed to characterize the PSMA expression profile in GBM. METHODS Formalin-fixed paraffin-embedded tissues of 26 GBMs were immunostained with PSMA antibody. Stained sections were scored, using 5 images per tumor, in total 130 observations. Sections were assessed for extent and intensity of PSMA expression, in tumor cells and neovascular endothelial cells. Extent of expression: 0% (none), 1-9% (very low), 10-39% (low), 40-69% (moderate), &amp;gt; 70% (high). Intensity of expression: no staining (none); barely perceptible staining (low); readily apparent at low magnification (moderate); and maximum-intensity staining (high). RESULTS Extent of PSMA expression in tumor cells was mostly very low (76 out of 130, 58%), but intensity was often moderate (42, 32%), low (41, 32%), or high (39, 30%). The most prevalent combination was very low extent with low or moderate intensity (both 30, 23%). Endothelial cells were absent in 61 (47%) sections. Extent of expression in endothelial cells was mostly high (28, 41%), and intensity was often moderate (25, 36%) or high (20, 29%). The most prevalent combination was high extent with moderate (14, 20%) or high intensity (13, 19%). CONCLUSION PSMA expression was variable and was seen in both vascular endothelial cells and tumor cells. The mechanism of PSMA expression in GBM may not be straightforward, but rather may vary by cell type and tumor mutation status. Further tissue studies to understand the specific mechanism are needed to establish the potential use of PSMA PET as a neuroimaging modality in GBM.
Abstract 9776: Cardiac Resynchronization Therapy Outcomes with Image-Guided Left Ventricular Lead Placement: A Meta-Analysis
Authors: Nancy M Allen Lapointe, Fatima Ali-ahmed, Frederik Dalgaard, Andrzej S Kosinski, Gillian D Sanders, Sana M Al-Khatib
Journal: Circulation (2021)

Introduction: To improve CRT outcomes, image-guided approaches targeting left ventricular (LV) lead placement at the segment of latest mechanical activation have been compared to non-image-guided approaches with mixed results. A meta-analysis was conducted to assess the association between an image-guided approach and CRT outcomes. Methods: A systematic literature review was performed to identify RCTs and prospective observational studies of CRT from October 2008 through October 2020 that compared any image-guided versus any non-image-guided approach for LV lead placement. Two independent reviewers screened titles and abstracts then reviewed full text of identified studies. One reviewer abstracted data and a second over-read for accuracy. Meta-analyses were performed for NYHA class improvement and changes in LV end systolic volume, LV end diastolic volume, and LVEF using random effects models. Results: Of 5715 citations screened, 5 RCTs with a total of 818 patients met the inclusion criteria. Speckle tracking echocardiography (STE) was the primary imaging method in all studies, but 3 studies included CT, CMR, SPECT, and/or PET in addition to STE. The comparator arms were standard of care in 4 studies and an electrically guided approach in one. Mean age ranged from 66 to 72 years, 76% were male, and 53% had ischemic cardiomyopathy. Among 747 evaluable patients, concordant or adjacent LV lead was achieved in 348 of 386 (90%) in the image-guided arm and 291 of 361 (81%) in the control arm. At 6 months, the image-guided approach was statistically significantly associated with a NYHA class improvement, but no other statistically significant differences were found (Figure). Conclusion: An image-guided CRT approach was associated with significant Improvement in NYHA class but not in echocardiographic measures, possibly due to small sample size and high LV concordance with area of latest activation in both study arms - the latter of which merits further investigation.
Abstract 11381: Low Physical Activity is Associated with Poor Prognosis and Proteins Associated with Cardiovascular Disease Among Swedish Heart Failure Patients
Authors: Amir Zaghi, Hannes Holmes, Amra Jujic, Johan Korduner, John Molvin, Erasmus Bachus, Martin Magnusson
Journal: Circulation (2021)

Introduction: Several studies suggest that cardiac rehabilitation through physical exercise could reduce heart failure (HF) morbidity and mortality. Hypothesis: Here, we aimed to evaluate the association of physical activity with plasma levels of 92 proteins associated with cardiovascular disease (CVD) as well as risk of re-hospitalization and mortality in patients hospitalized for HF. Methods: Four-hundred-and-thirty-three patients hospitalized for HF (mean age 75 years; 32% women) were screened for physical activity derived from questionnaires in the Swedish national public health survey. The median follow-up time to death and re-hospitalization was 842 (IQR, 390-1433) and 155 (IQR, 42-583) days, respectively. Associations between baseline reported physical activity scores, mortality and re-hospitalization risk were analyzed using multivariable Cox regression analysis. Plasma samples from 295 study participants were analyzed with a proximity extension assay consisting of 92 proteins. Associations between proteins and physical activity were explored using a false discovery rate of 5%, and significant associations were taken forward to multivariate analyses. Results: A total of 206 patients (48%) reported moderate and regular physical activity throughout the week. In the fully adjusted Cox regression model, absence of moderate to regular physical activity was associated with increased mortality (HR 1.50; CI95% 1.11-2.03; p=0.008), but not with re-hospitalization risk (HR 1.05; CI95% 0.84-1.32; p=0.684). Physical active time below 1 h throughout the week was associated with increased risk of mortality (HR 1.82; CI95% 1.36-2.43; p&lt;0.001)as well as re-hospitalization irrespective of cause (HR 1.26; CI95% 1.01-1.58; p=0.049). Sedentary lifestyle was associated with elevated plasma levels of 24 proteins, whereof several implicated in myocardial fibrosis, migration and apoptosis. Conclusions: Low weekly physical activity is associated with increased risk of mortality and re-hospitalization in hospitalized HF patients, independently of traditional risk factors. Further sedentary lifestyle was associated with elevated levels of several proteins earlier linked to myocardial fibrosis, migration and apoptosis.
Abstract 14203: Implications of Atrial Fibrillation on Clinical Outcomes of Patients With Heart Failure With Preserved Ejection Fraction
Authors: Irfan Shafi, Rashid Alhusain, Abdalaziz Awadelkarim, Chad Tidwell, Tyler Mumm, Tushar Mishra, Mohammed Ali, Singh Manmohan, Luis AFONSO, Anupama Kottam
Journal: Circulation (2021)

Background: Atrial fibrillation and heart failure with preserved ejection fraction(HFpEF) are closely interrelated, and atrial fibrillation confer poor prognosis in HFpEF patients. Objective: We sought to study outcomes and implications of atrial fibrillation among patients hospitalized with HFpEF. Methods: Patients with a principal discharge diagnosis of HFpEF between 2016 and 2018 were identified in the National Readmissions Database. Among those, patients with and without a secondary diagnosis of atrial fibrillation were categorized. HFpEF hospitalizations with atrial fibrillation were matched 1:1 fashion to HFpEF without atrial fibrillation using age, sex, and Charlson comorbidity index. Results: Of the 195,110 HFpEF hospitalizations, 66,584 had HFpEF with a secondary diagnosis of atrial fibrillation. Propensity score-matched comparison between HFpEF with and without atrial fibrillation showed higher in-patient mortality (3.18% vs. 2.58%, P=0.00), Cardiogenic shock (0.62% vs. 0.39%, P=0.00) and bleeding (2.09% vs. 1.08%, P=0.00) as compared with HFpEF without atrial fibrillation. Total charges were higher in HFpEF with atrial fibrillation compared to patients without atrial fibrillation ($ 46018.97 vs. $ 43692.16). The 30 days all-cause readmission rate among patients admitted with HFpEF and survived index hospitalization was 20.14% (95% CI 19.96 - 20.31%). Conclusion: In patients with HFpEF presence of atrial fibrillation was associated with higher inpatient mortality. Figure 1: Patient selection flow diagram Table 1: Outcomes of HFpEF Patients with and without Atrial Fibrillation in Propensity-Matched Groups.
Late breaker posters
Authors: E Gane, C Schwabe, KT Yoon, J Heo, R Scott, J Lee, Jil Lee, YO Kweon, M Weltman, S Harrison, B Tetri, K Cusi, R Loomba, D Christianson, N Rajicic, JS Martin, J Hamilton, Rmf Yuen
Journal: Journal of Hepatology (2021)
Abstract P316: Role Of Scleraxis In Cardiac Valve Development And Disease
Authors: Madhav Karthik Kodigepalli, Joy Lincoln
Journal: Circulation Research (2021)

Valvular heart disease is one of the major causes of cardiac-related deaths in the US and effective treatment is currently limited to surgical repair or replacement. Mature heart valves are composed of highly organized and stratified layers of extracellular matrix (ECM) regulated by valve interstitial cells (VICs). This stratification that is initiated during embryogenesis and completed during valve maturation after birth, needs to be maintained throughout life for normal valve function. Myxomatous degeneration is a common disease histologically characterized by imbalance in ECM composition and organization resulting in valve biomechanical failure. Yet, key regulators of ECM homeostasis are not well characterized. Scleraxis (Scx) is a bHLH transcription factor that we previously showed to be critical for heart valve development and its loss of function leads to defective VIC maturation and aberrant ECM organization. However, due to lack of efficient tools, the mechanistic function of Scx in valve development and disease in vivo remains to be understood. Herein, we performed temporal analysis of Scx transcript levels during development of murine homeostatic valves and identified that Scx is predominantly expressed in the VICs between E13.5 and P14. We also assessed Scx levels and ECM abnormalities in valve tissues derived from patients with cardiac valve diseases and identified several distinct populations of VICs with high Scx levels that partially colocalized with elevated collagen fragmentation and proteoglycan (PG) deposition in the neighboring ECM. Scx levels were also elevated in valves of Fbn1 C1039G/+ and osteogenesis imperfecta murine ( OIM ) mice that develop myxomatous valve abnormalities signifying a potential role in pathogenesis. To further study the function of Scx in valve development and disease in vivo , we have generated a conditional Scx-transgenic model (Scx-TG) that will allow for overexpression in targeted cell lineages upon Cre recombination. Additionally, we will employ Scx-Cre mouse model expressing Scx-promoter driven Cre -recombinase to perform Scx-expressing cell lineage analyses and high-throughput sequencing analyses to identify direct gene targets and protein-interaction partners of Scx to better understand its mechanistic role in regulating valve ECM homeostasis. Together these in vivo approaches will provide novel insights into the function of Scx in heart development and disease.
Abstract 10469: Cardiometabolic Risk Factors as Causal Mediators of the Relationship Between High Body Mass Index and Chronic Kidney Disease: A Two-Step Mendelian Randomization Study and Mediation Analyses
Authors: Frida Emanuelsson, Kaitlin Wade, Anette Varbo, Anne Tybjaerg-hansen, George Davey Smith, Borge G Nordestgaard, Marianne Benn, Nicholas Timpson
Journal: Circulation (2021)

Introduction: Observational studies suggest that obesity is a risk factor of chronic kidney disease (CKD). It is unclear whether this reflects a direct causal effect of obesity or an effect mediated by obesity-related metabolic changes. Hypotheses: We hypothesised that 1) obesity is a causal risk factor of CKD defined as eGFR &lt;60mL/min/1.73m 2 and 2) this causal effect is mediated through changes in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterols, triglycerides, glucose, blood pressure and C-reactive protein (CRP) levels. Methods: To assess causality and investigate mediation, we used a combination of observational, two-step Mendelian randomization, and mediation analyses on individual-level data from two cohorts of the Danish general population (N=117,213). Results: Observationally, higher BMI was associated with a lower eGFR (change in eGFR; -0.81, confidence interval [CI]: -0.89- -0.73)) and a higher risk of CKD (odds ratio [OR]:1.19; 95% CI: 1.16-1.22) per 5kg/m 2 higher BMI (p for trend for both &lt;2.9 x10 -40 ). Mendelian randomization analyses supported a causal effect of higher BMI on lower eGFR (change in eGFR -17.3 mL/min/1.73m 2 (95%CI: -19.3- -15.3), and risk of CKD (risk ratio [RR]6.99 (95%CI: 1.63-30.1) per 5kg/m 2 higher BMI. Measured BMI and the BMI allele score used in Mendelian randomization analyses were associated with changes in levels of LDL and HDL cholesterols, triglycerides, glucose, blood pressure, and CRP. Observational and Mendelian randomization analyses showed evidence to support a causal effect of changes in levels of systolic and diastolic blood pressure, LDL cholesterol and CRP with lower eGFR and higher risk of CKD. Of the excess risk of CKD coming from high BMI, elevated systolic and diastolic blood pressure mediated 18%(95%CI:14-22) and 9% (7-11), respectively. 9% (95%CI: 8-12) was mediated by elevated LDL cholesterol and 29% (95%CI: 23-35) by elevated CRP. Conclusion: Triangulating evidence from observational and Mendelian randomization analyses provided evidence to support a causal role of obesity on the risk of CKD and that this causal effect may be partly mediated by elevated systolic and diastolic blood pressure, CRP and LDL cholesterol levels.
Abstract 10669: The Association of Statin Dose and Mortality Risk Across Chronic Kidney Disease Stages in 665,858 United States Veterans
Authors: John Rizk, Jui-Ting Hsiung, Yousif Arif, Melissa Soohoo, Leila Hashemi, Maria Marroquin, Jessica Edward, Elani Streja
Journal: Circulation (2021)

Rationale: Statin therapy is associated with lower mortality risk in both general and chronic kidney disease (CKD) populations. While statin therapy is recommended for CKD patients, the intensity of statin doses remains disputed. Thus, we examined the relationship of different statin doses with all-cause and cardiovascular (CVD) mortality across CKD stages. Methods: The cohort consists of 665,858 US Veterans with statin prescriptions between 2004-2014 who were followed until 2014. Statin intensity was categorized into low, moderate, and high dose based on ACC/AHA guidelines. Statin dosage and all-cause/CVD mortality associations were estimated using Cox proportional hazards models adjusting for comorbidities, labs, history of percutaneous coronary intervention and coronary artery bypass grafting across CKD stages. Results: Cohort mean age is 62+/-12 years with 6% females and 18% Blacks. Median [IQR] of eGFR is 79[64,93] mL/min/1.73m2 with 80% non-CKD. At baseline, 38%, 59%, and 3% patients were taking a low, moderate, and high dose of statin. A lower to null risk of all-cause and CVD mortality were found in low statin dose patients (ref: moderate statin dose) for all CKD stages. Furthermore, the association of low statin dose with all-cause mortality incrementally declined as CKD stages progressed. A null association of high statin dose with mortality risk was observed for all stages, with the exception of CKD stage 5/ESRD patients, where a 30% and 39% higher all-cause and CVD mortality risk were observed. [Figure] Conclusion: A low statin dose was associated with lower CVD mortality risk compared to a moderate dose in non-CKD patients. Yet, a high dose was associated with higher all-cause and CVD death risk in CKD stage5/ESRD patients. Statin therapy is known to improve patient outcomes; however, different intensities of statin should be applied when dealing with patients with different CKD stages as advanced stages of CKD may require adjustment in statin dosing.