tbuckley/cabot-search huggingface dataset:
Abstract 11513: Impact of Family History of Coronary Artery Disease on Clinical Outcomes in Takotsubo Cardiomyopathy
Authors: Pengyang Li, Chengyue Jin, Can Cui, Peng CAI, Shamita A Manohar, Ling Jin, xin wei, Su Pan, Richard A Dixon, Qi Liu
Journal: Circulation (2021)

Introduction: Family history of coronary artery disease (CAD) is a critical risk factor for CAD, underscoring the contribution of genetic factors to disease pathogenesis and susceptibility. Takotsubo cardiomyopathy (TCM) simulates the clinical features of and frequently coexists with CAD. However, the association between family history of CAD (FHxCAD) and TCM is unclear. Aim: We examined the impact of FHxCAD on in-hospital clinical outcomes of TCM patients. Methods: This retrospective cohort study was conducted using the National Inpatient Sample database [2016-2018]. We identified 4,733 patients admitted to hospital with a primary diagnosis of TCM (ICD-10 coding system); 648 (13.7%) had a FHxCAD. We performed propensity score matching at 1:1 ratio (n=646, matched TCM with FHxCAD; n=646, matched TCM without FHxCAD), and we compared in-hospital outcomes and complications between TCM patients with or without a FHxCAD. Results: In the unmatched cohort, the TCM with FHxCAD group had a reduced incidence of cardiogenic shock, acute kidney injury (AKI) and acute respiratory failure (ARF); lower mortality rates; shorter length of stay (LOS); and decreased total charge compared to the TCM without FHxCAD group (p&lt;0.05). After propensity score matching, the TCM with FHxCAD group, when compared with the TCM without FHxCAD group, also had a lower incidence of cardiogenic shock (2.2% vs. 6.3%, p&lt;0.001; odds ratio [OR] 0.33, 95% confidence interval [CI], 0.18-0.61), AKI (5.1% vs. 8.7%, p=0.016; OR 0.57, 95% CI, 0.36-0.88), and ARF (5.7% vs. 12.7%, p&lt;0.001; OR 0.42, 95% CI, 0.28-0.63); decreased in-hospital mortality (&lt;11 vs. 3.1%, p=0.002; OR 0.2, 95% CI, 0.07-0.57); shorter LOS (2.66 ± 1.96 days vs. 3.40 ± 3.05 days, p&lt;0.001); and a reduced total charge (p=0.001), respectively. The incidence of cardiac arrest and ventricular arrhythmias did not differ significantly based on FHxCAD in the unmatched or matched cohorts. Conclusions: Family history of CAD was associated with favorable clinical outcomes in both unmatched and propensity-matched cohorts of in-hospital TCM patients. Further studies are necessary to identify mechanisms contributing to the association between in-hospital TCM outcomes and FHxCAD.
Abstract 12919: Impact of Small Valve Size After Transcatheter Aortic Valve Implantation on 1-year Outcomes in Women: Results From the WIN-TAVI Registry
Authors: Carlo Andrea Pivato, Davide Cao, Samantha Sartori, Clayton Snyder, Johny Nicolas, Mauro Chiarito, Annerieke Tavennier, Matteo Nardin, Samin K Sharma, Julinda Mehilli, Anna S Petronio, Marie c Morice, Alaide Chieffo, George Dangas, Roxana Mehran
Journal: Circulation (2021)

Introduction: Women undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis are more likely to have a small aortic annulus compared with men. However, there is lack of data on the prognostic relevance of bioprostheses size in women. Hypothesis: To assess the impact of a small valve size on clinical outcomes in women undergoing TAVI. Methods: The Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) registry was the first study to investigate the safety and efficacy of TAVI in women with aortic stenosis.Patients were stratified according to the size of aortic valve bioprosthesis, with small valve defined by a size≤23 mm and non-small valve defined by a size&gt;23 mm. The primary outcome of interests was the occurrence of Valve Academic Research Consortium (VARC)-2-efficacy endpoint, a composite of all-cause death, stroke, myocardial infarction, hospitalization for valve-related symptoms or heart failure or valve-related dysfunction at 1-year follow-up. Results: Out of 934 patients, 388 (41.5%) received a small valve and had a lower body mass index, lower surgical risk scores and were less likely to suffer from atrial fibrillation as compared with patients receiving a larger valve. The latter were more likely to require post-dilation (18.6% vs. 10.4%, p&lt;0.001) and had a trend for higher rates of residual aortic regurgitation grade ≥2 (8.7% vs. 5.1%, p = 0.051). At 1 year, the risk of the VARC-2 efficacy endpoint was similar between the two groups (16.0% in small valve vs. 16.3% in non-small valve, p = 0.8808; adjusted hazard ratio 1.34, 95% confidence interval 0.90 to 2.00), Figure. No significant differences in the occurrence of the secondary endpoints were noted after multivariable adjustment. Conclusions: Among women undergoing TAVI, the valve size was associated with different baseline and procedural characteristics but was not an independent predictor of clinical outcomes.
Clinicopathological Characteristics of Subcutaneous Panniculitis-like T-Cell Lymphoma in Asian Population: A Retrospective Cohort of 48 Patients
Authors: BEN Ponvilawan, Pornlada Likasitwatanakul, Panitta Sitthinamsuwan, Noppadol Siritanaratkul, Archrob Khuhapinant, Manasmon Chairatchaneeboon, Danai Samutpradit, Ployploen Phikulsod
Journal: Blood (2021)
Abstract 10084: Janus Activating Kinase 2 V617f Mutation Promotes Hypoxia Induced Pulmonary Hypertension in Mice
Authors: Yusuke Kimishima, Tomofumi Misaka, Tetsuro Yokokawa, Koichi Sugimoto, Keji Minakawa, Takafumi Ishida, Kazuhiko Ikeda, Yasuchika Takeishi
Journal: Circulation (2019)

Backgrounds: Pulmonary hypertension (PH) is one of major complications of hematological diseases such as myeloproliferative neoplasms (MPNs). An acquired mutation of JAK2 V617F, which constitutivel...
Abstract 8895: Design of Phase IV, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Trial Evaluating Sodium Zirconium Cyclosilicate for the Management of Hyperkalemia in Patients With Symptomatic Heart Failure With Reduced Ejection Fraction (REALIZE-K Trial)
Authors: Mikhail Kosiborod, David Cherney, Akshay S Desai, Mark Petrie, Jeffrey Testani, Subodh Verma, Ayman Al-Shurbaji, James M Eudicone, Donna Zarzuela
Journal: Circulation (2021)

Introduction: International guideline-recommended therapies for heart failure (HF) with reduced ejection fraction (HFrEF), including mineralocorticoid receptor antagonists (MRA), are underutilized, in part due to concerns of hyperkalemia (HK) especially among those at high risk. The REALIZE-K trial aims to evaluate the efficacy and safety of sodium zirconium cyclosilicate (SZC), a selective potassium (K + ) binder, to enable MRA use in patients with HFrEF at high risk for HK. Methods: REALIZE-K is a prospective, double-blind, placebo (PBO)-controlled randomized withdrawal trial enrolling symptomatic HFrEF (NYHA class II-IV and LVEF ≤40%) patients on guideline-directed medical therapy (but not full-dose MRA) with either HK (serum K + 5.1-5.9 mmol/L) or high risk for HK during MRA titration. All eligible patients enter a 1-month open-label run-in phase, during which patients with hyperkalemia receive SZC to correct HK; all patients undergo protocol-mandated titration of spironolactone (SPL) as tolerated to a target of 50 mg QD with supplemental SZC to maintain normokalemia (serum K + 3.5-5.0 mmol/L; Figure ). All patients tolerating ≥25 mg QD of SPL will be randomly assigned to continued SPL+SZC or SPL+PBO during an 8-month double-blind withdrawal phase. Serial K + monitoring will guide protocol-directed dosing of SZC/PBO and SPL during the randomized period. The primary study endpoint is the occurrence at 8 months of normokalemia on SPL ≥25 mg QD without the need for rescue therapy for severe HK in the SZC vs PBO group. Secondary endpoints include individual components of the primary endpoint and health status assessed by Kansas City Cardiomyopathy Questionnaire Total Symptom Score. Exploratory endpoints include time to first occurrence of the composite of CV death or worsening HF, and change in mean urine albumin-creatinine ratio. Conclusions: REALIZE-K will evaluate the efficacy and safety of SZC, enabling MRA therapy for HFrEF patients at high risk for HK.
Outcomes for Patients with Mantle Cell Lymphoma Post-Covalent BTK Inhibitor Therapy in the United States and Japan: A Study of Two Real-World Databases
Authors: Shinya Rai, Lisa M. Hess, Yongmei Chen, Lee Bowman, Paolo B. Abada, Heiko Konig, Richard A. Walgren, Yoshinori Tanizawa, Zhihong Cai, Masaomi Tajimi
Journal: Blood (2021)
Abstract 13601: Cardiovascular Outcomes of Transradial versus Transfemoral Percutaneous Coronary Intervention in End Stage Renal Disease. A Meta Regression Analysis
Authors: yasar sattar, Noora Alhajri, Mohammed Faisaluddin, David Song, Rajendra Shah, Sharaad Latachana, Mohamed Zghouzi, Waqas Ullah, Islam Y Elgendy, M C Alraies
Journal: Circulation (2021)

Introduction: Limited data is available on comparison of outcomes among transradial (TR) and transfemoral (TF) access of percutaneous coronary intervention (PCI) in End Stage Renal Disease (ESRD). Hypothesis: Which access route is better for better cardiovascular outcomes or lower procedural complications among ESRD patients. Methods: Online databases including MEDLINE and Cochrane Central were queried to compare cardiovascular outcomes among TR and TF in ESRD patients. The primary outcome of this meta-analysis was to compare the bleeding complications and in-hospital mortality difference between TR PI and TF PCI in patients with ESRD. The secondary outcomes included differences in Mortality, Cardiovascular accident (CVA), Myocardial infarction (MI), Bleeding, Transfusion, Cardiogenic shock, and Heart failure. Unadjusted odds ratios (OR) were calculated using a random effect model with a 95% confidence interval (CI) and P &lt;0.05 as a statistical significance. Results: A total of 5 studies including 7383 patients ( TR-PCI = 1208 ; TF-PCI = 6275) were included in this analysis. The overall mean age was 70 years; while the mean for TR-PCI and TF-PCI was 71 years and 69.1 years respectively. TR-PCI was associated with lower odds of bleeding (OR 0.48 95% CI 0.33, 0.69, p&lt;0.05, I2 0.00%) (Figure 1A), transfusion requirement (OR 0.52 95% CI 0.40, 0.68, p&lt;0.05, I2 0.00%), and mortality (OR 0.41 95% CI 0.26, 0.66, p&lt;0.05, I2 0.00%) (Figure 1B). We did not find any statistically significant difference in CVA (OR 1.06 95% CI 0.37, 3.00 p&gt;0.05, I2 0.00%), MI (OR 0.97 95% CI 0.57, 1.63, p&gt;0.05, I2 0.00%), CS (OR 0.53 95% CI 0.06, 4.42, p&gt;0.05, I2 48.48%) between TR and TF PCI in ESRD population. We didn’t find any effect modifier in our study on regression analysis. Conclusions: TR access is associated with better cardiovascular outcomes as compared to TF access PCI in ESRD patients with any coronary artery disease.
Utilization of Non-Invasive Sample Sources for Identification of Somatic and Germline Mutations in Hematologic Malignancies and Clonal Hematopoiesis
Authors: Eli M Soyfer, Hellen Nguyen, Simran Bhardwaj, Hew Yeng Lai, Nahid Haghighi, Angela Fleischman
Journal: Blood (2021)
Abstract 10926: Importance of Mitochondrial DNA Damage in Cigarette Smoke Extract-Induced Activation of Innate Immune System
Authors: Keitaro Ueda, Mari Ishida, CHIEMI SAKAI, Yusuke Kobayashi, Masao Yoshizumi, Takafumi Ishida
Journal: Circulation (2021)

Objective: Smoking is a well-known risk factor for atherosclerosis, yet the mechanism by which smoking causes atherosclerosis remains unclear. It has been reported that inflammation and DNA damage are involved in the formation and development of atherosclerosis. We have previously reported that nuclear DNA damage was increased in peripheral mononuclear cells of smokers compared to those of non-smokers, and that DNA damage was accumulated in atherosclerotic lesions. In this study, to clarify the mechanism by which smoking induces inflammation in vascular endothelial cells, we investigated the effect of cigarette smoke extract (CSE) on both nuclear and mitochondrial DNA damage and the subsequent cellular response in human umbilical vein endothelial cells (HUVEC). Methods and Results: CSE increased double-strand breaks in HUVEC. Notably, this increase was detected relatively late (after 3 days of CSE exposure) compared to other genotoxic agents. CSE also increased oxidative DNA damage both in the nucleus and mitochondria and induced mitochondrial dysfunction. Mitochondrial dysfunction decreased cytosolic protein levels of ICAD, an inhibitor of caspase-activated DNase (CAD), which causes nuclear DNA fragmentation, and increased CAD in the nucleus, suggesting that this is one of the mechanisms of nuclear DNA double-strand breaks. In addition, continuous stimulation by CSE induced the accumulation of cytosolic DNA. Interestingly, real-time PCR analysis revealed that the accumulated DNA in the cytosol was derived not only from the nucleus but also from mitochondria. We further examined whether DNA accumulated in the cytosol activated cytosolic DNA-sensing pathways. The production of cGAMP, a second messenger in cGAS (a DNA-sensing receptor) signaling, was increased by CSE. We also found that the mRNA expression of IL-6 was increased by CSE, and that the increase was suppressed by si-cGAS. Conclusions: This study showed that continuous exposure to CSE induces not only nuclear but also mitochondrial DNA damage, which leads to cytosolic DNA accumulation, and evokes chronic inflammation via the cGAS-STING pathway.
Abstract 11277: Early Diastolic Strain Rate in Relation to Long Term Prognosis Following Isolated Coronary Artery Bypass Grafting
Authors: Mats C Lassen, soeren Lindberg, Flemming J Olsen, Thomas Fritz-Hansen, Sune H Pedersen, Allan Z Iversen, Søren Galatius, Rasmus Mogelvang, Tor Biering-Sørensen
Journal: Circulation (2021)

Introduction: The ratio of early mitral inflow velocity to early diastolic strain rate (E/e’sr) is a novel echocardiographic measure to estimate early left ventricular (LV) filling pressure. Hypothesis: We hypothesize that E/e’sr is a predictor of outcome following coronary artery bypass grafting (CABG) and that it is superior to the conventionally used E/e’. Methods: Consecutive patients undergoing isolated CABG at Gentofte Hospital (n=652) were included. Prior to surgery, all patients underwent an extensive echocardiographic examination. The outcome was all-cause mortality. Cox proportional hazard regression models were used to assess the prognostic value of E/e’sr in relation to the outcome. Results: The mean age of the study population was 67±9 years, 84% were male, mean LV ejection fraction was 50±11%. During follow-up (median 3.8 years [IQR: 2.7; 4.9 years]), a total of 73 (11%) died. Both E/e’ and E/e’sr were significant predictors in univariable models. In a multivariable model adjusted for demographic, clinical and echocardiographic covariates, E/e’sr remained an independent predictor of outcome (HR:1.05 [1.01-1.10], p=0.049, per 10cm increase) whereas E/e’ did not (HR:1.05 [0.99-1.11], p=0.053, per 1-unit increase). The relationship between E/e’sr, and the outcome was significantly modified by GLS (p for interaction = 0.043) ( Figure ). In the multivariable model, E/e’sr was still significantly associated with the outcome in patients with high GLS (≥13.6%) (HR:1.18 [1.02-1.36], p=0.029) but not in patients with low GLS (HR 1.04 CI95%: [0.99-1.10], p=0.14). E/e’ was not a significant predictor of all-cause mortality after multivariable adjustment in neither of the groups. E/e’sr improved net reclassification with 0.33 when added to the EuroSCOREII model. Conclusions: Following CABG, preoperative E/e’sr is an independent predictor of all-cause mortality, especially in patients with preserved systolic function and superior to E/e’.
Relapse with BCR-ABL1 Elevation in Chronic Myeloid Leukemia after Progression to Multiple Myeloma from Monoclonal Gammopathy of Undetermined Significance with a Persistent <i>KMT2D</i> Mutation
Authors: Xiaofei Xu, Lan Zhang, Shengjie Wang, Keyi Jin, Chen DAN, Jian Huang
Journal: Blood (2021)
Abstract 12686: Frailty is Associated With Perioperative Major Adverse Cardiovascular Events After Non-Cardiac Surgery
Authors: Emaad Siddiqui, Darcy Banco, Jeffrey Berger, Nathaniel Smilowitz
Journal: Circulation (2021)

Introduction: Frailty is increasingly recognized for its association with adverse outcomes after surgery, but its excess risks have not been characterized in large representative cohorts. We investigated the prevalence of frailty and the associated incidence of major adverse cardiovascular events (MACE) among those hospitalized for non-cardiac surgery. Methods: Adults aged ≥45 years hospitalized for non-cardiac surgery between 2004-2014 were identified from the Healthcare Cost and Utilization Project’s National Inpatient Sample. A validated Hospital Frailty Risk Score (HFRS) based on International Classification of Diseases codes was used to classify patients as low (&lt;5), medium (5-15), or high (&gt;15) frailty risk. The primary outcome was MACE, defined as in-hospital mortality, myocardial infarction, and cardiac arrest. Multivariable logistic regression was used to estimate the adjusted odds of MACE by HFRS. Results: A total of 55,349,978 hospitalizations were identified, of which 81%, 18%, and 1% had low, medium, and high HFRS, respectively. Patients with higher HFRS had a greater burden of cardiovascular risk factors and comorbidities (Table). MACE occurred during 2.5% of all hospitalizations and was more common in patients with higher HFRS (high: 8.4%, medium: 7.4%, low: 1.3%, p&lt;0.001). Compared to low HFRS, medium (adjusted odds ratio [aOR] 2.34, 95% CI 2.31-2.38) and high (aOR 2.49, 95% CI 2.42-2.56) HFRS were associated with greater odds of MACE. The association between high (versus low) HFRS and MACE was consistent across age groups (aOR 4.26 [95% CI 3.96 - 4.57] for ages 45-64, aOR 2.64 [95% CI 2.51 - 2.79] for ages 65-74, and aOR 2.80 [95% CI 2.72 - 2.89] for ages ≥75). Conclusion: Higher frailty scores are associated with increased risks of MACE overall and within age subgroups. Implementation of HFRS as a standardized, electronic health record-based screening tool may identify frail surgical inpatients at risk for adverse perioperative outcomes.
Bispecific CD19-CD20 and CD19-CD22 CAR-T Cells with Glycogen Synthase Kinase (GSK)-3β Inhibitor TWS119 Treatment Have Superior Therapeutic Effects on Mantle Cell Lymphoma
Authors: Jingling Jin, Yijing Li, Yang Liu, Alexa A Jordan, Joseph McIntosh, Jovanny Vargas, Yuxuan Che, Yixin Yao, Michael Wang
Journal: Blood (2021)
Treatment of Ropeginterferon Alpha-2b Achieves Hematologic Remission and Molecular Response in Patients with Hydroxyurea- and/or Anagrelide-Resistant/Intolerant Myeloproliferative Neoplasms
Authors: Chih-Cheng Chen, Ming-Chung Kuo, Yi-Jiun Su, Cih-En Huang, Chia-Chen Hsu, Yu-Ying Wu, Ying-Ju Chen, Lee-Yung Shih
Journal: Blood (2021)
Abstract 13167: Multiscale Mechanisms of Right Ventricular Injury in Bronchopulmonary Dysplasia
Authors: Madison J Freeman, Timothy A Hacker, Kara N Goss, Naomi C Chesler
Journal: Circulation (2021)

Introduction: Bronchopulmonary dysplasia (BPD) is the most common complication of premature birth. Whether right ventricular (RV) injury or chronically increased afterload are more responsible for long-term RV dysfunction in BPD is unknown. We aim to determine key drivers of RV dysfunction in BPD using both experimental data and a computational model. We hypothesize that decreased mitochondrial energetics and active force generation are critical contributors. Methods: Male and female Sprague-Dawley rats were delivered at term to timed-pregnant dams and exposed to either room air (Nx) or 85% fraction inspired O 2 (Hx) for 4, 8, or 14 days. Multiscale experimental data was obtained at postnatal day 21 and used to parameterize the previously published computational model of the heart and circulation, which integrates myocardial mechanics and mitochondrial energetics. Results: Despite increased RV afterload in the 8-and 14-day exposure groups (Fig. 1A) and significant RV hypertrophy in the 14-day group (Fig. 1B), there was no change in ejection fraction (EF) due to high variability (Fig. 1C). We used the computational model to explore how multiscale features of RV injury impact RV EF (Fig. 1D). Whereas decreased mitochondrial function, decreased cross-bridge maximum force, and increased RV afterload further reduce predicted RV EF in the 14-day Hx rat with the lowest EF (red symbol) and RV EF in the 14-day Nx rat with the highest EF (blue symbol), EF can be restored in a simulated reversal of these injuries in the Hx rat. Conclusions: Our approach provides valuable insight into key features of RV injury in BPD. Different degrees and combination of injuries at multiple scales can explain functional heterogeneity and may enable more accurate predictions of long-term RV dysfunction. Figure 1: Measurements of (A) RV afterload, (B) RV Fulton index and (C) RV EF as well as computational model predictions of (D) RV EF for one 14D Hx (red) and one 14D Nx rat (blue).
Abstract 10733: Cardiac Magnetic Resonance Characteristics Including Feature Tracking in a Multi-Center Pediatric Study of Atypical Myocarditis
Authors: Elizabeth Caris, Jenna Schauer, Lamia Ait-Ali, Ravi Ashwath, Sowmya Balasubramanian, Nadine Choueiter, Jason Christensen, Matthew Cornicelli, Juan Carlos Muniz, David Parra, Edythe B Tham, Sathish Mallenahalli Chikkabyrappa, Luciana T Young, Brian Soriano, Sujatha Buddhe
Journal: Circulation (2021)

Introduction: Atypical myocarditis, presenting as isolated chest pain, elevated troponin and preserved cardiac output in childhood is rare. Beyond small volume single center case series, limited data are reported on CMR characteristics at initial presentation and follow up. Methods: This is a pediatric multi-center retrospective study. Patients with chest pain and elevated cardiac troponin who underwent an echo and CMR within 30 days of each other were included. Clinical, echo and CMR parameters were collected at presentation and follow up. CMR global longitudinal strain (GLS) was performed with feature tracking technology (TomTec). Cases were divided into CMR myocarditis positive (Myo+) and CMR myocarditis negative (Myo-) based on Lake Louise criteria. Findings were compared to 19 age matched controls. Results: A total of 108 cases were included (88 Myo+ and 20 Myo-). Majority were male (88%) with average age of 15.6 ± 2.1 years. Median troponin was 13 (0.18-260.1 ng/mL), median BNP was 270.8 (12-3949 pg/ml). Abnormal ECG findings were present in 79% at presentation. While CMR LVEF did not differ between cases (56 ± 9%) and controls (60 ± 4%, p 0.06), GLS was significantly worse in cases (-16.2 ± 2.7%) compared to controls (-19.2 ± 2.1%, p &lt;0.001). Unlike LVEF, GLS was significantly worse in Myo+ (-15.7 ± 2.8%) compared to Myo- cases (-18.0 ± 1.3%, p &lt; 0.001). Fifty-four subjects had follow up data with 35 repeat CMRs. Median follow up was 204 (30-944) days. Late gadolinium enhancement (LGE) persisted in 82% of the Myo+ cases. Of the cases with abnormal GLS at presentation, 77% had persistent LGE. At follow up, 14% of cases were on heart failure medications, 33% had abnormal GLS and 39% had abnormal LVEF (&lt;55%). Neither treatment with steroids or IVIG at presentation nor LGE on initial or follow up CMR were associated with the need for heart failure medications or persistent symptoms at follow up. Conclusions: In atypical myocarditis, CMR GLS can help differentiate between Myo+ and Myo- cases. Abnormal CMR GLS at presentation has higher association with persistence of LGE at follow up, irrespective of type of treatment. Future studies are needed to identify other characteristics that predict persistently abnormal findings important to clinical management and prognosis.