tbuckley/cabot-search huggingface dataset:
Abstract 9693: Predicting Biventricular Repair in Common Atrioventricular Canal by Cardiac Magnetic Resonance Imaging: The New Normal?
Authors: Andrea L Jones, Brian R White, Reena M Ghosh, Antara Mondal, Steve B Ampah, Deborah Y Ho, David M Biko, Matthew A Harris, Sara Partington, Kevin K Whitehead, Meryl S Cohen, Mark A Fogel
Journal: Circulation (2021)

Introduction: Patients with malaligned common atrioventricular (AV) canal (CAVC) are difficult to manage when one ventricle is borderline hypoplastic. The decision between the single ventricle pathway or attempting a biventricular repair depends upon pre-operative parameters which have previously been studied only by echocardiography. The purpose of this study was to determine the utility of cardiac magnetic resonance (CMR) in predicting success of a biventricular repair in CAVC. Methods: We performed a single center, retrospective cohort study of children with varying degrees of CAVC malalignment who underwent CMR prior to definitive repair (7/1/10 to 2/28/21). The primary outcome was successful biventricular repair. CMR measurements were performed by the investigators. To account for both dominant right ventricles (RV) and left ventricles (LV), ratios of ventricular and AV valve size were normalized as differences from their expected values. Associations were tested using univariable logistic regression. Multivariable regression models using combinations of two variables with p-values less than 0.2 were tested. Results: We included 28 patients (median age at CMR: 5.2 months, 43% male). Clinical and CMR variables are shown in Table 1. The optimal multivariable predictive model included the normalized LV end diastolic volume (EDV) to total ventricular EDV ratio and the LV-RV angle in diastole. Area under the receiver operator characteristic curve was 0.83 (p = 0.041). An LV EDV to total EDV ratio between 0.30 and 0.66 had a sensitivity of 92% and specificity of 63% for predicting successful biventricular repair. Including an LV-RV angle in diastole of less than 72 degrees resulted in a sensitivity of 83% and specificity of 81%. Conclusions: Multiple CMR measures were associated with surgical outcomes. CMR measures such as LV EDV to total ventricular EDV ratio and LV-RV angle in diastole can accurately predict successful biventricular canal repair.
Health-Related Quality of Life and Symptoms Among Patients with Relapsed or Refractory AL Amyloidosis Treated with Ixazomib-Dexamethasone Versus Physician's Choice: Results from a Randomized Phase 3 Trial
Authors: Vaishali Sanchorawala, Ashutosh D. Wechalekar, Kihyun Kim, Stefan Schönland, Heather J Landau, Kwok Fiona, Kenshi Suzuki, Angela Dispenzieri, Giampaolo Merlini, Raymond Comenzo, Dasha Cherepanov, Vanessa C Hayden, Arun Kumar, Richard Labotka, Douglas V. Faller, Efstathios Kastritis
Journal: Blood (2021)
Abstract 12885: A Challenging Case of Endocarditis— Multi-Disciplinary Approach is an Achievable Chimera
Authors: Vanessa Blumer, Omar Martinez, Jordan E Pomeroy, D Ryan Anderson, Brian Andonian, Joshua Parsons, Carolyn Glass, Michael H SKETCH, Gerald S Bloomfield, Cary C Ward
Journal: Circulation (2021)

A 60-year-old man with history of coronary artery bypass grafting and mitral valve repair presented with confusion, gait instability and lethargy. Cardiology was consulted after a transthoracic echocardiogram demonstrated a mobile mass on the mitral valve (MV). A subsequent transesophageal echocardiogram showed a large vegetation encompassing and adherent to the anterior annulus and leaflet. Serial blood cultures were negative. The initial differential considered causes of blood culture negative endocarditis (BCNE) with embolic phenomena to the central nervous system. This diagnosis was challenged after the patient developed progressive neurologic symptoms out of proportion to findings on brain imaging. A multidisciplinary team was established to revisit the available data and facilitate a coordinated care approach. The patient was found to fulfill 5 out of 8 criteria for hemophagocytic lymphohistiocytosis (HLH). Furthermore, an H-Score of 268 supported this diagnosis with a &gt;99% probability. Therapy was started with Dexamethasone 5mg/m 2 BID and Anakinra 100mg Q6h, resulting in a rapid improvement in mental status. Secondary HLH in adults is most commonly due to malignancy and infection. Although initial workup was negative, several days into the hospital stay Mycobacterium chimaera was detected on next-generation sequencing of microbial cell-free DNA (Karius test). M. chimaera is a non-tuberculous mycobacterium belonging to the Mycobacterium avium complex and has been associated with a global outbreak following cardiothoracic surgery related to exposure to 3T heater-cooler units (HCU). Endocarditis due to M. chimaera acquired during prior cardiac surgery, complicated by HLH, was considered the most likely unifying diagnosis. This case illustrates: (1) the differential diagnosis of BCNE and the benefit of microbial cell-free DNA testing in its diagnosis, (2) HLH as an unrecognized entity in adults and infectious endocarditis as a possible trigger, (3) the need for improved awareness of M. chimaera infection in patients who have been exposed to HCU presenting with compatible symptoms, and (4) the critical role of communication and a multidisciplinary approach to provide high-quality care in challenging cases such as this one.
Abstract 10985: Replacing Dietary Carbohydrates and Refined Grains with Different Alternatives and Risk of Cardiovascular Diseases in a Multi-Ethnic Asian Population
Authors: Charlie G Lim, Rob M van Dam
Journal: Circulation (2021)

Introduction: Cardiovascular diseases (CVDs) are a major cause of deaths worldwide, but prospective data on dietary risk factors for CVD in South and Southeast Asian populations are sparse. Objective: We aimed to evaluate the relation between macronutrient and food intakes and incidence of major adverse cardiovascular events (MACE) in a multi-ethnic Asian population. Methods: We used data from the Singapore Multi-ethnic cohort ( n = 12,408), a prospective cohort of ethnic Chinese, Malay and Indian adults aged 21–65 years recruited between 2004 to 2010. Dietary intakes were assessed using a validated food frequency questionnaire, and the incidence of MACE was ascertained through data linkage with national registries. Cox proportional hazards model was used to evaluate the associations between dietary intakes and MACE risk. Results: Over 125,241 person-years, 746 incident cases of MACE were documented. We observed a direct association between carbohydrate intake and MACE risk (HR 1.35, 95% CI 1.07, 1.71 highest vs. lowest quartile, P -trend 0.001). Replacing 5% of energy from carbohydrate with polyunsaturated fat (HR 0.79, 95% CI 0.69, 0.91), but not saturated fat (HR 0.95, 95% CI 0.83, 1.08), was significantly associated with a lower MACE risk. In terms of food groups, replacing 1 serving per day of refined grains with fruit (HR 0.93, 95% CI 0.87, 0.99), vegetables (HR 0.93, 95% CI 0.86, 1.00), and dairy (HR 0.93, 95% CI 0.87, 0.99) was associated with lower MACE risk. Cholesterol intake was associated with a higher MACE risk in ethnic Indians (HR 2.37, 95% CI 1.52, 3.71 highest vs. lowest quartile, P -trend &lt;0.001), but not in ethnic Malay or Chinese ( P -interaction 0.016). Conclusions: Moderating carbohydrate intakes by increasing polyunsaturated fat intake and replacing refined grains with fruits, vegetables, and dairy may lower CVD risk in Asian populations.
Abstract 9991: Can Isosorbide Dinitrate Save Lives of Hospitalized COVID Patients with Hypertension and a Defined Cardiac Injury?
Authors: Thomas Roesel
Journal: Circulation (2021)

Introduction: As defined by MB-CPK, hsTn-I, MB, or EKG and/or cardiac echo abnormalities, cardiac injury (CI) determines a median survival time (MST) of 10 days for hospitalized COVID patients (HCPs). HCPs without defined CI have an MST beyond 39 days (Huang, et al ., see Figure). Hypertension (HTN) presents in 17-41% of HCPs in various studies, with COVID mortality independent of HTN. Therefore, a randomized clinical trial (RCT) is proposed for HCPs with CI and incidental BP elevation to compare IV isosorbide dinitrate (ISDN) with usual anti-HTN care (UC). Vasodilatory ISDN lowers BP, and has been proposed an an anti-SARS-CoV-2 drug. Others report improved survival of ISDN treated Coxsackie B3 virus-infected mice as evidence for anti-viral activity. The endpoint for this CI RCT pilot of 100 ISDN-treat HCPs and 100 UC controls is mortality. Secondary endpoints are interval biomarkers to dissect ISDN anti-viral action. Methods: Log-rank analysis was performed with 1:1 allocation. Accrual time was 180 days with a 60-day follow-up. Power was 0.8 with a type I error of 0.05. Results: For 200 total subjects, an MST greater than 14.9 days in the ISDN arm was significant if UC stays at 10 days (see Figure). Conclusions: Testing repurposed ISDN as a COVID drug is feasible. A successful pilot with improved MST suggests ISDN has anti-SARS-CoV-2 action, since COVID mortality is independent of HTN. Biomarkers could include viral clearance, oxygenation, D-dimer, IL-6, LDH, as well as platelet and lymphocyte counts. The need to treat HCPs with elevated BP per guidelines permits study entry. Cross-over treatment occurs if a regimen fails. Immunomodulators and remdesivir are administered per COVID treatment guidelines for all HCPs. IV ISDN, bolused and/or infused, avoids 1 st pass hepatic effects. IV IDSN is approved in most countries, but not in the USA or Canada. A successful pilot would permit larger IV ISDN RCTs as IND RCTs, and can serve as a template for other treatments for HCPs with defined CI.
WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway
Authors: Ensong Guo, Rourou Xiao, Yifan Wu, Funian Lu, Chen Liu, Bin Yang, Xi Li, Yu Fu, Zizhuo Wang, Yuan Li, Yuhan Huang, Fuxia Li, Xue Wu, Lixin You, Tianyu Qin, Yiling Lu, Xiaoyuan Huang, Ding Ma, Gordon B. Mills, Chaoyang Sun, Gang Chen
Journal: The Journal of Experimental Medicine (2021)

Targeted therapies represent attractive combination partners with immune checkpoint blockade (ICB) to increase the population of patients who benefit or to interdict the emergence of resistance. We demonstrate that targeting WEE1 up-regulates immune signaling through the double-stranded RNA (dsRNA) viral defense pathway with subsequent responsiveness to immune checkpoint blockade even in cGAS/STING-deficient tumors, which is a typical phenotype across multiple cancer types. WEE1 inhibition increases endogenous retroviral elements (ERVs) expression by relieving SETDB1/H3K9me3 repression through down-regulating FOXM1. ERVs trigger dsRNA stress and interferon response, increasing recruitment of anti-tumor T cells with concurrent PD-L1 elevation in multiple tumor models. Furthermore, combining WEE1 inhibition and PD-L1 blockade induced striking tumor regression in a CD8+ T cell–dependent manner. A WEE1 inhibition–induced viral defense signature provides a potentially informative biomarker for patient selection for combination therapy with WEE1 and ICB. WEE1 inhibition stimulates anti-tumor immunity and enhances sensitivity to ICB, providing a rationale for the combination of WEE1 inhibitors and ICB in clinical trials.
Abstract 9569: Increased Incidence of ECG Abnormalities in General Population during the Covid-19 Pandemic
Authors: Hisako Tsuji, Ichiro Shiojima
Journal: Circulation (2021)

Background: To examine influence of COVID-19 pandemic on cardiovascular system in general population, ECG changes during the COVID-19 pandemic period were compared with those before the pandemic period. Methods: Incidence of newly appeared ECG abnormalities (T wave abnormalities and ST-segment depression including minor changes, and abnormal Q wave) was evaluated in subjects 40 to 74 years of age who had 12-lead ECG recording in annual health checkup offered to adult citizens of Moriguchi city, Osaka, Japan in 2019 and 2020. The incidence was compared with that of those who received ECG recording in 2018 and 2019 as the control value before the COVID-19 pandemic. Those with history of cardiovascular disease, any T wave abnormality, any ST-segment depression, abnormal Q wave, left bundle brunch block, or pace-maker rhythm at baseline ECG were excluded. Multivariate logistic regression analyses were performed adjusted for age, sex, hypertension, current smoking, diabetes, drinking habit and hypercholesterolemia. Results: There were 5,221 (mean age 63±10, men 40%) subjects who received ECG recording in 2018 and 2019 and 4,100 (mean age 63±10, men 41%) subjects who received ECG recording in 2019 and 2020. The incidence of newly appeared T wave abnormalities was 5.2 %, ST-segment depression was 2.8 % and abnormal Q wave was 1.1 % from 2018 to 2019, whereas the incidence of newly appeared T wave abnormalities was 5.8 %, ST-segment depression was 4.3 % and abnormal Q wave was 1.7 % from 2019 to 2020. The incidence of ST-segment depression (odds ratio (OR)=1.59, 95% confidence interval (CI)=1.27 to 1.98, p&lt;0.0001) and that of abnormal Q wave (OR=1.56, 95% CI=1.09 to 2.22, p=0.0149) from 2019 to 2020 was significantly higher compared to that from 2018 to 2019. Conclusions: Increased incidence of ST-segment depression and abnormal Q wave was observed during the COVID-19 pandemic period.
Abstract 13141: Accumulation of Aggrecan at Sites of Increased Pulmonary Arterial Pressure in Idiopathic Pulmonary Arterial Hypertension
Authors: Oscar van der Have, Timothy Mead, Christian Westoo, Niccolo Peruzzi, Ayse Ceren Mutgan, Christian Norvik, Anna Löfdahl, Martin Bech, André Struglics, Konrad Hoetzenecker, Hans Brunnstrom, Gunilla Westergren-Thorsson, Grazyna Kwapiszewska, Suneel S Apte, Karin Tran-lundmark
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal condition lacking curative pharmacotherapy. Expansion of the extracellular matrix occurs in early stages of pulmonary angiopathy, but the presence of individual matrix components warrants further investigation. Accumulation of the osmotically active matrix proteoglycan aggrecan has been associated with swelling and disruption of vessel wall integrity in systemic arteries. Whether aggrecan is present to any significant extent in PAH tissue, and what potential role it may have, is not known. Methods: Paraffin-embedded lung tissue from 11 patients with idiopathic PAH was imaged using synchrotron-based phase contrast micro-CT at the TOMCAT beamline, Swiss Light Source. Image analysis was performed in Fiji and Amira. Imaged blocks were subsequently sectioned for histology, immunohistochemistry with an aggrecan core protein antibody and RNAscope in situ hybridization. qPCR was performed to investigate gene expression. Failed donor lungs were used as controls. Results: Aggrecan core protein was identified in vascular lesions of all 11 patients with idiopathic PAH, localized to cellular rather than fibrotic or collagenous lesions. RNAscope in situ hybridization confirmed local production of ACAN mRNA in diseased vessels. Quantification of repeated immunohistochemistry demonstrated significantly increased accumulation of aggrecan in patients with idiopathic PAH compared to failed donor lung controls. ACAN and ADAMTS15 mRNA were also found to be up-regulated in pulmonary arteries from patients with IPAH, indicating ongoing proteolytic turnover. Image analysis and three-dimensional renderings of pulmonary arteries identified aggrecan in lumen-reducing lesions containing cellular connective tissue, at sites of intrapulmonary bronchopulmonary shunting and at sites of elevated pulmonary blood pressure. Conclusions: Our findings indicate local production and accumulation of aggrecan in pressure-related lesions of idiopathic PAH. This work strengthens the hypothesis that aggrecan plays a role in arterial adaptations to altered hemodynamics and is the first to suggest a role for aggrecan in pulmonary arterial homeostasis and idiopathic PAH.
Abstract 12502: Transcatheter Patent Ductus Arteriosus Closure is Associated With Improved Outcomes Compared to Surgical Ligation
Authors: Michael T Kuntz, Steven J Staffa, Dionne Graham, David Faraoni, Philip Levy, James DiNardo, Nicola Maschietto, Viviane G Nasr
Journal: Circulation (2021)

Introduction: Pharmacologic therapy for closure of a patent ductus arteriosus is not consistently successful. Surgical ligation (SL) or transcatheter closure (TC) may be needed. Large multi-center analyses comparing outcomes and resource utilization between SL and TC are lacking. We hypothesized that patients undergoing TC have improved outcomes compared to SL including mortality, length of stay (LOS), intensive care unit (ICU) admission, and ventilation. Methods: Using the 2016-2020 Pediatric Health Information System database, characteristics, outcomes, and charges of patients less than 1 year who underwent TC or SL were analyzed. Results: 678 inpatients undergoing TC (n=503) or SL (n=175) were identified. Surgical patients were younger (0.1 vs 0.53 yrs; P&lt;0.001) and more premature (60% vs 20.3%; P&lt;0.001). Comorbidities were more prevalent among SL patients: bronchopulmonary dysplasia (28.6% vs 16.3%; P&lt;0.001), necrotizing enterocolitis (9.7% vs 0.4%; P&lt;0.001), intraventricular hemorrhage (21.7% vs 2.4%; P&lt;0.001), sepsis (11.4% vs 0.6%; P&lt;0.001), and renal insufficiency (7.4% vs 0.8%; P&lt;0.001). Over time, TC represented an increasing proportion of cases (Figure 1). In-hospital mortality for TC was 0% vs 1.7%; P=0.02. Using inverse probability of treatment weighting by the propensity score, multivariable adjusted analyses demonstrated favorable outcomes in TC: ICU admission rates (adjusted odds ratio (aOR): 0.2; 95% CI: 0.11, 0.32; P&lt;0.001); mechanical ventilation (aOR: 0.3; 95% CI: 0.19, 0.56; P&lt;0.001); and shorter hospital (adjusted coefficient: 2 days shorter; 95% CI: 1.3, 2.7; P&lt;0.001) and postoperative (adjusted coefficient: 1.2 days shorter; 95% CI: 0.1, 2.3; P=0.039) LOS. Overall charges (adjusted coefficient: -$13,100, 95% CI: -26,400, 200; P=0.06) and readmission rates were similar. Conclusions: TC is associated with better outcomes including mortality and LOS. Rates of TC continue to increase compared to SL.
Abstract 11103: Associations of Smokeless Tobacco Use with Cardiovascular Disease Risk: Insights from the Population Assessment of Tobacco and Health Study
Authors: Mary Rezk-hanna, Umme Warda, Mary-Lynn Brecht, Neal L Benowitz
Journal: Circulation (2021)

Introduction: Combustible tobacco smoking is strongly associated with the development of cardiovascular disease (CVD). However, evidence is limited as to whether smokeless tobacco (ST) use is associated with CVD. Methods: Using data from 4347 adults in the Population Assessment of Tobacco and Health Study (2013-2014), we compared geometric mean concentrations of CVD-related harm biomarkers and biomarkers of exposure among current exclusive ST product users and exclusive cigarette smokers—in relation to nicotine exposure—and never tobacco users, adjusting for age, sex, race/ethnicity, income, BMI and CVD. Biomarker levels among exclusive ST users who were former established cigarette smokers were examined and compared to levels among exclusive cigarette smokers. Results: Compared to cigarette smokers, ST users had significantly higher concentrations of total nicotine equivalents (TNE) but lower concentrations of inflammatory (high-sensitivity C-Reactive-Protein, interleukin-6, intercellular adhesion molecule, fibrinogen) and oxidative stress (8-isoprostane) biomarkers (all P&lt;0.05). Biomarker levels among ST users were similar to never smokers. Exclusive ST users who were former cigarette smokers had lower levels of inflammatory and oxidative stress biomarkers and biomarkers of exposure (including cadmium, lead, 1-hydroxypyrene, acrylonitrile and acrolein), compared to cigarettes smokers (p&lt;0.05), despite having higher TNE levels (P&lt;0.05). In cigarette smokers, but not among ST users, inflammatory biomarkers and TNE were highly correlated. Conclusions: ST use is not associated with increases in biomarkers of CVD-related harm and exposure, compared to never smokers, despite exposure to nicotine at levels higher than those observed among cigarette smokers. These findings support the concept that increases in CVD risk among cigarette smokers is caused primarily by constituents of tobacco smoke other than nicotine.
A Divisive Ruling on Devices — <i>Genus Medical Technologies v. FDA</i>
Authors: Patricia J. Zettler, Eli Y. Adashi, I. Glenn Cohen
Journal: New England Journal of Medicine (2021)

The FDA has long taken the legal position that regulated devices could also be categorized as drugs. But according to a recent case, products meeting the definition of a device "must be regulated as devices." The decision comes amid growing challenges to FDA authority.
Experience of Low Dose (25mg/Kg) of Cyclophosphamide (Chennai-Chezhian-Kishore PTCy Protocol) As Post Transplant Cyclophosphamide (PTCy) Dose in Haploidentical Bone Marrow Transplant
Authors: Kishore Kumar, Chezhian Subash, Durai Prabhu, Bhagavathy Subramanian, Simon Raj Maria Doss MBBS, Dharani MBBS, Dilshada Pulikakkal
Journal: Blood (2021)
Abstract 10666: Epigenetic Risk Score Capturing Alcohol Consumption is Not Associated with Cardiac Structure and Function: The Framingham Heart Study
Authors: Helena Bui, Amena Keshawarz, Chunyu Liu, Jiantao Ma, Connie W Tsao, Vasan S Ramachandran, Susan Cheng, Daniel Levy
Journal: Circulation (2021)

Habitual, heavy alcohol consumption increases the risk of detrimental outcomes such alcoholic dilated cardiomyopathy; however, alcohol’s complex effects on cardiac structure and function are incompletely understood. We previously identified 144 differentially methylated CpGs associated with alcohol consumption and sought to create an epigenetic risk score (ERS) derived from these CpGs to examine 1) the cross-sectional association of the ERS with cardiac structure and function, and 2) longitudinal association of the ERS with incident heart failure and atrial fibrillation in Framingham Heart Study (FHS) participants (n=1,843). We first conducted analyses examining the cross-sectional association between each of the 144 alcohol-associated CpGs and the outcomes listed above. After application of Bonferroni correction (p=3.47E-04), two CpGs (cg07504977, cg16246545) were significantly associated with left ventricular posterior wall thickness (p=2.69E-05 and p=1.75E-04, respectively) and one CpG (cg11682350) was significantly associated with left ventricular global longitudinal strain (p=2.15E-04). cg07504977 annotates to the promoter of a lcRNA LINC00623, while cg16246545 maps to the PHGDH , a protein-coding gene implicated in serine synthesis. cg11682350 is not annotated to a gene. Cross-sectional analyses examining the association between the ERS and left ventricular mass (BSA-indexed; p=0.15) systolic diameter (p=0.92), diastolic diameter (p=0.87), fractional shortening (p=0.95), and global longitudinal strain (p=0.28), were not statistically significant, while ERS association with LV posterior wall thickness was nominally significant (p=0.03). Longitudinal associations for HF (p=0.18) and AF (p=0.65) were not significant. Though most of our results are not statistically significant, we plan to explore other means of generating alcohol ERS including by LASSO penalty coefficient thresholds, Gene Ontology biological pathways, and weighted gene expression network analyses. In conclusion, such alcohol-related ERS may be examined in relation to other phenotypes and serve as a predictive or diagnostic tool to monitor and elucidate the epigenetic pathways connecting environmental exposures and disease.