tbuckley/cabot-search huggingface dataset:
Abstract 13772: Anticoagulation Guideline Adherence in 4,500 Patients With Newly Diagnosed Atrial Fibrillation: Insights From the Prospective DUTCH-AF Registry
Authors: Jaap Seelig, Emmy M Trinks-Roerdink, Gordon Chu, Ron Pisters, Tim A de Vries, Hugo Ten Cate, Geert-Jan Geersing, Frans H Rutten, Menno V Huisman, Martin E Hemels
Journal: Circulation (2021)

Introduction: Non-adherence to guidelines and off-label dosing of oral anticoagulants (OAC) is common in atrial fibrillation (AF), but the extent hereof in newly diagnosed AF patients is uncertain. Methods: The DUTCH-AF registry prospectively enrolls patients with newly diagnosed AF since July 2018. We used data available up to November 2020. Anticoagulation guideline and label adherence were assessed at diagnosis of AF using the 2016 European guideline recommendations and the European Medicines Agency labelling. Predictors for label non-adherence were assessed using logistic regression. Results: Throughout the Netherlands, 4,500 patients were registered in DUTCH-AF. Mean age was 69.6±10.5 years, 41.5% were female. Anticoagulants were prescribed in 90.1% of patients with a class I OAC recommendation. In patients with a class IIa OAC recommendation, females were more often treated with anticoagulation than males (89.6% vs 81.2%, p&lt;0.001). Antiplatelet monotherapy and vitamin K antagonists were used infrequently, but its use was most common in patients with a high predicted stroke risk. Off-label use of non-vitamin K oral anticoagulants was uncommon (6.2%), but of the 394 patients who were prescribed a reduced dose, 34.3% were treated off-label (Figure). Independent predictors for off-label reduced dose use were (i) older age (odds ratio (OR) 1.07 per year, 95%-confidence interval (CI) 1.04-1.11, p&lt;0.001), (ii) lower creatinine clearance (OR 0.95 per ml/min, 95%-CI 0.94-0.96, p&lt;0.001), (iii) lower body mass index (OR 0.95 per kg/m 2 , 95%-CI 0.91-1.00, p=0.04) and (iv) concomitant antiplatelet therapy (OR 4.19, 95%-CI 1.88-9.34, p&lt;0.001). Conclusion: In newly diagnosed Dutch AF patients, non-adherence to anticoagulation guidelines and off-label dosing at diagnosis are uncommon, with deviations from recommendations seen more frequently in high-risk patients. These results provide important insights for practicing clinicians.
Abstract 11337: Sensitivity Analysis of an Electronic Health Record-Based Algorithm to Facilitate Detection of Familial Hypercholesterolemia: Results in Genetically Confirmed Familial Hypercholesterolemia
Authors: Nieky Mohammadnia, Willem A Bax, Jan cornel
Journal: Circulation (2021)

Introduction: Familial hypercholesterolemia (FH) is a genetic disorder resulting in elevated LDL-C levels and increased risk of cardiovascular disease. Algorithms have been developed to facilitate FH detection. We previously developed a continuous, electronic health record (EHR)-based algorithm using the Dutch Lipid Clinical Network (DLCN) criteria, with automated correction of LDL-C levels for use of lipid-lowering-therapy (LLT). In this study, we performed a sensitivity analysis of the algorithm in patients with previously genetically confirmed FH. Methods: We selected all patients with genetically confirmed FH, seen during 2018 and 2019. DLCN scores were calculated before and after correction for LLT at the most recent visit. The primary outcome was the number of FH patients with DLCN criteria ≥6 points for LDL-C (which would have been an indication for genetic testing) before and after correction for LLT. Secondary endpoint was the additional number of patients with ≥6 points after also adding data on patient- and family history. Results: We included 222 patients with genetically confirmed FH; mean (SD) age: 50 (17) years; female: n=134 (60,4%). In total, 210 patients (94,6%) used some type of LLT. Mean (SD) LDL-C was 3,0 (1,4) mmol/L before correction for LLT and 7,5 (3,7) mmol/L after correction for LLT. Before correction for LLT, the algorithm identified 3 patients (1,4%) with ≥6 DLCN points, increasing to 59 patients (26,6%) after correction for LLT and to 76 patients (34,2%) after adding data on patient-, and family history. Conclusion: We conclude that, even after correction for LLT and addition of data on patient-, and family history, the sensitivity of a DLCN-based algorithm appeared relatively low in a population with genetically confirmed FH. Correction for LLT is important to increase sensitivity of the algorithm. Interestingly, FH detection algorithms inevitably rely on phenotypical characteristics of patients, whereas the present data show that genotypical FH does not necessarily express as phenotypical FH recognized by the DLCN-based algorithm. These data highlight the need for improvement of the DLCN-based algorithm and the importance of cascade testing for FH.
Abstract 106: Efficient In Vivo Homology-Directed Repair Within Cardiomyocytes
Authors: Nathan J VanDusen, Yanjiang Zheng, Catalina E Butler, Qing Ma, Justin S King, William T Pu
Journal: Circulation Research (2021)

CRISPR/Cas9-based genome editing technologies provide powerful tools for genetic manipulation. Delivery of Cas9 and a homology directed repair (HDR) template using adeno-associated virus (AAV; CASAAV-HDR), was recently shown to enable creation of precise genomic edits, even within postmitotic cells. Here we studied CASAAV-HDR in cardiomyocytes. We constructed an AAV9 vector containing a gRNA targeting the ventricle specific Myl2 gene, and a promoterless HDR template that replaces the native Myl2 stop codon with a self-cleaving 2A peptide followed by mScarlet, a red fluorescent protein. When this vector was injected into Cas9 expressing newborn mice, we observed mScarlet expression within a remarkably high fraction of cardiomyocytes, approximately 45%. Expression was ventricle specific, consistent with the Myl2 expression profile. Similarly, when we targeted the atrial specific Myl7 gene, we observed mScarlet expression in ~20% of atrial cardiomyocytes. Amplicon sequencing of Myl2 and Myl7 transcripts showed that the vast majority of transcripts with an insertion were mutation-free, indicating that CASAAV-HDR is precise. Furthermore, CASAAV-HDR efficiency was comparable when AAV was delivered to fetal, neonatal, or mature mice. Next we targeted seven additional loci: Yap1, Tmem43, Nfatc3, Bdh1, Mkl1, Ttn, and Pln, fusing either an HA tag or mScarlet to each. Insertion efficiency varied dramatically between loci, with HDR efficiency generally correlating with target gene expression. TTN-mScarlet and mScarlet-PLN fusion proteins localized to the sarcomere and sarcoplasmic reticulum, respectively, consistent with the localization of the endogenous proteins. Collectively these data indicate that systemic delivery of CASAAV-HDR vectors can achieve efficient, precise, in vivo somatic genome modification that does not require cardiomyocyte proliferation. We successfully used this technology to monitor protein localization and anticipate it will be useful for many other applications, such as precise introduction of mutations to model disease or probe gene function. CASAAV-HDR may also enable efficient, permanent, and precisely targeted delivery of therapeutic transgenes to validated loci.
Abstract 11644: Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy in Adult Solid Organ Transplant Recipients
Authors: Nosheen Reza, Alejandro De Feria, Teresa Wang, Jessica Chowns, Lily Hoffman-Andrews, Jessica Kim, Nicole Hornsby, Amy Marzolf, Pavan Atluri, Howard C Herrmann, Anjali T Owens
Journal: Circulation (2021)

Introduction: Data on the incidence and prevalence of HCM in adult post-transplant patients are limited. We describe the characteristics of adult solid organ transplant recipients diagnosed with HCM at a single center. Methods: Solid organ transplant recipients with LV wall thickness &gt; 13 mm on TTE were included in this retrospective analysis. Clinical characteristics and outcomes were abstracted. Categorical variables were described as n (%). Continuous variables were described with medians and interquartile ranges (IQR) and compared using the Wilcoxon Rank Sum test. A 2-sided p value &lt; 0.05 was considered statistically significant. Results: Twelve transplant recipients — 3 (25%) lung, 5 (42%) kidney, 4 (33%) liver — were identified. Half (50%) were women, and 42% were non-White. One kidney transplant patient had a pathogenic variant in Myosin Binding Protein C (MYBPC3 c.3190+1G&gt;A), and one kidney transplant patient had a likely pathogenic variant in Myosin Heavy Chain 7 (MYH7 c.5561C&gt;T). Most (75%) had NYHA II-III symptoms. Five (42%) had hypertension. 10 (83%) were treated with tacrolimus and 2 (17%) with cyclosporine for a median 11.5 years (IQR 5.0,17.5). All had normal to hyperdynamic LVEF on first TTE (median LVEF 72.5% [IQR 60,75]). Median septal thickness at diagnosis was significantly greater than LV posterior wall thickness (17 vs. 13 mm, p &lt;0.001). Seven had resting LVOT gradients &gt;50 mm Hg. Nine (75%) were on beta-blocker, and 3 (25%) were concomitantly on calcium channel blocker. Four patients underwent successful septal reduction therapy: 2 (kidney) with septal myectomy and 2 (lung, kidney) with alcohol septal ablation. Conclusions: We report the largest series of adult solid organ transplant recipients with HCM. Symptomatic HCM with dynamic LVOT obstruction can develop in solid organ transplant recipients. Medical management and septal reduction therapy are options for severe symptomatic disease. Prospective study of LVH in these patients is needed.
Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (Dara-KRd), Autologous Transplantation and MRD Response-Adapted Consolidation and Treatment Cessation. Final Primary Endpoint Analysis of the Master Trial
Authors: Luciano J. Costa, Saurabh Chhabra, Natalie S. Callander, Eva Medvedova, Bhagirathbhai Dholaria, Rebecca W. Silbermann, Kelly N. Godby, Binod Dhakal, Susan Bal, Smith Giri, Anita d'Souza, Timothy M. Schmidt, Aric C. Hall, Pamela Hardwick, Robert F. Cornell, Parameswaran Hari
Journal: Blood (2021)
Abstract 10048: Accuracy of Detecting Atrial Fibrillation: A Systematic Review and Meta-Analysis of Wrist-Worn Wearable Technology
Authors: Seema Belani, Waseem Wahood, Patrick Hardigan, Andon Placzek, Stephen Ely
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is the most commonly diagnosed arrhythmia, and ECG remains the gold standard for diagnosis. Wrist-worn technologies are appealing for their ability to passively process near-continuous pulse signals. Hypothesis: Our systematic review and meta-analysis qualitatively and quantitatively analyzes available literature on wrist-worn wearable devices (Apple Watch, Samsung, and KardiaBand) and their sensitivity and specificity in detecting AF compared to conventional methods. Methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed, yielding 9 studies (N=1,581). Observational studies assessing the sensitivity and specificity of wrist-worn wearables in detecting AF in patients with and without a history of AF were analyzed using a fixed effect model with an inverse-variance method. Results: In patients with a history of AF, the overall sensitivity between device groups did not significantly differ (sensitivity: 96.83%; p=0.207). The overall specificity between device groups was statistically significant (specificity: 99.02%; p&lt;0.001). The effect size for this analysis was highest in the Samsung device group. Conclusions: Wrist-worn wearable devices demonstrate promising results in detecting AF in patients with paroxysmal AF. However, more rigorous prospective data is needed to understand the limitations of these devices in regard to varying specificities, which may lead to unintended downstream medical testing and costs.
Abstract 11562: Contrast Minimization Devices in the Cath Lab: Real-World Outcomes Within a VA Hospital
Authors: John M Suffredini, Marilyne Daher, Hani Jneid, Ali E Denktas, Mirza Khalid, DAVID PANIAGUA
Journal: Circulation (2021)

Introduction: Contrast-induced acute kidney injury (CI-AKI) remains one of the leading causes of hospital acquired AKI. Patients with baseline chronic kidney disease (CKD) and/or elevated risk scores are at increased risk of developing CI-AKI. Contrast minimization devices have been proposed as a mechanism for contrast usage reduction in the cath lab. Since May 2017, the cardiac catheterization lab at the Michael E DeBakey VA Medical Center has used the Osprey Medical DyeVert contrast minimization device. Methods: We retrospectively evaluated the outcomes of 120 patients with known CKD who underwent cardiac catheterization with the DyeVert Contrast Reduction System for contrast monitoring and minimization. Results: The results of 120 DyeVert cases from Q2 2019 through Q4 2020 were analyzed. The mean baseline eGFR of the evaluated patients was 50. Mean overall contrast media volume (CMV) savings were 37 +/- 21 mL per procedure or 36%. 90% of DyeVert cases achieved a procedure CMV/eGFR ratio &lt; 3. Mean attempted CMV/eGFR ratio was 2.5 versus actual ratio of 1.6 after device contrast diversion. Conclusions: Our results suggest that contrast minimization devices in the cath lab can reduce the overall contrast media volume usage and result in improved CMV/eGFR ratios for at-risk patients undergoing coronary angiography.
NTCP: a pharmacological target for multiple liver conditions
Authors: Jordi Gracia-Sancho, Jean-François Dufour
Journal: Gut (2021)

Despite major therapeutic advances to treat patients with chronic liver diseases, one target remains elusive in hepatology and this is the most important one: liver fibrosis. We can cure patients from chronic hepatitis C; we can vaccinate against hepatitis B virus and control chronic hepatitis B; we have new drugs to treat cholestatic liver diseases and several lines of treatment to treat patients with hepatocellular carcinoma. But the process driving the prognosis of patients with chronic liver disease and the scarring process of the hepatic parenchyma are beyond our armamentarium. Hepatic fibrosing is a highly complex process which has been extensively studied in patients and in great details in animal models. Activation of quiescent hepatic stellate cells into α-smooth muscle actin (α-SMA)-positive myofibroblasts is a key mechanism since once activated, these cells secrete collagens and other matrix components participating actively in the scarring process. Numerous potential druggable mechanisms have been investigated and pharmacologically tested with success in animal models. However, despite great interest from the academic community and from the pharma only a few drugs have been tested in clinical trials with disappointing results.

Salhab et al conducted an elegant series of experiments studying an unlikely target to treat hepatic fibrosis namely the Na+/taurocholate cotransporting polypeptide (NTCP).1 NTCP was the first bile acid transporter to be cloned. This feat was achieved in 1989 by Hagenbruch et al when he worked in the laboratory of the late P. Meier-Abt in Zurich using an expression cloning strategy.2 NTCP is expressed on the basolateral membrane of hepatocytes allowing the hepatocellular uptake …
Abstract 12400: Trends in Bivalirudin Resource Utilization Among Young Pediatric Ventricular Assist Device Recipients
Authors: Danielle S Burstein, Yuan-Shung V Huang, Hannah Katcoff, Heather Griffis, Joseph Rossano, Christina J Vanderpluym, Angela Lorts, Holger Buchholz, Katsuhide Maeda, Matthew J O'Connor, Jonathan Edelson, Kimberly Lin, Jennifer Conway
Journal: Circulation (2021)

Introduction: Despite recent data suggesting improved outcomes with bivalirudin (bival) vs. heparin in young children requiring ventricular assist devices (VAD) support, the significantly higher costs for bival remains a barrier. Data on bival resource utilization in this population is limited and may influence care practices. Methods: Index VAD hospitalization of pediatric VAD recipients age 0-6 yrs from 2009-2020 were identified in Pediatric Health Information System. Bival exposure was defined as any receipt of bival during hospitalization. Standardized costs inflated to 2020 US dollar and outcomes were compared using multivariate regression. Results: Of 639 young pediatric VAD recipients (median age 1 yr, IQR 0-2), 246 (40%) received bival with a significant increase over the past decade (trend p-value &lt;0.01; Figure 1). Bival was associated with lower overall hospital mortality (23% vs. 36%; adjusted OR 0.38, 95% CI 0.23-0.63) and mortality before transplant (19% vs 31%; adjusted OR 0.34, 95% CI 0.19-0.55) vs. heparin, even after adjusting for era, age, diagnosis, and center VAD volume. Length of stay (LOS) was longer for bival (median 126 days, IQR 81-184) vs. heparin (median 87 days, IQR 49-152); p&lt;0.01. After adjusting for LOS, overall hospital costs were similar between anticoagulation strategies ($931k bival vs. $859k heparin; adjusted cost ratio 1.09, 95% CI 0.96-1.24). Higher pharmacy costs associated with bival (cost ratio 1.67, 95% 1.05-2.66) were offset by lower laboratory (cost ratio 0.86, 95% CI 0.78-0.94) and supply costs (adjusted cost ratio 0.81, 95% CI 0.69-0.96). Conclusions: Bival use significantly increased over the past decade and is now used in &gt;90% young pediatric VAD recipients. Mortality is lower among bival recipients, even after accounting for era and patient-level factors, while hospital costs are similar among both anticoagulation strategies after adjusting for LOS, supporting the cost-effectiveness of bival in this population.
Abstract 3758: High Pulse Wave Velocity has a Strong Impact on Early Carotid Atherosclerosis in a Japanese General Population
Authors: Takuro Kubozono, Masaaki Miyata, Shuichi Hamasaki, Kazuto Saito, Ken Kusano, Osamu Kubozono, Chuwa Tei
Journal: Circulation (2007)

Background : Pathological changes in large arteries make an important contribution to the pathogenesis of cardiovascular disease. The etiology and progression of such changes involve both structural and functional components. Intima-media thickness (IMT) of carotid artery has been reported to be associated with cardiovascular mortality and morbidity. Pulse wave velocity (PWV), which reflects functional arterial stiffness, is reported to be a prognostic predictor of cardiovascular disease. The purpose of this study is to investigate the association between carotid IMT and cardiovascular risk factors in a Japanese general population. Methods : The study group consisted of 1843 subjects (1583 men, 260 women, mean age: 57±10 years) undergoing routine health checkups. IMT of common carotid artery was measured with high-resolution ultrasonography. Brachial-ankle (baPWV) and blood pressure (BP) was measured using automated device. Obesity was shown by body mass index ≥ 25.0 kg/m2. Hypertension was defined as systolic BP (SBP) ≥130 mmHg or diastolic BP (DBP) ≥ 85 mmHg. Dyslipidemia was identified by low density lipoprotein cholesterol (LDL) concentration ≥ 140mg/dl, triglyceride (TG) ≥ 150 mg/dl, or high density lipoprotein cholesterol (HDL) ≥ 40 mg/dl. Impaired fasting glucose (IFG) was defined as fasting glucose ≥ 110 gm/dl. Results : Univariate analysis demonstrated that carotid IMT significantly associated with age, BMI, SBP, DBP, baPWV, fasting glucose, LDL, TG, and HDL. Multiple logistic regression analysis for carotid atherosclerosis (carotid IMT ≥ 1.0 mm) was performed using obesity, hypertension, dyslipidemia, IFG, and high baPWV (≥ 400 cm/sec). After adjustment for age and gender, carotid atherosclerosis was significantly associated with high baPWV (OR: 2.256, 95% CI: 1.244 – 4.093, P &lt; 0.01) and hypertension (OR: 1.543, 95% CI: 1.009 –2.361, P &lt; 0.05). Conclusion : Carotid IMT correlated with conventional cardiovascular risk factors. Furthermore, high PWV was a stronger predictor of early carotid atherosclerosis rather than hypertension, dyslipidemia, and IFG in a Japanese general population.
Abstract 11041: Time Course of Recovery from Left Ventricular Systolic Dysfunction in Patients with Arrhythmia and Newly Diagnosed Heart Failure
Authors: Christian Schach, Thomas Koertl, Bianca Harler, Franzisk Muehleck, Paul Baum, Florian Zeman, Christine Meindl, Markus Resch, Lars S Maier, Rolf Wachter, Samuel T Sossalla
Journal: Circulation (2021)

Background: Newly diagnosed heart failure and concomitant persistent arrhythmia often is a challenging situation for clinicians, especially if left ventricular systolic dysfunction (LVSD) is otherwise not explainable. The time to recovery of arrhythmia-induced cardiomyopathy (AIC) is not well known and the prevalence of this disease is likely underestimated. Purpose: As AIC only can be diagnosed after rhythm control (RC) and thereafter recovery from LVSD (diagnosis ex juvantibus), we aimed to characterize the time course of recovery and describe the prevalence in such a specific cohort. Method and Results: We prospectively screened 95 patients hospitalized for newly diagnosed and otherwise unexplainable LVSD (left ventricular ejection fraction (LVEF) &lt;50%) and coexisting tachyarrhythmia (atrial fibrillation/flutter + heart rate (HR) &gt;100/min) in three cardiological centers. Coronary angiography and cardiac magnetic resonance imaging were performed to exclude other causes for LVSD. RC was achieved by electrocardioversion, ablation, pharmacologically or a combination of those. 50 of 68 included patients (age 69±11y, 63% male, LVEF 35.6±8%, mean±SD) were free from recurrent arrhythmia after 6 months and analyzed: AIC was diagnosed by any increase of ≥15% in absolute LVEF or an LVEF ≥50% with an improvement of ≥10% 6 months after RC; all others were diagnosed idiopathic DCM. LVEF was assessed by echocardiography at presentation and at follow-up visits 2, 4, and 6 months after RC. 9 patients did not meet the AIC-criteria, resulting in a prevalence of 82% for AIC. At presentation, AIC vs. DCM had smaller left ventricles (LVEDD 53.6±7.5 vs. 59.7±3.1mm, P&lt;0.05; LVESD 44.4±6.6 vs. 51.6±5.1mm, P&lt;0.01), biomarkers did not differ: NT-proBNP 4525±4535 vs. 4793±4076pg/mL, P=n.s., Troponin T-hs: 46.8±108.8 vs. 22.9±15.7ng/L, P=n.s.. 2 and 4 months after RC, 58% and 73% of patients fulfilled AIC criteria. Conclusion: The prevalence of AIC in patients in this specific collective with newly diagnosed and otherwise unexplainable LVSD with concomitant persistent tachycardia is surprisingly high and the time course of recovery suggests that the final diagnosis cannot be established before 6 months after rhythm restoration.
Efficacy of Brentuximab Vedotin and Bendamustine Combination in Relapsed/Refractory Hodgkin Lymphoma: Experience from a Tertiary Care Hospital
Authors: Abdullah M Alrajhi, Razan A. Aljalali, Lara H. Alghazi, Ibrahim Asiri, Adel Alnakhli, Fouad H. Alnajjar, Nawal F Alshehry, Ibraheem H. Motabi, Mohammed S. Alnoamani, Mohammed A. Marei, Mansour Alfayez, Imran K. Tailor
Journal: Blood (2021)