tbuckley/cabot-search huggingface dataset:
Abstract 10309: Pregnancy Outcomes in Women with Hypertrophic Cardiomyopathy
Authors: Muhammad Moolla, Kevin J John, Haran Yogasundaram, WALEED ALHUMAID, Sandra Campbell, Jonathan Windram, Anoop Mathew
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is a genetic disorder often complicated by heart failure, embolic stroke, and sudden cardiac death. Pregnancy causes hemodynamic changes which may be deleterious in patients with HCM. Existing cohort studies of maternal and fetal outcomes of pregnant patients with HCM are limited by small sample sizes. We performed a systematic review of maternal and fetal outcomes of pregnancy in patients with established HCM. Methods: We searched MEDLINE, EMBASE, and Cochrane Library databases for studies reporting maternal or fetal outcomes in pregnant patients with HCM. The primary outcomes were maternal death, stillbirth, and fetal death. Secondary maternal outcomes included: sustained ventricular tachycardia (VT), any VT (including sustained and non-sustained), atrial fibrillation (AF), syncope, caesarean delivery, and pre-eclampsia or eclampsia. The secondary fetal outcome was preterm birth. We used a random effects model to determine pooled incidences of outcomes. Results: A total of 18 studies with 5236 pregnancies were included. The incidence of maternal death was 0.2%. Similarly, the incidence of neonatal death was 0.2%. The incidence of maternal and neonatal death was too low across studies to derive pooled estimates. The rate of stillbirth was low at 1% (95% CI, 0-3%) and rate of preterm birth was 22% (95% CI, 18-25%). The rates of sustained VT, any VT, AF, heart failure, and syncope were 1% (0-1%), 6% (4-8%), 4% (2-6%), 5% (3-8%), and 9% (3-14%), respectively. Postpartum hemorrhage, preeclampsia or eclampsia, and cesarean section complicated 2% (1-4%), 4% (2-6%), and 43% (32-54%) of pregnancies, respectively. Conclusions: Women with HCM looking to become pregnant can be reassured that the risk of death, stillbirth, or neonatal demise are low. However, they are at risk for several non-fatal cardiac and pregnancy related complications.
Abstract 10848: Increasing Left Anterior Descending Artery Size is Associated with Worsening Myocardial Function in the Setting of Multisystem Inflammatory Syndrome in Children
Authors: Benjamin Olsen, Michael Nguyen, Zhaoxing Pan, Pei-ni Jone
Journal: Circulation (2021)

Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory syndrome after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular complications include left ventricular dysfunction and coronary artery abnormalities (CAA). Little is known, however, about the interaction between LV function and CAA. We aimed to assess the hypothesis that increased coronary artery size is inversely correlated with LV function utilizing left ventricular ejection fraction (LVEF) and indices of myocardial work. Methods: Two-dimensional and speckle-tracking echocardiograms were performed in 34 MIS-C patients at admission. Biplane LVEF and coronary artery Z scores were measured, and pressure-strain loops were used to calculate indices of myocardial work: global work index (GWI), global work efficiency (GWE), global wasted work (GWW), global constructive work (GCW), and global longitudinal strain (GS). Treating coronary artery Z-scores as a continuous variable, correlation analysis was performed. Results: LVEF and left anterior descending artery (LAD) Z-scores were inversely correlated (Spearman coefficient of -0.47; P =0.005). Both GWI and GCW demonstrated an inverse relationship with increasing LAD Z-scores, but both were not statistically significant (Spearman coefficient -0.21; P =0.239 and Spearman coefficient -0.21; P= 0.235). GS also exhibited a trend of worsening (less negative scores) with increasing LAD Z-scores but was not statistically significant (Spearman coefficient 0.29; P =0.095). GWE and GWW did not correlate with any coronary artery Z-scores and left main coronary or right coronary artery Z-scores did not correlate with any markers of function. Conclusion: Increasing LAD Z-score showed a statistically significant association with decreased LVEF. Additionally, while not statistically significant, GWI, GCW, and GS all demonstrated a trend of decreased indices of myocardial work as LAD Z-score increases. In conclusion, this data suggests that patients with higher coronary artery Z-scores at admission are at increased risk of myocardial dysfunction.
Abstract 14277: Diagnostic Accuracy of the 12-lead Electrocardiogram in the First 48 Hours of Life in Neonates From a Parent With Genotype Positive Long QT Syndrome
Authors: Kathryn E Tobert, Yalile Perez, Martijn Bos, Michael J Ackerman
Journal: Circulation (2021)

Introduction: Long QT syndrome (LQTS) is an autosomal dominant disorder characterized by a prolonged QT interval on a 12-lead electrocardiogram (ECG). Cascade genetic testing for LQTS is standard of care, including in infants, but takes 2-4 weeks for return of results. For newborns of parent with confirmed LQTS, the ECG is obtained after birth as an initial assessment, but QTc values during the immediate newborn period may be misleading. Thus, our objective was to determine the ECG’s diagnostic accuracy in the first 48 hours of life for neonates born to a parent with LQTS. Methods: We performed a retrospective review of the electronic medical records of neonates born to a parent with ≥ 1 pathogenic variant in a LQTS-causative gene for which at least 1 ECG in the first 48 hours of life was obtained. Clinical data was collected on all neonates with focus on the 12-lead ECG, family history, and genetic testing results. The sensitivity and specificity of the diagnostic ECG were calculated using QTc thresholds of 440, 460, and 470 ms. Results: Overall, 70 infants (35 [50%] females) met inclusion criteria and the mean QTc on the first ECG was 484 ± 61 ms. Following genetic testing, a LQTS-causing variant was identified in 46 infants (66%), including 22 (48%) with LQT1 ( KCNQ1 ), 12 (26%) with LQT2 ( KCNH2 ), and 8 (17%) with LQT3 ( SCN5A ). Mean QTc in the first 48 hours of life for neonates that ultimately were genotype-positive was 502 ± 59 ms compared to 451 ± 50 ms (p &lt; 0.001) for genotype-negative neonates. When using a recommended threshold QTc of ≥ 440 ms, 6/46 genotype-positive neonates (13%) were missed (underdiagnosed) and 13/24 genotype-negative neonates (54%) were overdiagnosed (sensitivity: 87%, specificity: 45%). At a QTc threshold ≥ 460 ms, 15 (21%) were classified erroneously (sensitivity: 85%, specificity: 67%) while at a threshold of ≥ 470 ms, 18 (26%) were misclassified (sensitivity: 76%, specificity: 71%). Conclusions: Although a baseline ECG should still be obtained before a newborn’s dismissal, reliance solely on the QTc for diagnosing LQTS and initiating therapy will result in an unacceptable number of misclassifications. Thus, genetic testing must be initiated prior to the baby’s discharge and proper anticipatory guidance is vital while awaiting genetic test results.
Abstract 13242: One Day Intravenous Sotalol Loading for Treatment of Atrial Arrhythmia
Authors: Steven Jacobs, Jess Oren, Randle Storm, Pugazhendhi Vijayaraman, Keturah Weaver, Nathan Sauers, Erin Van Enkevort, Parash Pokharel
Journal: Circulation (2021)

Introduction: Sotalol is commonly used for the management of atrial arrhythmias Recently, sotalol was approved for intravenous administration. The intravenous loading protocol is based on a computer simulation of plasma concentration rather than clinical data Availability of IV sotalol offers an opportunity to shorten the loading time. We developed a One Day Sotalol Loading Protocol (ODSL) utilizing the IV sotalol formulation. Hypothesis: ODSL feasible &amp; safe. It also results in significant health care cost reduction. Methods: Patients undergoing ODSL loading between June 2020 to Dec 2020 for management of AF were included in the analysis. The primary endpoint was successful initiation of sotalol therapy. The secondary endpoint was maintenance of sinus rhythm at 30 days. Safety endpoints included excessive prolongation of the QT C interval, ventricular arrhythmias and sinus bradycardia requiring dose adjustment. Patient co-morbidities and demographics were also evaluated. Cost savings analysis was performed to quantify health care savings Results: 55 patients were included in the analysis (30 paroxysmal AF and 25 persistent AF). The mean age was 70± 9.82 years old and 60.7% were men. The average ejection fraction was 52.91 ± 9.25% and average creatinine clearance was 83.58 ± 44.35mL/min. 51 patients (92.7%) underwent successful ODSL. Of these, 6 patients had dose reduction due to adverse events (fig 1). 7 (12.7%) patients had significant QT C prolongation during IV loading. ODSL was terminated in 4 patients: symptomatic bradycardia and prolonged QT C (1 pt) and failure of cardioversion (3 pts).42 (76%) of patients remained on sotalol and 32 (58%) maintained sinus rhythm at 30 day follow up. No ventricular arrhythmia was noted during the loading and monitoring period. Same day discharge led to an 18% reduction in health care costs. Conclusions: We present first real-world data demonstrating that abbreviated ODSL is feasible, safe, and leads to significant health care savings while freeing up resources and personnel. Further patient enrollment and data analysis is ongoing to further solidify this novel loading approach.
Abstract 11339: Novel Ecg Protocol for Early Detection of Cardiac Amyloidosis
Authors: Laura Gonzalez, Reynolds Delgado, Harveen Lamba
Journal: Circulation (2021)

Background: Due to recent improvements in treatment of Cardiac Amyloidosis (CA) early detection of the disease has become important. We present a novel ECG protocol for early detection of CA utilizing a ratio of the P wave amplitude to the R wave amplitude. It is known that the R wave amplitude decreases early in the disease progression, and the P wave amplitude may remain unchanged or increase. By analysis of amplitudes of the waves relative to each other, artifacts may be eliminated, and quantitative cutoff values obtained may accurately detect early disease. Methods: Six male patients with a known diagnosis of Transthyretin Amyloidosis were analyzed with lead II ECG. Three had wild type and three had the genetic form. For controls, six patients, matched for age and sex were analyzed. The control patients had no significant cardiac disease, a normal ECG, and normal left ventricle septal wall thickness. All ECGs were examined in a blinded fashion to obtain the quantitative ratio of the P wave amplitude to the R wave amplitude. Results: Median age of the two groups was comparable (74 vs 71 years, p=0.6). The CA group had a higher median septal thickness than the control (1.4 vs 1.05 cm, p=0.005) and a higher median ratio of the P wave to R wave amplitude (0.16 vs 0.09, p=0.002). A cut off of 0.11 for P wave to R wave amplitude was significantly associated with the diagnosis of CA (p=0.006). Conclusion: Despite the small sample size these data support the hypothesis that a lead II ECG analysis of the P wave to R wave ratio may be effective as an early screening tool for CA. Further large-scale studies are needed for validation and identification of appropriate and generalizable cut off values.
Abstract 9363: Ascending Aorta Dilation is Less Frequent in Bicuspid Aortic Valve With Coarctation of Aorta Compared to Isolated Bicuspid Aortic Valve
Authors: Anuja Shikhare, Moeez Hassan, Mary Coffey, Ismael Gonzalez Rangel
Journal: Circulation (2021)

Introduction: Bicuspid aortic valve (BAV) is known to be associated with aortopathy and aortic valve dysfunction. There is paucity of data in the pediatric population comparing ascending aorta (AA) dilation related to BAV in patients with and without coarctation of aorta (CoA). Hypothesis: We assess the hypothesis that BAV is associated with decrease in incidence of AA dilation in patients with CoA when compared to patients with isolated BAV. Methods: A retrospective cross-sectional study was done for all BAV patients 0-26 years of age seen from 2012 through 2021 in the outpatient pediatric cardiology clinic. The patients were subdivided into two groups: associated CoA (cBAV) and isolated BAV (iBAV) . Exclusion criteria were pregnancy, connective tissue disorders and/or aortic valve interventions. Patients with late repair of CoA ( ≥ 9 years) were excluded from the analysis of AA diameters because persistent hypertension, associated with late repair, could be a risk factor for AA dilation. Aortic insufficiency and aortic stenosis were defined by color Doppler and Doppler velocity by echocardiogram. Aortic dilation was defined by Z-score above 2.0. 95% score confidence intervals were used to compare the proportion of patients with an outcome in the two groups. Results: 345 patients with bicuspid aortic valve were included (67.5% male, median age 13). CoA history was present in 32 patients (9.3%). Of the 27 patients with CoA included to assess AA dilation, two patients did not need intervention for CoA. Incidence of AA dilation was 11.1% in cBAV and 28.7% in iBAV (CI: [-26.5%, 0%]; p= 0.05). AS was noted in 63 (18.3%) and AI in 184 (53.3%) of the 345 patients. AI was less common in cBAV at 34.4% than in iBAV at 55.3% (CI: [-35.9%, -2.7%]; p= 0.024). Incidence of AS was 9.4% in cBAV and 19.2% in iBAV (CI: [-17.5%, 5.6%]; p= 0.17). Conclusions: In conclusion, our study suggests that the ascending aorta in pediatric patients with BAV and CoA (who underwent early repair or did not meet criteria for intervention) may have less frequent dilation than in those with isolated BAV. Patients with BAV and CoA also have lower risk for aortic insufficiency and may have lower risk for aortic stenosis. The results are limited by the small sample size of patients with CoA and further study is recommended.
Abstract 11131: Discharge on Sacubitril/Valsartan vs. ACEi/ARB in Older Patients with HFrEF: A Decision Analysis Approach
Authors: Ronnie Zipkin, J. Aaron Barnes, Anna Tosteson, Thomas A Gaziano, Lauren Gilstrap
Journal: Circulation (2021)

Introduction: Based on the results of PARADIGM-HF and PIONEER-HF, angiotensin-receptor neprilysin inhibitors (ARNI) offer improved survival and lower readmission rates for HFrEF compared to angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). However, there is concern that increased hypotension and higher drug costs may limit the effectiveness of ARNIs in clinical practice, especially among older adults with Part D prescription coverage. The aim of this study is to use decision analytic modeling to estimate the association between discharge on ARNI vs. ACEi/ARB and patient outcomes, and then determine if it varies by age. Methods: We then used a 2-state absorbing Markov chain model with a 1-month cycle length to simulate 5-year survival for patients discharged on ARNI or ACEi/ARB, accounting for the risks of death and readmission, estimated from trials, as well as the risk of in-hospital mortality, drug switching, and discontinuation, estimated from Medicare claims data. In the model, the weighted averages for mortality and readmission reduction were estimated published risk reductions from the PIONEER-HF trials (first two months) and PARADIGM-HF (subsequent 8 months) trials. Results: Across all age groups, patients discharged on ARNI had higher 5-year survival compared to patients discharged on ACEi/ARB ( Table 1 ). Moreover, the absolute and relative benefit of ARNI over ACEi/ARB, even after accounting for drug discontinuation and switching, was similar across age groups. The number needed to treat (NNT) with ARNI rather than ACEi/ARB to prevent 1 death over 5 years ranged from 56-63. Conclusions: There is a small, but clinically significant, survival benefit to discharge on ARNI vs. ACEi/ARB across all age groups, even after accounting for drug switching and discontinuation. Additional work is needed to determine if there is additional heterogeneity of treatment effect in subgroups of high-risk, older adults.
BIOM-08. DNA METHYLATION-BASED SUBGROUPING PREDICTS SURVIVAL BENEFIT FROM LOMUSTINE/TEMOZOLOMID COMBINATION THERAPY IN MGMT PROMOTOR-METHYLATED GLIOBLASTOMA
Authors: Johannes Weller, Andreas Waha, Matthias Schneider, Clemens Seidel, Joachim Steinbach, Peter Hau, Uwe Schlegel, Jörg-Christian Tonn, Oliver Grauer, Michael Sabel, Dietmar Krex, Oliver Schnell, Florian Ringel, Ghazaleh Tabatabai, Roland Goldbrunner, Alexander Radbruch, Patrick Schuss, Erdem Güresir, Hartmut Vatter, Martin Glas, Matthias Schmid, Niklas Schäfer, Theophilos Tzaridis, Frank Giordano, Thomas Zeyen, Christina Schaub, Robert Németh, Torsten Pietsch, Ulrich Herrlinger
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The CeTeG/NOA-09 trial showed that lomustine/temozolomide chemotherapy prolongs survival for newly diagnosed MGMT-methylated glioblastoma patients. Previous reports on temozolomide monotherapy suggested, that the survival benefit of temozolomide in MGMT-methylated tumors may be restricted to the RTK II methylation subgroup and absent in RTK I and MES subgroups. To identify patients with a particularly strong benefit from CCNU/TMZ, we explored the association of methylation subgroups with outcome after lomustine/temozolomide therapy. METHODS All patients from the CeTeG/NOA-09 trial with sufficiently available tumor tissue (n = 98) underwent 850K methylation array analysis of their tumor and methylation subgroup annotation (Heidelberg brain tumor methylation classifier v11b4; calibrated score &amp;gt; 0.5 required). Overall survival (OS) was compared between a pooled cohort of tumors of the RTK I/MES subgroups and RTK II tumors. RESULTS In the CCNU/TMZ arm of CeTeG/NOA-09, OS was prolonged in RTK I/MES (n = 16; median not reached, 4-year OS 69%) as compared to RTK II patients (n = 14; median 20.6 months, 4-year OS 23%; p = 0.004 logrank test). In the standard temozolomide arm of CeTeG/NOA-09, OS tended to be shorter in RTK I/MES (n = 7; median 23.7 months, 4-year OS 17%) as compared to RTK II patients (n = 17; median 35.2 months; 4-year OS 38%, p = 0.15). CONCLUSION The CCNU/TMZ-dependent survival prolongation in patients with RTK I/MES tumors as opposed to RTK II seen in CeTeG/NOA-09 suggests that methylation-based subgrouping could be predictive for CCNU/TMZ efficacy in newly diagnosed MGMT-methylated glioblastoma.
Mutation Landscape and Prognostic Correlates of <i>ASXL1</i> Variants in Primary and Secondary Myelofibrosis
Authors: Giacomo Coltro, Paola Guglielmelli, Giada Rotunno, Carmela Mannarelli, Chiara Maccari, Costanza Salvadori, Fiorenza Irushani Vanderwert, Francesco Mannelli, Cristina Salvati, Alessandro Vannucchi
Journal: Blood (2021)
Abstract 10183: Augmentation of Cardiac Micrornas Enhanced Cardiac Mesenchymal Cell Differentiation Into Cardiomyocyte Like Cells
Authors: Senthilkumar Muthusamy, ASHA V V. NATH, Shilpa Ajit, ANIL K KUMAR
Journal: Circulation (2021)

Introduction: Infusion of cardiac mesenchymal cells (CMCs) showed improved cardiac function in myocardial infarction models. Cell based therapy to treat cardiac injuries have shown modest success due to limitations, including poor retention and differentiation. Current studies are focused to improve engraftment and differentiation potential of the therapeutic cells. Here, we used cardiac miRNAs in CMCs to increase their differentiation potential towards cardiac lineage. Hypothesis: Increased expression of cardiac miRNAs in CMCs could allow them to differentiate into cardiomyocyte like cells. Methods: Mouse CMCs were isolated from the adult mouse heart and analyzed for the expression of cardiac miRNAs. The CMCs were transiently transfected with cardiac miRNAs cocktail (miR-1, miR-133, miR-208 and miR-499) and cultured for 48h. (n=3) The potential miRNAs targets such as HDAC4 (miR-1), Snail-1 (miR-133), myostatin (miR-208) and Sox6 (miR-499) were analyzed using western blot and immunostaining. The miRNAs cocktail transfected CMCs were cultured for 7 days and analyzed for the expression of cardiac specific genes with RT-PCR. (n=3) Results: Quantitative PCR analysis showed that the cardiac miRNAs were either less or not expressed in CMCs, whereas transient transfection significantly elevated them. Western blot analysis showed significant downregulation of cardiac miRNAs targets HDAC4 (0.62±0.06), Snail1 (0.61±0.03), Sox6 (0.75±0.01) and Myostatin (0.3±0.04). Immunostaining confirmed significant reduction of these target proteins. Cardiac miRNAs cocktail transfected CMCs showed significantly increased expression of cardiac specific genes such as mef2c (3.87±1.54), Gata4 (3.73±1.07), Tnni3 (3.31±1.01), Nkx2.5 (3.89±0.37) Actc1 (4.27±1.57), Tnnt2 (2.49±1.12) and Cx40 (2.37±0.61). The expression of fibroblast markers such as Col1a and Thy1 were reduced upon enriching the cardiac miRNAs in the CMCs. Conclusions: Our results demonstrate that enrichment of cardiac miRNAs in CMCs increase their differentiation into cardiomyocyte lineage, which could improve their therapeutic efficacy. Further in vivo experiments would reveal functional benefits from these improved CMCs for clinical use.
Abstract 13176: Impact Of Cardiac Shock Wave Therapy On Myocardial Perfusion And Left Ventricular Ejection Fraction In Patient With Angina: A Meta-analysis
Authors: Azka Latif, Muhammad J Ahsan, Mohsin Mirza, Abhishek Thandra, vikas kapoor, Muhammad Zoraiz Ahsan, Aiman Smer
Journal: Circulation (2021)

Introduction: Cardiac shock wave therapy (CSWT) using low-intensity shock waves is a non-invasive therapeutic option in the management of chronic refractory angina. This meta-analysis aimed to review the available studies on CSWT and observe its anti-anginal efficacy. Methods: PubMed, Embase, Cochrane, ClinicalTrials.gov, and Google Scholar were searched for studies evaluating the efficacy of CSWT in patients with refractory angina from January 1, 2000, until March, 2021. The primary outcome was the assessment of left ventricular ejection fraction (LVEF) before and after CWST. The secondary outcome was myocardial perfusion before and after CSWT. The analysis was performed using a random-effects-model using the Mantel-Haenszel method and results presented as 95% confidence interval using STATA version 15.1 software. Results: Twenty-four studies (20 observational and 4 Controlled Trails) with a total of 503 patients were included in the meta-analysis. The mean age was 64.92 ± 9 years and 25% were females. In patients undergoing CSWT, left ventricular ejection fraction improved significantly in patients undergoing CSWT (SMD: 0.31, 95% CI: 0.14 to 0.48, P = 0.0003, I 2 = 41%, Figure 1B). Likewise, myocardial perfusion improved significantly in patients undergoing CSWT (SMD: 0.74, 95% CI: 0.39 to 1.090, P = &lt;0.05, I 2 = 84%, Figure 1A). Conclusions: Based on our results, CSWT is a promising noninvasive modality for the management of refractory angina in patients with stable coronary artery disease and on optimal medical therapy.
Efficacy of a third BNT162b2 mRNA COVID-19 vaccine dose in patients with CLL who failed standard 2-dose vaccination
Authors: Yair Herishanu, Galia Rahav, Shai Levi, Andrei Braester, Gilad Itchaki, Osnat Bairey, Najib Dally, Lev Shvidel, Tomer Ziv-Baran, Aaron Polliack, Tamar Tadmor, Ohad Benjamini
Journal: Blood (2021)