tbuckley/cabot-search huggingface dataset:
Abstract 9868: Novel Oral Anticoagulants versus Vitamin K Antagonists in Patients with Atrial Fibrillation and Bioprosthetic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Muhammad Memon, Emaan Amin, Asad Ali Siddiqui, Waqar Eisha, Faisal Asma, Mohammad Khan, Abdul Minhas
Journal: Circulation (2021)

Background: Vitamin K antagonists (VKAs) such as warfarin are traditionally prescribed in patients with atrial fibrillation (AF) and bioprosthetic valves (BPVs) to prevent thromboembolic events. However, various studies have proposed novel oral anticoagulants (NOACs) as an effective and safer option to use. Therefore, we conducted a systematic review and meta-analysis to compare their relative efficacy and safety profiles. Methods: Pubmed, Cochrane Central, and Embase were searched up until May 15, 2021 for randomized clinical trials (RCTs) and observational studies determining efficacy and safety of NOACs or VKAs in AF patients who had undergone BPV replacement. Outcomes of interest were: stroke or systemic embolism (SSE), major bleeding, all-cause mortality, and intracranial hemorrhage (ICH). Subgroup analysis by study design (RCT and observational) was performed. Summary estimates were reported as random effects risk ratios (RRs) with 95% confidence intervals (CIs). Results: A total of 12 studies (4 RCTs and 8 observational) with 6436 patients (mean age 72.1 years; 51.4% males) were included in the analysis. In comparison to VKAs, NOACs demonstrated a significant reduction in ICH (RR 0.41 [95% CI 0.25,0.67]; p=0.0003; I 2 = 0%) and major bleeding (RR 0.63 [95% CI 0.53,0.74]; p&lt;0.00001; I 2 = 0%) at a mean duration follow up of 23.8 months. However, no difference was observed in risk of SSE (RR 0.77 [95% CI 0.50,1.19]; p=0.23; I 2 = 53%) and all-cause mortality (RR 0.98 [95% CI 0.78,1.22]; p=0.84; I 2 = 15%). Observational studies and RCTs did not significantly differ across all outcomes in the subgroup analysis. Conclusions: This meta-analysis suggests that NOACs are effective at reducing risk of ICH and major bleeding in AF patients with BPVs in contrast to VKAs. Future large-scale RCTs can aid in corroborating the legitimacy of these results.
Abstract 13751: Association Between Demographics of Cardiovascular Disease Fellowship Program Directors and Fellow Recruitment: Insights From Association of American Medical Colleges Database
Authors: Ankur Kalra, Monil Majmundar, Ashish Kumar, Jeff D Foley, Bharat Rawlley, vishali moond, Sneha Kandi, Itohan Aikhionbare, Sanjana Datla, Meghana Chanamolu, Harshvardhan Zala, Khurram Nasir, Rishi Puri, Samir R Kapadia, Grant W Reed, Venu Menon
Journal: Circulation (2021)

Introduction: We sought to investigate trends in cardiovascular (CV) disease fellows’ demographic characteristics over the past decade, and the association between fellow recruitment and demographics of fellowship program directors (PD). Methods: We procured de-identified demographic data pertaining to first-year CV fellows and fellowship PDs from the Association of American Medical Colleges from 2010-2019 and 2019/2020. In the cross-sectional study, we analyzed trends in demographics of fellow recruitment using the Jonckheere-Terpstra trend test, and the association between demographics of fellows and PDs using multivariate logistic regression. We used fellow characteristics such as age, gender, medical school, US citizenship, fellowship program location, and PD gender in the multivariate model. Results: We included 9,153 fellows from 243 fellowship programs from 2010 to 2019. The characteristics of demographics of fellows and their trends are extrapolated in Figure . We found an increasing trend of female fellows (p=0.003), and fellows with non-US citizenship (p=0.021), and a declining trend of fellows with Asian ethnicity (p for trend 0.033) without a change in trends for other races. There was an association between race of PD and fellow recruitment [White: adjusted odds ratio (aOR) (95% confidence interval (CI)): 1.30 (1.19-1.43), p&lt;0.001; Black: aOR (95% CI): 2.03 (1.22-3.39), p=0.007; Asian: aOR (95% CI): 1.29 (1.17-1.42), p&lt;0.001; Hispanic: aOR (95% CI): 4.14 (3.18-5.39), p&lt;0.001]. Conclusions: Over ten years in CV fellowship recruitment, fellows’ demographic profiles have changed; however, the racial profile has remained constant. We found an association between the race of fellowship PDs and their respective fellow recruitment, irrespective of the type of race/ethnicity.
INNV-11. COMPLETE RESPONSE TO SELPERCATINIB IN A PATIENT WITH RECURRENT GLIOBLASTOMA AND RET AMPLIFICATION
Authors: Ashley Chen, Cameron Czech, Katherine Morgan, Simon Khagi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Glioblastoma (GBM) is a malignant central nervous system tumor that remains largely incurable. Limited treatment options currently exist after disease progression on the standard of care first-line therapy. However, repurposing the use of approved therapies in patients with potentially targetable genomic alterations continues to be an emerging area of interest. Here, we present the first reported case of a patient with isocitrate dehydrogenase wild-type GBM with an underlying RET amplification who demonstrated a near-complete response (CR) while receiving therapy with the targeted RET inhibitor, selpercatinib. CLINICAL PRESENTATION A 48-year-old male with no significant past medical history presented with sudden onset of dizziness and confusion. Magnetic resonance imaging (MRI) revealed two rim enhancing lesions in the right parietal lobe and the patient underwent surgical resection with subsequent pathology revealing a GBM. Genomic analysis identified a RET amplification. After standard adjuvant therapy, the patient was treated with selpercatinib 160 mg twice daily as a continuous regimen with near CR on MRI after six weeks of treatment. The patient was continued on therapy for a total of eight months before having disease progression requiring discontinuation of selpercatinib and was then transitioned to the next line of therapy for disease stabilization. To better characterize the response, further whole-exome sequencing and analysis were performed on the original specimen. CONCLUSION Although selpercatinib is approved in RET-fusion positive lung and thyroid cancer, we present a remarkable case of a recurrent, RET-amplified GBM having a CR to selpercatinib. The case highlights the excellent blood-brain barrier penetration of selpercatinib, as well as its potential role in RET-amplified GBM. Larger biomarker-enriched studies are needed to confirm the results of this case report. However, given the rare incidence of RET alterations in GBM, findings from this report can help guide and support optimal treatment strategies for patients with RET-altered GBM.
The Impact of IDH1c.315C&amp;gt;T Single Nucleotide Polymorphism on Outcomes in Acute Myeloid Leukemia: A Propensity Score-Adjusted Cohort Study
Authors: Elizabeth Corley, Moaath Mustafa Ali, Hanan Alharthy, Kathryn Kline, Danielle Sewell, Jennie Y. Law, Seung Tae Lee, Sandrine Niyongere, Vu H. Duong, Maria R. Baer, Ashkan Emadi
Journal: Blood (2021)
Abstract 13540: Quantifying the Respiratory Effort From Right Heart Catheterization Can Assist in Evaluating Heart Failure Severity
Authors: Noa Markovitch, Shmuel Rispler, Yair Feld, Amir Solomonica, Sergey Yalonetsky, Anees Musallamis, Ariel Roguin, Arthur Kerner, Amir Landesberg
Journal: Circulation (2021)

Introduction: Right heart catheterization (RHC) provides objective assessment of heart failure (HF) severity. However, it is strongly affected by respiratory fluctuations, therefore various methods were suggested to correct these fluctuations. In contrast, we hypothesized that measurement of the respiratory effort in addition to the standard indices provides additional valuable information. Moreover, it can assist in the interpretations of the standard indices. Methods: We simultaneously measured the hemodynamic and respiratory indices in HF patients undergoing RHC. The pulmonary wedge pressure (PCWP) is modulated by the changes in the intrathoracic pressure. The latter is determined by the respiratory effort. To quantify the respiratory effort, the PCWP was decomposed into cardiac and respiratory waves. The respiratory effort (P RESP ) was defined as the peak to peak amplitude of the respiratory wave that modulated the PCWP. Results: HF patients (N=45) exhibited a high P RESP of 9.1±5.3 mmHg, ~3.5-fold higher than the reported normal respiratory modulations, while they are lying and at rest [Range: from 2.0 mmHg to 23.3 mmHg]. In some patients the P RESP exceeded the amplitude of cardiac `a` and `v` waves. The difference between end expiratory PCWP (PCWP EE ) and mean PCWP increased linearly with P RESP , by slop of 0.380±0.001 (R 2 = 0.76, p&lt;0.001). The end expiratory PCWP rose with P RESP , by 0.68±0.05 mmHg for every 1 mmHg of P RESP (p&lt;0.01). Interestingly, identical changes in the PCWP with P RESP were obtained in all the patients, independently of the HF etiology. The P RESP sheds light on the severity of dyspnea. It enables simple and precise evaluation of the PCWP EE from regular breathing. Lung congestion severity is determined by the transmural gradient between the intravascular pressure and the tissue surrounding pressure. Correction for P RESP yields more accurate evaluation of this transmural pulmonary vascular pressure. Conclusions: P RESP provides additional essential dimension on the severity of dyspnea and HF. It simplifies the measurement method and enables to derive the PCWP EE . The latter deviates from the mean PCWP in cases of severe dyspnea. It assists in evaluating the real transmural pulmonary vascular pressure.
Validation of <i>NMT1</i> and <i>NMT2</i> As Novel Drug Targets in Adult Acute Myeloid Leukemia: Rationale for N-Myristoyltransferase Inhibition with Pclx-001 for Clinical Trials
Authors: Jay Gamma, Aishwarya Iyer, Megan Yap, Zoulika Zak, Krista Vincent, Cassidy Ekstrom, Erwan Beauchamp, Lynne Postovit, John R. Mackey, Naveen Pemmaraju, Gautam Borthakur, Joseph Brandwein, Luc G. Berthiaume
Journal: Blood (2021)
Abstract 10752: Clinical Predictive Models for Cardiovascular Disease Should Adjust for Race, Ethnicity and Social Determinants of Health to Inform More Equitable Interventions: Findings from a Targeted Review
Authors: Jane L Snowdon, Elisabeth L Scheufele, Jill Pritts, Phuong-Tu Le, Xinzhi Zhang, Irene Dankwa-Mullan
Journal: Circulation (2021)

Introduction: Clinical models of cardiovascular disease (CVD) that incorporate relevant predictors can provide powerful insights into the complex, inter-related mechanisms of CVD pathophysiology, risk for adverse outcomes, and correlations with social determinants of health (SDoH) to inform practice guidelines and targeted interventions. Despite the growing body of evidence demonstrating the role of race, ethnicity and SDoH on CVD outcomes, limited evidence exists about incorporating these factors into models. Hypothesis: We assessed the hypotheses that clinical predictive studies on CVD risk, outcomes, prognosis and treatment interventions: (1) do not fully examine race, ethnicity and SDoH factors, and (2) may not leverage adequate data sources fully representative of a population of interest or may lack the decisional context to ensure robustness. These are critical limitations that could lead to inaccurate predictions, perpetuating bias and ultimately health and racial inequities. Methods: This targeted literature review yielded 533 potentially relevant PubMed articles (2018-2019) after duplicate removal. Article titles and abstracts were reviewed for eligibility where 375 met the exclusion criteria (age &lt;18 years old, outside North America, no clinical outcomes, language non-English) and were removed. The remaining 158 potentially relevant articles were screened and 116 met the criteria for exclusion (e.g. stroke, heart transplant). After screening, 42 citations were identified for full-text screening, of which 35 articles met criteria for inclusion. Results: Studies employed advanced statistical and machine learning methods to predict CVD risk (10/29%), mortality (19/54%), survival (7/20%), complication (10/29%), disease progression (6/17%), functional outcomes (4/11%) and disposition (2/6%). Most studies incorporated sex (34/97%), co-morbid conditions (32/91%), and behavioral risk factor (28/80%) variables. Race/ethnicity (23/66%) and SDoH variables (e.g. education (3/9%)) were less frequently observed. Conclusions: In conclusion, clinical risk and predictive models often do not adjust for or consider race, ethnicity and SDoH to improve model accuracy to inform more equitable interventions and decision-making.
Abstract 12015: Inflammation of SARS-CoV2-infected Human Pluripotent Stem Cell-Derived Cardiomyocytes and the Effects and Side Effects of Remdesivir
Authors: Sangsung Kim, Minwoo Kim, In Ho Park, SeongHo Bae, Zandi Keivan, Eun-Jeong Yang, Kyuwon Cho, Sung-Rae Cho, James Kohler, Baek Kim, Raymond F Schinazi, Jong-Won Oh, Jeon-Soo Shin, Young-sup Yoon
Journal: Circulation (2021)

Introduction: The global pandemic of the coronavirus 2019 disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to respiratory failures, COVID-19 patients exhibited cardiac complications. Studies observed the direct infection and replication of SARS-CoV2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) accompanied by cytopathic effects. However, the underlying mechanisms of SARS-CoV-2-mediated CM death remain poorly understood. In addition, the therapeutic potential of remdesivir (RDV) on CMs has yet to be answered. Methods and Results: We confirmed that SARS-CoV-2 is infectious to and effectively replicates in hPSC-CMs and is cytopathic to hPSC-CMs. We also found that RDV effectively inhibited viral replication at a concentration of 50 nM. RNA-seq analyses demonstrated that expression of immune responsive genes was elevated in SARS-CoV-2 infected hPSC-CMs. Immunostaining and an ELISA assay further revealed formation of inflammasomes and secretion of inflammasome-mediated cytokines, such as IL-1β, IL-18, and IL-6 in SARS-CoV-2 infected hPSC-CMs. RNA-seq analyses showed gene profile changes in SARS-CoV-2 infected hPSC-CMs corroborating with activation of inflammatory signals and cell death pathways. While gene profiles of 0.1 μM RDV-treated SARS-CoV-2-infected hPSC-CMs showed reversal of such changes, a high dose (10 μM) RDV-treated CoV-2-infected hPSC-CMs showed changes in 44% of genes expressed compared to non-RDV-treated CoV2-infected hPSC-CMs. Among those, expression of protein stability related genes, such as genes associated with autophagy and protein ubiquitination increased while expression of antiviral responsive genes decreased. In addition, a high dose of RDV inhibited expression of mitochondrial genes, particularly MitoComplex I and V compositions, which are related to energy production. Conclusions: This study demonstrates that SARS-CoV2 induced inflammasome in hPSC-CMs, which can underlie cardiac damage in addition to direct cytopathic effects. In addition, RDV can reduce inflammasome when introduced early after SARS-CoV2 infection while a high-dose can aggravate cytopathic effects by potential toxicity to mitochondria.
Bystander interventions and survival after exercise-related sudden cardiac arrest: a systematic review
Authors: Nicholas Grubic, Braeden Hill, Dermot Phelan, Aaron Baggish, Paul Dorian, Amer M Johri
Journal: British Journal of Sports Medicine (2021)

To evaluate the provision of bystander interventions and rates of survival after exercise-related sudden cardiac arrest (SCA).Systematic review.MEDLINE, EMBASE, PubMed, CINAHL, SPORTDiscus, Cochrane Library and grey literature sources were searched from inception to November/December 2020.Observational studies assessing a population of exercise-related SCA (out-of-hospital cardiac arrests that occurred during exercise or within 1 hour of cessation of activity), where bystander cardiopulmonary resuscitation (CPR) and/or automated external defibrillator (AED) use were reported, and survival outcomes were ascertained.Among all included studies, the median (IQR) proportions of bystander CPR and bystander AED use, as well as median (IQR) rate of survival to hospital discharge, were calculated.A total of 29 studies were included in this review, with a median study duration of 78.7 months and a median sample size of 91. Most exercise-related SCA patients were male (median: 92%, IQR: 86%-96%), middle-aged (median: 51, IQR: 39-56 years), and presented with a shockable arrest rhythm (median: 78%, IQR: 62%-86%). Bystander CPR was initiated in a median of 71% (IQR: 59%-87%) of arrests, whereas bystander AED use occurred in a median of 31% (IQR: 19%-42%) of arrests. Among the 19 studies that reported survival to hospital discharge, the median rate of survival was 32% (IQR: 24%-49%). Studies which evaluated the relationship between bystander interventions and survival outcomes reported that both bystander CPR and AED use were associated with survival after exercise-related SCA.Exercise-related SCA occurs predominantly in males and presents with a shockable ventricular arrhythmia in most cases, emphasising the importance of rapid access to defibrillation. Further efforts are needed to promote early recognition and a rapid bystander response to exercise-related SCA.
Abstract MP264: Heterogeneous Distribution Of Mutations In Myosin Binding Protein-c Paralogs
Authors: Darshini a Desai, Vinay Rao, Anil Jegga, Perundurai Dhandapany, Sakthivel Sadayappan
Journal: Circulation Research (2021)

Rationale: Myosin binding protein-C ( MYBPC ) is a sarcomeric protein which regulates the force of contraction in striated muscles. Mutations in the MYBPC family of genes, slow skeletal( MYBPC1 ), fast skeletal ( MYBPC2 ) and cardiac ( MYBPC3 ) can result in cardiac and skeletal myopathies, yet their evolutionary pattern, pathogenicity and impact on MYBPC structure remain to be elucidated. Objective: To assess conserved and epigenetic patterns of MYBPC family mutations. Methods and Results: Leveraging a machine learning approach, the Genome Aggregation Database (gnomAD) provided 12353, 6227 and 5279 variants in MYBPC1 , MYBPC2 and MYBPC3 genes, respectively, followed by analysis with the Ensembl variant effector predictor. Missense variants comprised 62-68% of total variants in which the first and second nucleotide (nt) positions in the codons were highly altered, with G/A substitution nt substitution the most predominant. Arginine was the most mutated amino acid, important because most disease-causing mutations in MYBPC are arginine in origin. Domains C5 and C6of MYBPC were found to be hotspots for most mutations in the MYBPC family. A high percentage of truncated mutations in MYBPC3 cause cardiomyopathies. Arginine and glutamate were the top hits in MYBPC1 and MYBPC3, respectively, and tryptophan and tyrosine were the most common among the three paralogs changing to premature stop codons and causing protein truncations at the carboxy terminus. Conclusion: A heterogeneous epigenetic pattern was identified among the three MYBPC paralogs. Genomic databases using machine learning approaches can be used to diagnose and design therapeutics to treat muscle disorders caused by MYBPC mutations.
Abstract 12935: Lack of Correlation Between Echocardiographic Parameters and Cardiac Hemodynamics in Patients With Severe Aortic Stenosis
Authors: Mirna Ragheb, Triston Eastman, Amir Ravandi, Malek Kass, Ashish Shah
Journal: Circulation (2021)

Introduction: Aortic stenosis (AS) affects ~10% of population over 65 years of age. Severe AS is defined as mean trans-aortic pressure gradient (MG) of ≥40 mmHg and/or aortic valve area (AVA) of &lt;1.0 cm 2 . Patients’ symptoms correlate with cardiac output, and the ability to augment with exercise. However, the relationship between AVA/MG and stroke volume/cardiac output is not well defined. Hypothesis: We aimed to identify the relationship between conventional echocardiography-based parameters (i.e., AVA/MG) and non-echocardiography-based hemodynamics in AS. Methods: Consecutive patients with severe symptomatic AS undergoing TAVI between June and September 2020 at St. Boniface Hospital in Manitoba, Canada were recruited. Hemodynamics was measured using whole-body impedance-based Non-Invasive Cardiac System (NICaS). Evaluated hemodynamics include stroke volume index (Svi), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) and were compared to conventional parameters. Results: Thirty patients (37% females; mean age 79.0 ± 1.7 years) were enrolled. Average MG was 41.8 ± 2.2 mmHg (16.94 - 70.0) and mean AVA was 0.81 ± 0.04 cm 2 (0.30 - 1.10). A linear regression model revealed a poor correlation between AVA and both Svi and CI (r 2 =0.012 and 0.025, respectively). Similarly, MG correlated poorly with Svi and CI (r 2 =0.017 and 0.024, respectively). Interestingly, 60% patients displayed a low-flow state (defined as Svi &lt;35 ml/m 2 ), despite a normal left ventricular ejection fraction (EF &gt;50%, r 2 =0.011). Conclusions: There is incongruence between hemodynamics and conventional parameters defining severe AS. A subset of patients have low-flow state, despite normal left ventricular function. It is plausible that some of these patients, based on their hemodynamics, may benefit from valvular intervention earlier, even at a lower MG. Long-term hemodynamic assessment may guide identification of outcomes in AS patients post-TAVI.
Immune Checkpoint Analysis of T Effectors and Regulatory T Cells in Patients with CML Reveals Increased Expression at Diagnosis and with Refractory Disease
Authors: Patrick Harrington, Richard Dillon, Deepti H. Radia, Donal P. McLornan, Claire Woodley, Susan Asirvatham, Kavita Raj, Natalia Curto-Garcia, Shahram Kordasti, Claire N. Harrison, Hugues de Lavallade
Journal: Blood (2021)
Abstract 10565: A Systematic and Reliable Process for Performing Cost Containment Analysis within the Operating Room
Authors: Joseph R Nellis, Neel Prabhu, James M Meza, Nicholas D Andersen, Joseph W Turek
Journal: Circulation (2021)

Purpose: Healthcare spending within the United States increased 4.6% in 2019 and represented over $3.8 trillion, or 17.7% of our GDP. The operating margin for most hospitals is 1-3%. As costs continue to rise, insurers will continue to shift these financial risks and responsibilities onto hospitals and hospitals eventually onto surgeons. Methods: Using a recently introduced surgical receipt function within Epic, we set out to develop cost containment strategies within congenital cardiac surgery at Duke University Hospital. Surgical receipt data was obtained between January 1, 2020 and January 1, 2021. Variability in case costs and product utilization were identified. Findings were discussed with surgeons to identify high impact changes with low barriers to implementation. Results: Between January 1, 2020 and January 1, 2021, there were 340 index cases and 449 unique surgical receipts. Four procedures representing 54 patients accounted for more than 50% of the total annual direct operating room supply costs (LVAD, 5 patients, 22.7% of annual costs; Norwood, 20 patients, 12.7%; RV-PA shunt, 16 patients, 9.9%; PVR, 13 patients, 9.4%). Exploration chest for postoperative hemorrhage was associated with the highest variability in case cost. In addition to mechanical devices and valves, cost drivers included the use of disposable vascular clips, suture brand preference between surgeons, and surgical patch material utilization which accounted for 3.7%, 6.6%, and 26.5% of overall annual direct operating room supply costs. Conclusions: We project 6-6.5% in annual savings due to changes in suture and surgical clip utilization. Changes to surgical patch utilization should carry an additional 4-4.5% in savings. The surgical receipt represents a reliable and uniform way of reporting surgical costs with broader implications for all surgical subspecialties.