tbuckley/cabot-search huggingface dataset:
Abstract 12395: Nitroglycerin Reduces Pulsatile Arterial Load But Not Steady State Load In Aortic Stenosis Patients Before Or After Transcatheter Aortic Valve Implantation
Authors: Ning Song, Audrey Adji, Sara Hungerford, Mayooran Namasivayam, Christopher S Hayward, Andrew Jabbour, David Muller
Journal: Circulation (2021)

Background: Pulsatile arterial load is represented by the characteristic impedance (Zc) of the ascending aorta. In aortic stenosis (AS) patients, Zc is thought to contribute significantly to left ventricular afterload in addition to aortic transvalvular gradient. We evaluated the effect of nitroglycerin, a potent vasodilator, on Zc non-invasively in AS patients before or after transcatheter aortic valve implantation (TAVI). Methods: Simultaneous aortic pressure from radial arterial tonometry and flow from cardiac magnetic resonance phase contrast imaging were obtained. Radial waveforms were converted to central aortic pressure using SphygmoCor 8.1 (AtCor Medical) and calibrated using brachial cuff values. Zc was derived from aortic pressure and flow by averaging the impedance modulus in frequency domain analysis. Data acquisition was repeated after administration of 300 micrograms of sublingual nitroglycerin to investigate its effect on pulsatile and steady state load. Results: Analysis was performed in 9 AS patients (3 female, age 68-81 years) with a left ventricular ejection fraction &gt; 55%, of whom 5 had undergone recent TAVI. When compared with baseline measurements, nitroglycerin reduced mean arterial pressure (107 ± 11 pre vs 87 ± 5 post, mmHg), central pulse pressure (67 ± 15 pre vs 48 ± 13 post, mmHg), forward stroke volume (83 ± 15 pre vs 70 ± 13 post, ml) and Zc (129 ± 42 pre vs 95 ± 32 post, dynes.cm/s 5 ). However, there was no change in compliance or steady state systemic vascular resistance (2163 ± 445 pre vs 2045 ± 485 post, dynes.cm/s 5 ). Conclusion: Nitroglycerin significantly reduces pulsatile arterial load in AS patients without reducing steady state load. Our non-invasive technique can reliably assess changes in hemodynamic loading conditions, and larger longitudinal paired analysis of nitroglycerin response before and after TAVI may help predict AS patients at risk of poorer outcomes from ventriculo-arterial coupling mismatch following treatment.
A Phase 1/2, Open-Label, Multicenter Study of Isatuximab in Combination with Cemiplimab in Patients with Lymphoma
Authors: Carmelo Carlo-Stella, Pier Luigi Luigi Zinzani, Anna Sureda, Luís Francisco Araújo, Olivier Casasnovas, Cecilia Carpio, Su-Peng Yeh, Krimo Bouabdallah, Guillaume Cartron, Won Seog Kim, Raul Cordoba, Youngil Koh, Alessandro Re, Daniela Alves, Martine E.D Chamuleau, Steven Le Gouill, Armando Lopez-Guillermo, Maria Ilidia Moreira, Marjolein W.M. Van Der Poel, Giovanni Abbadessa, Robin Meng, Ran Ji, Lucie Lepine, Rao Saleem, Vincent Ribrag
Journal: Blood (2021)
Abstract 14396: Cardioprotective Effects Of Glycyrrhizin On Hyperglycemic Cardiac Tissues
Authors: Munmun Chattopadhyay, Vikram Thakur, Binata Joddar
Journal: Circulation (2021)

Introduction: Myocardial fibrosis and dysfunction is one of the major cardiac complications of long-term diabetes. Prolonged hyperglycemia is known to induce myocardial dysfunction often leading up to heart failure. Hypothesis: The objective of this study was to investigate the cardioprotective effect of glycyrrhizin (GLC) on myocardial damage in engineered in-vitro human cardiac tissues. Engineered 3D tissue chips present an ideal microenvironment via therapeutically relevant interfaces to study molecular- and cellular-level events and mimic human-specific disease states, and identify new therapeutic targets in vitro. Methods: AC16 human cardiomyocyte cells were used to 3D bioprint cardiac tissue chips based on prior published work. In our study, the 3D bioprinted cardiac tissue chips (CTC) were cultured using normo- (5mM) and hyper-glycemic (25mM) conditions for up to 48 hrs. For the GLC treatment group, a subset of CTC cultured using hyperglycemic conditions were treated with 50 mM of GLC for 24 hours. Results: CTC cultured under hyperglycemic conditions demonstrated altered levels of connexin-43 (CX43) and Troponin-I implying cardiomyocyte injury. Exposure to hyperglycemia revealed changes in epigenetic markers: histone methylation marker (H3K9me)-1, Sirtuin-1, and Histone Deacetylase (HDAC)-2 as well as in inflammatory and stress related mediators such as heat shock protein (HSP)-60, receptor for advanced glycation end products (RAGE), toll like receptor (TLR)-4, high mobility group box (HMGB)-1 and CXC chemokine receptor (CXCR)-4. CTC exposed to 25mM glucose for 24 hours resulted in the downregulation of HSP60 and Sirtuin-1. Prolonged exposure to hyperglycemia led to decrease in the expression of CX43 and CXCR4; thereby adversely affecting cardiomyocyte function. Upregulated expression of DNA-binding nuclear protein HMGB1 along with changes in H3K9me1 indicated long-term hyperglycemia-induced damage to cardiomyocytes. GLC treated CTC exhibited a decrease in the expression of RAGE, TLR4 and also demonstrated altered expression of CX43, CXCR4, and troponin I. Conclusions: This study suggests that GLC possesses cardioprotective effects in human cardiomyocytes exposed to prolonged hyperglycemia.
Abstract 11240: Capillary Rarefaction and Right Ventricular Dysfunction in Advanced HFrEF: Human Tissue Histomorphometry Analysis
Authors: Vojtech Melenovsky, Tomas Kucera, Tomas Mracek, Tereza Havlenova, Vilma Kaplanova, Krystina Cunatova, Jan Benes, Aneta Pierzynova, JaromÃr Å rÃ¡mek, Josef Kautzner
Journal: Circulation (2021)

Introduction: Right ventricular dysfunction (RVD) limits survival in heart failure (HF). Besides pulmonary hypertension (PH), load-independent mechanisms may contribute to RVD. In experimental PH, loss of myocardial capillary density (rarefaction) was implicated in the faster decline of RV function. Hypothesis: To elucidate the role of rarefaction in development of RVD in HFrEF. Methods: We examined RV fractional area change (RV FAC%) prior heart Tx (median -57 days) in 124 consecutive HTx candidates (non-LVAD) and harvested RV free wall at HTx from patients in the bottom (Q1: 10-17%) and top (Q4: 32-42%) quartiles of pre-HTx RV FAC%. As controls (Con), we obtained RV samples from 20 unused heart donors. Quantitative histomorphometry and mRNA gene expression were studied. Results: HF (65% non-ischemic) and Con were matched by similar age, gender and BMI. HF patients had larger and more dysfunctional RV (RVD1 46 vs 32 mm, p&lt;0.001, RV FAC 25±10%). Compared to Con, RV from HF displayed significant upregulation of genes for PDK4 (Pyruvate Dehydrogenase Kinase4), NPPA (Natriuretic peptide A), BDH1 (β-OH-butyrate dehydrogenase), and downregulation of MYH6 (Myosin Heavy Chain 6). In HF vs Con, RV CM diameter was increased (25±6 vs 15±4 μm, p&lt;0.001), but RV capillary density was lower (939±474 vs 1457±670 n/mm -2 , p=0.007), even if adjusted to CM diameter (39 vs 102 mm -1 , p=0.0005) or area (Fig). HF patients from Q1 and Q4 RV FAC differed by higher PH (mPA 37 vs 31 mmHg, p=0.01), larger RV size (48 vs 43 mm, p=0.01) and higher PCWP (27 vs 22, p=0.002), but there was no difference in capillary density (unadjusted or per CM diameter/area, Fig) or gene expression profile, HF etiology or comorbidities. Conclusions: Compared to Con, RV of HF patients shows reduced capillary density, metabolic and myofilament remodeling. Yet, HF patients with lower RV FAC% do not differ from those with less impaired RV function, suggesting that capillary rarefaction per se does not explain progression of RVD in HF.
Abstract 10844: Integration of Electronic Health Records with Genetics: Burden of Arrhythmia Phenotypes in Monogenic Electrophysiologic Disorders
Authors: Navid A Nafissi, Jawan Abdulrahim, CAROL HAYNES, William E Kraus, Jonathan P Piccini, James P Daubert, Albert Sun, Lydia Kwee, Svati H Shah
Journal: Circulation (2021)

Background: Monogenic disorders are relatively common in aggregate, affecting 1/40 individuals, but are underdiagnosed. Electronic health records (EHR) integrated with population-based genetic sequencing provides an opportunity to study the prevalence and penetrance of these disorders. We integrated EHR records with genetic sequencing and identified clinical phenotypes in carriers of rare variants in arrhythmia-related genes. Methods: Whole exome sequencing was performed on 8,783 individuals from the CATHGEN cohort, a study of sequential individuals undergoing cardiac catheterization at Duke University. Variants in 47 arrhythmia-related genes were identified and assessed for pathogenicity using the ClinVar database. ACMG criteria were applied to define pathogenic/likely pathogenic (P/LP) variants. Individuals carrying a P/LP variant were grouped by electrophysiologic (EP) disorder and matched 1:5 to noncarriers based on age, sex, and race. Individuals with other P/LP cardiovascular disease variants or variants of unknown significance in arrhythmia-related genes were excluded. Phenotypic data were annotated through curated and manual EHR review. Results: Forty P/LP variants in 10 arrhythmia-related genes were identified in 51 individuals. In the arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), and long QT syndrome (LQTS) groups, P/LP variant carriers met diagnostic criteria in 33%, 0%, and 4% of carriers, respectively. In the LMNA -related dilated cardiomyopathy (LMNA) group, 83% of variant carriers were phenotype positive. ECG findings alone were significantly different in variant carriers compared with noncarriers in the ARVC, BrS, and LQTS groups, whereas clinical outcomes including heart transplantation and ventricular tachycardia were significantly different in the LMNA group. Interestingly, clinical features associated with EP disorders, such as syncope and ICD implantation, were not significantly different between variant carriers and noncarriers in any group. Conclusions: Based on EHR review, P/LP variants in arrhythmia-related genes among individuals referred for cardiac catheterization are associated with variable phenotypic expression in different EP disorders.
Abstract 14143: In-Hospital Outcomes of Left Ventricular Assist Device Implantation in Patients With Heart Failure and Connective Tissue Disease
Authors: Jelani Grant, Rafael Hernandez, Juliann Gilchrist, Jennifer Maning, Louis T Vincent, Bertrand Ebner, Odunayo Olorunfemi, Rosario A Colombo
Journal: Circulation (2021)

Introduction: The use of left ventricular assist devices (LVAD) for patients with end-stage heart failure (HF), either as a bridge to transplant or destination therapy, continues to grow. Optimal patient selection is essential to decrease the risk of adverse events. The aim of our study was to evaluate outcomes of LVAD in patients with HF and connective tissue disease (HF-CT). Methods: Using the National Inpatient Database (NIS) we identified patients 18 years and older hospitalized for index LVAD procedure from 2016 to 2018. Patients were stratified according to CT disorder status. The primary outcome of interest was in-hospital mortality. Secondary outcomes included the need for renal replacement therapy (RRT), post-operative infection, stroke, and transfusion requirements. A multivariate regression analysis model was used to adjust for statistically significant differences in baseline characteristics between the groups. Results: A total of 30,206 patients underwent LVAD implant, of these 240 (0.8%) had CT disease. HF-CT patients were more likely to be female (47.5% vs 23.2%, p &lt; 0.001), less likely to have pulmonary hypertension (12.5% vs 21.1%, p = 0.001) and liver disease (2.2% vs 9.5%, p &lt; 0.001); and more likely to have anemia (18.4% vs 12.2%, p = 0.009). There was no significant difference in in-hospital mortality (8.3% vs 11.9%, p = 0.090). Unadjusted incidence of stroke (21.1% vs 7.4%, p = 0.002) and renal replacement therapy (2.1% vs 6.7%, p =0.090) was lower for HF-CT patients. However, this difference was not related to the presence of CT disease on multivariate analysis. Conclusions: While some studies have raised concerns of increased adverse events among patients with HF-CT undergoing LVAD implant, our analysis showed that in-hospital survival and short-term post-operative outcomes of HF-CT patients appear to be comparable to patients without CT disease. A clinical history of CT disease by itself should not preclude patients from undergoing LVAD implant.
Abstract 10353: Independent Validation of the Ecg Risk Score for Sudden Death Risk Stratification in Pediatric Hypertrophic Cardiomyopathy
Authors: Anna Walinder Osterberg, Virginie Beausejour-Ladouceur, Elizabeth A Stephenson, Seema Mital
Journal: Circulation (2021)

Background: Hypertrophic cardiomyopathy (HCM) is the leading cause of sudden cardiac death (SCD) in children and young adults. An ECG risk score tested in a Swedish cohort of 155 children with HCM had 97% sensitivity, 80% specificity, 45% positive predictive value (PPV), and 99% negative predictive value (NPV) for SCD risk prediction. Our goal was to validate the ECG risk score in an independent HCM cohort. Methods: Phenotype-positive pediatric HCM patients seen at a single center between 1987-2019 with at least 5 years follow-up from diagnosis, or a SCD event within 5 years of diagnosis, were retrospectively identified. First-evaluation ECGs were analyzed by a single operator blinded to patient outcomes. ECG risk score was calculated using QRS electrical axis, amplitude, duration, ST/T-wave abnormalities and QTc duration. The primary outcome was a composite of SCD, aborted sudden cardiac arrest, and appropriate shock from a prophylactic ICD. Results: Of 144 eligible patients with a median follow-up 14.6 yrs, 22 experienced SCD events within five years from diagnosis at a median age 12.1 yrs. The ECG risk score in patients experiencing a SCD event was 2-fold higher i.e. 8 (IQR 7-10) compared to the remaining cohort i.e. 4 (IQR 2-8) (p&lt;0.001). An ECG risk score &gt;5 had a sensitivity of 95% (CI 77%-100%), specificity 56% (46%-65%), PPV 28% (24%-33%), NPV 99% (91%-100%), and a receiver operating characteristic area under the curve of 0.76 for its ability to discriminate between patients with and without SCD events ( Figure 1 ). Compared to the discovery cohort, the score had strong sensitivity and NPV, but lower specificity and PPV. Conclusions: The ECG risk score for SCD risk stratification performed well in an independent Canadian validation cohort but overestimated SCD risk. Futher analysis will determine if inclusion of the ECG risk score can enhance the performance of currently available SCD risk prediction models for pediatric HCM.
Abstract 9456: Changes in Cardiovascular Health During Young Adulthood and Subclinical Atherosclerosis in Middle Age
Authors: xiaomin ye, zhenyu xiong, Xiaodong Zhuang, Xinxue Liao
Journal: Circulation (2021)

Introduction: The benefits of reaching ideal cardiovascular health (CVH) is well known, but it is unclear whether positive CVH changes form young adulthood to middle age reduces subclinical atherosclerosis risk. Hypothesis: This study examined whether changes in CVH form young adulthood to middle age was associated with subclinical atherosclerosis. Methods: Data was analyzed from the Coronary Artery Risk Development in Young Adults (CARDIA) study. CVH was examined at Year 0 and 20 using 7 metrics (smoking, body mass index, diet, physical activity, blood pressure, fasting glucose, total cholesterol), each categorized as high (12 to 14 points), moderate (8 to 11) and low (0 to 7). Coronary artery calcium (CAC) was identified at Year 20 and 25. Carotid intima-media thickness (IMT) was identified at Year 20. Results: Among 2935 participants (56.2% women, 46.7% black), change of CVH metrics was -1.26 (2.13). For per 1-unit increase in CVH changes, the adjusted odds ratio of presence of CAC is 0.86 (95% CI 0.82, 0.90) and of IMT is 0.81 (95% CI 0.73, 0.90). Compared with stable moderate CVH, improvement from moderate to high CVH was associated with a lower risk of CAC (OR, 0.64 [95% CI 0.43, 0.96]), while retrogression from moderate to low CVH was associated with a higher risk of CAC (OR, 1.45 [95% CI 1.19, 1.76]). Conclusions: Positive changes of CVH during young adulthood is associated with negative subclinical atherosclerosis risk in middle age, indicating the importance of reaching an ideal cardiovascular health status through young adulthood.
Phase II trial of response-based radiation therapy for patients with localized germinoma: a Children’s Oncology Group study
Authors: Ute Bartels, Arzu Onar-Thomas, Sunita K Patel, Dennis Shaw, Jason Fangusaro, Girish Dhall, Mark Souweidane, Aashim Bhatia, Leanne Embry, Christine L Trask, Erin S Murphy, Shannon MacDonald, Shengjie Wu, James M Boyett, Sarah Leary, Maryam Fouladi, Amar Gajjar, Soumen Khatua
Journal: Neuro-Oncology (2021)

Abstract Background The study aimed to evaluate whether simplified chemotherapy followed by dose-reduced irradiation was effective for treating patients (ages 3–21 years) with localized germinoma. The primary endpoint was 3-year progression-free survival (PFS) rate. Methods Patients with a complete response to chemotherapy with carboplatin and etoposide received 18 Gy WVI + 12 Gy boost to the tumor bed. Patients with partial response proceeded to 24 Gy WVI + 12 Gy. Longitudinal cognitive functioning was evaluated prospectively on ALTE07C1 and was a primary study aim. Results One hundred and fifty-one patients were enrolled; 137 were eligible. Among 90 evaluable patients, 74 were treated with 18 Gy and 16 with 24 Gy WVI. The study failed to demonstrate noninferiority of the 18 Gy WVI regimen compared to the design threshold of 95% 3-year PFS rate, where, per design, patients who could not be assessed for progression at 3 years were counted as failures. The Kaplan-Meier (KM)-based 3-year PFS estimates were 94.5 ± 2.7% and 93.75 ± 6.1% for the 18 Gy and 24 Gy WVI cohorts, respectively. Collectively, estimated mean IQ and attention/concentration were within normal range. A lower mean attention score was observed at 9 months for patients treated with 24 Gy. Acute effects in processing speed were observed in the 18 Gy cohort at 9 months which improved at 30-month assessment. Conclusions While a failure according to the prospective statistical noninferiority design, this study demonstrated high rates of chemotherapy responses, favorable KM-based PFS and OS estimates in the context of reduced irradiation doses and holds promise for lower long-term morbidities for patients with germinoma.
Measurable Residual Disease in Extracellular Vesicles from Bone Marrow and Peripheral Blood of Patients with Multiple Myeloma: A Proof-of-Concept Study
Authors: Rui Bergantim, Mélanie A.G. Barbosa, Sara Peixoto da Silva, Bárbara Polónia, Hugo R. Caires, José E. Guimarães, M. Helena Vasconcelos
Journal: Blood (2021)
Risk factors for mortality in patients with COVID-19 needing extracorporeal respiratory support
Authors: Jordi Riera, Sara Alcántara, Camilo Bonilla, Phillip Fortuna, Aaron Blandino Ortiz, Ana Vaz, Carlos Albacete, Pablo Millán, Pilar Ricart, María Victoria Boado, Pablo Ruiz de Gopegui, Patricia Santa Teresa, Elena Sandoval, Helena Pérez-Chomón, Alfredo González-Pérez, Jorge Duerto, Ricardo Gimeno, Joaquín Colomina, Vanesa Gómez, Gloria Renedo, José Naranjo, Manuel Alfonso García, Emilio Rodríguez-Ruiz, Pedro Eduardo Silva, Daniel Pérez, Javier Veganzones, Roberto Voces, Sergi Martínez, Pablo Blanco-Schweizer, Marta García, Héctor Villanueva-Fernández, María Paz Fuset, Stephani María Luna, María Martínez-Martínez, Eduard Argudo, Luis Chiscano, Roberto Roncon-Albuquerque
Journal: European Respiratory Journal (2021)

<b>When indicating ECMO in patients with COVID-19, centre case volume, age, driving pressure and the duration of symptoms (not the length of MV) should be taken into account. Large drainage cannula and high PEEP levels during the first days are recommended.</b>https://bit.ly/3DGjGkk
Abstract 10073: Characterization of Mechanical Circulatory Support in Peripartum Cardiomyopathy
Authors: Nadia H Bakir, Ioana B Florea, Joel D Schilling, Gregory A Ewald, Kunal D Kotkar, Akinobu Itoh, Muhammad F Masood
Journal: Circulation (2021)

Introduction: Peripartum cardiomyopathy (PPCM) is a severe complication of pregnancy which is hallmarked by non-ischemic reduction in left ventricular ejection fraction (LVEF) to &lt;45% late in gestation or shortly postpartum. This study evaluated outcomes among women who required mechanical circulatory support (MCS) for end-stage heart failure in the setting of PPCM. Methods: Thirty female patients 18-46 years of age underwent cardiac surgery for PPCM between 2012-2020. Primary heart transplant patients (n=2) were excluded. PPCM patients with a new MCS requirement (n=28) were classified by device type and escalations in device support. Results: Mean age was 29±7 years and 21 patients (75%) were African American. Median time from delivery to MCS requirement was 418 [91-1201] days. Nineteen (68%) patients required temporary MCS (tMCS): 12 (63%) on intraaortic balloon pump, 9 (47%) on veno-arterial extracorporeal membrane oxygenation, and 4 (21%) on Impella. Nine (32%) patients underwent left ventricular assist device (LVAD) implant after failure of medical therapy. LVEF and left ventricular end-diastolic diameter (LVEDD) at MCS insertion were 14±5mm and 68±11mm, respectively. LVEF progressed to 24%±16% post-insertion and 29%±17% one year (Figure 1). Of the 19 tMCS patients, 5 (26%) required escalations with additional modalities. Ten (53%) patients were bridged to durable LVAD. Complications included right ventricular failure (n=4), stroke (n=2), sepsis (n=1), dialysis (n=5), and cardiac arrest (n=3). Duration of support was 9±7 days for tMCS and 996±625 days for LVAD. Overall survival to discharge was 89% (n=25). Twelve patients underwent transplant (43%) and two (7%) recovered native heart function. Conclusions: Severe PPCM can be effectively managed with tMCS as a bridging strategy to either transplant or durable LVAD. Patients will often require multiple escalations in resource-intensive therapy, but outcomes are excellent with vigilant management.