tbuckley/cabot-search huggingface dataset:
Abstract P500: Naltrindole And Naltrindole Derivatives Exhibit Potent Cardioprotection In Myocardial Ischemia Reperfusion Injury
Authors: Sunit Singh, Alexis Verwoert, Michael Bamimore, Arjun Nair, Tameka Dean, Kayla Harrell, Cameron Stinson, Qian Chen, Robert Barsotti, Lindon Young
Journal: Circulation Research (2021)

Previously, naltrindole (NTI; selective delta opioid receptor antagonist) was shown to improve post-reperfused cardiac function and reduced infarct size when given prior to ischemia (I)/ reperfusion (R) in ex-vivo rat hearts. Conversely, naloxone (NX, broad-spectrum opioid antagonist) and nor-binaltrophine (BNI, selective kappa receptor antagonist) were similar to control hearts. In this study, the effects of NTI derivatives naltriben (NTB, delta receptor antagonist) and guanidonaltrindole (GNTI, kappa receptor antagonist) were compared to NTI, BNI, and NX. Isolated hearts from male SD rats (300g) were subjected to global I(30min)/R(45min). Treatments were given 5 min before I (preconditioning) and during the first 5 min of R. Left ventricular (LV) cardiac function was measured using a pressure transducer. At the end of reperfusion, infarcted heart tissue was compared to total tissue weight. Data were evaluated using ANOVA. As shown in Table 1, NTI, NTB, and GNTI significantly improved post-reperfused cardiac function and reduced infarct size compared to control hearts. NTI and NTB elicited direct effects on cardiac function when given during preconditioning in contrast to all other study groups and were the most robust at reducing infarct size and restoring post reperfusion cardiac function. The negative inotropic effects of NTI and NTB were correlated with a decrease in the rise of ischemic pressure. GNTI also elicited significant improvement in post-reperfused cardiac function and reduction of infarct size compared to BNI which suggests a separate cardioprotective mechanism that this NTI derivative may exert in contrast to kappa opioid receptor inhibition. Results suggest that NTI and derivatives, GNTI and NTB, are cardioprotective against I/R injury resulting in reduced ischemic peak pressure (NTI/NTB) and infarct size. In future studies, we will examine the mechanism of the protective effects of NTI and derivatives in hearts subjected to I/R injury.
Abstract 12303: Management of Severe and Moderate Hypercholesterolemia in Young Adults
Authors: Shauna L Newton, Alexander P Hoffmann, Sara Haidermota, Pradeep Natarajan, Michael C Honigberg
Journal: Circulation (2021)

Introduction: Cardiovascular guidelines advise statin therapy for adults aged 20-75 years with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL with a goal of lowering LDL-C by ≥50%. Further, early-life accumulation of cholesterol exposure increases future cardiovascular risk independent of total cumulative cholesterol exposure, highlighting the importance of LDL-C management in young adults. However, real-world management of hypercholesterolemia in young adults is not well described. Methods: Using the Mass General Brigham clinical data registry, we isolated 2 cohorts of patients with hypercholesterolemia who had cholesterol testing on ≥2 occasions and were 20-39 years old at the time of a qualifying LDL-C value between 2005-2018: those with LDL-C ≥190 mg/dL (Cohort 1) and LDL-C 160-&lt;190 mg/dL (Cohort 2). Follow-up LDL-C values were extracted through 2019. Primary endpoints were 50% reduction in LDL-C for Cohort 1 and 30% reduction for Cohort 2. Results: Cohort 1 (severe hypercholesterolemia) included 5,475 patients (37.9% female, mean [SD] age 32.6 [5.1] years at qualifying LDL-C), and Cohort 2 (moderate hypercholesterolemia) included 12,608 patients (39.6% female, mean [SD] age 32.6 [5.1] years). In Cohort 1, 1,638 individuals (29.9%) achieved ≥50% LDL-C reduction overall (31.7% of men vs. 27.1% of women, P&lt;0.001; Figure ) over median (IQR) 7.8 (4.5-11.3) years of follow-up. The youngest individuals were less likely to achieve 50% LDL-C reduction (e.g., 20-24 years old: 24.8% vs. 35-39 years old: 32.7%; P trend &lt;0.001). In Cohort 2, 4,515 individuals (35.8%) achieved ≥30% LDL-C reduction over median (IQR) 7.5 (4.2-11.1) years of follow-up. Conclusions: In a large, integrated healthcare system, &lt;30% of young adults with severe hypercholesterolemia achieved guideline-directed LDL-C-lowering over 8 years of follow-up. These findings highlight the need for strategies to promote guideline-recommended cholesterol management in young adults.
Abstract 11368: Association of New-Onset Atrial Fibrillation with the Development of Frailty in Older Veterans: A Propensity Matching Study
Authors: Otoniel Ysea-Hill, Marlena Fernandez, Angelica Torres, Marie Pitteloud, Jilla Azarbal, Gustavo Vargas, Victor Cevallos, Alexis P Rodriguez, Jorge Ruiz
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia in older adults and has been previously shown to be associated with frailty. There is a lack of data regarding the trajectory of patients with new-onset AF and the development of frailty. The study aim was to determine the association between new-onset atrial fibrillation and the development of frailty over time in an older adult population. Methods: This is a retrospective cohort study using propensity score matching (PSM) among Veterans ≥60 years receiving primary care at Miami VAHS between July 2013-June 2014. Socio-demographic and clinical information was obtained from EHR and chart review. Patients were followed from their initial visit until onset of frailty, death, or end of study (June 2020). We assessed baseline and follow-up (FU) frailty using a 30-item VA Frailty Index (VA-FI). Veterans were categorized as non-frail (FI&lt;.21) and frail (FI≥.21). Frail subjects at baseline were excluded. Patients with recent AF diagnosis were matched with controls using PSM with one-to-one nearest neighbor matching without replacement. Matching covariates used to calculate propensity score were age, race, ethnicity, and BMI, with a tolerance level of .01. Veterans were not matched for gender due to very small female population. Using a multivariate cox regression analysis, we determined the risk of developing frailty among patients with AF and controls. Results: After PSM, 415 Veterans with AF and 415 controls were included, mean age 78.58 (SD=8.54), 98.07% males, 76.02% Caucasian, 87.47% Non-Hispanic, 53.86% married, and mean BMI 29.21 (SD=6.85). Median FU was 4.05 (IQR=5.09) years. At the end of FU, 274 (34.99%) Veterans developed frailty, of those, patients with AF showed higher rates of frailty (42.89%, n=178), compared to controls (26.08%, n=96), p&lt;.001. In comparison to controls, Veterans with AF were more likely to develop frailty, HR:3.15 (95%CI:2.42-4.10), p&lt;.001. Conclusions: In this study, the risk of development of frailty was higher in older Veterans with AF, compared to controls without AF. Careful monitoring of older adults with AF for concurrent morbidity may reduce incident frailty in this population.
Abstract 13006: Right Ventricular Dilation and Mortality in Acute COVID-19
Authors: Kaiwen Sun, Sithu Win, Nisha I Parikh, Priscilla Hsue, Matthew Durstenfeld
Journal: Circulation (2021)

Introduction: Myocardial injury is associated with COVID-19 mortality, but the prognostic value of adverse right ventricular (RV) remodeling on transthoracic echocardiogram (TTE) is uncertain. Therefore we studied the association between RV dilation and in-hospital mortality in acute COVID-19. Methods: We included all adults hospitalized with COVID-19 between March 2020 and February 2021 who had a clinical TTE performed during hospitalization at UCSF Health (Parnassus, Mission Bay, or Mount Zion) or Zuckerberg San Francisco General. Clinical and echo data were extracted from the electronic medical record. Biomarkers (BNP &amp; troponin) were log transformed. The primary exposure was qualitative assessment of RV dilation on TTE and the primary outcome was in-hospital mortality. We conducted analysis with STATA MP 16.1 using logistic regression models with adjustment for age and sex (Model 1) and age, sex, log(BNP), log(troponin), and mechanical ventilation (Model 2) and compared models with and without RV size with the likelihood ratio test. Results: There were 225 people hospitalized with COVID-19 who had a clinical TTE performed. The mean age was 62.9 years old, 77 (34%) were female, and 48 (21%) died. The majority of patients identified as Latinx (40%), and most patients received Medicaid (58%). Of 212 TTEs adequate to assess RV size, 47 (22%) had RV dilation of whom 16 (34%) died compared to 31 (19%) with normal RV size (RR 1.81, 95%CI 1.09-3.01, p=0.03). Of 185 TTEs adequate to assess RV function, 18 (10%) had RV dysfunction of whom 6 (33%) died compared to 12 (18%) with normal RV function (RR 1.86, 95%CI 0.89-3.84, p=0.12). There were no differences in tricuspid annulus plane systolic excursion or RV systolic excursion velocity. Adjusted for age and sex, RV dilation was associated with mortality (OR 2.16, 95%CI 1.02-4.58; p=0.045), with a larger effect among those with RV dilation and dysfunction (OR 3.40, 95% CI 0.93-12.4, p=0.063). This effect was attenuated after adjusting for BNP, troponin and mechanical ventilation at the time of TTE (OR 1.61, 95%CI 0.52-4.98, p=0.41). Conclusions: RV dilation on TTE is associated with mortality in acute COVID-19, although the effect is attenuated after accounting for mechanical ventilation and biomarkers.
Abstract 10509: Aquaporin 1 Differentially Controls Endothelial Cell Senescence by Epigenetic and SASP Modulation
Authors: Soheil Saeedi, Gergely Karsai, Giovanni G Camici, Thomas F Lüscher, Beer H Jürg
Journal: Circulation (2021)

Introduction: Aquaporin 1 (AQP1) has been implicated in oxidant sensing, but little is known about its differential role in metabolism and function of proliferating (PEC) and senescent (SEC) endothelial cells. We sought to investigate 1) role of AQP1 in modulation of epigenetic modification and senescence-associated secretory phenotype (SASP) in PEC and SEC, and 2) reversal effects of Aqp1 deletion/inhibition on endothelial senescence and dysfunction. Methods: We executed Aqp1 deletion or selective blockade of AQP1 pore (with Bacopaside II 10 μM) to inhibit H 2 O 2 transport in human aortic endothelial cells (PEC p.5 vs SEC p.15 ) and examined its effects on cellular senescence (via SA-β-galactosidase staining) and function (via in vitro angiogenesis and migration assays), and H 2 O 2 -modulated epigenetic modification and SASP (via biochemical assays). Results: We found that AQP1 facilitates physiological H 2 O 2 supply which is necessary for angiogenesis and cell migration in PEC accompanied by marked increase in AMPK T172 phosphorylation and inhibition of acetyl-coA carboxylase (ACC) that provides acetyl-coA for an increased histone 3 (H3) acetylation. Importantly, Aqp1 deletion/inhibition significantly induced senescence and mitochondrial dysfunction in PEC associated with increased SA-β-gal positive cells, upregulated SASP (TNF-α and ICAM-1), and downregulated Idh2. By contrast, decreased AMPK T172 phosphorylation and H3 acetylation accompanied by increased SA-β-gal positive cells, upregulated SASP and mitochondrial dysfunction seen in SEC were reversed by Aqp1 deletion/inhibition. In SEC, we have shown that Aqp1 deletion restores angiogenesis and migration comparable to PEC. Conclusion: We conclude that AQP1 differentially controls metabolism and function in young and senescent ECs via epigenetic and SASP modulation and that AQP1 inhibition represent new possibilities for rejuvenating senescent ECs and treating cardiovascular disease.
The Efficacy of Plerixafor Plus Recombinant Human Granulocyte Colony-Stimulating Factor for Autologous Stem-Cell Mobilization and Transplantation for Patients with Lymphoma and Plasma Cell Diseases
Authors: Xutao Guo, Yongqiang Wei, Xiaolei Wei, Haiqing Zheng, Yunxia Zhang, Haohao Lei, Qi Wei, Qifa Liu, Ru Feng
Journal: Blood (2021)
Abstract 9968: Classification and Treatment of Post-Operative Atrial Arrhythmias in Pulmonary Thromboendarterectomy Surgery
Authors: Sai Vanam, Muhammad B Munir, Douglas Darden, Masihullah Barat, Lucas Keyt, Tanner Long, Gregory Feld, Jonathan C Hsu, Ulrika Birgersdotter-green, Gordon Ho, David Krummen, Farshad Raissi, Timothy Fernandes, David Poch, Nick Kim, Demosthenes G Papamatheakis, Kim Kerr, Victor Pretorius, Michael M Madani, Frederick Han, Kurt S Hoffmayer
Journal: Circulation (2021)

Background: Atrial arrhythmias (AA) are common after cardiac surgeries including pulmonary thromboendarterectomy (PTE) surgery. However, the arrhythmia classification, treatment and impact of these AA after PTE surgery is unclear. Hypothesis: We hypothesized that most AA after PTE are paroxysmal and have a significant impact on post-operative outcomes. Methods: We reviewed the charts of 883 consecutive patients who were referred to University of California San Diego for PTE. Demographics, lab results and imaging were extracted from chart review. Predictors and outcomes were analyzed using a multivariate backward logistic regression model or independent samples t test respectively. Results: A total of 158 patients (18%) of patients developed an atrial arrhythmia. Paroxysmal atrial fibrillation (AF) was most common (72%, n=113). Persistent AF occurred in 8% of patients (n=12) and atrial flutter occurred in 21% (n=33) after PTE. The average days to onset of AA was 5.6 +/-4.4 days. Strongest predictors of AA (shown in attached figure) were chronic obstructive pulmonary disease (OR 2.8, p=&lt;0.01) and epicardial pacing requirement (OR 4.6, p=&lt;0.01). Patients who developed an AA had significantly prolonged post-operative length of stays (LOS) (14.7 days vs 11.9 days, p=&lt;0.01) compared to those who did not. Amiodarone was given in 73% (n=115) of patients and cardioversion was performed in 15% (n=23) of AA patients. Conclusions: AA are common after PTE surgery. Paroxysmal atrial fibrillation was seen most commonly. Patients who had COPD or required epicardial pacing were at highest risk of developing an AA. AA have a significantly prolonged post-operative LOS. The majority of patients received antiarrhythmic therapy with amiodarone (73%) and a minority underwent cardioversion (15%)
Abstract 10466: Randomized Clinical Trials Assessing Patients with Acute Myocardial Infarction-Related Cardiogenic Shock - A Systematic Review of Used Cardiogenic Shock Definitions and Outcomes
Authors: Jakob Josiassen, Martin Frydland, Christian Hassager, Jacob E Moller, Anders Perner, Johannes Grand
Journal: Circulation (2021)

Introduction: Cardiogenic shock (CS) is a critical complication to acute myocardial infarction (AMI), with short-term mortality rates exceeding 40%. However, the definition of CS varies between trials, which may comprise interstudy comparability. Aim: The aim of the current study was to review differences and similarities of CS definitions used in randomized clinical trials (RCT) assessing patients with AMI-related CS. Methods: From the electronic databases MEDLINE and EMBASE we identified 19 AMI-related CS trials comprising a total of 2674 unique patients with CS. Results: Seven trials investigated left ventricular assist devices, eight investigated medical treatments, three percutaneous coronary interventions, and one trial investigated targeted temperature management. The inclusion criteria, baseline hemodynamics, endpoints and mortality varied markedly between trials. Hypotension was the most frequent inclusion criterion (17 (90%) trials), with a systolic blood pressure value &lt;90mmHg combined with vasopressor use as the most frequent definition, Figure. Twelve (63%) trials had signs of impaired end-organ perfusion as an inclusion criterion and 10 (53%) signs of impaired cardiovascular function most frequently low cardiac index and reduced left ventricular ejection fraction. Ten (53%) trials included patients resuscitated from a cardiac arrest, three trials excluded cardiac arrest-patients whereas six trials did not state whether cardiac arrest was an exclusion criterion. Mortality ranged from 8 % to 73%. Conclusions: RCTs of AMI-related CS show marked heterogeneity in inclusion criteria and outcomes potentially hampering interstudy comparability. Consensus criteria for CS appear needed for future selection of patients.
Abstract 11567: Congenital Heart Disease Classification Improves SRTR Risk Estimation of Waitlist and Early Post-Transplant Mortality for Pediatric Heart Transplantation
Authors: Ryan J Butts, James Kirklin, Ryan Cantor, Hong Zhao, Byron Jaeger, Deipanjan Nandi, Scott R Auerbach, Emile Jean St-Michele, Kurt Schumacher, Shawn C WEST, Jennifer Conway, Leah K Toombs, David M Peng
Journal: Circulation (2021)

Introduction: Risk estimation for waitlist and 1-year post-transplant mortality utilized by SRTR for pediatric heart transplantation dichotomizes patients based upon presence or absence of congenital heart disease (CHD). Hypothesis: Current SRTR risk estimations can be improved by adding further detail in categorization of CHD. Methods: A retrospective analysis of the Pediatric Heart Transplant Society (PHTS) database of pediatric (&lt;18yo) heart transplant listings from 2010 to 2020 was performed, excluding patients listed for retransplantation. Cox hazard models were developed for waitlist mortality during the first year following listing (WaitDeath) and one year post-transplant mortality (TxDeath). The initial model was constructed using covariates included in the current SRTR model and a second model was developed by adding CHD classifications (SRTR+) including: single ventricle vs. biventricular heart disease, ventricular morphology, and surgical interventions. Results: The WaitDeath model included 5,790 patients in which 722 of which died. In the SRTR WaitDeath model, CHD had a HR of 1.8 (95%CI of 1.4-2.3) compared to cardiomyopathy patients. Where as in SRTR+ model, patients with different types of CHD had HR’s that ranged from 1.5 to 2.1 (Table 1). The TxDeath model included 4,185 patients in which 304 which died. (Table 1) In the SRTR model of TxDeath, patients with CHD had a HR of 3.9 (2.9-5.1) compared to cardiomyopathy patients, whereas in the SRTR+ model patients with different types of CHD had HRs that ranged from 2.4-5.3 (Table 1). Conclusions: Inclusion of granular CHD data may improve waitlist and post-transplant mortality risk estimation in pediatric heart transplant patients, allowing for more refinement in allocation policies and understanding of difference in post-transplant outcomes across sites. This data supports further refinement of current SRTR risk adjustment models.
Abstract 14259: Exercise Training Attenuates Activin Type II Receptor Signaling in the Aged Heart
Authors: Abhilasha Shiv Chandra Singh, Andy Yu, Bliss Chang, Haobo Li, Anthony Rosenzweig, Jason D Roh
Journal: Circulation (2021)

Introduction: Exercise training (ExT) improves functional capacity in older adults with heart failure (HF). However, the molecular mechanisms by which ExT exerts these benefits are unclear. We previously showed that cardiac activin type II receptor (ActRII) signaling increases in aging and HF, and that ActRII inhibition can improve cardiac exercise capacity in aged C57BL/6 mice, a model of age-related HFpEF. Whether cardiac ActRII signaling is modulated by ExT is unknown. Hypothesis: We hypothesized that ExT would attenuate cardiac ActRII signaling in aged mice. Methods: A moderate intensity ExT protocol (treadmill running, 10m/min, 10° incline, 45min/day, 8 weeks) was performed in 25month-old (mo) female C57BL/6 mice (OE). Functional (exercise capacity), molecular, and gravimetric assessments of HF were compared to young (YS, 4mo) and old (OS, 27mo) sedentary controls, along with indicators of downstream ActRII signaling (FSTL3 expression, SMAD3 phosphorylation, senescence, apoptosis markers). Results: After 8 weeks of ExT, exercise capacity increased in OE mice by 2.5±9.9% versus -24.1±4.6% in OS mice (p=0.05). ExT did not induce significant changes in cardiac hypertrophy or natriuretic peptide expression in aged mice, but decreased lung weight to body weight ratios (3.8±0.2(YS) vs 7.4±0.7(OS) vs 5.3±0.4(OE) mg/g, p=0.001). Cardiac ActRII signaling increased with aging and was attenuated with ExT (FSTL3/GAPDH: 1.0±0.01(YS) vs. 2.9±0.1(OS) vs. 1.0±0.2(OE) p=0.01; pSMAD3/SMAD3: 0.8±0.2(YS) vs. 1.5±0.04(OS) vs. 1.1±0.1(OE), p=0.1). Moreover, parallel changes occurred in markers of cardiac senescence (p16: 1.0±0.02(YS) vs. 1.6±0.1(OS) vs. .3±0.02(OE), p=0.02) and apoptosis (BAX: 0.8±0.2(YS) vs. 1.8±0.05(OS) vs. 1.1±0.1(OE), p=0.0007; cleaved caspase 3: 0.8±0.01(YS) vs. 2.2±0.01(OS) vs. 1.0±0.02(OE), p=0.0001), which have been shown to be regulated by ActRII signaling. Conclusions: These findings suggest aerobic ExT attenuates the cardiac ActRII signaling observed in aged mice and slows the age related decline in exercise capacity. Age-associated pathologies linked to ActRII signaling, including cellular senescence and apoptosis, were similarly modulated by ExT.
Abstract 9826: Impact of Ischemic Heart Disease on Inpatient Outcomes of Atrial Fibrillation
Authors: Shakeel Jamal, Jawad Hassan, Asim Kichloo, Sardar H Ijaz, mona mahmoud, Muhammad Ajmal, Timir K. Paul, Beth Bailey
Journal: Circulation (2021)

Introduction: Comparative outcomes of hospitalizations for Atrial Fibrillation (AF) with and without coexisting ischemic heart disease (IHD) have limited large scale data. Coexistence of AF and IHD is common and exposed patients are at high risk for ischemic/hemorrhagic events. We assess baseline characteristics and outcomes in these hospitalized patients using National Inpatient Sample (NIS). Hypothesis: Ischemic heart disease worsens the inpatient clinical outcomes of atrial fibrillation. Methods: We conducted a retrospective analysis of hospitalizations for AF using data from NIS between 2013 and 2014. International classification of diseases, 9th revision was used to identify the target population. The primary outcome was inpatient mortality, hospital length of stay and cost. Results: A total of 1531704 hospitalizations for AF were identified, of these, 863, 352 hospitalizations were without IHD and 668, 342 hospitalizations were with secondary diagnosis of IHD. AF with IHD cohort was older (mean age, 76.4 vs 74.4, p &lt;0.001), had low proportion of females (41% vs 55%, p &lt;0.001), higher proportion of whites (83.4% vs 81.6%, p &lt;0.001) and high comorbidities such as hypertension, diabetes mellitus, chronic kidney disease and congestive heart failure. AF with IHD had significant higher inpatient mortality (OR 1.02, CI 1.01-1.04), increased length of hospital stay (6 vs 5.8 days, mean difference 0.05, p &lt;0.001) and higher cost of hospital stay (mean difference, 7122 USD, p &lt;0.001). There was higher prevalence of cardiogenic shock (OR 2.97, CI 2.86-3.09), cardiac arrest (OR 1.58, CI 1.53-1.62), complete heart block (OR 1.46 (CI 1.40-1.53) and acute kidney injury (OR 1.10, CI 1.09-1.11) in AF with IHD cohort. Conclusion: AF with coexisting IHD is associated with higher inpatient mortality, increased cost of hospital stays, and prolonged length of hospital stay as well as higher comorbidity burden.