tbuckley/cabot-search huggingface dataset:
Abstract 13704: Early Trends in Cardiac Allograft Vasculopathy After Implementation of the New 2018 Donor Heart Allocation Protocol in the United States
Authors: David M Tehrani, Soohyang S Kim, Jeffrey J Hsu, Ali Nsair, William F Fearon, Rushi Parikh
Journal: Circulation (2021)

Introduction: The new donor heart allocation policy implemented in October 2018 prioritizes hemodynamically unstable patients with the greatest need for urgent transplantion. The impact of this policy change on the incidence of cardiac allograft vasculopathy (CAV) has not been described. Methods: We performed a retrospective analysis of adult (≥ 18 years) heart transplant recipients registered in the UNOS database between 10/18/2015 - 11/25/2019 to evaluate the effect of the new allocation system on angiographic CAV at 1 year. Recipients undergoing first-time single organ heart transplant with 1 year follow-up were stratified based on the old (10/18/2015 - 10/17/2018) or new (10/18/2018 - 11/25/2019) allocation system. Recipient and donor demographic and cardiovascular risk factors, wait-list factors, and transplant factors with a p-value &lt; 0.10 in univariable analysis were included in multivariable logistic regression models to identify independent predictors of accelerated CAV. Results: Of 8,724 transplant recipients (mean age 54 ± 13 years, 73% male), 6,661 (76%) and 2,063 (24%) were listed in the old and new allocation systems, respectively. The old cohort consisted of 4,409 (66%) classified as Status 1A, while the new cohort consisted of 168 (8%) classified as Status 1 and 944 (46%) as Status 2. The incidence of accelerated CAV was 520 (7.8%) in the old allocation cohort compared with 130 (6.3%) in the new allocation cohort (p=0.02). In adjusted analyses, the new allocation system was significantly associated with a reduction in CAV (OR=0.72, 95% CI: 0.59-0.89, p=0.002; Table). This association persisted even after restricting the cohort to the highest acuity patients—Status 1A (old) and Status 1 or 2 (new) (OR=0.75, 95% CI: 0.57-0.99, p=0.04). Conclusions: The new donor heart allocation system is significantly associated with lower rates of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.
Abstract 10494: The Impact of Complete versus Partial Preservation of the Sub-Valvular Apparatus on Left Ventricular Function in Mitral Valve Replacement
Authors: Clarissa Ng Yin Ling, David Bleetman, Fulya A Demir, Mehdi Eskandari, Habib Khan, Max Baghai, Ranjit Deshpande, Mark J Monaghan, Olaf Wendler
Journal: Circulation (2021)

Introduction: In mitral valve replacement (MVR), sudden increase in afterload and disruption of the annular-chordal-papillary-left-ventricular wall causes LV dysfunction in the early postoperative period. Preservation of the posterior mitral leaflet apparatus (MVR-P) has a favourable outcome on LV function. However, there is paucity of data on the impact of complete preservation of the sub-valvular apparatus (MVR-C). Objective: We investigated the impact of MVR-P and MVR-C on baseline and 3-months postoperative LV ejection fraction (EF) and global longitudinal strain (GLS). Methods: We retrospectively analysed a cohort of 29 MVR-P and 19 MVR-C patients with complete echo data at our unit, who were operated between 2012-2017. Between-group changes in LVEF and GLS were compared using independent sample T-test. Results: Median age was 59 years (IQR 50-69 years). Baseline LVEF was 58% (51 - 60%). Baseline GLS was -18.4 (-21.2 - -15.5). There were no significant differences between all baseline demographics including age (p=0.45), underlying MV pathology (p=0.1), baseline LVEF (p=0.48) and GLS (p=0.15). There was significantly less worsening of GLS in MVR-C group as compared to the MVR-P group (p=0.023), indicating better preservation of LV function. There was also a lower decrease in LVEF in the MVR-C as compared to the MVR-P group, although the difference was not statistically significant (p=0.23). Conclusion: MVR with complete preservation of the sub-valvular apparatus shows a favourable impact on the longitudinal function of the heart at 3 months. Further studies with larger patient numbers are indicated to investigate the long-term results of this surgical approach.
Abstract 11919: Igg1 Phosphorylcholine Diminishes Murine Atherosclerosis and Ameliorates Plaque Stability via Reduced Intraplaque Angiogenesis and Hemorrhage
Authors: Margreet R de Vries, Fabiana Baganha, Erna Peters, Knut Pettersson, Paul H Quax
Journal: Circulation (2021)

Introduction: Phosphorylcholine (PC), one of the main oxLDL epitopes, is an important pro-inflammatory damage associated molecular pattern. Epidemiologic data show that natural anti-PC IgM protect against cardiovascular disease. Within atherosclerotic lesions, inflammation and angiogenesis are linked via VEGFA secreting CD163 + macrophages. PC antibodies are recognized for their anti-inflammatory properties, the effect of PC antibodies on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH) is yet unknown. Hypothesis: Newly developed IgG1 PC antibody (PCmAb) inhibits lesion development via IPA and IPH reduction in murine vein graft atherosclerosis. Methods: Hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery and weekly ip injections of (5mg/kg) PCmAb (n=11) or vehicle (n=12) until sacrifice at day 28. Vein graft morphometry and lesion composition including IPA and IPH were evaluated via immunohistochemistry. In vitro PCmAb effects were investigated in Hemoglobin (Hb):Haptoglobin(Hp)-cultured THP-1 macrophages and HUVECs. Results: PCmAb significantly decreased vein graft media area (13%), intima lesion (25%), and increased lumen area with 53% compared to vehicle. PCmAb improved lesion stability by increasing collagen content (18%) and decreased macrophages presence (31%). VCAM-1 and ICAM-1 expression in the vessel wall were also reduced (29%, 36%). PCmAb resulted in 23% decreased CD163 + macrophages content in vein grafts whereas CD163 expression was reduced in Hb:Hp stimulated macrophages. PCmAb significantly reduced neovessel density (34%) and significant reduced EC proliferation and migration with and without oxLDL stimulation. Moreover, PCmAb enhanced maturation of intraplaque angiogenic vessels by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a 62%reduction of IPH. Conclusions: PCmAb effectively inhibits murine atherosclerotic lesion formation. PCmAb reduces IPA and IPH by decreased neovessel density and macrophages influx via reduced expression of VCAM-1 and ICAM-1, and increased neovessel maturation in vein graft atherosclerosis. PCmAb holds promise as a new therapeutic approach for plaque stability.
Tagraxofusp, an Anti-CD123 Therapy, in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm: Subanalyses of a Pivotal Trial By Age and Baseline Disease Involvement
Authors: Naveen Pemmaraju, Marina Konopleva, Kendra Sweet, Anthony S. Stein, Sumithira Vasu, David A. Rizzieri, Eunice S. Wang, Hagop Kantarjian, Christopher L Brooks, Tariq I. Mughal, Andrew A. Lane
Journal: Blood (2021)
Abstract 12055: Immediate Effect of Yoga Based Om-Meditation on Heart Rate Variability During Different Phases of Menstruation
Authors: Mansha Kanuga, Satish G Patil
Journal: Circulation (2021)

Introduction: Stress may play a role in causing menstrual irregularities predisposing to increased risk for cardiovascular disease (CVD). Stress and cyclic variations in endogenous hormone levels during the menstrual cycle (MC) may affect heart rate variability (HRV), a measure of cardiac autonomic function (CAF) and mental stress. Strategies that reduce stress and improve HRV may prevent menstrual irregularities and thus CVD. We evaluated the effect of yoga-based OM-meditation on HRV during different phases of MC in young healthy females. Methods: A non-randomized controlled study was conducted on healthy young females (n=20) with normal menstrual cycle. Meditation group subjects (n=10) practiced Om-meditation while control group subjects (n=10) relaxed quietly for 10 minutes. Each subject received an intervention thrice during menstrual, proliferative and secretory phase. Data was collected before and immediately after every intervention. BMI, blood pressure (BP), heart rate (HR) and HRV were measured. Frequency domain method was used for an analysis of HRV. Results: The mean age of participants was 19.2±0.79 and 19.3±0.82 years; and mean period of MC was 31.1±2.76 and 30.3±2.4 days in meditation and control group respectively. There was no change in the baseline values of BMI, BP and HR between two groups and were within normal range. Between group analysis (ANCOVA) of HRV spectrum showed that Om-meditation had significantly decreased low frequency (LF) component of HRV (p&lt;0.05) and LF/HF ratio (p&lt;0.05); and increased high frequency (HF) component (p&lt;0.05) of HRV during all the three phases of MC. Conclusion: These results suggest that practice of Om-meditation for 10 minutes can induce beneficial changes in HRV by reducing sympathetic activity and shifting autonomic balance towards parasympathetic dominance. Om-meditation may reduce mental stress and optimize CAF during different phases of MC. However, this needs an evaluation in a larger trial.
Abstract 14035: IL-4Ra-Mediated CD206 <sup>+</sup> Macrophage Activation Promotes Adverse Remodeling in the Failing Heart
Authors: Qiongxin Wang, Mohamed Ameen Ismahil, Gregg Rokosh, Yujie Zhu, Tariq Hamid, Sumanth Prabhu
Journal: Circulation (2021)

Background: In heart failure (HF), cardiac macrophages are largely comprised of CD206 + cells that locally self-renew independent of the blood monocyte pool. We tested the hypothesis that cardiac CD206 + macrophages expressing interleukin (IL)-4Rα are key mediators of adverse left ventricular (LV) remodeling in HF. Methods and Results: Adult male C57BL/6 mice underwent non-reperfused myocardial infarction (MI) to induce HF. HF mice (vs. sham mice) exhibited progressive expansion of cardiac CD206 + macrophages up to 8 w post-MI (accounting for ~80% total macrophages), whereas cardiac CD206 - macrophages peaked at 48 h and then decreased by 90% at 1 w post-MI and beyond. Cardiac CD206 + macrophage levels negatively correlated with LV ejection fraction, and positively correlated with remote zone fibrosis. These cells were predominantly CCR2 - and nearly half expressed IL-4Rα, whereas CD206 - macrophages, monocytes, neutrophils, and T-cells had markedly lower IL-4Rα expression. Bone marrow-derived macrophages (BMDMs) polarized with IL-4 (M[IL-4]) induced myofibroblast activation in vitro . Intramyocardial adoptive transfer of M[IL-4] macrophages (1 x 10 6 cells) into naïve mice induced progressive LV chamber dilation and dysfunction, and augmented cardiac fibrosis over 4 w. Next, sham and HF mice with similar LV remodeling at 4 w post-MI were given IL-4Rα-specific or control antisense oligonucleotides (ASOs) 40 mg/kg i.p. every 3 d for 4 w. HF mice receiving IL-4Rα ASOs exhibited profoundly diminished cardiac CD206 + IL-4Rα + (and total CD206 + ) macrophage levels, substantially less macrophage proliferation and phagocytosis, and improvement of LV dysfunction, hypertrophy, and fibrosis. Moreover, both M[IL-4] CD206 + BMDMs and CD206 + IL-4Rα + macrophages in failing hearts expressed high levels of Fizz1 (found in inflammatory zone 1). Blocking FIZZ1 expression and/or secretion blunted the profibrotic capacity of M[IL-4] CD206 + BMDMs in vitro . Conclusion: CD206 + IL-4Rα + macrophages proliferate and expand in the failing heart and are key drivers of pathological remodeling and fibrosis, in part through the secretion of FIZZ1. Inhibition of CD206 + macrophage IL-4Rα signaling may be a fruitful therapeutic approach for alleviating LV remodeling in HF.
Abstract 12643: Sub-Endocardial Viability Index and Survival in the HF-ACTION Trial
Authors: Patrick L Stafford, Kenneth C Bilchick, Kajal Shah, Olivia Ondigi, Hunter Mwansa, Victor Mwansa, Khadijah Breathett, Amber E Johnson, Younghoon Kwon, James D Bergin, Mohammad Abuannadi, Nishtha Sodhi, Nishaki Mehta, Sula Mazimba
Journal: Circulation (2021)

Introduction: Myocardial perfusion relative to left-ventricular workload may be estimated by the sub-endocardial viability index (SVI). This can be calculated myocardial oxygen supply-demand balance, which is the ratio of diastolic to systolic pressure-time indices, i.e. [(DBP - PAWP) x (60sec/heart rate - 0.2sec)] / (SBP x 0.2sec), assuming fixed 0.2sec for systole. Low SVI indicates reduced sub-endocardial perfusion and was hypothesized to associate with negative outcomes in HFrEF patients. Methods: HF-ACTION was a randomized trial evaluating the efficacy of aerobic exercise training and usual care versus usual care in chronic HFrEF patients. SVI was calculated in HF-ACTION trial patients with complete hemodynamic data. PAWP was calculated using the Nagueh formula from echocardiographic-derived measurements ([PAWP=1.24*(E/e’) +1.9] with e’ = [(e’lateral + e’septal)/2]). The association of SVI with the combined endpoint of death or hospitalization, as well as all-cause death, was assessed. Results: Of 2331 patients in HF-ACTION, 807 had complete data. The mean SVI was 1.59 ± 0.47. The Cox proportional hazards model for the combined endpoint and all-cause death had HR of 0.66 per unit increase in SVI (p&lt;0.00001, 95% CI 0.55-0.79) and 0.67 (p=0.04, 95% CI 0.46-0.98), respectively. Survival during 4 year follow-up was worse below the mean SVI (p=0.0073) ( Figure 1) . In 26 patients below the critical sub-endocardial ischemia SVI of 0.7, survival was worse (p=0.0013) ( Figure 2) . Conclusion: Reduced SVI, a metric of the adequacy of sub-endocardial perfusion, is associated with negative outcomes in HFrEF patients. Figure 1. Figure 2.
<i>RACGAP1</i> variants in a sporadic case of CDA III implicate the dysfunction of centralspindlin as the basis of the disease
Authors: Sandeep N. Wontakal, Mishan Britto, Huan Zhang, Yongshuai Han, Chengjie Gao, Sarah Tannenbaum, Benjamin H. Durham, Margaret T. Lee, Xiuli An, Masanori Mishima
Journal: Blood (2021)

Congenital dyserythropoietic anemias (CDAs) are rare disorders defined by morphologic abnormalities of erythroid precursors that lead to ineffective erythropoiesis. 1,2CDA type III (CDA III), characterized by multinucleated erythroblasts in the bone marrow, represents the rarest form, with only 60 patients described in the literature.Studies in 2 independent families identified a causative dominant missense mutation in KIF23, which encodes MKLP1, 3 the kinesin subunit of centralspindlin, a key regulator of cytokinesis. 4In addition to the familial cases, a few sporadic cases of CDA III have been reported indicating an autosomal recessive pattern of inheritance. 1,2However, no genetic cause has been identified in such cases.Here, we describe a sporadic CDA III case associated with compound heterozygous variants in RACGAP1, which encodes CYK4/MgcRac-GAP, the other subunit of centralspindlin.We demonstrate these variants cause cytokinesis failure in human erythroid cells as a result of altered target specificity in Rho-family GTPase signaling.
Abstract 13005: The Prognostic Role of Systemic Arterial Pulsatility Index in Surgical Aortic Valve Replacement
Authors: Kajal P Shah, Yaqub Betz, Jarred Strickling, Olivia Ondigi, Hunter Mwansa, David Zhuo, David Shisler, Steven Philips, Nishtha Sodhi, Mohammad Abuannadi, Younghoon Kwon, James D Bergin, Kenneth C Bilchick, Sula Mazimba
Journal: Circulation (2021)

Introduction: Ventricular-arterial coupling (VAC) dynamics reflect the interaction between myocardial and vascular functions and are known to influence cardiac outcomes. Systemic arterial pulsatility index (SAPi = [systemic systolic pressure-systemic diastolic pressure]/pulmonary capillary wedge pressure) is a metric of VAC, incorporating pulse pressure and left ventricular filling pressure. We hypothesized that SAPi would be associated with adverse outcomes in patients undergoing surgical aortic valve replacement (SAVR) and or concomitant coronary artery bypass graft surgery (CABG). Methods: This was a retrospective analysis of patients who underwent SAVR +/- CABG at a tertiary academic center from 2008 to 2016. SAPi was calculated using right heart catheterization hemodynamics prior to surgery. Logistic regression model was used to evaluate the relationship between SAPi and mortality. Results: Among 133 patients (mean age 73.4, 43% female) who underwent SAVR, 37 (28%) underwent concomitant CABG. The median SAPi was 4.3 (IQR 2.76-6.40). Patients with SAPi &gt; 4.3 had a lower risk of mortality during the mean follow up of 6.9 years (OR 0.39 95% CI 0.18-0.85). Increasing SAPi was associated with a lower risk of mortality (OR 0.88 per unit increase in SAPi, 95% CI 0.76-0.99). A receiver operator characteristic curve is shown in Figure 1 with SAPI as a continuous variable adjusted for age. Area under the curve was 0.64 (95% CI 0.533-0.743). Conclusions: SAPi, a hemodynamic marker of VAC, was associated with mortality in patients undergoing SAVR +/- CABG. SAPi may have potential utility in pre-operative risk stratification of patients undergoing SAVR +/- CABG.
Abstract 10057: Subclinical Atrial Fibrillation is More Prevalent in Heart Failure with Preserved Ejection Fraction Compared to the General Population
Authors: Eunice Yang, Susan Heckbert, Jie Ding, David D Spragg, Hugh G Calkins, Sanjiv J Shah, Moyses Szklo, Wendy Post, Kavita Sharma
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is a common in patients with heart failure with preserved ejection fraction (HFpEF), and is associated with higher filling pressures, reduced exercise capacity, and reduced survival. The prevalence of subclinical AF in HFpEF remains unknown. Hypothesis: We hypothesized that subclinical AF was more prevalent in individuals with HFpEF when compared to individuals without clinical heart failure history. Methods: We evaluated subclinical AF in 101 HFpEF patients with no prior diagnosis of clinical AF using 14 day ambulatory ECG patch monitoring (Ziopatch XT, iRhythm Technologies). We compared the prevalence of subclinical AF in HFpEF with controls drawn from 3303 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) exam 6 follow-up, excluding those with known heart failure or high H2FpEF score who underwent the same ECG patch monitoring. Case-control comparisons of participants between the ages of 55 to 93 years were performed using multivariable logistic regression to adjust for demographic and clinical comorbidities, as well as patch monitoring duration. Results: 80 HFpEF patients and 1356 MESA participants were included. The HFpEF patients were younger (69 [63, 76] v. 72 [66, 80], p=0.02), more obese (BMI of 36 [30, 45] v. 27 [24, 30], p&lt;0.001) and more likely to have diabetes (34 v. 21%, p=0.01). There was a higher proportion of African Americans in the HFpEF group (57.5 v. 22.8%, p&lt;0.001). The prevalence of subclinical AF was 9.8% in HFpEF group and 6.2% in MESA participants. After multivariable adjustment for age, sex, race, body mass index, hypertension, diabetes, smoking pack-years and total analyzable time on ECG monitor there was a significantly higher odds of subclinical AF in HFpEF compared to MESA (OR 4.26 [1.2, 16.2], p=0.03). Conclusions: HFpEF patients have a higher prevalence of subclinical AF than the general population. Screening for atrial arrhythmias may be appropriate in HFpEF patients for timely initiation of thromboembolic prophylaxis, and may identify individuals at greater risk for clinical decompensation in light of the well documented risks associated with AF in HFpEF.
A cortical circuit for audio-visual predictions
Authors: Aleena R. Garner, Georg B. Keller
Journal: Nature Neuroscience (2021)

Abstract Learned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli. However, it is not well understood how these interactions are mediated or at what level of the processing hierarchy they occur. Here we describe a neural mechanism by which an auditory input can shape visual representations of behaviorally relevant stimuli through direct interactions between auditory and visual cortices in mice. We show that the association of an auditory stimulus with a visual stimulus in a behaviorally relevant context leads to experience-dependent suppression of visual responses in primary visual cortex (V1). Auditory cortex axons carry a mixture of auditory and retinotopically matched visual input to V1, and optogenetic stimulation of these axons selectively suppresses V1 neurons that are responsive to the associated visual stimulus after, but not before, learning. Our results suggest that cross-modal associations can be communicated by long-range cortical connections and that, with learning, these cross-modal connections function to suppress responses to predictable input.
A pilot study of PCR community mass testing for COVID-19: who attends and who tests positive?
Authors: Kate Levin, Beatrix von Wissmann
Journal: The Lancet (2021)

BackgroundPCR community mass testing for COVID-19 was delivered in three sites in Greater Glasgow and Clyde with high incidence of COVID-19, between Nov 30 and Dec 9, 2020. The purpose of mass testing was active case finding in communities. The aim of the study was to examine who attends mass testing and who tests positive, and how this differs from regular testing where only asymptomatic people attend.Methodsχ2 tests compared age, sex, deprivation, and ethnicity data collected from the three sites with target population Ward profile data published by Glasgow City Council for each site. Regular symptomatic test data for a period before and after the mass testing period were also analysed (Sept 1–Nov 29, 2020, and Dec 11–15, 2020). Data were modelled using logistic regression for outcome test result (positive vs negative or void) for mass and regular testing datasets. Demographic variables, as well as symptomatic or asymptomatic were included in the model. Modelling of the dataset combining mass and regular testing included interaction terms to detect differences in determinants between testing methods.Findings7497 PCR tests were done. There was under-representation in attendance of more deprived quintiles (p<0·0001 under a χ2 test), Black or minority ethnic groups (p<0·0001), males (p=0·039), older people (≥65 years; p=0·012), and children (<16 years; p=0·0062). Two of the sites had a high proportion of symptomatic cases (1331 [31%] and 1939 [65%]), for whom the percentage positive was substantially higher (203 [15·3%] and 229 [11·8%]) than asymptomatic individuals (76 [2·6%] and 39 [3·7%]; p<0·0001). Multivariable modelling found that increasing age (odds ratio 4·64 [95% CI 1·95–11·06] for 45–64 years [3·77, 1·59–8·93 for 30–44 years] compared with 0–4 years), ethnicity (1·98 [1·19–3·29] for Asian compared with White) and symptoms (4·59 [3·09–6·83] for symptoms vs no symptoms) were significantly associated with testing positive in mass testing. When test data were modelled simultaneously, an interaction term found females, Africans, and people who identified as other ethnic background were significantly more likely to test positive in mass testing compared with regular testing.InterpretationSome groups were under-represented in PCR community mass testing. Specifically, people living in more deprived areas, ethnic groups, older people, and children were less likely to attend a mass testing site. Adults, older people, and ethnic minority groups were more likely to test positive, and testing of symptomatic individuals, as well as asymptomatic individuals, would maximise case finding.FundingNone.