tbuckley/cabot-search huggingface dataset:
Abstract 16604: Significant Correlation Between Arterial Velocity Pulse Index and Muscle Sympathetic Nerve Activity in Hypertensive Patients
Authors: hiroyuki sugimoto, Hisayoshi Murai, Takuto Hamaoka, Yusuke Mukai, Yoshitaka Okabe, hideki tokuhisa, Soichiro Usui, Kenji Sakata, Masayuki Takamura
Journal: Circulation (2020)

Introduction: Augmented sympathetic nerve activity (SNA) in hypertension (HT) is regarded as a therapeutic target, but there is few non-invasive markers to evaluate SNA in clinical practice. It is reported to associate with SNA which increased arterial reflected wave plays the important role in disease progression in HT, and it is reported to associate with SNA. Recently, Arterial Velocity Pulse Index (AVI) are developed as an index of arterial reflected waves, however the relationship between AVI and SNA is still uncertain. Methods: Patients with essential HT and matched non-hypertensive control subjects were included in this study. HT was diagnosed as systolic blood pressure (SBP) ≧ 140 mmHg or diastolic blood pressure (DBP) ≧ 90 mmHg. Patients with secondary HT was excluded. AVI was measured from left upper arm by NAS-1000 (Nihon Koden, Japan). SNA was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) from peroneal nerves. Results: 50 HT patients and 50 control subjects were included. Age, SBP and DBP were significantly increased in HT group compared to control (Age 63±14 vs 42±16 years, p&lt;0.001; SBP 144±16 vs 115±9 mmHg, p&lt;0.001; DBP 80±14 vs 67±9 mmHg, p&lt;0.001). MSNA and AVI were significantly increased in HT group compared to control (MSNA 34±10 vs 25±8 bursts/min, p&lt;0.05; AVI 28±9 vs 17±5, p&lt;0.05). In univariate analysis, AVI was significantly correlated with MSNA, age, and SBP in HT group. However, no significant relationship was observed between AVI and MSNA in multivariate analysis. Therefore, HT group was divided into two groups according to their severity (group 1, SBP&lt;160mmHg, N=30; group 2, SBP&gt;160 mmHg, N=20). AVI in group 1 showed significantly correlation with MSNA (r=0.49, p&lt;0.05), but no correlation was seen in group 2. Conclusions: AVI was significantly increased in patients with HT compared to control, and AVI is significantly associated with MSNA in HT patients with SBP&lt;160mmHg. These results indicate that AVI is helpful to estimate augmented SNA in patients with mild or moderate hypertension. Further study is warranted to exam the relationship AVI and SNA in reality.
Abstract 16571: An Appraisal on Prognostic Value of Left Atrial Strain in Exercise Echocardiography
Authors: Zi Ye, William Miranda, Garvan Kane, Robert B McCully, Jae K Oh
Journal: Circulation (2020)

Introduction: Diastolic dysfunction impairs exercise capacity and has prognostic value in exercise echocardiography. We aimed to assess whether left atrial strain (LAS), which is reduced with worsening in diastolic function, is associated with all-cause death or heart failure hospitalization in patients undergoing treadmill echocardiography. Methods: We performed 2D-speckle tracking analysis of LAS in 1636 consecutive patients (mean age 64±13 and 59% men) who underwent treadmill echocardiography between 1/2013 and 1/2014. We used the 2016 ASE recommendation to define diastolic function and elevated LV filling pressure. Results: Of 1636 study subjects, 95% had LV ejection fraction ≥ 50%. Diastolic function was normal in 44% of patients and abnormal in the remaining (23% grade I, 9% grade II, 1% grade III, and 23% indeterminate). During a mean follow-up of 5.5±1.8 years, 210 patients (12.8%) experienced the composite outcome (157 death and 88 heart failure hospitalization). Lower LASreseroivr, LASbooster and LA emptying fraction (LAEF) were all associated with increased risk for the adverse outcome independent of age, sex, clinical and echocardiographic parameters, and after further adjustment for diastolic function (abnormal vs. normal) (all p≤0.001). The association of LASbooster with the outcome attenuated in a model with LASreservoir or LAEF (both p&gt;0.1). Adding LASreservoir to clinical and echocardiographic parameters provided incremental prognostic value (continuous net reclassification improvement=0.09, p=0.04), but not LAEF or LASbooster. Patients with LASreservoir &lt;34.2% (lowest tertile) had more than doubled risk for death or heart failure hospitalization than those with LASreservoir ≥34.2% after multivariable adjustment in the entire cohort (adjusted hazard ratio 2.2, 95%CI: 1.53 - 3.23), as well as in those with normal stress test (n=1217, adjusted HR, 3.53, 95%CI: 2.29 - 5.53) or those without elevated resting LV filling pressure (n=1466, adjusted HR: 2.08, 95%CI: 1.46 - 2.96). Conclusions: LASreservoir provides independent prognostic information in patients undergoing exercise echocardiography.
Abstract 15668: Noninvasive Mapping Can Predict Success of Ablation for Atrial Fibrillation
Authors: Namita Ravi, Kian Waddell, Wouter-Jan Rappel, Miguel Rodrigo, Sanjiv M Narayan
Journal: Circulation (2020)

Introduction: It is currently not possible to non-invasively identify patients with atrial fibrillation (AF) who may respond acutely to ablation. We hypothesized that high resolution body surface mapping can identify specific distributions of AF in individuals that predict acute success from ablation. Objective: To correlate 64 lead body surface ECG in AF to acute ablation response and non-invasively identify patients in whom ablation does and does not terminate AF. Method: Fig A shows 64 body surface electrodes in N=17 consecutive AF patients (14 persistent AF, 67 ± 9.06 years). Spectral dominant frequency (DF) from 4096-point FFT, cycle length, AF electrogram amplitude were measured in 200-300 time slices of duration 60s between patches on the body surface representing each atrium (Fig A). Results: Ablation terminated AF in N=7/17 patients (41.2%, Fig. B). Patients with AF termination had more organized AF than those without termination, indicated by lower DF on body surface mapping of the regions corresponding to left (5.00 ± 1.33 vs 5.47 ± 1.30, p &lt; 0.001) and right atrium (5.16 ± 1.50 vs 5.50 ± 1.01, p &lt; 0.003) (Fig C shows composite). DF was stable without statistically significant variations across 20s slices spanning the full minute, supporting interpretability of mechanisms from this analysis (p = NS). Further, AF signal amplitude averaged across left and right atria was lower in patients with AF termination (65.47 ± 36.9 vs 120.13 ± 99.9, p &lt; 0.001) (Fig D). Conclusion: Body surface analysis of AF can non-invasively identify patients in whom ablation may acutely terminate AF. Future studies should determine if this approach can predict who may ultimately achieve long term freedom from AF, and whether body surface signatures are representative enough to be analyzed days prior to the procedure.
Steroid Ligands, the Forgotten Triggers of Nuclear Receptor Action; Implications for Acquired Resistance to Endocrine Therapy
Authors: Rachel Bleach, Stephen F. Madden, James Hawley, Sara Charmsaz, Cigdem Selli, Katherine M. Sheehan, Leonie S. Young, Andrew H. Sims, Pavel Souček, Arnold D. Hill, Marie McIlroy
Journal: Clinical Cancer Research (2021)

Abstract Purpose: There is strong epidemiologic evidence indicating that estrogens may not be the sole steroid drivers of breast cancer. We hypothesize that abundant adrenal androgenic steroid precursors, acting via the androgen receptor (AR), promote an endocrine-resistant breast cancer phenotype. Experimental Design: AR was evaluated in a primary breast cancer tissue microarray (n = 844). Androstenedione (4AD) levels were evaluated in serum samples (n = 42) from hormone receptor–positive, postmenopausal breast cancer. Levels of androgens, progesterone, and estradiol were quantified using LC/MS-MS in serum from age- and grade-matched recurrent and nonrecurrent patients (n = 6) before and after aromatase inhibitor (AI) therapy (&amp;gt;12 months). AR and estrogen receptor (ER) signaling pathway activities were analyzed in two independent AI-treated cohorts. Results: AR protein expression was associated with favorable progression-free survival in the total population (Wilcoxon, P &amp;lt; 0.001). Pretherapy serum samples from breast cancer patients showed decreasing levels of 4AD with age only in the nonrecurrent group (P &amp;lt; 0.05). LC/MS-MS analysis of an AI-sensitive and AI-resistant cohort demonstrated the ability to detect altered levels of steroids in serum of patients before and after AI therapy. Transcriptional analysis showed an increased ratio of AR:ER signaling pathway activities in patients failing AI therapy (t test P &amp;lt; 0.05); furthermore, 4AD mediated gene changes associated with acquired AI resistance. Conclusions: This study highlights the importance of examining the therapeutic consequences of the steroid microenvironment and demonstrable receptor activation using indicative gene expression signatures.
INSM1 Expression in Breast Neoplasms with Neuroedocrine Features
Authors: Jasna Metovic, Isabella Castellano, Eleonora Marinelli, Simona Osella-Abate, Anna Sapino, Paola Cassoni, Mauro Papotti
Journal: Endocrine Pathology (2021)

According to the 2019 WHO classification of breast tumors, neuroendocrine neoplasms (NENs) are classified into well-differentiated NE tumors (NET) and poorly differentiated NE carcinomas (NEC), while other breast cancers (BCs) of special and no special type with neuroendocrine (NE) features are not incorporated in this scheme anymore. We aimed to assess whether INSM1, a novel NE marker, could have a role in breast NEN subtyping. We selected 63 BCs operated from 2003 to 2018, classified as BCs with NE features, with available clinico-pathological data. Following 2019 WHO criteria, this cohort was reclassified into 37 NETs/NECs, the remaining 26 tumors representing solid-papillary (7), mucinous (7), and mixed type (12) carcinomas with NE differentiation. Chromogranin A (CGA) and synaptophysin (SYN) immunostains were reviewed, and INSM1 was tested by immunohistochemistry. Thirty CGA- and SYN-negative no special type BCs served as negative control. INSM1 was expressed in 52/63 cases of the whole cohort (82.54%). INSM1 positive and negative cases had no significantly different clinico-pathological characteristics. INSM1 expression was not significantly different between the newly reclassified NET/NEC group and other BCs with NE features. No immunoexpression was observed in control BCs. The sensitivity and specificity of INSM1 for the NE phenotype was 82.5% and 100%, respectively, compared to 61.9% and 100% for CGA, and 95.2 and 100% for SYN. In conclusion, INSM1 is as accurate as traditional NE biomarkers to identify NE differentiation in BC. In analogy to standard NE markers, INSM1 could not distinguish NET and NEC from the other BC histotypes with NE differentiation.
Pneumatic Vitreolysis with Perfluoropropane for Vitreomacular Traction with and without Macular Hole
Authors: Clement K. Chan, Calvin E. Mein, Adam R. Glassman, Wesley T. Beaulieu, Claire T. Calhoun, Glenn J. Jaffe, Lee M. Jampol, Mathew W. MacCumber, Maureen G. Maguire, Raj K. Maturi, Hani Salehi-Had, Soraya Rofagha, Jennifer K. Sun, Daniel F. Martin
Journal: Ophthalmology (2021)
17P Impact of body mass index (BMI) on prognostic and predictive value of stromal tumour-infiltrating lymphocytes (sTILs) in triple-negative breast cancer (TNBC): A pooled analysis of six neoadjuvant trials
Authors: J. Furlanetto, C. Denkert, M. Untch, B. Sinn, B. Lederer, A. Schneeweiss, V. Mueller, M. van Mackelenbergh, E. Stickeler, P.A. Fasching, C. Schem, T. Karn, F. Marmé, V. Nekljudova, S. Loibl
Journal: Annals of Oncology (2021)
Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression
Authors: Raoul J. P. Bonnal, Grazisa Rossetti, Enrico Lugli, Marco De Simone, Paola Gruarin, Jolanda Brummelman, Lorenzo Drufuca, Marco Passaro, Ramona Bason, Federica Gervasoni, Giulia Della Chiara, Claudia D’Oria, Martina Martinovic, Serena Curti, Valeria Ranzani, Chiara Cordiglieri, Giorgia Alvisi, Emilia Maria Cristina Mazza, Stefania Oliveto, Ylenia Silvestri, Elena Carelli, Saveria Mazzara, Roberto Bosotti, Maria Lucia Sarnicola, Chiara Godano, Valeria Bevilacqua, Mariangela Lorenzo, Salvatore Siena, Emanuela Bonoldi, Andrea Sartore-Bianchi, Alessio Amatu, Giulia Veronesi, Pierluigi Novellis, Marco Alloisio, Alessandro Giani, Nicola Zucchini, Enrico Opocher, Andrea Pisani Ceretti, Nicolò Mariani, Stefano Biffo, Daniele Prati, Alberto Bardelli, Jens Geginat, Antonio Lanzavecchia, Sergio Abrignani, Massimiliano Pagani
Journal: Nature Immunology (2021)
Sex-related differences in the pharmacological treatment of heart failure
Authors: Juan Tamargo, Ricardo Caballero, Eva Delpón
Journal: Pharmacology & Therapeutics (2021)

Heart failure (HF) represents a leading cause of morbidity and mortality. However, HF trials highlighted many differences between men and women with HF. Thus, women represent approximately a quarter of people with HF with reduced ejection fraction (HFrEF), while they account for over half of those with HF with preserved EF (HFpEF). There are also sex-related differences (SRDs) in the pharmacokinetics, pharmacodynamics and safety profile of some guideline-recommended drugs for the treatment of HF. As compared with men, women with HFrEF are less often treated with guideline-recommended HF drugs, experience more frequent and severe adverse reactions when these drugs are prescribed at the same doses in both sexes, and recent evidence suggests that women might need lower doses than men, bringing into question which are the optimal doses of HF drugs in women and men separately. However, information on SRDs in drug efficacy and safety in patients with HFrEF is very limited due to the underrepresentation of women and the lack of sex-specific evaluations of drug efficacy and safety in HF clinical trials. As a consequence, current clinical guidelines do not provide sex-specific recommendations, even when significant differences exist, at least, in drug safety. The aim of this article is to review the SRDs in the pharmacokinetics, efficacy and safety of guideline-recommended HF drugs and to identify emerging areas of research to improve our understanding of the SRDs, because a better understanding of these differences is the first step to achieve a personalized treatment of HF in women and men.
Abstract 16233: Systemic Arterial Pulsatility Index is a Potential Metric for Microvascular Dysfunction
Authors: Douglas Sawch, Benjamin Ruth, Sula Mazimba, Jamieson M Bourque, Kenneth C Bilchick, Nishtha Sodhi
Journal: Circulation (2020)

Introduction: Coronary microvascular dysfunction is associated with both atherosclerosis and heart failure (HF). We aimed to evaluate the prognostic value of global coronary flow reserve (CFR) and systemic arterial pulsatility index, a metric of ventricular-arterial coupling, (SAPi = [systemic systolic pressure-systemic diastolic pressure]/pulmonary capillary wedge pressure) in patients with known or suspected coronary artery disease. Methods: This was a retrospective analysis at an academic tertiary care center for patients who underwent right heart catheterization (RHC) and positron emission tomography (PET) imaging within a 6 month period. Global CFR was evaluated with PET imaging and SAPi was calculated using cardiac hemodynamics from RHC. Patients were evaluated for endpoints of non-fatal myocardial infarction, revascularization, and death. Cox proportional hazards regression modeling was used to examine the associations between CFR &amp; SAPi with death and other adverse cardiovascular events. Results: Among 74 patients with complete imaging and hemodynamic data (mean age 64.23 ± 11.18 years, 54.67% female) the mean SAPi was 4.87 ± 3.09 and CFR was 52.95 ± 16.17. Increased SAPi as a continuous variable trended towards decreased mortality [HR: 0.814 (95% CI 0.663-1.016, chi square 3.31, p=.07).] Increased CFR as a continuous variable was significantly associated with decreased mortality [HR: 0.964 (95% CI 0.936-0.993, chi square 6.03, p&lt;0.05). Neither were associated with non-fatal myocardial infarction or early revascularization. There was a weak trend toward correlation between SAPi and CFR (r=0.19, p=0.11). Conclusions: SAPi a hemodynamic marker of ventricular arterial coupling was weakly associated with CFR. On the other hand, CFR was significantly associated with death in patients with known or suspected coronary artery disease. Future work is needed to assess the correlation between SAPi and coronary microvascular dysfunction.
Na <sub>v</sub> 1.7 target modulation and efficacy can be measured in nonhuman primate assays
Authors: Richard L. Kraus, Fuqiang Zhao, Parul S. Pall, Dan Zhou, Joshua D. Vardigan, Andrew Danziger, Yuxing Li, Christopher Daley, Jeanine E. Ballard, Michelle K. Clements, Rebecca M. Klein, Marie A. Holahan, Thomas J. Greshock, Ronald M. Kim, Mark E. Layton, Christopher S. Burgey, Jordi Serra, Darrell A. Henze, Andrea K. Houghton
Journal: Science Translational Medicine (2021)

Rhesus C-fiber microneurography, heat responsivity, and olfactory fMRI can be used as translatable biomarkers of Na v 1.7 target modulation.
Abstract 13111: Factors Associated With Patient Engagement in Shared Decision-Making for Stroke Prevention Among Older Adults With Atrial Fibrillation: Implications for Patient-Provider Communication
Authors: Jordy Mehawej, Jane Saczynski, Hawa O Abu, Benita Bamgbade, Marc Gagnier, Darleen Lessard, Katherine Trymbulak, Connor Saleeba, Catarina I KIEFE, Robert Goldberg, David D McManus
Journal: Circulation (2020)

Introduction: Though engaging patients with atrial fibrillation (AF) in the decision-making process for stroke prevention is encouraged by guidelines, little is known about the extent of, and the factors associated with, patient engagement in this process. Hypothesis: Patient engagement in shared decision-making (SDM) would be modest and that older participants will less likely engage in SDM for stroke prevention. Methods: Data are from the ongoing SAGE (Systematic Assessment of Geriatric Elements)-AF study which enrolled older adults aged 65 years and older with AF from clinics in Massachusetts and Georgia. Participants on an oral anticoagulant (OAC) reported whether they were engaged in the decision to be on an OAC by answering “Yes” to the question: “Did you participate actively in choosing to take an OAC?”. We used multiple logistic regression analysis to examine the sociodemographic, geriatric, psychosocial, and clinical factors associated with patient engagement in SDM for stroke prevention. Results: Participants (N= 807) were on average 75 years old and 48% were female. Approximately, 61% engaged in the decision to be on an OAC. Participants aged 80 years and older (aOR= 0.53; 95 % CI:0.31-0.89) and those cognitively impaired (aOR= 0.69; 95 % CI: 0.48, 0.99) were less likely to engage in SDM than respective comparison groups. Participants who reported being very knowledgeable of their AF associated risk of stroke had higher odds of engaging in SDM than those with less knowledge (aOR= 3.06; 95 % CI:1.59, 5.90). Conclusions: Clinicians should identify older patients and those who are cognitively impaired who are less likely to engage in SDM for stroke prevention, promote patient engagement, and provide support to ensure sustained engagement that would enhance long-term treatment outcomes for patients with AF.
Abstract 16060: Cardiac Magnetic Resonance Imaging Diastolic Indices Correlate With Cardiac Catheterization Filling Pressures in Pediatric Heart Transplant Recipients
Authors: Wubishet Belay, Justin Godown, David W Bearl, Kristen George-Durrette, Kimberly Crum, Maryanne Chrisant, Lazaro E Hernandez, Jonathan H Soslow
Journal: Circulation (2020)

Background: Atrial and ventricular filling pressures are routinely used in pediatric heart transplant (HTx) recipients to assess graft function. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of diastolic function, but data are lacking in pediatric HTx. We hypothesized that CMR indices of diastolic function correlate with filling pressures, providing a non-invasive approach to assessment of ventricular dysfunction. Method: Pediatric HTx recipients were prospectively enrolled at the time of cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) and right atrial pressure (RAP) were measured. CMR included standard volumetric analysis and T1 and extracellular volume (ECV) mapping in the short axis at the mid-left ventricle (LV) to evaluate extracellular matrix expansion. Filling curves were calculated by contouring every phase in the short axis stack and global longitudinal and circumferential strain (GLS, GCS) were calculated using feature tracking. Correlations were analyzed using Spearman’s correlation. Results: A total of 31 patients with a mean age of 16.2 y/o were included, 9 with biopsy-proven acute rejection. The median time from transplant was 6.9 years and the mean LVEF was 58%. Peak LV ejection rate/end-diastolic volume (PER/EDV) correlated with PCWP (rho=-0.43, p=0.02, Fig 1) and RAP (rho=-0.40, p=0.03). GLS and GCS correlated with RAP (rho=0.51 p=0.007, and rho=0.38 p=0.05, respectively); GLS also correlated with PCWP (rho=0.46, p=0.02). Native T1 time-correlated with PCWP (rho=0.54, p=0.003), while the correlation between ECV and PCWP did not reach statistical significance (rho=0.37, p=0.06). Conclusion: CMR can be a useful non-invasive modality to assess for early signs of diastolic dysfunction in patients after pediatric HTx. Further research is needed to describe the clinical significance of these associations.
Abstract 16145: Reduced Ejection Fraction at Diagnosis is an Independent Predictor of Mortality in Transthyretin Amyloid Cardiomyopathy
Authors: Syed Bukhari, Zubair Bashir, Daniel Shpilsky, Yvonne S Eisele, Prem Soman
Journal: Circulation (2020)

Introduction: The prevalence of reduced ejection fraction (HFrEF) in transthyretic cardiac amyloidosis (ATTR-CA) and its prognostic implications have not been well studied. Hypothesis: We hypothesized that reduction in ejection fraction in ATTR-CA is associated with poor prognosis. Methods: We analyzed all patients with the diagnosis of ATTR-CA. ATTR-CA was diagnosed by positive PYP and negative serum studies for AL amyloidosis. The transthoracic echocardiogram (TTE) at the time of PYP was used to identify patients with reduced EF &lt;50% (ATTR-rEF) and preserved EF ≥ 50% (ATTR-pEF). Kaplan-Meier curve for survival between the two groups and adjusted cox proportional hazard models were generated. Results: Of the 124 ATTR-CA patients (mean age of 79.9 ± 7.4, 87% men, 90% Caucasians), 51 (41%) were ATTR-rEF. Compared to ATTR-pEF, at the time of PYP, ATTR-rEF were more symptomatic ( NYHA-FC ≥ 3, 61% vs 26%, p&lt;0.001), had lower prevalence of obstructive coronary artery disease (CAD)(37% vs 55%, p=0.05), worse mean diastolic dysfunction (3 vs 2.15, p&lt;0.01), lower tricuspid annular plane systolic excursion (TAPSE &lt;1.7, 59% vs 25%, p&lt;0.001) and reduced renal function ( creatinine, 1.63 ± 0.85 vs 1.27 ± 0.55 mg/dl, p&lt;0.01). There was no difference in terms of biomarkers (BNP, p=0.1 and troponin, p=0.3) and interventricular septal thickness (p=0.2). Over a mean follow up period of 1.5 years, 27 (22%) patients died. ATTR-rEF was associated with higher mortality compared to ATTR-pEF (35% vs 12%, p=0.002; HR 3.7, 95%CI 1.62-8.63, p&lt;0.01, fig. 1A). After adjustment for multiple cofounders including TAPSE and serum creatinine, reduced EF was an independent predictor of mortality (HR 3.02, 95% CI 1.30-7.10, p=0.01). When divided into EF≥ 50%, EF 41-49% and EF ≤ 40%, there was stepwise increase in the risk of mortality (p&lt;0.01, fig. 1B). Conclusion: HFrEF is present in more than one-third of patients with ATTR-CA at the time of diagnosis, and is an independent predictor of mortality in ATTR-CA.