tbuckley/cabot-search huggingface dataset:
Abstract 8890: Heart-Type Fatty Acid Binding Protein Impairs Angiogenesis via the Erk/stat1/vegf Signaling Pathway
Authors: Ting-Ting Chang, Jaw W Chen, Yen-Wen Wu
Journal: Circulation (2021)

Introduction: Angiogenesis is an important process for repairing tissues after damage, including ischemic stroke, myocardial infraction, and ischemia. The heart-type fatty acid binding protein (H-FABP) is a cytoplasmic protein and previous studies indicated that the increased level of H-FABP was associated with acute coronary syndrome and ischemic stroke. Given the potential contribution of H-FABP to the pathological of cardiovascular diseases, it is important to know the direct mechanisms of H-FABP in angiogenesis. Methods and Results: Human coronary endothelial cells (HCAECs) and endothelial progenitor cells (EPCs) were used for the in vitro study. H-FABP treatments impaired the tubular formation, migration, and wound healing abilities of HCAECs and EPCs cultured from both stable coronary artery disease (CAD) patients and healthy subjects. H-FABP directly enhanced the phosphorylation of ERK and STAT-1. The inhibition of ERK by U0126 or the knockdown of STAT-1 by siRNA could reverse the damage of cell tubular formation and migration from H-FABP. Furthermore, exogenous of H-FABP could down-regulate the expression of VEGF. The administration of STAT-1 siRNA could reverse the level of VEGF reduced by H-FABP. In the matrigel plug neovascularization assay, the H-FABP-treated group had attenuated angiogenesis with decreased hemoglobin and capillary density levels. On the other hand, ox-LDL and TNF-α were used as stimulators in the in vitro experiments. The expressions of H-FABP were increased and the cell functions were impaired in the ox-LDL and TNF-α-treated cells. And, administration of H-FABP siRNA could recover the damage from ox-LDL and TNF-α. Conclusions: To sum up, we proved that H-FABP could directly impair angiogenesis via the ERK/STAT1/VEGF signaling pathway in endothelial cells, suggesting the critical role of H-FABP for vasculopathy. The findings of this study may not only improve our understanding about the critical mechanisms of vascular disease, but also provide the important rationale to the potential role of H-FABP as a novel therapeutic target in angiogenesis.
CTNI-09. TRIDENT PHASE 3 TRIAL (EF-32): FIRST-LINE TUMOR TREATING FIELDS (TTFields; 200 KHZ) CONCOMITANT WITH CHEMO-RADIATION, FOLLOWED BY MAINTENANCE TTFIELDS/TEMOZOLOMIDE IN NEWLY-DIAGNOSED GLIOBLASTOMA
Authors: Wenyin Shi, Lawrence Kleinberg, Suriya Jeyapalan, Samuel Goldlust, Seema Nagpal, Stephanie Combs, David Roberge, Ryo Nishikawa, David Reardon, Rachel Grossman, Martin Glas
Journal: Neuro-Oncology (2021)

Abstract INTRODUCTION Tumor Treating Fields (TTFields; 200 kHz; non-invasive, loco-regional antimitotic treatment) is approved for newly-diagnosed glioblastoma (ndGBM). In the Phase 3 EF-14 trial, post-surgical radiotherapy/temozolomide, followed by maintenance TTFields/temozolomide significantly increased overall survival (OS) and progression-free survival (PFS) in patients with ndGBM versus TMZ alone. Addition of maintenance TTFields did not increase systemic toxicity; and related adverse events (AEs) were mainly dermatological. In preclinical models, addition of TTFields increased the benefit of radiotherapy. Two pilot studies showed that TTFields concomitant with radiotherapy/temozolomide is feasible and well-tolerated. The benefit of TTFields concomitant with radiotherapy/temozolomide will be investigated in the TRIDENT trial. METHODS TRIDENT (EF-32; NCT04471844) is an international, pivotal, phase 3 randomized trial comparing triple-combination of TTFields/radiotherapy/temozolomide versus standard radiotherapy/temozolomide. Patients in both arms will receive maintenance TTFields/TMZ. Arrays of the Optune® System will be used to deliver TTFields (200 KHz) for ≥18 hours/day concomitant with radiotherapy. TTFields treatment will be continued until second disease progression (RANO) or 24 months, whichever occurs first. Patients with pathologically-confirmed ndGBM, ≥ 18 years of age (≥ 22 years of age; US), KPS ≥ 70, post-surgery/biopsy, and amenable for radiotherapy/temozolomide will be stratified by extent-of-resection and MGMT promoter methylation status. The primary endpoint is median OS. Secondary endpoints include median PFS (RANO), 1-year and 2-year survival rates, overall radiological response (ORR; RANO), PFS (PFS-6M, PFS-12M, PFS-2Y), severity and frequency of AEs (CTCAE V5.0), pathological post-treatment changes in resected GBM tumors, quality-of-life (EORTC QLQ-C30), and OS correlation to TTFields duration-of-usage. The hypothesis is that first-line TTFields/RT/TMZ triple-combination will significantly improve OS compared to radiotherapy/temozolomide; each followed by maintenance TTFields/temozolomide. Sample size (N=950; 475/arm) was powered for a HR &amp;lt; 0.8 with 5% type I error. Survival will be measured from time-of-randomization. The TRIDENT trial is currently enrolling patients. RESULTS/CONCLUSIONS N/A TiP.
Abstract 10256: Presence, but Not Severity, of Coronary Artery Calcium Predicts Covid-19 Mortality
Authors: Matthew S Delfiner, Evan Carabelli, Isaac R Whitman, Arjun S Patel, Suraj Mishra, Chethan Gangireddy, Anjali Vaidya, Meredith A Brisco-Bacik, Pravin Patil, Michael P Gannon
Journal: Circulation (2021)

Introduction: Coronary artery calcium score (CACS) is a known predictor of cardiac events, however its association with inpatient mortality in COVID-19 infection remains unknown. Hypothesis: We hypothesized that elevated CACS is associated with increased mortality in inpatient patients with COVID-19. Methods: Inpatients with COVID-19 between March and May, 2020 at a single center were identified. All patients had a non-contrast chest CT during admission, and CACS and Multi-Ethnic Study of Atherosclerosis (MESA) percentile were retrospectively measured. Patients were grouped in quartiles: no CACS (0 AU), mild CACS (1-99 AU), moderate CACS (100-399 AU), and severe ( &gt; 400 AU). Inpatient mortality was compared between groups using logistic regression adjusted for age and troponin level. Results: One hundred thirty-nine patients were included with 107 (80%) surviving to discharge. Eighty-two patients self-identified as black or African American (59%) and 66 were female sex at birth (47%). The mean CACS for the survivors was 319 AU and 406 AU for non-survivors (p = 0.02). The mean MESA percentile for survivors and non-survivors was 41% and 60%, respectively (p = 0.03). Fifty-nine patients had no CACS, 19 had mild CACS, 28 had moderate CACS, and 33 had severe CACS. Fifty-three of the no CACS group survived (89%), 13 of the mild group survived (68%), 17 of the moderate group survived (60%), and 24 of the severe group survived (73%). After adjustment for age and troponin level, CACS &gt; 0 AU versus those with CACS of 0 AU had 4-fold higher odds of mortality (OR 4.0, 95%CI 1.3 - 12, p= 0.02). However, there was no significant increased odds of death within higher quartiles of CACS (OR 1.4, 95%CI 1.0 - 2.1, p=0.08). Conclusion: The presence of coronary artery calcium positively correlates with inpatient COVID-19 mortality, even after accounting for age and myocardial injury. Severity of CACS, however, is not associated with mortality.
Abstract 11613: Prognostic Implication of Early Drop in Systolic Blood Pressure During the First 48 Hours in Patients with Acute Heart Failure from REALITY-AHF Registry
Authors: Taishi Dotare, Daichi Maeda, Tsutomu Sunayama, Takashi Iso, Keisuke Kida, Takeshi Kitai, Nobuyuki Kagiyama, Tetsuo Yamaguchi, TAKAHIRO OKUMURA, Atsushi Mizuno, Shogo Oishi, YASUTAKA INUZUKA, Eiichi Akiyama, Satoshi Suzuki, Masayoshi Yamamoto, Tohru Minamino, Yuya Matsue
Journal: Circulation (2021)

Background: Although it has been suggested that excessive drop in systolic blood pressure (SBP) in the acute phase of acute heart failure potentially has a negative impact on prognosis, the association between changes in SBP during acute phase and prognosis has yet to be clarified. Methods and Results: This is the sub-analysis of REALITY-AHF (Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure) study, which was a prospective, multicenter, observational registry which registered patients with acute heart failure admitted through emergency department (ED). Peak drop in SBP was defined as the difference between the baseline SBP values and the lowest values during the first 48 hours of hospitalization. After ED arrival, SBP was measured at the time of admission, 90 minutes, 6 hours, 24 hours, and 48 hours of ED admission. Patients were divided into three groups according to the value of peak SBP drop . A total of 1,656 patients were included in our study. Patients with greater peak SBP drop group was associated with higher baseline SBP and vasodilator use after admission. Cox proportional hazard analysis demonstrated greater peak SBP drop (per 10mmHg decrease) was independently associated with 180-day (hazard ratio, 1.12; 95% confidence interval, 1.01–1.23; P=0.027) and 1-year (hazard ratio, 1.12; 95% confidence interval, 1.03–1.21; P=0.006) mortality even after adjustment for confounding factors including baseline SBP (Figure). Conclusions: Early drop in SBP during first 48 hours of hospitalization was associated with all-cause mortality in patients with acute heart failure.
Abstract 10265: Sex Hormones Impact the Progression of Aortic Stenosis - A Murine Model
Authors: Marie-Ange Fleury, Marine CLISSON, Mohamed-salah Annabi, Martine Voisine, Maxime Hervault, Anne-Julie Boilard, Mylene Shen, Mathieu Tailleur, Andre Marette, Nancy Cote, Marie-annick Clavel
Journal: Circulation (2021)

Introduction: Lesions observed in aortic valve stenosis (AS) have been shown to be sex-specific, with women presenting with extensive fibrotic remodeling while men develop more calcium deposits. This study aimed to evaluate the influence of sex and sex-hormones on the pathophysiology of AS. Methods: Two hundred and ten (210) LDLr -/- ApoB 100/100 IGF-II +/- mice were separated into 6 groups: 1) intact males (IM), 2) intact females (IF), 3) castrated males at 8 weeks (CM), 4) ovariectomized females at 8 weeks (OF), 5) CM with testosterone supplementation (CMT), and 6) OF with 17β-estradiol supplementation (OFE). Mice were fed a high fat / high sucrose / high cholesterol diet for 6 months. Hemodynamic progression of AS was measured by transthoracic echocardiography (at 12 and 36 weeks) and aortic valves were collected for histological and digital droplet PCR analysis. Results: Hemodynamic progression of AS was comparable in IF and IM (24.2±5.7 vs. 25.8±5.3 cm/s; p=0.68), but IF presented with less severe hemodynamic AS. Between the 3 groups of male mice, AS progression and calcification of the explanted aortic valves at 36 weeks were more important in IM (increase in peak velocity: 24.2±5.7 cm/s; p&lt;0.001) compared to CM (6.2±1.4; p=0.42), and CMT (15.1±3.5; p=0.002). In the 3 groups of female mice, there was no statistical differences in AS progression or valve remodeling. Digital PCR analysis revealed an important upregulation of the osteogenic gene RunX2 in IM (p&lt;0.0001) and downregulation of the pro-calcifying gene ALPL in IF (p&lt;0.05). Conclusions: Male sex and testosterone play a role in the upregulation of pro-calcific genes and calcification of the aortic valve, thus in the hemodynamic progression of AS. Female mice appeared to be protected against calcification, characterized by downregulation of pro-osteogenic genes, but presented similar AS hemodynamic progression. Impact of sex-hormone in females requires further studies.
Abstract 9875: Pain is More Severe in Women Than Men with Heart Failure Transported by Emergency Medical Services
Authors: Asa B Smith, Miyeon Jung, Susan J Pressler
Journal: Circulation (2021)

Introduction: Presence and severity of pain may differ between women and men with heart failure (HF) transported by emergency medical services (EMS), but few studies have examined these differences. The aims were to compare (1) presence of pain, (2) pain severity, and (3) demographic and clinical factors associated with pain presence and severity between women and men with HF. Methods: Data were analyzed from electronic medical records of 6,582 patients with HF transported by EMS. Presence of pain was operationalized by having a primary complaint of pain during transport. Pain severity was recorded among patients with a primary complaint of pain (n=400) on a 0-10 scale, with 10 indicating worst pain. Demographic (gender, age, race) and clinical variables (vital signs, conditions, medications, devices) were retrieved from the medical record. Descriptive statistics and multiple linear and logistic regression were used to address the aims. Results: The sample was 57.6% women and 42.4% men. The mean age was 64.2 (SD 14.5). Self-reported race was 58.2% Black and 41.8% White. Pain was frequent, with 23% of women and 23% of men presenting with a primary complaint of pain. Pain severity was ‘moderately high’ to ‘high’, with a mean of 7.2 (SD 2.9) among women and 6.4 (SD 3.2) among men (p=0.005). In logistic regression models, significant explanatory factors for pain presence in women were younger age (OR=0.97; p&lt;0.001), MI history (OR=1.85; p&lt;0.001), and absence of shortness of breath (OR=0.72; p&lt;0.001). In men they were younger age (OR=0.97; p&lt;0.001), MI history (OR=2.05; p&lt;0.001), and presence of an implantable cardioverter-defibrillator (OR=1.64; p=0.022). In multiple regression models, higher pain severity in women was explained by younger age (β=-0.04; p=0.012) and higher systolic BP (β=0.02; p=0.001) The adjusted R 2 was 0.09. In men, higher pain severity was explained by younger age (β=-0.08; p=0.003) and Black race (β=-1.65; p=0.007). The adjusted R 2 was 0.05. Conclusions: Presence of pain was similar between women and men with HF, but women had more severe pain. Pain severity was explained by different factors in women and men. Prospective studies of pain with gender-focused analyses and additional explanatory factors to account for more variance are needed.
Genetic ablation of PRDM1 in antitumor T cells enhances therapeutic efficacy of adoptive immunotherapy
Authors: Toshiaki Yoshikawa, Zhiwen Wu, Satoshi Inoue, Hitomi Kasuya, Hirokazu Matsushita, Yusuke Takahashi, Hiroaki Kuroda, Waki Hosoda, Shiro Suzuki, Yuki Kagoya
Journal: Blood (2021)
Anti-obesity drug discovery: advances and challenges
Authors: Timo D. Müller, Matthias Blüher, Matthias H. Tschöp, Richard D. DiMarchi
Journal: Nature Reviews Drug Discovery (2021)

Enormous progress has been made in the last half-century in the management of diseases closely integrated with excess body weight, such as hypertension, adult-onset diabetes and elevated cholesterol. However, the treatment of obesity itself has proven largely resistant to therapy, with anti-obesity medications (AOMs) often delivering insufficient efficacy and dubious safety. Here, we provide an overview of the history of AOM development, focusing on lessons learned and ongoing obstacles. Recent advances, including increased understanding of the molecular gut–brain communication, are inspiring the pursuit of next-generation AOMs that appear capable of safely achieving sizeable and sustained body weight loss. The development of therapies that are capable of safely achieving sizeable and sustained body weight loss has proved tremendously challenging. Here, Müller et al. provide an overview of the history of anti-obesity drug development, focusing on lessons learned, ongoing challenges and recent advances in the field.
Abstract 11000: Cardiovascular Outcomes in Patients with Diabetes and Hypertrophic Cardiomyopathy, Hospitalized for Heart Failure
Authors: Moza Almohannadi, SOHA DARGHAM, Jassim M Al suwaidi, Hani Jneid, Charbel Abi Khalil
Journal: Circulation (2021)

Introduction: Diabetes is a widely prevalent pathology complicating many cardiovascular diseases. Hypothesis: We hypothesized that patients with hypertrophic cardiomyopathy (HCM) hospitalized for heart failure (HF) have a worse outcome in the presence of diabetes. Methods: The National Inpatient Sample (NIS) was analysed to identify records from 2005-2015 of patients hospitalized for HF as a complication of HCM. We assessed the cardiovascular and socio-economic trend of patients with diabetes and HCM hospitalized for HF, and compared them to those without diabetes. Results: Diabetes prevalence increased from 24.8% to 32.7% in all HMC patients hospitalized for HF. In diabetes patients, mean age of patients decreased from 71 ±13 to 67.6 ±14.2 (p&lt;0.01) but hospitalizations increased from 0.2 to 0.5 cases/100 000 US adults (p&lt;0.01) (Figure 1). Mortality, cardiogenic shock, ventricular tachycardia (VTach), atrial fibrillation (AF) decreased with time. Length of stay (LOS) was stable, but charges almost doubled. Age (adjusted OR= 1.04 [1.03-1.05]), female gender (adjusted OR= 1.50 [0.72-0.88]) and the presence of several comorbidities assessed using the Elixhauser score (adjusted OR= 1.09 [1.07-1.11]) predicted a higher risk of mortality in those patients. When compared to non-diabetic patients, diabetes patients were younger and had more comorbidities. Unexpectedly, the risk of mortality (adjusted OR= 0.68 [0.56-0.81]), ventricular tachycardia (adjusted OR= 0.79 [0.72-0.88]), ventricular fibrillation (adjusted OR= 0.28 [0.14-0.56]) and atrial fibrillation (adjusted OR 0.80 [0.76-0.85]) were lower in patients with diabetes. However, LOS was higher in patients with diabetes, so were charges. Conclusions: Diabetes is paradoxically associated with lower mortality and lower rates of complications (namely arrhythmias) in HCM patients hospitalized for HF
Abstract 14209: Natural History of Resolved Left Ventricular Thrombi
Authors: Yehia Saleh, Mahmoud Abdelnabi, Ola Abdelkarim, Nouran Eshak, Abdallah Almaghraby
Journal: Circulation (2021)

Introduction: Left ventricular thrombi (LVT) are associated with a significantly increased risk of systemic thromboembolism with its major clinical complications especially cerebrovascular stroke. Several societal guidelines recommend a duration of 3 to 6 months of anticoagulation (AC). However, evidence regarding LVT recurrence after AC discontinuation is lacking. Hypothesis: To determine the clinical characteristics associated with LVT recurrence in patients with resolved LVT after AC discontinuation. Methods: Follow-up data of 52 patients with resolved LVT derived from the Comparative Study of Oral Anticoagulation in Left Ventricular Thrombi (No-LVT Trial) was retrospectively analyzed. Results: 47 patients (90.38%) had no recurrence of LVT while 5 patients (9.61%) had LVT recurrence at a mean follow-up duration of 86.17±20.54 and 81±26.08 days, respectively. There was no statistically significant difference in age, gender, diabetes, hypertension, smoking or etiology of heart failure between the two groups. Baseline and follow-up left ventricular ejection fraction (LVEF) were lower in patients with recurrent LVT (32.4±5.37% and 40.34±4.08% respectively) compared to the no recurrence group (39.36±4.68% and 54.24±5.09% respectively) which was statically significant (p=value of 0.003*, &lt;0.0001* respectively). Conclusions: In patients with resolved LVT, low LVEF was the strongest predictor of LVT recurrence after AC discontinuation. Further research is required to determine clinical characteristics associated with LVT recurrence and indications for extended duration of AC in LVT treatment.
Abstract 11681: An Extremely Rare Case of Intercostal Artery Rupture After Percutaneous Coronary Intervention
Authors: Monarch Shah, Sanya Chandna, Kavin raj, Pratik B Patel, Christian Toquica Gahona
Journal: Circulation (2021)

Introduction: There are a few case reports of Intercostal artery injury after pleural tap and trauma but none after a PCI. Case: A 61-year-old Caucasian male with PMH of T2DM, Hypertension, Hyperlipidemia, former tobacco chewing, family history of premature CAD presented to ED with midsternal chest pressure of 2 hours and three weeks of dyspnea on exertion. He was seen earlier in the outpatient office where an ECHO showed an EF of 55%, and a Nuclear stress test showed moderate inferior ischemia. CT coronary Angiogram showed complex plaques in Mid RCA and mid LAD. Troponin and EKG were normal. A diagnosis of unstable angina was suspected, and he was loaded with clopidogrel and heparin drip. He underwent emergency cardiac catheterization via a trans-radial approach. The standard J wire was switched to an angled-tip stiff Terumo guidewire due to difficulty traversing the aortic arch. The guidewire briefly went down the descending thoracic aorta. There was complex, eccentric stenosis of 99% in mid LAD and mid-RCA, which were stented with DES. The patient developed right chest pain radiating to his back. He became hypotensive, and Hemoglobin dropped from 13 to 8g/dl. CT scan showed a large right-sided hemothorax, and a chest tube was placed. He was resuscitated, and Angiogram showed three pseudoaneurysms and rupture of the right 8 th intercostal artery with active contrast extravasation. The right 9 th intercostal artery had one pseudoaneurysm. Both the vessels were embolized by an interventional radiologist. Discussion: Intercostal arteries arise from descending thoracic aorta. It is likely the catheter advanced into the descending aorta and the intercostal artery resulting in injury. Proper guidewire advancement under fluoroscopy and confirming the position of guidewire before advancing the guiding catheter may prevent this complication. Prompt recognition and emergency treatment with a chest tube and IR-guided embolization should be done.
Abstract 10746: Left Atrial Strain and the Risk of Arrhythmias on Extended Ambulatory Cardiac Monitoring: The Multi-Ethnic Study of Atherosclerosis
Authors: Matthew Huber, Jay A PANDIT, Paul Jensen, Kerri Wiggins, Ravi B Patel, Benjamin Freed, Alain G Bertoni, Sanjiv J Shah, Susan Heckbert, James S Floyd
Journal: Circulation (2021)

Introduction: Abnormalities in left atrial (LA) function can be identified before the development of overt LA structural changes. Little is known about the relationship between LA mechanics and the risk of subclinical atrial and ventricular arrhythmias. Methods: 1,441 participants of the Multi-Ethnic Study of Atherosclerosis completed speckle-tracking echocardiography and Zio Patch monitoring from 2016-2018 (mean age 73 years, 52% female); participants in atrial fibrillation (AF) during echocardiography or cardiac monitoring were excluded. Absolute values of LA reservoir, booster pump, and conduit strain were measured. We evaluated associations of LA strain measures with atrial arrhythmias (presence of monitor-detected AF, AF burden, frequency of premature atrial contractions [PACs], frequency of supraventricular tachycardia [SVT] runs) and with ventricular arrhythmias (frequency of premature ventricular contractions, presence of non-sustained ventricular tachycardia [NSVT], frequency of NSVT runs). Primary analyses adjusted for demographic variables, blood pressure, smoking, diabetes, and clinical cardiovascular disease (4%). Results: Cardiac monitoring (median 14 days) detected AF in 3%. Each standard deviation (5.4%) lower (worse) LA reservoir strain was associated with a 64% higher risk of monitor-detected AF (95% CI 16-137%), 33% higher PAC frequency (95% CI 22-46%), and 15% higher SVT frequency (95% CI 7-24%). Adjustment for kidney function, NT-proBNP, LA volume, and LV ejection fraction and global longitudinal strain had little impact on associations. Findings were similar for LA booster pump strain and null for LA conduit strain (Figure). Associations of LA reservoir and booster pump strain with ventricular arrhythmias were completely attenuated after adjustment for LV function. Conclusions: In a multi-ethnic community-based cohort, abnormal LA mechanics may be an important risk factor for subclinical atrial arrhythmias.