tbuckley/cabot-search huggingface dataset:
Abstract 18819: Clinical Outcomes Following Implantation of a Centrifugal Flow Left-Ventricular Assist Device and Concomitant Cardiac Valve Procedures
Authors: Carmelo A Milano, Francis D Pagani, Mark S Slaughter, Duc Thinh Pham, David R Hathaway, Kevin B Najarian, Keith D Aaronson
Journal: Circulation (2013)

Purpose: Patients undergoing implantation of left ventricular assist devices (LVAD) often undergo concomitant cardiac valve procedures, but the added procedural risk has not been studied in detail. We reviewed patients receiving a centrifugal flow LVAD system in the ADVANCE Bridge to Transplant Trial (BTT) and Continued Access Protocol (CAP) to evaluate the impact of concomitant valve procedures on early outcomes. Methods: The ADVANCE BTT and CAP trial enrolled 381 patients (pts) through November 2012. This group was divided into two subgroups: pts who underwent a concomitant valve procedure in addition to LVAD implant (VP) and those who did not undergo a concomitant valve procedure (no VP). Preop characteristics, adverse events and Kaplan-Meier survival were compared for the two groups. Results: A total of 19.7% (75/381) of pts underwent VP at the time of LVAD implantation. The most frequent procedure was tricuspid valve repair or replacement, performed in 14.7% of pts, followed by aortic (3.4%), and mitral (2.1%) valve procedures. Patients undergoing a VP were younger and had more recent onset of heart failure. Other pre-implant variables were similar for the two groups. Length of time on cardiopulmonary bypass was increased for VP pts, but mean length of hospital stay did not differ. Proportions of pts having perioperative tamponade, bleeding, arrhythmias, or strokes were similar. VP pts had more right heart failure (RHF) requiring inotropic therapy (37.3% vs. 22.9%, P =0.01); however, there was no difference in RHF requiring RVAD support (2.7% vs. 2.6%, P =1.00). Overall Kaplan Meier survival for the two groups was similar, 97.3% VP vs. 98.0% No VP at 30 days and 88.2% VP vs. 90.5% No VP at 6 months ( P =0.57). Survival was also similar for aortic (N=13) versus tricuspid (N=56) procedures, with 6 month survival 90.0% and 88.5%, respectively ( P =0.75). Conclusion: Tricuspid repair was the most common VP. Increased post-op RHF may have reflected more pre-op right heart dysfunction in this patient subgroup. Overall, the concomitant valve group experienced very good survival, suggesting that VP can be performed at the time of LVAD implant with minimal additional risk.
Abstract 13040: Repeated Social Defeat Stress Enhances Neutrophil Extracellular Traps Formation in vivo and in vitro: Implication in the Exaggerated Atherosclerosis in Chronic Social Stress-exposed Apoe <sup>-/-</sup> Mice
Authors: Keita Yamamoto, Hiroyuki Yamada, Kensuke Terada, Shinichiro Motoyama, Naotoshi Wada, Makoto Saburi, Masakazu Kikai, Noriyuki Wakana, Satoaki Matoba
Journal: Circulation (2016)

Introduction: Neutrophil extracellular traps (NETs) has been reported to promote atherosclerosis through induction of NETosis, a new type of neutrophil cell death; however, the role of NETosis in psychosocial stress-induced atherosclerosis remains undefined. Methods and Results: Eight-week-old male apoE -/- mice were exposed to the repeated social defeat (RSD) by housing with a larger CD-1 mice in a shared home cage with a clear perforated divider. They were repeatedly subjected to vigorous physical contact for 5-10 min each day on 10 consecutive days. Control mice were housed in the same gage without physical contact. After 6 weeks of high-cholesterol diet feeding, atherosclerotic lesion area of the aortic root was significantly increased in RSD mice compared with control mice (19.4% vs 13.9%, P &lt; 0.05). There was no significant difference in body weight, food intake, mean blood pressure, and lipid profile between the 2 groups. Although both of Ly6G-positive and Mac3-positive area in immunofluorescent staining were comparable between the 2 groups, Ly6G-positive area in RSD mice was much strongly co-localized with MPO (16.4% vs. 6.6%; P &lt; 0.05) and H3Cit (15.1% vs. 9.0%; P &lt; 0.05), suggesting the augmented NETosis in RSD mice. Consistently, serum IL-1β level was markedly higher in RSD mice (2.9-fold; P &lt; 0.05). The percentages of circulating neutrophils (Ly6G + CD11b + F4/80 - CD11c - ) were significantly increased in RSD mice compared with control mice (27.1% vs. 13.0%; P &lt; 0.05), whereas the fractions of circulating inflammatory monocytes (Lin - CD11b + Ly6C + ) and bone marrow (BM) monocyte-lineage progenitor cells were equivalent between the 2 groups. To further examine the NETs formation of individual neutrophils in vitro, BM neutrophils (Ly6G + ) were isolated by flow cytometry and stimulated by PMA for 4 hr. The percentages of MPO- and H3Cit-positive cells were significantly increased by 2.5-fold in RSD mice compared with control mice ( P &lt; 0.01). Conclusions: Our findings demonstrated for the first time that RSD promotes NETs formation in BM neutrophils as well as in atherosclerotic lesions, which precede high-cholesterol diet-induced monocytosis, suggesting that NETosis could be a new therapeutic target in psychosocial stress-induced atherosclerosis.
Abstract 18766: Myocardial Blood Flow and Viability in Children Post Palliation of Hypoplastic Left Heart Syndrome Assessed With MRI
Authors: Carsten Rickers, Michael Jerosch-Herold, Philip Wegner, Christopher Hart, Eileen Pardun, Inga Voges, Hans Heiner Kramer
Journal: Circulation (2013)

Introduction: Myocardial blood flow in the systemic right ventricle in Hypoplastic Left Heart Syndrome (HLHS) is largely unknown.The aim of this study was to examine with MRI regional and global myocardial perfusion reserve, viability and function in HLHS after completion of Fontan circulation. Methods: In 42 HLHS patients (6.0 ±2.3 yrs) and 14 heart healthy controls (6.8 ±3.9 yrs), MRI first-pass perfusion (0.03 mmol/kg Gd-DTPA; TR/TE/α=2.6/1.1/20°) and late gadolinium enhancement (LGE) imaging was performed using a 3 Tesla scanner (Philips Achieva). Quantitative myocardial blood flow at rest and stress (Adenosin 140 mcg/kg/min) was calculated in 4 anatomical RV segments per slice using a model independent deconvolution. A total of 672 segments were analysed. CMR results were compared to conventional x-ray guided coronary angiography in all HLHS pts. Results: HLHS patients showed impaired myocardial perfusion reserve (MPR, hyperemic/resting flow) as compared to the right or left ventricle of healthy children (2,4 ±0,6 vs. 3,1±0,9 (RV); p&lt;0,05 or 2,58±0,70 vs. 3,4±1,13 (LV); p&lt;0,01). HLHS subgroups with a large rudimentary LV (n=25) showed lower septal perfusion, areas of non-viable myocardium (20.8 vs 3%) and a lower cardiac index (2.3±0.7 vs. 3.3±0.8 l/m 2 /min; p&lt;0,05). The diameter of the pre-coronary segment of the hypoplastic aorta did not correlate with myocardial blood flow. All HLHS patients had patent epicardial coronary arteries. Conclusion: The global impairment of coronary flow reserve in HLHS patients after Fontan may indicate altered vasoreactivity due to extensive aortic surgery. Furthermore, in HLHS subgroups with a large rudimentary LV, scar tissue and a reduced cardiac index can be observed. These findings may be of prognostic significance for the long-term outcome in HLHS.
Abstract 12939: <sup>18</sup> F-Sodium Fluoride Positron Emission Tomography for Molecular Imaging of Coronary Atherosclerosis Based on Computed Tomography Analysis
Authors: Toshiro Kitagawa, Hideya Yamamoto, Shinya Toshimitsu, Ko Sasaki, Atsuhiro Senoo, Yutaka Hirokawa, Yasuki Kihara
Journal: Circulation (2016)

Background: Arterial 18 F-sodium fluoride ( 18 F-NaF) uptake on positron emission tomography (PET) has been reported to reflect active atherosclerosis with osteogenesis and inflammatory stimulus. We evaluated the relation of 18 F-NaF uptake to computed tomography (CT)-based coronary atherosclerosis. Methods: We enrolled 25 patients with ≥1 coronary atherosclerotic lesions detected on cardiac CT, who underwent 18 F-NaF PET/CT. Each lesion was evaluated with luminal stenosis and plaque types (calcium plaque = CP, non-calcified plaque = NCP, and partially calcified plaque = PCP) on coronary CT angiography. For CP and PCP, focal calcium density and volume were measured on plain CT images. For NCP and PCP, the presence of CT-based high-risk features (minimum CT density ≤30 Hounsfield units, and vascular remodeling index ≥1.1) was determined. Focal 18 F-NaF uptake of each lesion on PET/CT was quantified by maximum tissue-to-background ratio (TBR max ). Results: A total of 87 lesions were studied. In a patient-based analysis, 12 patients having a past history of myocardial infarction or unstable angina showed higher maximum TBR max per patient than those without (Fig 1). In a lesion-based analysis, PCP had higher TBR max than CP and NCP, and the lesions with high-risk features had higher TBR max than those without (Fig 2, 3), while TBR max did not correlate with focal calcium density (r = 0.05, p = 0.65) or volume (r = 0.18, p = 0.12). On multivariate analysis adjusted for the presence of &gt;50% stenosis, focal calcium density and volume, and location of lesions, the plaque type of PCP showed a significant correlation with increased TBR max (β = 0.57, p &lt; 0.0001). Conclusions: Coronary arterial 18 F-NaF uptake, independently of calcium amount, is related to the heterogeneous and high-risk features of coronary atherosclerosis based on CT analysis. 18 F-NaF PET/CT may provide a new molecular imaging approach to identify high-risk patients and coronary lesions, in combination with cardiac CT.
Abstract 18743: Diagnostic and Prognostic Value of Gremlin-1 In Patients With Acute Congestive Heart Failure
Authors: Michael Behnes, Martina Brueckmann, Siegfried Lang, Parviz Ahmad-Nejad, Michael Neumaier, Martin Borggrefe, Ursula Hoffmann
Journal: Circulation (2013)

PURPOSE: Gremlin-1 is an inhibitor of bone morphogenetic proteins regulating cardiomyocyte formation. Gremlin-1 is involved in fibrotic and inflammatory processes and correlates with the degree of cardiac fibrosis. Congestive heart failure is characterized by an adverse structural remodelling of the myocardium. This study evaluates serum levels of Gremlin-1 in patients being suspected of acute congestive heart failure (aCHF) in the emergency department. PATIENTS AND METHODS: 401 patients presenting with symptoms of acute dyspnea and/or peripheral edema in the emergency department were evaluated. Patients were followed up to five years after presentation in the emergency department. Blood samples for measurement of Gremlin-1 (Human Grem1 ELISA®, USCN Life Science Inc.), Osteopontin (OPN) (R&amp;D Systems, Inc.) and NT-proBNP (Dimension System, Siemens AG) were collected at the initial clinical presentation. RESULTS: Median Gremlin-1 levels were significantly higher in patients with aCHF (291 ng/ml, n=122) as compared to patients without aCHF (205 ng/ml, n=279) (p=0.0001). Median Gremlin-1 correlated significantly with OPN (r=0.16, p=0.002) and NT-proBNP (r=0.24, p=0.001). Median Gremlin-1 levels were higher in patients with a left ventricular (LV) dysfunction (258 ng/ml, n=91) compared to patients with a normal LV function (221 ng/ml, n=135) (p=0.05). Median Gremlin-1 levels were higher in ACC/AHA class C/D patients (246 ng/ml, n=215) compared to class A/B patients (208 ng/ml, n=133) (p=0.02). Median Gremlin-1 levels were significantly higher in patients being rehospitalized because of aCHF (1 year: 477 ng/ml (n=34) vs. 215 ng/ml (n=367), p=0.0001; 5 years: 301 ng/ml (n=73) vs. 212 ng/ml (n=328); p=0.001) and in patients who died during follow-up (1 year: 255 ng/ml (n=57) vs. 218 ng/ml (n=344), p=0.04; 5 years: 229 ng/ml (n=129) vs. 210 ng/ml (n=272); p=0.08). CONCLUSIONS: Gremlin-1 serum levels were increased in patients suffering from aCHF. Gremlin-1 correlated with OPN, NT-proBNP, functional NYHA and structural AHA/ACC classification. Increased Gremlin-1 levels were associated with long-term aCHF related rehospitalization and all-cause mortality after 5 years.
Abstract 18829: Cardiac Resynchronization Therapy Among Patients With Heart Failure With Reduced Ejection Fraction and Right Bundle Branch Block: A United States Population Based Study
Authors: Marjan Mujib, Nabila K Mazumder, Dhaval Kolte, Sahil Khera, Chandrasekar Palaniswamy, Prakash Harikrishnan, Sachin Sule, Wilbert S Aronow, William H Frishman, Gregg C Fonarow, Ali Ahmed
Journal: Circulation (2013)

BACKGROUND: Little is known about the efficacy of cardiac resynchronization therapy (CRT) in patients with heart failure with reduced ejection fraction (HFREF) and right bundle branch block (RBBB). The objective of this study was to assess utilization of CRT in the United States, selected inpatient outcomes, and associated patient and hospital characteristics. METHODS: We screened hospital discharges from the 2002-2010 Healthcare Cost and Utilization Project Nationwide Inpatient Samples. ICD-9-CM diagnosis codes 428.20-428.23 were used to identify primary HFREF and ICD-9-CM code 426.4 was used to identify any RBBB. Patients who underwent CRT were identified using ICD-9-CM procedure codes. Discharge weights were used to measure national estimates. Outcomes ascertainable from these data and associated hospital and patient characteristics were analyzed. RESULTS: Of 13,590 HFREF patients with RBBB, only 1368 (10%) underwent CRT during 2002-2010 in the United States. No CRT was done in 2002. Utilization of CRT among HFREF with RBBB patients increased from 0.4% in 2003 to 20% in 2010 (50 times increase, P for Trend &lt;0.001). Predictors of CRT utilization were younger age, male gender, white race, elective admission, urban-teaching hospital, private insurance status and &lt;2 comorbidities. Compared to patients who did not receive CRT, those with CRT had significant shorter length of stay (4.7 vs. 5.1 days, P&lt;0.001), but higher in-hospital charges (135,099 vs 33,400 USD, P&lt;0.001). Overall, in-hospital mortality rate was 2.5% (335/13,590); however, not a single in-hospital death occurred among those who received CRT. CONCLUSIONS: The numbers (and proportions) of CRT among HFREF with RBBB patients in the United States increased steadily increased from 2002 to 2010. CRT recipients had a significant reductions in hospital length of stay and increases in hospital charges. Further studies are needed to estimate the association of CRT and long-term outcomes.
Abstract 18756: Apelin is Crucial for the (Pro-Inflammatory) Activation of Endothelial Cells in Advanced Plaque Progression
Authors: Dennie Tempel, Wijnand den Dekker, Petra Burgisser, Gerard Pasterkamp, Caroline Cheng, Henricus Duckers
Journal: Circulation (2013)

Recent findings have linked activation of endothelial cells (ECs) into a more pro-inflammatory phenotype with new vessel growth in atherosclerotic plaques, and plaque destabilization. Apelin signaling is a potent vascular regulatory pathway that mainly functions through ECs. Apelin levels are increased in human atherosclerotic lesions, but the effect of apelin on advanced atherosclerotic lesions remains unknown. Apelin infusion in ApoE KO mice with advanced lesionsresulted in enhanced plaque vulnerability without altering the lesion size ( P &lt;0.01, n=10). Apelin proved to increase plaque neovascularization and hemorrhaging ( P &lt;0.05, n=10). In addition, apelin infusion resulted in endothelial expression of adhesion factors and cytokines, e.g. VCAM-1 and MCP1 ( P &lt;0.05, n=10). In line, in vitro analysis demonstrated that apelin acts synergistically with the pro-inflammatory cytokine, TNFα, in enhancing the endothelial expression of adhesion factors and cytokines, including VCAM-1 and MCP1 ( P &lt;0.05, n=6) and loss of the endothelial barrier function ( P &lt;0.05, n=6) . In addition, apelin activates eNOS by phosphorylation and may thereby aggravating the pro-inflammatory state of the ECs, by ROS generation. For, apelin enhanced phosphorylated eNOS in cultured ECs under all conditions ( P &lt;0.05, n=6), whereas ROS production was only augmented by apelin when combined with TNFα ( P &lt;0.05, n=6). We provide for the first time, evidence for the role of apelin in advanced plaque destabilization by promoting growth of the intraplaque vasculature and by activation of endothelial cells into a disease-prone phenotype.
Abstract 18773: Discovery and Translation of Novel Long Intergenic Non-Coding RNAs in Inflammatory Cardio-Metabolic Disorders
Authors: Xuan Zhang, Jane F Ferguson, Chenyi Xue, Yichuan Liu, Christine Hinkle, Mingyao Li, Muredach Reilly
Journal: Circulation (2013)

Objective: The purpose of this study is to identify long intergenic non-coding RNAs (LincRNAs) modulated by inflammation utilizing human experimental endotoxemia and to explore their association with cardiometabolic traits. Methods and results: We performed deep high-throughput RNAseq (~500 million reads per sample) in adipose tissue and whole blood of a healthy subject before and after endotoxin (LPS 1 ng/Kg) administration. Of 8,179 LincRNAs identified by Cabili et al (Gene &amp; Development 2011. 25:1915-1927), we detected 514 present in adipose and 266 in blood, with 69 (13.6%) and 56 (21.2%) LincRNAs respectively modulated by LPS with just six LPS-modulated lincRNAs overlapping in both tissues. In both tissues, LincRNAs had lower expression and more tissue specificity than protein coding RNAs. RNAseq of adipose and blood in 2 additional individuals during endotoxemia was used to confirm findings and qPCR used to validate top findings in an additional 7 study participants. Linc-ARFIP1-4 and Linc-CMC1-2 were consistently reduced by LPS in blood, but not in adipose. Interestingly, Linc-DMRT2 and Linc-TP53I13, the top adipose LPS-modulated LincRNA, was more abundant in human primary adipocytes than monocyte and macrophage cultured in vitro while adipose samples obtained from obese subjects exhibited lower Linc-DMRT2 and Linc-TP63I13 expression (77% and 50% lower respectively, P&lt;0.05) compared to lean individuals (N=10/group). To further investigate biological roles, we generated lentiviral-vectors with short hairpin RNAs (shRNAs) targeting Linc-DMRT2 and Linc-TP53I13 as well as Linc-AQPEP, the top expressed adipose-specific LincRNA. Preliminary studies demonstrated more than 50% knockdown of these lincRNAs in human adipocytes with shRNA application and functional studies are ongoing to characterize their impact on adipocyte differentiation, lipid storage and insulin sensitivity. Conclusion: These novel data from a human endotoxemia experiment suggest that inflammatory modulation of adipose LincRNAs might modulate adipose functions in cardio-metabolic disorders.
Abstract 12949: Elamipretide ( <i>Bendavia</i> <sup>TM</sup> ) Restores 4-Hydroxy-2-Nonenal Protein Adducts and Aldehyde Dehydrogenase-2 Activity and mRNA Expression in Left Ventricular Myocardium of Dogs With Advanced Heart Failure
Authors: Ramesh C Gupta, Vinita Singh-Gupta, Kefei Zhang, Jiang Xu, Hani N Sabbah
Journal: Circulation (2016)

Background: 4-hydroxy-2-nonenal (4HNE), a reactive aldehyde, is generated in the failing heart and contributes to cardiomyocyte injury and death. Aldehyde dehydrogenase-2 (ALDH2) plays a key role in detoxifying mitochondrial (MITO) reactive aldehydes. We showed that chronic therapy with elamipretide (ELA), a novel MITO targeting peptide, improves LV systolic function, normalizes MITO function and reduces the burden of reactive oxygen species (ROS) in LV of dogs with microembolization-induced heart failure (HF). Hypothesis: This study tested the hypothesis that chronic therapy with ELA normalizes protein levels of 4-HNE-adducts and ALDH2 activity and expression in LV myocardium of HF dogs (LV ejection fraction ~30%). Methods: LV tissue from 14 HF dogs randomized to 3 months therapy with subcutaneous injections of ELA (0.5 mg/kg once daily, n=7) or subcutaneous injections of saline (control, CTR, n=7) and tissue from 6 normal (NL) dogs was used in the study. Level of 4-HNE-protein adducts was quantified using an Elisa kit. ALDH2 activity was assayed spectrophotometrically in LV MITO fractions by monitoring NADH formation from NAD to NADH at 340 nm. Protein levels of ALDH2 and porin (an internal loading control) were determined by Western blotting and band intensity quantified in densitometric units (du). mRNA expression of ALDH2 and GAPDH was measured in using real-time PCR. Results: Data are shown in the table. Levels of 4HNE-protein adducts were significantly increased and ALDH2 activity, mRNA expression and protein levels significantly decreased in CTR compared to NL dogs. ELA normalized 4-HNE levels, ALDH2 activity and expression. There were no differences in the level of porin or GAPDH among the 3 study groups. Conclusions: Chronic therapy with ELA normalizes ALDH2 and 4-HNE levels in LV myocardium of HF dogs. By limiting myocardial ROS burden, ELA contributes to cardiac end-organ protection and hence, to overall improvement in global LV function.
Abstract 18851: Cardiovascular Disease: The Leading Cause of Pregnancy-Related Death in California 2002-2005
Authors: afshan B hameed, Elyse Foster, Christy McCain, Christine Morton, Elliott Main
Journal: Circulation (2013)

Introduction: The California Pregnancy-Associated Mortality Review (CA-PAMR) was started in 2006 by the California Department of Health, Maternal, Child, and Adolescent Health Division in response to rising rates of maternal mortality with the goal of understanding and reducing maternal morbidity and mortality. Methodology: CA-PAMR uses an enhanced surveillance methodology to identify and investigate maternal deaths, as described previously. An expert committee reviewed medical records to determine pregnancy-related deaths, their clinical causes, contributing factors and opportunities for quality improvement. Results: From 2002-2005, there were 2,147,492 live births and 732 women died while pregnant or within 1 year of pregnancy. Among them, 207 were determined to be pregnancy-related: 53 were from cardiovascular disease (CVD) and two-thirds (n=33) of those from cardiomyopathy (CMP). Compared to women who died from non-cardiac causes, women who died from any CVD were twice as likely to be African-American (39% vs. 17%, p&lt;.01) and obese (BMI&gt;30) (42% vs. 26%, p&lt;.05), and had documented substance abuse during pregnancy (27% vs. 10%, p&lt;.01) and to die ≥ 42 days postpartum (31% vs. 6%, p&lt;.01). Almost a quarter (22%) of CVD deaths had a concomitant diagnosis of hypertension or preeclampsia. Similarly, the CMP deaths were three times as likely to be African-American (46% vs. 18%, p&lt;.01), twice as likely to be obese (47% vs 27%, p&lt;.05), four times as likely with substance abuse (37% vs. 9%, p&lt;.01), and to die ≥ 42 days postpartum (46% vs. 5%, p&lt;.01). Concomitant diagnosis of hypertension or preeclampsia occurred in 30% of CMP deaths. Overall, for those diagnosed before death (n=29), the mean time from symptom onset to diagnosis was 26 days (range=0, 223 days) and from diagnosis to death was 79 days (range 0, 347 days). Patient and health care provider factors were identified as having contributed to 86% and 71% of the deaths respectively, and 30% of the CVD deaths were considered potentially preventable. Conclusion: Medical expert review of maternal deaths has provided additional insight into CVD deaths that occur during or after pregnancy. Earlier recognition and referral of a symptomatic patient by obstetric providers may help prevent serious morbidity and mortality.