tbuckley/cabot-search huggingface dataset:
Abstract 19327: Reduced Handgrip Strength Predicts Clinical Outcomes in Patients with Advanced Heart Failure Undergoing Ventricular Assist Device Placement
Authors: Christine J Chung, Christina Wu, Orlanda Ferreira, Meaghan Jones, Tomoko S Kato, Hiroo Takayama, Yoshifumi Naka, Daniel E Forman, Donna M Mancini, Paul Christian Schulze
Journal: Circulation (2012)

BACKGROUND: Heart failure (HF) is a systemic syndrome associated with derangement of skeletal muscle structure and metabolic function which contributes to diminished exercise tolerance, patient frailty and increased morbidity and mortality. The objective of this study was to evaluate handgrip strength as a marker of muscle function and frailty for prediction of clinical outcomes after ventricular assist device (VAD) implantation in patients with advanced HF. METHODS: Handgrip strength was measured in 53 patients with advanced HF 2.6±5.2 days prior to VAD implantation and over 6 months following surgery. We analyzed dynamics in laboratory values, post-operative complications and 30-day mortality. RESULTS: There was no difference in grip strength of the dominant versus non-dominant hands at baseline and up to 6 months after VAD implantation. Baseline handgrip strength correlated with levels of albumin (r=0.29, p=0.04). Handgrip strength progressively improved, with a statistically significant increase seen at four months and sustained at 6 months following VAD implantation (non-dominant hand: 13±28% increase at 4 months and 18±34% at 6 months, p&lt;0.05 versus baseline). Receiver operating characteristic curve analysis determined that handgrip strength&lt;30% of body weight distinguished patients with greater likelihood of early post-operative mortality with a sensitivity of 72% and specificity of 80% (area under curve 0.8). Patients with handgrip strength&lt;30% of body weight had 83% survival during the first 30 days after VAD implantation compared to 100% in those with handgrip strength &gt;30% of body weight. CONCLUSION: Patients with advanced HF lose the difference in grip strength between the dominant and non-dominant hands seen in normal reference populations further supporting the existence of a global myopathy in advanced HF. Non-dominant handgrip strength less than 30% of body weight is associated with higher mortality in the early postoperative period following VAD implantation. These findings indicate that measures of skeletal muscle function and patient frailty may have important prognostic value in the pre-operative evaluation of patients with HF undergoing VAD placement.
Abstract 19592: Exercise Training Prevents Obesity Normalizing Cardiac Mirna-208a and Med13 Levels in Obese Zucker Rats
Authors: Tiago Fernandes, Diego L Barretti, Ursula P Soci, Edilamar M Oliveira
Journal: Circulation (2012)

Aerobic exercise training (ET) has been established as an important treatment for obesity, since it counteracts aberrant cardiac metabolism and weight gain; however, underlying mechanisms remain to be further determined. MicroRNAs (miRNAs) inhibit protein expression by base-pairing with the 3’ UTRs of mRNA targets. MiRNA-208a is a cardiac-specific miRNA that regulates β-MHC content and systemic energy homeostasis via MED13, a subunit of the Mediator complex. We investigated whether ET regulates the miRNA-208a and their target MED13 related with the weight loss in obese Zucker rats (OZR). OZR (n=10) and Lean (L, n=10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT) were studied. Swimming ET consisted of 60 min of duration, 1x/day/10 weeks, with 4% caudal body weight workload. OZR groups showed a significant augment in the body weight compared with L groups. However, ET was effective in reducing weight gain in OZRT (59%) compared with OZR group. In accordance, ET reduced 20% visceral fat weight in OZRT compared with OZR group. These alterations were accompanied by resting bradycardia (12%), reduction of triglycerides (57%) and low density lipoprotein (61%) and increased of high density lipoprotein (42%) and peak VO 2 (21%) in the OZRT compared with OZR group. No difference was observed in blood pressure and glucose between groups. Cardiac miRNA-208a levels analyzed by real-time PCR increased 57% in OZR paralleled with a decrease of 39% in MED13 protein levels analyzed by western blot compared with L group. In contrast, ET corrected the cardiac miRNA-208a and MED13 levels in OZRT compared with L group. Furthermore, ET reduced the increased cardiac mass (13%), normalized β-MHC gene and protein levels and improved the loss of diastolic function caused by obesity. These results suggest that ET can prevent weight gain via increased of cardiac MED13 and pathological cardiac hypertrophy via β-MHC reduction by regulation of miRNA-208a, indicating the heart in the systemic metabolic control and the miRNA-208a as potential therapeutic target for metabolic and cardiac disorders.
Abstract 19598: Evaluation of Left Ventricle Function and Oxidative Metabolism in Large Animal Model of Chronic Heart Failure
Authors: Miikka Tarkia, Matti Haavisto, Christoffer Stark, Tommi Vähäsilta, Timo Savunen, Marjatta Strandberg, Virva Lepomäki, Mikko Pietilä, Pekka Saukko, Anne Roivainen, Antti Saraste, Juhani Knuuti
Journal: Circulation (2012)

Background and aims: Large animal model of chronic heart failure (HF) has been difficult to produce. Recently described pig model ofsurgical 2 step occlusion of the left anterior descending (LAD) coronary artery with distal ligation and proximal ameroid constrictor resulted in large anterior myocardial infarct (MI) with reasonable good survival (approx. 75% of animals alive at three months). We wanted to study by echocardiography and positron emission tomography (PET) the effects of proximal ligation of LAD in pig on LV remodelling and oxygen consumption during 3 months of follow-up. Methods: Male farm pigs ageing 3 weeks had either sham operation (control, n=4) or LAD occlusion (HF, n=8). Three months later, LV volumes (Modified Simpsons cylinder formula) were measured by transthoracic echocardiography (TTE). Myocardial kinetics k 1 and mono-exponential clearance rate of 11 C-acetate K mono were measured with PET to assess myocardial perfusion and oxidative metabolism, respectively. Results: None of the controls had MI, whereas seven of eight animals in the HF group had anterior MI scar as confirmed by TTC staining. PET perfusion showed average MI size of 26 ± 17 % of the LV in HF pigs. Echocardiography showed larger LV diastolic and systolic volumes in HF pigs than sham-operated pigs (diastolic volume 302±116 vs.109±28 ml, p=0.03; systolic 202±108 vs. 52±16 ml, p=0.05), whereas EF was lower (37±12 vs. 53±5 %, p=0.03). In the remote non-infarcted myocardium, perfusion and oxygen consumption was lower in HF than control pigs (k 1 0.78±0.13 vs. 1.26±0.41 ml/g/min p=0.01, K mono 0.114±0.024 vs. 0.146±0.008 min -1 , p=0.03). Conclusions: Surgical 2 step occlusion of the left anterior descending (LAD) coronary artery in pigs resulted in large area of myocardial infarction, reduced systolic function and LV remodelling. Consistent with HF, myocardial perfusion and oxygen consumption was reduced. Effects of therapeutic interventions on myocardial perfusion and oxygen consumption can be monitored in this model of chronic HF.
Abstract 19385: Comparison between Oral Rapamycin Plus Bare Metal Stent versus Drug Eluting Stent for the Prevention of Restenosis in the Treatment of Coronary Disease with Percutaneous Coronary Interventions. Four Years Results from the ORAR III Trial
Authors: Alfredo E Rodriguez, Alfredo M Rodriguez-Granillo, Carlos Fernandez-Pereira, Juan Mieres, Gustavo Risau, Bibiana Rubilar, David Antoniucci, Igor F Palacios, Patrick W Serruys
Journal: Circulation (2012)

Background. One and three years results of ORAR III trial previously published showed a significant reduction in costs with oral rapamycin plus bare metal stent (OR) compared with drug eluting stents (DES) without significant differences in death, myocardial infarction (MI) and stroke for the prevention of restenosis. ( NCT00552669 ) Methods: From January 2006 to September 2007 in 3 hospitals in Buenos Aires, Argentina, 200 patients (pts) were randomized either to OR (n=100) or DES (n=100). Primary endpoint compared clinical efficacy and safety of OR vs DES treatment for denovo coronary lesions evaluated by the composite of death, MI and stroke (D,MI,S); Target Vessel Failure (TVF) defined as cardiac death, MI and Target Vessel Revascularization (TVR) and TVR alone at 4 years of follow up. A sub-analysis of pts over and under 65 years old was also done (40 pts in OR and 48 pts in DES ≥ 65 years). OR was given as a bolus of 10 mg the day before PCI followed by 3 mg/daily during the following 13 days. DES group received clopidogrel for at least one year and OR group for a month. Exclusion criteria were MI in the last 24 hours, in stent restenosis and previous PCI in the last six months. Results: Baseline demographic, clinical and angiographic characteristics were similar. 1.6 +/- 0.7 vs 1.7 +/- 0.8 (p=0.3) lesions per pt were treated in OR vs DES respectively, and 171 stents in OR vs 176 in DES groups were deployed (p=0.9). 4 years clinical follow up was accomplished in 99% of pts. In DES group 45.9% of pts were still receiving thyenopiridines vs. 18.9% of OR (&lt;0.001). D,MI,S was 11.0% in OR group vs. 23.0% in DES, p=0.02; TVF was 25.0% in OR vs 37.0% in DES, p=0.06 and TVR was 14.5 % in OR group vs 20.8% in DES group, p=0.17. When analyzing pts ≥ 65 years dyslipemia was the only significantly different baseline characteristic. At 4 years D,MI,S was 7.5% (OR) vs. 25.0% (DES), p=0.03, TVF 22.5% (OR) vs 45.8% (DES); p=0.02 and TVR was 14.0% in OR vs 21.9% in DES groups (p=0.26); there were no differences in outcomes of pts &lt; 65 years old. Conclusions: Four years follow up of this randomized trial revealed significant differences in the composite of death, MI and stroke in favor of OR therapy in overall population and in pts &gt; 65 years old without differences in TVR. No differences were seen between groups under 65 years.
Abstract 9163: Head-to-head Comparison Between the Prognostic Role of Two Functional Tests in a Population of Elderly Patients with Chronic Heart Failure
Authors: Angela Beatrice Scardovi, Renata De Maria, Alessandro Ferraironi, Laura Gatto, Tiziana Di Giacomo, Marco Renzi, Roberto Ricci
Journal: Circulation (2011)

Background The six-minute walk test (6MWT) and the cardio-pulmonary exercise testing (CPx ) provide a valid assessment of functional performance in patients ( pts ) with HF but in elderly pts a comparison on prognostic validity of the 2 techniques has not been yet performed. Aims: We sought to compare the prognostic ability of the two functional tests in risk stratification of elderly CHF pts. Methods: We prospectively followed-up 170 stable HF outpatients on optimized medical therapy by using a thorough clinical, laboratory and instrumental evaluation, including the 6MWT and the CPX . The composite end-point was death or hospitalizations for cardiovascular causes. Results Mean age was 71±11 years, 28 % were female, 43% had ischemic heart disease, 18 % were in NYHA class III, 70% were on beta-blockers, 13% had an advanced diastolic disfunction, echocardiographic left ventricular ejection fraction ( LVEF ) was 44±13 %, mean BNP was 358±482 pg /ml . The mean distance covered during the 6MWT was 329±104 m. Peak workload was 71±11 watts, peak oxygen consumption (PVO2) was 13.2±4 ml/kg/min, the slope of the regression line relating ventilation to CO2 output, (VE/VCO2 slope) was 34±7 Exercise oscillatory breathing was found in 79 pts (46 %). During a median follow-up of 13 months, 18 patients died of cardiovascular causes and overall 51 met the combined end point of death or cardiovascular hospitalization. Distance walked correlated significantly to PVO2 (r=0.47, p&lt;.0001). By Cox multivariable analysis, independent predictors of outcome were mean distance covered during the 6MWT (HR 0.996, CI 95% 0.992-0.999), LVEF (HR 0.962, CI 95% 0.938 - 0.985) and PVO2 (HR 0.883, CI 95% 0.790-0.987). Conclusions: Among elderly CHF pts 6MWT is not only a simple and reliable first-line test for quantification of exercise intolerance but retains a prognostic value independent of CPX derived PVO2. This is a cornerstone in functional assessment because the 6MWT is widely diffused, safe and may be more feasible than CPX in a population of elderly HF pts.
Abstract 19413: Regulation of I <sub>Ks</sub> Current Amplitude by Differential Trafficking Patterns and Interactions Of KCNQ1 and KCNE Subunits
Authors: Yuhong Wang, Min Jiang, Mei Zhang, Scott Henderson, Gea-Ny Tseng
Journal: Circulation (2012)

KCNQ1 (Q1, pore-forming subunit) and KCNE1 (E1, modulatory subunit) associate to form the slow delayed rectifier (I Ks ) channel that functions as ‘repolarization reserve’ in human heart. We have shown that in adult guinea pig (GP) cardiomyocytes Q1 &amp; E1 cluster to different subcellular compartments, and the degree of Q1/E1 colocalization affects the I Ks amplitude. We have also shown that KCNE2 (E2) is expressed in human heart, and can associate with Q1 or Q1/E1 to suppress the I Ks amplitude. Objectives: To study the patterns of trafficking and interactions of Q1, E1 and E2. Methods: Q1, E1 and E2 are labeled with eGFP (Q1-G) or mono-dsR (Ex-R, x = 1 or 2) and expressed in COS-7 cells, neonatal rat (NRVM) and adult GP (AGPV) ventricular myocytes; the latter 2 by adenoviral (Adv) gene transfer. Protein trafficking/interactions are monitored by live cell imaging, in conjunction with patch clamping, immunocytochemistry &amp; immunoblotting. Results: Time courses of Q1-G &amp; Ex-R distribution in COS-7 cells suggest that they are translated, packaged and shipped to the cell surface independent of each other. They meet on the cell surface and form Q1-G/Ex-R complexes. Q1-G/Ex-R complexes are endocytosed and colocalized in a cytosolic tubulo-vesicular system. We identify 2 main effects of Ex-R on Q1-G trafficking: (1) Ex-R accelerates Q1-G recovery after photobleaching, (2) 24-48 hr after transfection, E2-R brings Q1-G with it to lysosomes for increased degradation. The distribution patterns of Q1-G and Ex-R in NRVM are similar to those in COS-7 cells. However, under the same Adv incubation conditions, Q1-G and Ex-R are expressed at a much lower level in AGPV than NRVM. In AGPV, Q1-G is distributed mainly as cytosolic striations while Ex-R mainly on cell surface, similar to the native Q1 and Ex immunofluorescence patterns seen in control myocytes. Conclusions: Assembly of Q1 &amp; E1 into I Ks does not occur early during biogenesis. Q1 &amp; E1 meet after they reach the plasma membrane and travel together thereafter. E1 increases the mobility of Q1, while E2 increases Q1 degradation in lysosomes. In adult cardiomyocytes the expression levels and subcellular distribution patterns of Q1 &amp; Ex are tightly regulated, with the sarcomere structure playing a key role in Q1 localization.
Abstract 8900: Urinary β <sub>2</sub> -Microglobulin-Creatinine ratio is Associated with High Risk in Chronic Heart Failure Patients
Authors: Yoichiro Otaki, Hiroki Takahashi, Tetsu Watanabe, Tetsuro Shishido, Akira Funayama, Shinpei Kadowaki, Taro Narumi, Shunsuke Netsu, Shintaro Honda, Hiromasa Hasegawa, Mitusnori Ishino, Satoshi Nishiyama, Takanori Arimoto, Takehiko Miyashita, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2011)

Background It has been reported that renal dysfunction has strong association with clinical outcomes in chronic heart failure (CHF) patients. Recent study demonstrated that several urinary markers were related to cardiac prognosis in CHF patients. Urinary μ 2 -microglobulin-creatinine ratio (UBCR) is a marker for renal tubular damage (RTD) and related to rapid deterioration of renal function. However, association between UBCR and cardiac prognosis has been not studied. The purpose of the present study was to examine whether: (1) UBCR is correlated with severity of heart failure; and (2) UBCR can predict clinical outcomes in CHF patients. Methods and Results We measured UBCR, urinary microalbumin-creatinine ratio, N-acetyl-beta-D-glucosamidase and estimated glomerular filtration rate (eGFR) in 193 CHF patients. Patients were prospectively followed during a median follow up period of 353 days. There were 46 cardiac events, including 10 cardiac deaths and 36 re-hospitalizations for worsening heart failure. Levels of UBCR increased with advancing NYHA functional class. Patients with cardiac events had higher levels of UBCR than those without. In the univariate Cox proportional hazard analysis, age, NYHA functional class, brain natriuretic peptide, eGFR and UBCR were independent risk factor for cardiac events. A multivariate Cox proportional hazard analysis revealed that UBCR is an independent predictor of cardiac events in CHF patients. We defined RTD as UBCR &gt; 300 μg/g according to our previous report. Kaplan-Meier analysis demonstrated that cardiac event rate was higher in patients with RTD than in those without. In addition, Kaplan-Meier analysis demonstrated that RTD could strictly classify the prognosis of CHF patients without chronic kidney disease. Conclusion UBCR was related to the severity of heart failure and associated with high risk in CHF patients. RTD, as implicated by UBCR, could add clinical information about cardiac prognosis in CHF patients.
Abstract 19631: MicroRNAs Modulation in a Mice Model of Physiological Left Ventricular Hypertrophy
Authors: Nidiane C Martinelli, Carolina R Cohen, Stefanie Schneider, Stefanie Schneider, Katia Dos Santos, Michael E Andrades, Nadine Clausell, Andreia Biolo, Luis E Rohde
Journal: Circulation (2012)

INTRODUCTION: Physiological left ventricular hypertrophy (LVH) has distinct phenotypic adaptations that might me modulated by microRNAs (miRs) which are fine-tune regulators of gene expression. We tested the hypothesis that physiological LVH has differential miRs expression in mice subjected to a voluntary exercise protocol. METHODS: Balb/c mice were kept in cages with exercising wheels (Exercise group - EXE; n=15 sacrificed on day 7 and n=17 sacrificed 35 days after training) or in cages without wheels (Sedentary group - SED; n=12 in each time point). LVH was evaluated by the left ventricular weight/body weight ratio (LVW/BW). MiRs were extracted with miRNeasy kit (Qiagen, USA). A microRNA microarray based on the miRBase version 16 (LC Sciences, Houston, Texas, EUA) was carried out using a pool of miRs extracted from the LV. After miR extraction, 50 pM of synthetic cel-miR-39 were spiked-in as a standard control. RT-qPCR was performed with microRNA Reverse Transcription Kit® and TaqMan Probes® (Applied Biosystems Inc., USA). RESULTS: After 7 days of training there was an increase of 7% in LVW/BW ratio on EXE compared to SED group (3.6±0.2 vs. 3.3±0.1, respectively; p=0.004) and this result was sustained at 35 days (12% increase; 3.7±0.2 vs. 3.3±0.1, respectively; p&lt;0.001). 7 DAYS analyses: expression of miR-26b and miR-143 was decreased in the EXE compared to the SED group (0.5-fold, p=0.017 and 0.7-fold, p=0.018, respectively). miR-150 showed an increased expression in the EXE group (3.0-fold, p=0.001). 35 DAYS analyses: expression of miR-27a was down-regulated (0.8-fold, p=0.03), while miR-150 was up-regulated (1.9-fold, p=0.016) in the EXE group. miRs previously described to be involved in cardiovascular diseases (miR-21, miR-195 and miR-499) were similar between groups. CONCLUSIONS: Our data suggest that physiological LVH was associated to significant modulation of miRs that might regulate affect metabolic adaptations (miR-26b:GSK3B) and apoptosis pathway activation (miR-150:FOXO4). Also miRs could have an effect on cellular growth and hypertrophy (miR-27a:IGF1 and miR-143:MTPN).
Abstract 19333: Ectonucleoside Triphosphate Diphosphohydrolase-1 (ENTDP-1/CD39) Regulates the Inflammatory Response in a Murine Model of Venous Thrombosis
Authors: Yogendra Kanthi, Jessica J Ray, Nataliya N Dolgacheva, Matthew C Hyman, Keigo Fukase, Anuli C Anyanwu, Nadia R Sutton, Scott H Visovatti, Hui Liao, Amy Baek, Sascha N Goonevardena, Jose A Diaz, Thomas W Wakefield, David J Pinsky
Journal: Circulation (2012)

Background: Deep vein thrombosis (DVT) is a major health concern in the United States, carrying significant morbidity, mortality and socioeconomic cost. CD39 (ectonucleoside triphosphate diphosphohydrolase 1) is a circulating and membrane-spanning protein on the surface of endothelial and some leukocyte populations that is responsible for the phospohydrolysis of ATP to ADP and ADP to AMP. We hypothesized that CD39 plays a protective role in modulating inflammatory responses in a murine model of DVT. Methods: C57BL/6 (WT) and CD39-/- mice underwent inferior vena cava (IVC) ligation. IVCs were harvested at 48h and 6 days post IVC ligation. Vena cava and thrombi were characterized. Leukocytes infiltrating the vein wall were quantified per high power field (hpf) by H&amp;E. Additionally, gene expression of macrophage markers was evaluated using qRT-PCR. Results: Thrombosed IVC weights were higher six days post IVC ligation in CD39-/- mice compared to IVC-ligated WT mice (35.6 mg ± 4.0 vs. 19.5 ± 2.6, n=3 per group, p&lt;0.05, respectively). Additionally, CD39-/- mice had a trend toward increased leukocyte infiltration into the vessel wall at all timepoints with an 80% increase in total leukocytes at 48h (225 ± 26 cells/hpf, n=3 vs. 124 ± 29 cells/hpf n=4, p=0.061, respectively), driven by neutrophilic (PMN) predominance (181 ± 15 cells/hpf, n=3 vs. 103 ± 23 cells/hpf, n=4, p 0.046, respectively) followed by a later trend toward increased macrophage and lymphocyte infiltration in CD39-/- mice. Consistent with these findings, CD39 gene-deletion was associated with a &gt;40-fold increase in mRNA expression of CCR2 (52.35 ± 0.73 vs. 1.17 ± 0.10, n=2 per group, p&lt;0.0002, respectively), a marker of pro-inflammatory macrophages, in the vessel wall compared to WT 6 days post IVC ligation. CD39-/- mice also had 15-fold increased expression (9.62 ± 0.43 vs. 0.62 ± 0.56, n=2 per group, p=0.006, respectively) of CD301b versus WT mice 6 days post IVC ligation. Conclusion: CD39 appears to be a critical regulator of the early and late inflammatory responses in murine DVT with increased thrombus burden, leukocyte infiltration and inflammation-related gene expression in CD39 gene-deleted mice. CD39 may serve a previously unexplored, protective role in the pathophysiology of DVT.