tbuckley/cabot-search huggingface dataset:
Abstract 9278: Neutrophil to Lymphocyte Ratio is associated with All-cause, Cardiovascular and Ischemic Heart Disease Mortality: the National Health and Nutrition Examination Survey
Authors: Kaustubh C Dabhadkar, Abhishek J Deshmukh, Jawahar L Mehta, Arshed A Quyyumi, Peter W Wilson
Journal: Circulation (2012)

Introduction: The neutrophil to lymphocyte (NTL) ratio has emerged as a predictor of mortality following acute coronary syndrome, but the predictive role of NTL ratio on mortality has not yet been studied in epidemiologic study. Objective: We examined association between NTL ratio and risk of all-cause, cardiovascular (CVD) and ischemic heart disease (IHD) mortality in a nationally representative cohort. Methods: Participants between ages 30 and 74 enrolled in the National Health and Nutrition Examination Survey (NHANES) III study from 1988 to 1994 had WBC count with differential, and known CVD risk factors (age, sex, race, BMI, diabetes, hypertension, smoking history, total cholesterol, HDL cholesterol, history of CVD, family history of CVD, medication use) measured. All-cause, CVD and IHD mortality through 2006 were obtained via linkage with the National Death Index. Cox proportional hazards model was used to estimate hazards ratio (HR) and 95% confidence interval (CI) for mortality after adjusting for known CVD risk factors and total WBC count. Results: 10296 participants (mean age 50 ± 13.5 years, 52.8 % females, and 39.3 % ethnic minorities) had complete data. Mean NTL ratio was 2 ± 1. During 140, 958 person-years follow-up (median follow-up: 14.4 years), there were 2188 deaths including 674 CVD deaths and 502 IHD deaths. In multivariate analysis, comparing participants in NTL ratio quartile 4 to quartile 1, the adjusted HR was 1.37 (95% CI, 1.21-1.56) for all-cause mortality, 1.58 (95% CI, 1.25-1.99) for CVD mortality, and 1.75 (95% CI, 1.33-2.3) for IHD mortality. Increasing quartiles of NTL ratio were a strong marker of risk for future all-cause, CVD and IHD mortality (p for trend &lt; 0.001 for each outcome). Conclusion: In a nationally representative sample of US adults, higher NTL ratio conveyed greater hazard for all-cause, CVD and IHD mortality. NTL ratio may reflect a simple, yet effective marker of cardiovascular risk and merits further study.
Abstract 9356: Pre-procedure C-reactive Protein and Erythrocyte Sedimentation Rate but not Lipoprotein-associated Phospholipase A2 Predict Clinical Outcomes after Drug-eluting Stents Implantation in Patients with Stable Coronary Disease on Chronic Statin Therapy
Authors: Yuri Karpov, Vitaly Buza
Journal: Circulation (2012)

Background: Pre-procedure high-sensitive C-reactive protein (hs-CRP) level has a prognostic value after PCI. There are few data about the value of other inflammation markers: lipoprotein-associated phospholipase A2 (Lp-PLA2), erythrocyte sedimentation rate (ESR), white blood count (WBC) in predicting periprocedural and long-term outcomes after drug-eluting stent (DES) especially in patients on chronic statin therapy. Methods: A total of 602 patients (mean age 60.4±9.4 years, 86.0 % males) with stable CAD on chronic statin therapy underwent successful PCI with at least one DES implanted. Baseline demographic, procedural characteristics, Lp-PLA2, hs-CRP, ESR, WBC were collected. Tn I was assessed in all patients 12-18 h after the PCI. Periprocedural MI was defined as measure of the Tn I of more than three times the 99th percentile of the upper reference limit. The patients were prospectively followed before discharge with 1 year of follow-up. Results: During the in-hospital period major adverse cardiovascular events (MACE) (death, myocardial infarction (MI), stroke, stent thrombosis (ST)) occurred in 10.6% of the patients. Incidence of MACE was essentially due to periprocedural MI (10,3%). Multivariate logistic regression identified ESR level (OR 1.018 95% CI 1.004-1.032, p=0.013) before PCI and total length of stents implanted (OR 1.023, 95% CI 1.008-1.037, p=0.002) as independent predictors of MACE before discharge. At 1 year of follow-up MACE (death, MI, [[Unable to Display Character: с]]linically-driven target lesion revascularization (TLR)) occurred in another 9.3% of the patients. TLR was performed in 5.4% of the patients. Multivariate logistic regression identified baseline hs-CRP (OR 1.7, 95% CI 1.13-2.56, p=0.01) and ESR (OR 2.25, 95% CI 1.21-4.19, p = 0.011) levels, stenting CABG grafts (OR 8.34, 95% CI 1.95-35.6, p = 0.004) as independent predictors of MACE at 1 year. hs-CRP (OR 1.75, 95% CI 1.15-2.67, p = 0.009) and ESR (OR 2.42, 95% CI 1.15-5.13, p = 0.02) levels were independent predictors of TLR at 1 year. WBC and Lp-PLA2 were not predictive of MACE neither acutely nor at 1 year. Conclusion: Pre-procedure CRP and ESR but not Lp-PLA2 and WBC levels correlate with clinical outcomes including TLR in patients with stable CAD on chronic statin therapy undergoing DES implantation.
Abstract 9118: Inhibition Of Interleukin-1 Activity By Anakinra Improves Endothelial, Coronary And Aortic Function In Patients With CAD And Coexistent Rheumatoid Arthritis By Reducing Apoptosis And Oxidative Stress
Authors: Ignatios Ikonomidis, Stavros Tzortzis, Ioanna Andreadou, George Pavlidis, Chrysoula Katseli, Pelagia Katsimbri, Ioannis Paraskevaidis, John Parissis, Maria Anastasiou-Nana, John Lekakis
Journal: Circulation (2012)

Background: Interleukin-1 mediates atherogenesis and coronary vasoreactivity. Anakinra, a human recombinant interleukin-1a receptor antagonist, is used forthe treatment of rheumatoid arthritis (RA) and shows favourable effects onendothelial and arterial function in RA patients. We investigated the effects of anakinra on coronary endothelial and arterial function in CAD patients with coexistent RA. Methods: Forty patients with chronic CAD and RA were randomized to receive a single injection of anakinra (100mg s.c.) or placebo and after 48 hours the alternative treatment in a double-blind trial and 23 age and sex matched subjects with similar risk factors served as controls. At baseline and 3 hours after treatment we assessed a) coronary flow reserve (CFR) of the LAD using Doppler echocardiography, b) aortic strain (AS), c) flow mediated endothelial dependent dilation of the brachial artery (FMD) by ultrasonography d) soluble Fas, Fas ligand, nitrotyrosine (NT) and protein carbonyls (PC) serum levels. All controls had no clinical history for CAD and a negative for ischaemia treadmill exercise test. Results: Patients had impaired FMD, CFR and AS compared to controls(p&lt;0.001). At baseline, NT was related with AS and FMD (r=-0.401 andr=-0.386),while Fas and FasL with CFR (r=-0.450 and r=-0.362) (p&lt;0.05). After 3 hours of anakinra treatment, there was an improvement in FMD, CFR and AS compared to placebo, reaching values similar to those in controls (FMD: 5.1±2.3%, vs.13.9±3.5% vs. 8.1±3.6%, p=0.006, CFR: 2.1±0.7 vs. 3.0±1.1 vs.3.4±0.7, p&lt;0.001, AS: 4.4±2.3% vs. 9.6±3.6% vs. 8.0±2.8 %, p=0.003). Furthermore, there were a decrease in NT (median 6.66 vs. 6.15 nM/L), PC (0.131vs. 0.091 nmol/mg protein), Fas (51.8 vs. 49.3 pg/ml) and FasL levels (47.6 vs. 40.95 pg/ml) after anakinra (p&lt;0.05). No significant changes were observed after placebo. Conclusion: IL-1 inhibition improves endothelial function and consequently, coronary and aortic wall function, probably through reduction of nitrooxidative stress and apoptosis.
Abstract 9206: Myocardial Mechanics in Asymptomatic Versus Symptomatic Patients with Severe Aortic Stenosis
Authors: Shemy Carasso, Diab Mutlak, Jonathan Lessick, Doron Aronson, Yoram agmon
Journal: Circulation (2012)

Background: Symptomatic patients (pts) with severe aortic stenosis (AS) demonstrate abnormal left ventricular (LV) mechanics. We compared LV mechanics in asymptomatic and symptomatic pts with severe AS using 2-D myocardial strain imaging. Methods: The study group included 62 pts with severe AS (aortic valve area [AVA] ≤1.0cm2), normal LV ejection fraction (LVEF&gt;50%), and without segmental wall motion abnormalities. LV longitudinal and circumferential strain and rotation were measured in 30 asymptomatic pts and compared to 32 age and gender-matched pts with AS-related symptoms and to 25 normal subjects without AS. Results: Patients with asymptomatic severe AS demonstrated less decreased longitudinal strain, higher (supernormal) apical circumferential strain, and extreme (supernormal) apical rotation, compared to symptomatic patients. Conclusions: Compensatory mechanisms of myocardial mechanics in asymptomatic pts with severe AS (increased apical circumferential strain and rotation) are lost with the appearance of symptoms. Thus, myocardial mechanics may help in the follow up of pts with severe AS and timing of valve surgery.
Abstract 9449: Dynamic Left Ventricular Dyssynchrony Assessed by Three Dimensional Speckle-Tracking Area Strain during Dobutamine Stress Has a Negative Impact on Cardiovascular Events in Patients with Idiopathic Dilated Cardiomyopathy
Authors: Kensuke Matsumoto, Hidekazu Tanaka, Kazuhiro Tatsumi, Takuma Sawa, Yasuhide Mochizuki, Yoshiki Motoji, Junichi Imanishi, Tatsuya Miyoshi, Mana Hiraishi, Akihiro Kaneko, Takayuki Tsuji, Keiko Ryo, Yuko Fukuda, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2012)

Background: Left ventricular (LV) dyssynchrony is not a stable phenomenon, but rather, changes dynamically with changes in hemodynamic conditions. Since the prognostic impact of dynamic dyssynchrony has not yet been elucidated, our objective was to investigate, by using novel three-dimensional (3-D) speckle-tracking area strain, the clinical impact of dynamic dyssynchrony on patients with idiopathic dilated cardiomyopathy (DCM). Methods: Forty-eight DCM patients with ejection fractions of 33±9% (all &lt;45%) were prospectively recruited, and 3-D speckle-tracking area strain was used to measure both contractile reserve and changes in dyssynchrony during dobutamine stress (20μ g/kg/min). The standard deviation of time-to-peak area strain from 16 LV segments was adopted as the LV dyssynchrony index. Event-free survival was then tracked over a 12-month period. Results: A ≥6.94% increase in the dyssynchrony index during dobutamine stress (Δdyssynchrony index) was the best predictor of cardiovascular events with 90% sensitivity and 82% specificity. Multivariate Cox analysis indicated that not only the absence of contractile reserve ([[Unable to Display Character: &amp;#8710;]]global area strain ≤3.89%, p=0.03), but also the presence of dynamic dyssynchrony ([[Unable to Display Character: &amp;#8710;]]LV dyssynchrony ≥6.94%, p=0.04) was an independent predictors of cardiovascular events. Patients with dynamic dyssynchrony had a significantly poorer prognosis than those without (log rank p&lt;0.001). Importantly, absence of dynamic dyssynchrony and presence of contractile reserve during dobutamine stress were associated with the most favorable outcome (100%), whereas the reverse condition was associated with the worst outcome (20%, p&lt;0.001). Conclusions: Dynamic dyssynchrony during dobutamine stress constitutes a potential predictor of cardiovascular events in patients with DCM, while assessment of dynamic dyssynchrony in combination with contractile reserve may further improve prognostic risk stratification.
Abstract 9397: Predictors of Disease Progression in Pediatric Dilated Cardiomyopathy
Authors: Kimberly Molina, Lynn Sleeper, Seema Mital, Steven Colan, Peter Shrader, Piers Barker, Renee Margossian, Girish Shirali, Karen Altmann, Charles Canter, Elizabeth Radojewski, Elif Tierney, Jack Rychik, Lloyd Tani
Journal: Circulation (2012)

Objective: Identify predictors of disease progression in pediatric dilated cardiomyopathy (DCM). Methods: The Pediatric Heart Network Ventricular Volume Variability Study evaluated chronic DCM patients with serial prospective echocardiographic and clinical data collection over an 18 month follow-up. Inclusion criteria were age &lt;22 years and DCM disease duration &gt; 2 months with exclusion of those needing IV inotropic or mechanical support, and those listed status 1A/1B for transplant. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, IV inotropes, mechanical support, or death during follow-up. Predictors of disease progression were identified using logistic regression and classification and regression tree (CART) analysis. Results: Of the 127 patients, 28 (22%) met criteria for disease progression during the 18 month follow-up period. Multivariable analysis (c-statistic=0.90) identified older age at diagnosis (OR=1.16 per yr, p=0.003), larger left ventricular (LV) end-diastolic m-mode dimension z-score (LVEDDz) (OR 1.77, p&lt;0.001) and lower septal peak systolic tissue Doppler velocity z-score (OR=0.68, p=0.04) as independent predictors of disease progression. CART analysis risk-stratified patients for significant disease progression with 89% sensitivity and 94% specificity based on LVEDDz ≥7.7, LV ejection fraction &lt;38.2%, LV inflow propagation velocity (color m-mode) z-score &lt; -0.28, and age at diagnosis ≥ 8.5 months. (Figure 1) Conclusion: In pediatric patients with DCM, diagnosis after late infancy and echocardiographic parameters of LV size, systolic and diastolic function were independently associated with disease progression, and may be used to reliably risk stratify DCM patients.
Abstract 9237: An Adaptor Protein Afadin Regulates Lymphatic Vessel Development by Modulating RhoA Activation
Authors: Keisuke Takeuchi, Takashi Majima, Jun Miyoshi, Hisakazu Ogita
Journal: Circulation (2012)

Afadin is an intracellular binding partner of nectins, the cell-cell adhesion molecules; it plays important roles in the formation of cell-cell junctions. Afadin knockout mice show early embryonic lethality, therefore little is known about the function of afadin in organ development. To elucidate the role of afadin in the vascular system in vivo, we generated endothelial cell-specific afadin-null mice by the Cre-LoxP system. These afadin conditional knockout (cKO) mice were almost embryonically lethal as a result of severe subcutaneous edema. Defects in the lymphatic vessels of the skin were observed, although the abnormality in the blood vessels was not detected. We also found that severe disruption of the VE-cadherin-mediated cell-cell junctions occurred only in lymphatic endothelial cells, but not in blood endothelial cells. Since depletion of afadin did not affect the ability of differentiation and proliferation of lymphatic endothelial cells, the disruption of cell-cell junctions in the lymphatic vessels is considered to be the primary reason to cause the embryonic lethality in afadin cKO mice. We further investigated the molecular mechanism by which the phenotype in afadin cKO was specifically observed in the lymphatic vessels in the in vitro assays using blood and lymphatic microvascular endothelial cells (BMVECs and LMVECs). Knockdown of afadin caused the elongated shapes and cell-cell junction disruption in LMVECs, but not BMVECs. In afadin-knockdown LMVECs, enhanced F-actin bundles were formed at the cell periphery and the activation of RhoA was strongly increased in comparison with afadin-knockdown BMVECs. Given that the excessive RhoA activation can induce the force to shrink the cells, these results indicate that afadin has different effects on blood and lymphatic endothelial cells by controlling the activation of RhoA, which critically regulates the development of mouse embryos.
Abstract 9386: Attenuation of Post-infarct Cardiac Hypertrophy by Allogeneic Cell-mediated Supplemental Igf-1 Propeptide Delivery
Authors: Maria Paola Santini, Bhawana Poudel, Tommaso Poggioli, Daniel Bilbao, Elham Zarrinpashneh, Padmini Sarathchandra, Nadia Rosenthal
Journal: Circulation (2012)

Background: Cardiovascular remodelling after myocardial infarction leads to cardiac function impairment due to left ventricle dilation, distortion of ventricular shape and mural hypertrophy. Therefore, ventricular remodelling can be considered a primary target for therapeutic treatment. We previously documented that cardiac-specific overexpression of the propeptide insulin-like growth factor 1Ea (IGF-1Ea) contributed to beneficial cardiac repair after ischemic damage by employing anti-inflammatory and antioxidant molecules, decreasing scar formation and enhancing cardiac function. The above benefits suggest that IGF-1 may be therapeutically important in cardiovascular diseases. However, the precise mechanisms in clinical-like procedures are not yet elucidated and IGF-1 family of growth factors are therefore poorly recognized pharmacologically. We hypothesized that IGF-1Ea-mediated delivery by allogeneic cell therapy could favour long-term decrease of left ventricle remodelling after myocardial infarction. Methods and Results: To support long-term expression of the propeptide IGF-1Ea, we infected pluripotent P19Cl6-MLC2vGFP cells with a lentivirus carrying the Igf-1Ea gene under the CMV promoter. These cells, which efficiently differentiate into cardiomyocytes activating a GFP transgene, were injected into the ventricular wall of C57BL/6 mice (n=11) after myocardial infarct induction in an allogeneic transplantation model. Mice injected with cells not expressing the transgene were used as control. IGF-1Ea delivery improved long-term local systolic function measured as percentage of anterior wall motion (60% vs 20%, p&lt;0.01) and correlated with increased cell retention, decreased hypertrophic response through downregulation of the angiotensin signalling and activated pro-angiogenic program compared to mice transplanted with cells not expressing the transgene. Conclusions: this study indicates that allogeneic cell-mediated IGF-1Ea delivery is a good candidate in pharmacological and clinical studies to contribute to long-term beneficial remodelling of the heart in response to myocardial infarct.
Abstract 9396: Bayesian Methods Affirm the Use of Percutaneous Coronary Intervention to Improve Survival in Patients with Unprotected Left Main Coronary Artery Disease
Authors: John A Bittl, Yulei He, Alice K Jacobs, Sharon-Lise T Normand
Journal: Circulation (2012)

Introduction: Several randomized clinical trials (RCTs) have supported the Class I recommendation for coronary artery bypass grafting (CABG) for unprotected left main coronary artery disease (ULMCAD). In the absence of RCTs directly comparing percutaneous coronary intervention (PCI) with medical therapy (MT) for this indication, the new Class IIa recommendation for PCI to improve survival in selected patients with ULMCAD has been statistically inferred from several studies comparing CABG with PCI. Hypothesis: We tested whether Bayesian approaches supported the recommendation for PCI to improve survival in patients with ULMCAD. Methods: We performed a Bayesian cross-design and network meta-analysis of 12 studies (4 RCTs, 4 observational matched studies and 4 other cohort studies) comparing CABG with PCI (N=4,574 patients) and of 7 studies (2 RCTs and 5 observational studies) comparing CABG with MT (N=3,224 patients). Results: The odds ratios (ORs) for 1-year mortality after PCI versus CABG using Bayesian cross-design meta-analysis were not different among RCTs (OR 0.99, 95% Bayesian credible interval [BCI] 0.67-1.43), matched cohort studies (OR 1.10, 95% BCI 0.76-1.73), and other types of cohort studies (OR 0.93, 95% BCI 0.58-1.35). A network meta-analysis suggested that MT alone is associated with higher 1-year mortality than the use of PCI for patients with ULMCAD (Figure). Conclusions: Bayesian methods support the current revascularization guidelines and suggest that PCI may improve survival over MT alone for patients with ULMCAD. An integrated approach analyzing data from both observational and randomized studies using Bayesian methods may yield new insights to enhance the translation of trial data into clinical practice.
Abstract 9628: Association of Electrogram Features and Critical Reentrant Ventricular Tachycardia Sites with Nonischemic Scar on Late Gadolinium Enhanced Cardiac Magnetic Resonance
Authors: Takeshi Sasaki, Takeshi Sasaki, Christopher F Miller, Rozann Hansford, Menekhem M Zviman, Joseph E Marine, David Spragg, Alan Cheng, Harikrishna Tandri, Sunil Sinha, Aravindan Kolandaivelu, Stefan L Zimmerman, David A Bluemke, Gordon F Tomaselli, Ronald D Berger, Henry R Halperin, Hugh Calkins, Saman Nazarian
Journal: Circulation (2012)

Introductions: The association of local electrogram features with nonischemic scar morphology and distribution on electroanatomic maps (EAM) has not been investigated. We aimed to quantitatively assess the association of nonischemic scar on late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) with local electrograms and critical sites in patients with nonischemic cardiomyopathy (NICM). Methods: LGE-CMR was performed in 19 patients with NICM. Scar characteristics were classified by scar transmurality and intramural scar types (endocardial, mid-wall, epicardial, patchy, transmural) on LGE-CMR short-axis planes (Figure, upper panel). EAM points were registered to the corresponding LGE-CMR images. Multivariable regression analysis clustered by patient was performed to assess the association of myocardium thickness, scar transmurality and intramural scar types, with electrogram bipolar/unipolar amplitude, duration and deflections. LGE-CMR characteristics of critical ventricular tachycardia (VT) sites were also investigated. Results: In pooled analyses, higher scar transmurality was significantly associated with lower bipolar (Figure, lower panel)and unipolar electrogram amplitude, longer duration and more deflections (P&lt;0.0001). Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P&lt;0.0001) and patchy scar (vs. endocardial, mid-wall, epicardial scar, P&lt;0.05). Most of the critical sites (16 sites; 89%) were located in scar with &gt;25% scar transmurality. Myocardial wall thickness, scar transmurality and intramural scar types were independently associated with electrogram features on multivariable regression analyses. Conclusions: Electrogram features on endocardial EAM are associated with scar morphology and distribution on LGE-CMR in NICM. This result may optimize procedural strategies including the decision to obtain epicardial access.