tbuckley/cabot-search huggingface dataset:
Abstract 18357: Vulnerable Carotid Plaque is Characterized by a Difference in Mobility Between Plaque Core and Cap
Authors: Oleg Kerbikov, Sergey A Voynov, Ekaterina N Borskaya, Elena B Shakhnovich, Nataliya A Yaroshchuk, Tamara V Krutova, Alexander V Averyanov
Journal: Circulation (2013)

Vulnerable carotid plaque can cause an ischemic stroke, but its detection is elusive. The aim was to study the mechanical properties of carotid plaques using ultrasound speckle tracking. Methods: Study population consisted of 61 (aged 53-89, median 68) patients with carotid atherosclerosis: 21 with acute atherothrombotic stroke (7 day after stroke onset) and 40 without symptoms. The stroke subtype was classified according to TOAST criteria. In total, 21 symptomatic and 47 asymptomatic plaques were analyzed. For plaque-free area (PFA) and for each plaque, maximum circumferential and longitudinal strains (S[[Unable to Display Character: с]], Sl) and strain rates (SRc SRl) were measured (with separate measurements for plaque cap, core and base). Plaque characteristics (echogenicity, length, degree of stenosis) were also assessed. Results: plaque and PFA differed in Sl and SRl values, whereas no difference was observed for Sc and SRc (Table 1). Sc and SRc for cap and core of echolucent plaques were higher as compared with hyperechogenic ones (Table 1). For echolucent plaques a significant difference in Sc and SRc was also detected between segments, and the highest values were observed in cap (Table 1). However, for symptomatic plaques, Sc and SRc of plaque core were significantly higher than values for cap (Table 1). Plaque internal motion coefficient Pim=(core SRc - cap SRc)/base SRc was developed to quantify the relative motion of different plaque segments against each other. According to ROC curve analysis, plaques with Pim&gt;0.09 are associated with ischemic event (sensitivity 76%, specificity 65%, AUC=0.76, p&lt;0.001). Logistic regression confirmed that Pim&gt;0,09 is an independent predictor of plaque vulnerability, OR=5.26, 95% CI 1.4-19.3 controlling for age, gender, plaque length, degree of stenosis and echogenicity. Conclusions: Echolucent plaques are more mobile than hyperechogenic ones. In symptomatic plaques, the increased deformation of inner core may be linked with plaque vulnerability.
Abstract 9871: Enhanced Active Metabolite Generation and Platelet Inhibition With Prasugrel Compared to Clopidogrel Regardless of Genotype in Thienopyridine Metabolic Pathways
Authors: Oscar Ö Braun, Dominick J Angiolillo, José L Ferreiro, Joseph A Jakubowski, Kenneth J Winters, Mark B Effron, Suman Duvvuru, Timothy M Costigan, Scott S Sundseth, Joseph R Walker, Jorge F Saucedo, Neal S Kleiman, David Erlinge, Christoph Varenhorst
Journal: Circulation (2012)

Background: Clopidogrel (Clop) response is modulated by genetic polymorphisms. In particular, the CYP2C19*2 allele has been associated with impaired response, while conflicting results have been reported for CYP2C19*17, ABCB1 and PON1 genotypes. We assessed the impact of CYP2C19, PON1 and ABCB1 polymorphisms on Clop and prasugrel (Pras) pharmacodynamic (PD) response and pharmacokinetic (PK) profile. Methods: Aspirin-treated patients (n=194) with coronary artery disease enrolled in two independent, prospective, randomized, multicenter studies comparing Clop (75 mg) and Pras (10 mg) were genotyped and classified according to standard definitions of predicted CYP2C19 metabolizer phenotype (ultra metabolizers (UM) = *17 carriers; reduced metabolizers (RM) = *2 carriers). PD assessments were made using LTA, VerifyNow P2Y12 and VASP-PRI (platelet reactivity index) after 14 days of maintenance dosing. PK parameters of active metabolite (AM) exposure of both Clop and Pras were calculated in a cohort of 98 patients. Results: For Clop, genetic variants in CYP2C19 , but not ABCB1 or PON1 , affected the PK and PD. For Pras, none of the measured genetic variants affected PK or PD. Compared with Clop, platelet inhibition with Pras was greater even in CYP2C19 UM phenotype (figure). Pras generated more AM and achieved greater platelet inhibition than Clop irrespective of CYP2C19, ABCB1 and PON1 polymorphisms. Conclusion: Pras generated higher levels of AM and achieved greater platelet inhibition than Clop in all CYP2C19 genotypes. Neither ABCB1 nor PON1 genetic variation affected Pras or Clop PD or PK response.
Abstract 18398: Amelioration of Cardiovascular Dysfunction by Nobiletin in Diabetic Rats
Authors: Nishad Parkar, Veeranjaneyulu Addepalli
Journal: Circulation (2013)

Introduction: Strategies that interrupt the Matrix Metalloproteinase-2 (MMP-2) and Matrix Metalloproteinase-9 (MMP-9) system have been shown to reduce the ensuing threatening risk factors of cardiovascular complications of diabetes by alteration in Extracellular Matrix Hypothesis: We hypothesized that interruption of MMP-2 and 9 can reduce cardiovascular dysfunction of diabetes. Objective of this study was to investigate efficacy of Nobiletin in treatment of cardiovascular dysfunction of diabetes. Nobiletin is a citrus flavonoid with MMP-2 and MMP-9 inhibitory activity. Methods: Diabetes was induced by Streptozotocin (55 mg/kg i.p.) in wistar male rats. Four week after the induction of diabetes rats were treated with Nobiletin (25 mg/kg, and 50 mg/kg) for a period of three weeks. At the end of eight week hemodynamic parameters like arterial pressure, heart rate and left ventricular pressure were recorded. Contractile response to phenylephrine (10-5 M) and relaxation responses to acetylcholine (10-9 to 10-4 M) were obtained from aortic rings of diabetic rats. Cardiac hypertrophy was measured and histopathology was done using Masson’s Trichrome stain method. Gel zymography was performed to evaluate MMP-2 and MMP-9 levels. Results: Diabetes resulted in significant reduction in heart rate, mean arterial pressure, + dp/dtmax and -dp/dtmax (223 ± 26, 83 ± 9 mmHg, 2673 ± 323 and -2035 ± 216 mmHg/s respectively) when compared with normoglycemic group (285 ± 26, 102 ± 8 mmHg, 3546 ± 324 and -3132 ± 235 mmHg/s respectively). Treatment with 50 mg/kg Nobiletin significantly ameliorated these parameters (254 ± 27, 98 ± 9, 3175 ± 357 and - 2932 ± 243 mmHg/s respectively) compared to vehicle treated diabetic group. Endothelium-dependent relaxation responses induced by acetylcholine were decreased in diabetic rats (% relaxation 56.3 ± 1.83) and significantly higher in combination treated group (% relaxation 31.3 ± 2.31). When compared with diabetic control group, collagen, MMP-2 and MMP-9 levels were significantly decreased in combined treated group. Conclusion: Results of the present study suggest that Nobiletin attenuate cardiovascular dysfunction in diabetic rats by inhibition of MMP-2 &amp; MMP-9 and can be a potential non glycaemic approach for the treatment.
Abstract 18436: Systems Biology Identifies a Gene Driving Expression of Metabolic Syndrome in Lyon Rats
Authors: Anne E Kwitek, Jinkai Wang, MC John Ma, Amanda Mennie, Janette Pettus, Yi Xing
Journal: Circulation (2013)

The metabolic syndrome (MetS) is a collection of co-occurring complex disorders including obesity, hypertension, dyslipidemia, and insulin resistance. The Lyon Hypertensive (LH) and Lyon Normotensive (LN) rats are models of MetS sensitivity and resistance, respectively. To identify genetic loci influencing phenotypes underlying MetS, an F2 intercross between LH and LN was studied to identify physiological quantitative trait loci (pQTL) contributing to plasma lipid and leptin levels, blood pressure, and body weight/adiposity. We performed mRNA-seq in F2 rats to identify the loci regulating gene expression, or expression (e)QTL, followed by gene expression network analyses. Systems biology methods were applied to identify candidate MetS genes, including genes previously shown to be MetS-related. We found an eQTL hotspot on RNO17, which was also located within pQTLs for MetS-related traits. The genes regulated by this eQTL hotspot were mainly in two co-expression network modules (a mitochondria related module and a gene regulation related module) and causally affect many MetS-related traits. Multiple evidences strongly and consistently support RGD1562963, a gene regulated in cis by this eQTL hotspot as the eQTL driver gene directly affected by genetic variation between LH and LN rats. Our study sheds light on the intricate pathogenesis of MetS and that systems biology with high-throughput sequencing is a powerful method to study the etiology of complex multifactorial diseases.
Broken Hearts, Broken Brains and the Blues
Authors: Pam Mitchell
Journal: Circulation (2012)

Upwards of 30% of people with stroke, coronary heart disease and many other chronic disorders are clinically depressed. This is in contrast to roughly 5% of the general population. In this lecture we will explore the current biobehavioral theories about why depression might be so much more prevalent in acute and chronic cardiocerebrovascular disease, how our genes might interact, and what we can do to improve the quality of life for our patients with broken hearts, broken brains and the blues.
Abstract 9721: Clinical Significance of Transthoracic Doppler Echocardiography in Patients With a Proximal Left Coronary Artery Lesion That Could Not be Evaluated With Computed Tomography Angiography
Authors: Makoto Saito, Hideki Okayama, Haruhiko Higashi, Hiroe Morioka, Jun Aono, Toyofumi Yoshii, Takumi Sumimoto, Kazuhisa Nishimura, Katsuji Inoue, Jitsuo Higaki
Journal: Circulation (2012)

Background The aim of this study was to evaluate the clinical significance of transthoracic Doppler echocardiography (TTDE) in patients with suspected angina pectoris (AP), who had a proximal left anterior descending coronary artery (LAD) lesion that was difficult to evaluate with computed tomography coronary angiography (CTCA). Methods Among 387 consecutive patients with suspected AP who had CTCA performed, 58 had a proximal LAD lesion that was difficult to evaluate and were included in this study. These patients had TTDE and coronary angiography performed on the same day (mean age, 74±8 yrs; men, 39; Agaston score, 1110 ± 1360). Proximal left coronary flow was measured in the short axis (SAX) at the aortic root using color Doppler guidance. When coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared. When color aliasing did not disappear, the color baseline was shifted until the color flow showed “isovelocity”. Using QCA-CMS analytical software, severe and moderate stenoses were defined as a %diameter stenosis &gt; than 70% and 40-70%, respectively. Results Proximal coronary flow was detected in 45 of 58 patients. In these 45 patients, there were 5 patients with severe stenosis and 14 patients with moderate stenosis. The isovelocity in the two groups with stenosis was significantly higher than that in the group without stenosis (148±42 vs 97±48 vs 41±21 cm/s, p&lt;0.001). ROC curve analysis showed that the optimal cut-off values of isovelocity to detect severe and moderate stenoses were &gt; 92 cm/s (area under the curve, 0.96; sensitivity, 100%; specificity, 90%) and &gt; 57 cm/s (area under curve, 0.92; sensitivity, 90%; specificity, 77%). Conclusion TTDE could evaluate proximal LAD stenosis with good accuracy in about 80% patients with AP, who had a proximal LAD that could not be evaluated with CTCA. This method may play a complementary role to identify latent proximal LAD stenosis.
Abstract 18332: Diagnostic Yield of Transesophageal Echocardiography for Infective Endocarditis in Patients Referred for Suspected Endocarditis
Authors: Michela Slucca, Daniel M Spevack
Journal: Circulation (2013)

Background: The expert panel that authored the 2011 Appropriate Use Criteria for Echocardiography considered the use of transesophageal echocardiography (TEE) to be appropriate when used to diagnose infective endocarditis (IE) with a moderate or high pretest probability. The panel appropriate use score was 9, the highest possible score achievable. Few published data are currently available to support this recommendation. We aimed to define the diagnostic yield of TEE in a population with moderate or high pretest probability for IE. Methods: Consecutive TEE reports (n=6,189) acquired between 1/1/2005 and 12/31/2012 at our institution were reviewed for the presence of possible or definite endocarditis. TEE were acquired from 5,347 individual patients. Endocarditis was considered to be present if a new vegetation was demonstrated or there was obvious abscess formation. The diagnostic yield for endocarditis was compared between exams performed for different indications. Results: The study group was 62 ± 15 years old and 55% male. Most TEE (78%) were performed on inpatients. TEE findings are reported in the Table. The yields for definite and possible IE were 9% and 8% respectively amongst subjects with bacteremia referred for suspected IE. Those referred for suspected IE had increased odds for finding definite IE (odds ratio (OR) 4.2, 95% CI: 2.7, 6.6, p&lt;0.001). Amongst those referred for suspected IE, prosthetic valve (OR 2.4, 95% CI: 1.5, 3.8, p&lt;0.001) and pacemaker/ICD (OR 16, 95% CI: 6, 44, p&lt;0.001) were independent predictors of definite IE. Conclusion: The diagnostic yield for finding IE on TEE in subjects with bacteremia referred for suspected IE is reasonably high. Our findings support the current recommendations for use of TEE in this population.
Abstract 9890: First-Year Brain Natriuretic Peptide as a Biomarker after Heart Transplant Predicts Outcome and Severity of Cardiac Allograft Vasculopathy
Authors: Matthew Rafiei, Jignesh Patel, Michelle Kittleson, Ryan Shiozaki, Lily Stern, Babak Azarbal, Lawrence Czer, Fardad Esmailian, Jon Kobashigawa
Journal: Circulation (2012)

Purpose: Brain natriuretic peptide (BNP) has been reported to be a biomarker for poor outcome after heart transplant. Elevated BNP levels have been associated with reduced survival and an increase in the development of cardiac allograft vasculopathy (CAV). It has not been established whether high levels of BNP at 1-year post-transplant also correlate with severity of cardiac allograft vasculopathy per the new ISHLT cardiac allograft vasculopathy nomenclature. Methods: We evaluated 238 patients who received a heart transplant between 2001-2007. Patients were separated into three groups based on BNP levels at the 1st-year: 157 patients with BNP &lt;100 pg/mL, 56 patients with BNP 100-250 pg/mL, and 25 patients with BNP &gt;250 pg/mL. Study patients were followed for 5 years for endpoints of survival, freedom from cardiac allograft vasculopathy (stenosis 30%), and freedom from non-fatal major adverse cardiac events (NF-MACE: MI, CHF, stroke, and need for angioplasty or pacemaker/ICD) and 1st-year freedom from any-treated rejection. Results: Patients with BNP &gt;250 pg/mL at the 1st-year had significantly lower survival, freedom from NF-MACE, and freedom from cardiac allograft vasculopathy compared to the lower groups of BNP. Severity of cardiac allograft vasculopathy was higher in the BNP &gt;250 group compared to the other two groups. Of those patients who developed cardiac allograft vasculopathy, the high BNP group had more patients who developed CAV2 or CAV3 compared to patients with BNP 100-250 and BNP &lt;100 pg/mL (24% vs. 4% vs. 7%, respectively; p=0.01). The high BNP group also had less freedom from any-treated rejection than the other two groups. Conclusion: Elevated 1st-year levels of BNP &gt;250 pg/mL appears to be a biomarker for poor outcome and the subsequent development of more severe cardiac allograft vasculopathy. Targeted change in immunosuppression such as switch to proliferation signal inhibitors might be considered for this high risk population.
Abstract 18492: Effectiveness of Lifestyle Intervention by Obesity Status: Does One Size Fit All?
Authors: Kristen M Azar, Lan Xiao, Jun Ma
Journal: Circulation (2013)

Most U.S. adults are overweight or obese with severe obesity projected to increase 130% within 2 decades. Little is known about the effectiveness of efficacious lifestyle intervention by severity of obesity once adapted to real-world settings. This study compared by baseline body mass index (BMI) category (25-≤30, 30-≤35, or 35+) the effects of 2 primary care-based lifestyle interventions among overweight or obese adults with pre-diabetes and/or metabolic syndrome randomized to receive usual care alone (n = 81) or usual care plus a coach-led (n = 79) or self-directed (n = 81) behavioral weight-loss intervention. Each used a Diabetes Prevention Program-based 12-week core curriculum plus technology-mediated coach contact and self-monitoring for a total of 15 months. Between-group differences at 15 months were evaluated by intention-to-treat and tests of group by baseline BMI category interactions in repeated-measures (3, 6 and 15 months) mixed models (SAS, version 9.2). Compared to usual care, the coach-led intervention resulted in significantly greater reductions from baseline to 15 months in BMI (primary outcome) and weight for all categories, in waist circumference (WC) for BMI 25≤30 and 35+, and in fasting plasma glucose levels for BMI 30≤35 and 35+ (largest P = .02). In contrast, self-directed intervention led to greater improvements than did usual care in BMI ( P = .03) and weight ( P = .02) only for BMI 25≤30, in WC for BMI 30≤35 ( P = .03), and in glucose levels for BMI 35+ ( P = .02). Moreover, BMI and weight ( P = .01) and WC ( P = .04) reductions for BMI 35+ were significantly greater in the coach-led vs. self-directed intervention. Overweight participants (BMI 25 ≤ 30) responded comparably to interventions, both of which were more effective than usual care. In conclusion, baseline BMI may influence treatment effectiveness. Clinicians and researchers should take an individual’s baseline BMI into account when developing or recommending a weight-loss treatment strategy.
Abstract 18649: Tracking Spironolactone-Induced Regression of Myocardial Fibrosis and Myocyte Hypertrophy in Mice With Contrast-Enhanced Magnetic Resonance Imaging
Authors: Otavio R Coelho-Filho, Ravi V Shah, Tomas G Neilan, Richard Mitchell, Heitor Moreno Jr, Raymond Y Kwong, Michael Jerosch-Herold
Journal: Circulation (2013)

Background: In heart failure (HF) with preserved left ventricular ejection fraction, interstitial fibrosis and cellular hypertrophy are early markers of the adverse tissue remodeling in response to pressure-overload. Methods: Wild-type mice were assigned to three experimental groups: placebo (n=15), receiving tap water for 7 weeks; L-NG-Nitroarginine methyl ester (L-NAME) (n=22) (3mg/ml of L-NAME in drinking water, Sigma, USA) for 7 weeks; and L-NAME (3mg/ml) + spironolactone (n=21) (L-NAME-S), with spironolactone delivered by subcutaneous pellets at 50mg/kg/day. Extracellular volume (ECV) expansion, as a measure of interstitial fibrosis, and intracellular lifetime of water, τ ic , as a measure of cardiomyocyte hypertrophy, were assessed by pre and post-contrast T1 measurements. Minor (D min ) and major (D maj ) cell-diameters were measured on FITC-wheat germ agglutinin stained sections. Results: L-NAME without spironolactone increased mean arterial pressure (86.8±7.4 mmHg at baseline to 124.4±6.1 mmHg after 7 weeks of L-NAME therapy, P&lt;0.001) and left venrtciular (LV) mass (162.9±19.4 μg for L-NAME vs. 98.5±14.4 μg for placebo, P &lt;0.001), with a modest decrease in LV systolic function (LV ejection fraction 51.3±8.2% for L-NAME vs. 60.3±3.2% for placebo, P &lt;0.001). Spironolactone reduced the mean arterial pressure and LV mass in L-NAME-treated mice. Spironolactone also reduced the myocardial ECV (0.43±0.09 for L-NAME vs. 0.25±0.03 for L-NAME+S, P&lt;0.001), myocyte hypertrophy (τ ic, 0.42±0.11 for L-NAME vs. 0.12±0.05 for L-NAME+S). The on-therapy effect of spironolactone on myocardial ECV and τ ic was observed even after adjustment for mean arterial pressure in linear regression (myocardial ECV: adjusted multiple R 2 = 0.71, P&lt;0.001). ECV and τ ic had strong correlations with connective tissue fraction and cell size, measured by histology. Conclusion: CMR can track the progression and regression of interstitial fibrosis, cellular and LV hypertrophy in a murine model of hypertensive heart disease on exposure to spironolactone. This ability to non-invasively phenotype changes in cellular and tissue-based ventricular remodeling with therapy is critical to furthering our understanding of pathobiology of HF progression and its reversal.
Abstract 18565: Trends and Outcomes in the Use of Extracorporeal Membrane Oxygenation for Adults in the United States: A 10 year survey
Authors: Hirad Yarmohammadi, Sue Duval, Renuka Jain
Journal: Circulation (2013)

Introduction: Extracorporeal membrane oxygenation (ECMO) has been used in hospitalized patients with severe cardiac and respiratory failure. However, little is known about trends in ECMO utilization and survival, particularly in adults. Methods: We evaluated the use of ECMO in the United States between 2001 to 2009 using the Nationwide Inpatient Sample (NIS) database. National estimates were measured using sampling weights of NIS. We excluded children and those patients who underwent ECMO during open-heart surgery. Results: National estimates of ECMO use in the United States increased from 165 patients in 2000 to 1450 patients in 2009. The incidence rate was significantly increased from 5.4 patients per million to 44.3 per million (p &lt;0.0001). Despite 9-fold increase in use of ECMO in ten years, the mortality rate remained high and did not significantly change (p=0.5) (Figure). ECMO use in the elderly (&gt;65) accounted for one quarter of hospitalizations, and did not change in frequency over last 10 years (p&lt;0.15). Conclusions: This is the largest study of ECMO utilization in adults. Over ten years, despite widespread increase in use of this technology, there was no significant change in mortality rate and mortality remains high. Further studies will need to identify those patients most likely to benefit from ECMO
Abstract 11282: Maintaining Prostaglandin E2 Levels Prevents Rejection of Implanted Allogeneic Mesenchymal Stem Cells and Restores Post-Infarction Ventricular Function
Authors: Sanjiv Dhingra, Peng Li, Xi-Ping Huang, Jian Guo, Jun Wu, Shu-Hong Li, Wang-Fu Zang, Pawan K Singal, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2012)

Sanjiv Dhingra, 2012 Finalist and Presenting Author
Abstract 18830: Mitochondrial Suppression Due to Loss of Sirt3 Deacetylase Activity Causes Pulmonary Arterial Hypertension
Authors: Roxane Paulin, Peter Dromparis, Gopinath Sutendra, Vikram Gurtu, Sotirios Zervopoulos, Lyndsay Bowers, Alois Haromy, Linda Webster, Steeve Provencher, Sebastien Bonnet, Evangelos, D. Michelakis
Journal: Circulation (2013)

Roxane Paulin, 2013 Finalist and Presenting Author