tbuckley/cabot-search huggingface dataset:
Abstract 9265: Effects of One Year of Endurance Exercise Training on ‘Dynamic’ Starling Mechanisms in Heart Failure with Preserved Ejection Fraction
Authors: Naoki Fujimoto, Shigeki Shibata, Jeffrey L Hastings, Anand Prasad, Paul S Bhella, Graeme Carrick-Ranson, Dean Palmer, Benjamin D Levine
Journal: Circulation (2011)

Background: Left ventricular (LV) and arterial stiffening occurs with aging, which can be prevented by lifelong exercise training. Heart failure with preserved ejection fraction (HFpEF) is a disease of the elderly with stiff LV and arteries. However, it is unknown whether exercise training in HFpEF could improve beat-to-beat ‘dynamic’ Staring mechanism, which reflects the interaction between LV and arterial stiffness or LV-arterial coupling. Methods: Seven patients with HFpEF (age 75 ± 6 yrs) and 9 healthy sedentary controls (age 71 ± 3 yrs) were enrolled and participated in 1 year of endurance exercise training. Maximal oxygen uptake (VO 2 max) was measured during incremental treadmill exercise. All subjects underwent right heart catheterization; beat-to-beat LV end-diastolic pressure (LVEDP; estimated from pulmonary arterial diastolic pressure) and stroke volume (SV) index (from pulse contour analysis) were obtained during controlled breathing (0.2 Hz, 12 breaths/min) before and after 1 year of training. Spectral transfer function analysis was used as an index of the dynamic Starling mechanism (Shibata JAP2011), and effects of exercise training on the ‘dynamic’ Starling mechanism in HFpEF and healthy controls were compared. By the end of the 1 year of training, the exercise duration was about 200 minutes/wk. Results: VO 2 max was significantly larger in healthy controls at baseline. After exercise training, VO 2 max was unaffected in HFpEF, but increased in healthy controls (HFpEF: 12.6 ± 3.6 vs. 12.8 ± 3.3 ml·kg -1 ·min -1 , p = 0.71, healthy control: 22.8 ± 3.4 vs. 27.2 vs. 4.3 ml·kg -1 ·min -1 , p &lt; 0.01, ANOVA p &lt; 0.01). The ‘dynamic’ Starling mechanism (transfer function gain between LVEDP and the SV index) at baseline was impaired in HFpEF patients compared to the healthy control (HFpEF 0.26 ± 0.14 vs. 0.40 ± 0.09 ml·ml -2 ·mmHg -1 , p = 0.026). Transfer function gain was improved by 65% after exercise training in healthy controls (p = 0.035), while gain in HFpEF was not improved by exercise training (0.26 ± 0.14 vs. 0.29 ± 0.17 ml·ml -2 ·mmHg -1 , p = 0.78). Conclusion: A year of exercise failed to improve beat-to-beat LV-arterial coupling in HEpEF, while it was improved in healthy controls. These results may partly explain why no improvement was observed in VO 2 max in HFpEF.
Abstract 18418: Insulin Resistance Does Not Increase Risk Of Incident Atrial Fibrillation: The Framingham Heart Study
Authors: Joao D Fontes, Asya Lyass, Joseph M Massaro, Renate B Schnabel, Thomas J Wang, Ramachandran S Vasan, Steven A Lubitz, Jared W Magnani, Patrick T Ellinor, Caroline S Fox, Emelia J Benjamin
Journal: Circulation (2010)

Background:  Atrial Fibrillation (AF) is the most common chronic arrhythmia and it causes significant morbidity and mortality. Diabetes and obesity are increasing in prevalence and are associated with elevated risk of atrial fibrillation (AF). Whether insulin resistance is an intermediate step for the development of AF is uncertain. We hypothesized that insulin resistance (IR) is associated with an increased risk of incident AF.   Methods:  We evaluated 7,338 Framingham Heart Study Offspring participants who attended either the fifth (1991-1994) or seventh (1998-2001) examination cycles. We excluded 534 participants with missing homeostatic model assessment index (HOMA-IR), 624 participants with diabetes, 144 with AF at or prior to baseline exam and 1,463 under the age of 50. IR was defined as the top quartile of HOMA-IR index. We examined the association of IR to incident AF with multivariable Cox proportional hazard models adjusting for established AF risk factors using the 3 models described in the  Table.    Results:  Of the 4583 eligible participants (55% women; mean age 59 years), 279 developed AF over up to 10 years. In all three models IR was not significantly associated with incident AF.   Conclusions:  In this study, we did not observe a significant association between IR and incident AF. Given the increasing burdens of diabetes and AF, the intermediate pathways between these two entities merits continued attention.
Abstract 18130: Acute Changes of Glucose and Insulin Levels During Oral Glucose Tolerance Test are Related to Changes in Arterial Stiffness and Wave Reflection
Authors: Ignatios Ikonomidis, Charis Koukoulis, Vasiliki Lambadiari, Fotini Spanoudi, Stavros Tzortzis, Vlassis Tritakis, Helen Triantafyllidi, John Lekakis, Georgios Dimitriadis, Maria Anastasiou-Nana
Journal: Circulation (2011)

Background: Hyperglycemia is linked with arterial stiffness, a factor with significant prognostic value. We investigated whether the acute changes of glucose and insulin levels during oral glucose tolerance test (OGTT) are related with acute changes in arterial stiffness. Methods: In 60 consecutive subjects without known diabetes a standard 75-gr oral glucose tolerance test (OGTT) was performed and glucose and insulin levels were measured at 0, 30, 60, 90 and 120min after glucose loading. At the same time intervals, we measured the carotid- femoral pulse wave velocity (PWVc) using the Complior and aortic PWV (PWVa) and augmentation index (AI) using an oscillometric method (Arteriograph,TensioMed). We categorized patients in those with normal (n=21) and those with abnormal OGTT. Results: During OGTT, we found that increasing glucose levels were related with increasing PWVc and PWVa (r=0.28, r=0.42, p&lt;0.01) and increasing insulin levels were related with decreasing AI (r=-0.27) in all patients. Patients with abnormal OGTT had higher baseline PWVc (10.4±2 vs. 9.1±1.8 m/sec), PWVa (9.4±1.9 vs. 6.9±1.8 m/sec), AI (24±9 vs. 17±11 %), insulin (14±6 vs. 11±4μU/ml) and glucose(114±26 vs. 93±7 mg/dl) and similar age sex and BMI than those with normal OGTT (p&lt;0.05).Compared to baseline, AI was reduced by 44% at 30 min and 17% at 60 min in patients with normal OGTT (p&lt;0.01) compared to 7.8% and 11 % in abnormal OGTT (p=0.7). In all patients, the % decrease in AI at 30 min was related with the corresponding %increase in insulin (r=-0.46, p&lt;0.05) but not with % change in glucose. The % increase in glucose levels at 60, 90 and 120 min during abnormal OGTT was related to the % increase in PWVa (r=0.46, r=0.34, r=0.55, p&lt;0.05), PWVc (r=0.40, r=0.32, r=0.33, p&lt;0.05) and AI (r=0.36, r=0.34, r=-0.35, p&lt;0.05). Conclusions. Patients with normal OGTT show an acute decrease in AI related with the increase in insulin level likely because of insulin stimulation of endothelial NO synthesis. During abnormal OGTT, this beneficial effect of insulin on AI is blunted likely because of insulin resistance and the acute changes in glucose levels are linked with an increase in arterial stiffness. Thus, insulin resistance determines the acute changes of arterial stiffness after postprandial hypeglycemia.
Abstract 15866: Size and Ionic Currents of Unexcitable Cells Coupled to Cardiomyocytes Distinctly Modulate Cardiac Action Potential Shape and Pacemaking Activity
Authors: Luke C McSpadden, Nenad Bursac
Journal: Circulation (2011)

Potential electrical coupling between cardiomyocytes (CMs) and endogenous or exogenously added unexcitable cells can profoundly alter cardiac action potential (AP) initiation, shape, and conduction...
Abstract 15608: Independent association Between Exercise Testing Parameters and Cardiovascular Events Beyond Traditional Risk Factors in People without History of Cardiovascular Disease
Authors: Abhijeet Dhoble, Bhanu P Gupta, Brian Lahr, Thomas G Allsion, Iftikhar Kullo, Francisco Lopez-Jimenez, Ray W Squires, Gerald Gau, Randal J Thomas, Kopecky L Stephen
Journal: Circulation (2011)

Introduction: We investigated whether exercise treadmill test (ETT) parameters and conventional cardiovascular (CV) risk factors contribute independently to adverse cardiovascular events in a coron...
Abstract 13866: ADHD Stimulant Medication Use is Associated With Cardiac Autonomic Dysfunction and Arterial Stiffness in Children and Adolescents
Authors: Aaron S Kelly, Kyle D Rudser, Donald R Dengel, Christopher L Kaufman, Michael I Reiff, Anne L Norris, Andrea M Metzig, Julia Steinberger
Journal: Circulation (2013)

Background: Stimulant medications are used as the primary treatment for attention deficit hyperactivity disorder (ADHD) among children and adolescents but little is known about their effects on car...
Abstract 18022: High On-Treatment Platelet Reactivity Measured by Various Platelet Function Tests: Is the Current VASP-PRI Cutoff Too Low?
Authors: Young-Hoon Jeong, Kevin P. Bliden, Udaya S. Tantry, Yongwhi Park, Seok-Jae Hwang, Paul A. Gurbel
Journal: Circulation (2011)

Background: High on-treatment platelet reactivity (HPR) to ADP measured by multiple methods has been linked to adverse post-PCI clinical event occurrence. The correlation of HPR cutoffs is still a matter of debate, since the predictive value and HPR group size are different depending on platelet function assays. To determine the comparable cutpoint, we correlated cutpoints for HPR determined by various assays in the same patient cohort. Methods: Platelet measures [5µM ADP-induced light transmission aggregation (LTA5μ MADP); P2Y12 reaction units by VerifyNow (PRU), and platelet reactivity index by VASP assay (PRI)] were evaluated (n=936 pairs, cohort I) in stable CAD patients during P2Y12 receptor inhibitor treatment. These assays also performed in PCI-treated patients receiving standard aspirin and clopidogrel therapy (n=584, cohort II). The HPR cutpoints were defined as LTA 5μ MADP &gt;46%, PRU &gt;235, and PRI &gt;50%. Results: In the stable CAD patients, LTA 5μ MADP showed significant correlations with PRU and PRI (r ≥0.688). In ROC curve analysis using the cutpoint of LTA 5μ MADP (&gt;46%), the matched values of PRU and PRI were &gt;234 (AUC 0.943, p&lt;0.001, sensitivity 87.3% and specificity 87.8%) and &gt;60% (Figure A). Among PCI-treated patients, the prevalence of HPR was highest based on PRI &gt;50% (69%) compared with other criteria (≤55%). The comparable values for LTA 5μ MADP &gt;46% were PRU &gt;235 (AUC 0.850, p&lt;0.001, sensitivity 85.3% and specificity 70.4%) and PRI &gt;59% (Figure B). Conclusion: The published cutoff values for HPR by LTA 5μ MADP and PRU were well correlated, whereas published PRI &gt;50% cutoff value may overestimate the risk of HPR. Updated cutoff of PRI &gt; 60% may better stratify the risk for HPR and can be used in future trials.
Abstract 2843: Neuraxial Modulation for Refractory Ventricular Arrhythmias in Humans: Value of Thoracic Epidural Anesthesia and Left Cardiac Sympathetic Denervation
Authors: Tara Bourke, Marmar Vaseghi, Yoav Michowitz, Vineet Sankhla, Yash Lokhandwala, N Swapna, Calambur Narasimhan, Aman Mahajan, Noel G Boyle, Kalyanam Shivkumar
Journal: Circulation (2009)
Abstract 2733: Association of Psychological Disorders and Structural Coronary Arterial Disease
Authors: Nakash Grant, David Choe, Sumit Khandhar, Naser Ahmadi, Gary P Foster
Journal: Circulation (2008)

Background : Growing numbers of American Veterans are diagnosed with psychological disorders and myocardial infarctions without known preexisting cardiac risk factors. Confronted with this information, we studied the association between psychological disorders and the presence of coronary artery calcium. High risk coronary calcification [Agatston method coronary artery calcium score (CAC) &gt;100] is associated with a striking increase in cardiovascular events (hazard ratio&gt;10) making it an excellent surrogate marker. Methods : From a database of VA patients who have undergone cardiac computed tomography, 483 were studied (age 59±12 years, 86% male). Regression analysis was utilized for comparison of CAC score for individuals with depression, anxiety, post-traumatic stress disorder (PTSD) and substance abuse.. Results : After adjustment for age, gender and cardiac risk factors, the odds ratio of CAC≥100 vs. CAC=0 was 1.24 (95% CI 1.02–2.08, p=0.044) for depression, 2.04 (95% CI 1.11– 6.17, p=0.027) for anxiety, 2.28 (95% CI 1.15–5.76, p=0.026) for PTSD and 2.61 (95% CI 1.14 – 6.03, p=0.022) for substance abuse as compared to normal cohort. Conclusion : Veterans with psychological disorders were found to have a significantly higher coronary artery calcification score than those without such disorders. These findings are independent of age, gender and other traditional cardiac risk factors.
Primary overall survival (OS) from OPTiM, a randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.
Authors: Howard L Kaufman, Robert Hans Ingemar Andtbacka, Frances A. Collichio, Thomas Amatruda, Neil N. Senzer, Jason Chesney, Keith A. Delman, Lynn E. Spitler, Igor Puzanov, Yining Ye, Ai Li, Jennifer L. Gansert, Robert Coffin, Merrick I. Ross
Journal: Journal of Clinical Oncology (2014)

9008a Background: T-VEC is an oncolytic immunotherapy derived from herpes simplex virus type-1 designed to selectively replicate in tumors and produce GM-CSF to enhance systemic antitumor immune responses. OPTiM is a randomized, phase 3 trial of T-VEC or GM-CSF in patients (pts) with unresected melanoma with regional or distant metastases (NCT00769704). OPTiM met the primary endpoint of a statistically significant improvement in durable response rate (DRR) with T-VEC vs GM-CSF (Andtbacka et al. ASCO 2013). The primary analysis of OS is reported here. Methods: Key entry criteria were age ≥ 18 yrs, ECOG ≤1, unresectable melanoma stage IIIB/C or IV, injectable cutaneous, SC, or nodal lesions, LDH ≤1.5X ULN, ≤ 3 visceral lesions (excluding lung), none > 3 cm. Pts were randomized 2:1 to intralesional T-VEC (initially ≤ 4 mL x106 pfu/mL then after 3 wks, ≤ 4 mL x108 pfu/mL Q2W) or SC GM-CSF (125 µg/m2qd x 14 days q28d). The primary endpoint was DRR: partial or complete response continuously for ≥ 6 mos starting within 12 mos. Responses were per modified WHO by blinded central review. The primary analysis of OS (290 planned events) had 90% power to detect a HR of 0.67 with two sided α=0.05. Results: 436 pts are in the ITT set: 295 (68%) T-VEC, 141 (32%) GM-CSF. 57% were men; median age was 63 yrs. An increase of 4.4 mos in OS with T-VEC vs GM-CSF was observed (p =0.051): HR 0.787 (95% CI: 0.62, 1.00); median (95% CI) OS was 23.3 (19.5, 29.6) mos with T-VEC vs 18.9 (16.0, 23.7) mos with GM-CSF. Objective response rate with T-VEC was 26% (95% CI: 21%, 32%) with 11% CR, and with GM-CSF was 6% (95% CI: 2%, 10%) with 1% CR. DRR for T-VEC was 16% (95% CI: 12%, 21%) and 2% for GM-CSF (95% CI: 0%, 5%), p<0.0001. Most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. No ≥ grade 3 AE occurred in ≥ 3% of pts in either arm. Conclusions: In pts with unresectable Stage IIIB-IV melanoma, T-VEC demonstrated a significant improvement in the DRR vs GM-CSF with a tolerable safety profile. An improvement in OS approaching statistical significance was seen in the ITT population. Clinical trial information: NCT00769704.
Abstract 10572: Vitamin K Supplementation Slows the Progression of Aortic Valve Calcification
Authors: Ralf Koos, Sebastian Reinartz, Nikolaus Marx, Rainer Hoffmann, Vincent Brandenburg
Journal: Circulation (2013)

Introduction: Vitamin K and vitamin K-dependent proteins play pivotal roles in preventing ectopic calcification. It has been suggested that patients on long-term treatment with vitamin K antagonist...
Abstract 13739: Potential Benefit of Statin Therapy in Patients with Non-Obstructive Coronary Artery Disease
Authors: Benjamin J Chow, Gary R Small, Stephan Achenbach, Mouaz Al-Mallah, Daniel Berman, Matthew J Budoff, Filippo Cademartiri, Tracy Callister, Hyuk-Jae Chang, Victor Y Cheng, Kavitha Chinnaiyan, Augustin Defago, Allison M Dunning, Millie J Gomez, Martin Hadamitzky, Joerg Hausleiter, Ronald P Karlsberg, Phillip A Kaufmann, Troy M LaBounty, Fay Y Lin, Erica Maffei, Khurram Nasir, Micheal J Pencina, Gilbert L Raff, Leslee J Shaw, Todd C Villines, James K Min
Journal: Circulation (2011)

Background: Recent analyses have challenged the benefit of statin and aspirin therapy for primary prevention in patients at high cardiovascular risk. Equally uncertain is the optimal therapy for patients with non-obstructive coronary atherosclerosis diagnosed using coronary computed tomographic angiography (CCTA). The objective of this study was to analyze the potential mortality benefit associated with statin and aspirin therapy in patients diagnosed of non-obstructive CAD. Methods: 27,125 consecutive patients underwent CCTA at 12 enrolling centres (CONFIRM Registry). Patients with a history of myocardial infarction, obstructive CAD (≥50%) or coronary revascularization were excluded. Also excluded were patients lacking statin or aspirin information. Patients were allocated to statin and aspirin use if they were taking the respective medications at the time of CCTA. Patient were followed for all-cause mortality. Results: A total of 10,418 patients (5712 normal and 4706 non-obstructive CAD) met the enrolme...
Abstract 17808: Increased Left Ventricular Apical Rotation and Rotation Rate at Rest Predicts Significant Coronary Artery Disease in Patients with Diabetes
Authors: Ravi Rasalingam, Mark R Holland, Stephanie N Johnson, Kyle R Bilhorn, Daniel H Cooper, James G Miller, Julio E Perez
Journal: Circulation (2010)

Introduction: Identifying patients with Diabetes that have significant coronary artery disease (CAD) is challenging, with little data to support current non-invasive screening strategies. Analyses ...
Effect of mutational status on response, PFS, or OS after treatment with IL-2 for metastatic melanoma.
Authors: R. W. Joseph, R. J. Sullivan, D. Panka, G. Manoukian, A. Percy, R. Harrell, R. L. Bassett, M. B. Atkins, P. Hwu, M. A. Davies
Journal: Journal of Clinical Oncology (2010)

8597 Background: High dose IL-2 (HD-IL2) is the only FDA-approved treatment that induces durable complete responses (CR) and survival in patients (pts) with metastatic melanoma (MM), but it does so in only 5-10% of pts. Approximately 80% of melanomas have a mutation in either BRAF or NRAS. It is unknown if these mutations influence clinical responses to HD-IL2. We reviewed the clinical outcomes, pt and tumor characteristics, and mutational status of MM pts treated with HD-IL2. Methods: All pts (n = 209) were treated at the University of Texas MD Anderson Cancer Center (MDACC) or Beth Israel Deaconess Medical Center (BIDMC) from 2004-2009. IL-2 600,000-720,000 U/kg IV was administered every 8 hours for up to 14 doses in 5 days every 3 weeks. Tumor response was assessed by RECIST criteria after 2 cycles unless obvious progression occurred after 1 cycle. For pts with available tumor tissue (n = 64), DNA was isolated and tested for activating BRAF and NRAS mutations by mass-spectroscopy based genotyping. Mutation status was compared to best clinical response, progression free survival (PFS), and overall survival (OS). Results: Mutation results for 64 pts are available: 70% BRAF (45), 11% NRAS (7), and 19% Wild-Type (12) for both (WT/WT). Pts who achieved a CR, partial response (PR), or stable disease (SD) survived longer than pts with PD (median OS not met vs 339 days, p<0.01). There was no correlation between response, PFS, or OS and mutational status of the tumor. Women were more likely to harbor a BRAF mutation than men (91% vs 59%, p<0.01), and the mean age of pts with BRAF mutations tended to be younger (45 vs 52 years, p = 0.05). There was no correlation between the mutational status and ulceration, breslow thickness, or mitotic index of the primary tumor. Conclusions: Mutational status of tumors does not appear to impact response rate, PFS, OS to HD-IL2 for the treatment of MM. BRAF mutations are more likely to occur in females and younger patients. Genotyping of additional specimens is ongoing and will be included in the final analysis of the data. All (n = 64) BRAF (n = 45) NRAS (n = 7) WT/WT (n = 12) OS (median, years) 1.94 1.84 5.34 3.09 PFS (median, days) 57 57 171 48 % Response (CR/PR/SD) 30% 31% 29% 25% No significant financial relationships to disclose.
Abstract 232: Vascular Dysfunction Induced By High Pressure Levels Is Mediated By Rac-1
Authors: Carmine Vecchione, Maria Teresa Gentile, Alba Di Pardo, Umberto Bettarini, Giuseppe Lembo
Journal: Circulation (2007)

Oxidative stress plays a crucial role in the vascular dysfunction present in hypertension. The molecular mechanism involved are not completely elucidated. One of the principal source of oxidative stress at vascular level is the NADPH oxidase enzyme which needs Rac-1 to be activated. Aim of our study was to evaluate the role of Rac-1 in vascular dysfunction induced by high pressure levels. To test this hypothesis, carotid of mice were placed on pressure system and subjected to increasing levels of pressure (100 and 180 mmHg). In particular, after a period of perfusion (1h) with 100 mmHg vessels were subjected to 180 mmHg for three hours. At the end of perfusion period the vascular reactivity was tested. Our results demonstrate that vessels perfused with 180mmHg (n=8) showed an impaired vasorelaxation to acetylcholine as compared to vessels perfused with 100 mmHg (n=7) (% max vasorelaxation: 47±3 vs 88±7, p&lt;0.01). Vasorelaxation to nitroglycerin was comparable between vessels perfused respectively at 100 and 180 mmHg. Some vessels were used to evaluate oxidative stress (n=5) by dihydroethidium and Rac-1 activity (n=8) by Rac-1/PAK complex. Our results demonstrate that high pressure levels induced an increased oxidative stress and more interesting an increased Rac-1 activity as compared to vessels perfused with 100 mmHg. Thus, to clarify the role of Rac-1 in high pressure evoked oxidative stress and vascular dysfunction, some vessels (n=6) were infected with adenoviral vector containing Rac-1 dominant negative. In this experimental setting vessels perfused at 180 mmHg showed an oxidative stress and endothelial vasorelaxation comparable to that observed at 100 mmHg (% max vasorelaxation: 79±6 vs 85±7, n.s.), thus demonstrating a key role of Rac-1 in oxidative stress and endothelial dysfunction evoked by high pressure levels. Thus, Rac-1 could represent the target of novel therapeutic strategies for reducing vascular damage in hypertension.