tbuckley/cabot-search huggingface dataset:
Abstract 14197: Industrial Developmental Toxicant Emissions and Congenital Heart Disease in Urban and Rural Alberta, Canada
Authors: Deliwe P Ngwezi, Lisa K Hornberger, Jesus Serrano-Lomelin, Deborah Fruitman, Alvaro Osornio-Vargas
Journal: Circulation (2015)

Background: We have previously demonstrated a downward temporal association between mixtures of organic solvents released into air from industrial sources and congenital heart disease (CHD) in Alberta. Hypothesis: In the current study we hypothesized that the downward temporal associations between developmental toxicants (DTs) and CHD would have a different industrial sector participation in the urban and rural areas of Alberta. Methods: We extracted yearly emissions of DTs (tonnes) from Canada’s National Pollutant Release Inventory as released to air between 2003-2010. We identified at the postal code level, all CHD cases born between 2004-2011 through our provincial-wide echocardiography database. We calculated yearly urban and rural CHD crude rates. Urban and rural were defined according to Forward Sortation Areas. Principal Component Analysis was undertaken to reduce the dimensionality of the number of DTs and the yearly solution was applied to rural and urban areas to test correlations with corresponding yearly CHD rates. Results: Three principal components (PCs) were identified: PC1 consisted of a mixture of organics and gases, PC2 consisted of a mixture of organics only and PC3 consisted of metals. There were strong positive correlations between CHD rates and urban PC1 emissions from mining and manufacturing, (r=0.76, p=0.03; 0.74, p=0.04); whereas in rural areas, PC1 emissions from mining and utilities and PC2 emissions from mining and manufacturing were associated with rates of CHD, (r=0.71, p=0.05; r=0.74, p=0.04 and r=0.86, p=0.01; r=0.74, p=0.04, respectively). PC3 showed no positive correlations (Table 1). Conclusions: CHD rates are consistently strongly correlated with mixtures of organic compounds and gases, with different patterns of chemicals and sectors involved in the urban and rural settings. This provides an opportunity to further investigate spatial correlations between DTs and CHD rates at a higher resolution scale.
Abstract 18966: Right Ventricular Dysfunction is Common in Patients With Breast Cancer Experiencing Cardiotoxicity During Adjuvant Trastuzumab Therapy
Authors: Anna Calleja, Frédéric Poulin, Michael McDonald, Diego H Delgado, Paaladinesh Thavendiranathan
Journal: Circulation (2013)

Background: Cardiotoxicity (CTOX) during cancer chemotherapy is commonly identified using a threshold reduction in left ventricular ejection fraction (LVEF) from pre-therapy values. Right ventricular (RV) dysfunction is not considered in the definition of CTOX. We examined the hypothesis that RV dysfunction will be present in a subset of patients experiencing CTOX. Methods: We retrospectively analyzed echocardiograms (echo) performed in consecutive breast cancer patients referred to a heart function clinic for management of CTOX during adjuvant trastuzumab therapy. All patients had an echo performed during the first clinical visit and were not on cardio-protective therapy. RV function was assessed using fractional area change (FAC) and global longitudinal peak systolic strain (VVI software, Siemens, Figure) using a 4 chamber view. Ten healthy volunteers were used as controls for RV strain measurements. Results: A total of 27 female pts (age 53 ± 12yrs) were included. Mean 2D biplane LVEF was 53.5 ± 9.3% with 13/27 having an LVEF &lt;55%. The mean RV FAC for all patients was 39.6 ± 9.0%, with 7/27 (26%) having an abnormal FAC (&lt;35%). LVEF was normal in 4 of these 7 patients. Including all 6 RV segments mean RV global longitudinal strain was -17.1 ± 7.4% versus -25.4 ± 2.2% in controls (p=0.001). Limiting the analysis to the 3 RV lateral wall segments, the mean longitudinal strain in patients was -22.9 ± 3.6% versus -30.0 ± 3.3% in controls (p=0.007). Using a strain cut off value of -23.5% for the lateral wall (2SD below mean for normal), 9/20 (45%) with normal FAC had had abnormal RV peak systolic longitudinal strain. Conclusion: Amongst patients referred for management of CTOX, 26% had significant RV systolic dysfunction. However, and additional 45% of the patients had subclinical RV dysfunction based on a reduced RV longitudinal strain. RV dysfunction should be considered as an important parameter in the assessment of patients referred for the assessment of cardiotoxicity.
Abstract 18962: Impact of Angina on Cardiovascular Outcomes in Patients With Stable Ischemic Heart Disease: A Post-Hoc Analysis From the COURAGE Trial
Authors: Subroto Acharjee, Mandeep S Sidhu, Pamela M Hartigan, Koon K Teo, John A Spertus, David Maron, William S Weintraub, William E Boden
Journal: Circulation (2013)

BACKGROUND: Previous data on the prognostic value of angina on clinical outcomes in patients with stable ischemic heart disease (SIHD) has been conflicting. We studied the impact of presence and severity of angina on clinical outcomes among participants in the COURAGE trial. METHODS: Based on presence or absence of angina at baseline, 2,280 patients with SIHD were divided into 2 subgroups. Those with angina were further stratified based on angina severity determined by Canadian Cardiology Society (CCS) class. Hazard ratios for clinical outcomes were calculated using the group with silent ischemia (CCS = 0) as referent. RESULTS: Table 1 shows cumulative event rates and hazard ratios among study participants after 4.6 years of follow-up. Although presence or absence of angina did not have any impact on clinical outcomes, patients with CCS III angina did have a significantly higher rate of death/MI/ACS, largely due to greater ACS (unstable angina) events. CONCLUSIONS: Patients with SIHD on optimal medical therapy had similar rates of “hard” cardiovascular endpoints regardless of presence or severity of angina. Those with severe (CCS III) angina at baseline had higher incidence of unstable angina with negative biomarkers, a finding that merits further investigation in future clinical trials.
Abstract 18952: Differential Cardiac Gene Expression at the Time of VAD Placement Differentiates Eventual VAD-Recovery From VAD-Dependence
Authors: Charles F McTiernan, Ravi Ramani, Dennis McNamara, Bonnie Lemster, Christian Bermudez, Robert Kormos, Ana Segura, Deborah Vela, O.H. Frazier, John Gorcsan
Journal: Circulation (2013)

Introduction: Only ~5% of Ventricular assist device (VAD) supported end stage heart failure (HF) patients recover enough cardiac function to allow VAD removal. VAD use introduces significant risks, yet it is difficult to identify patients with the greatest recovery potential and who may benefit from VAD removal. The RECOVER trial ( NCT00687856 ) seeks novel functional and molecular markers to identify those patients that may recover sufficient cardiac function to allow successful VAD removal. Hypothesis: Gene expression analysis of the ventricular core recovered at the time of VAD placement can differentiate those patients who eventually develop VAD-independence ( R) from those remaining VAD-dependent ( D ). Methods: Two groups of VAD-supported patients with non-ischemic HF were studied; R group (n=9 patients) and D (n=14). R group patients (8/9) had &gt;6mo freedom from HF after VAD removal. R vs D did not differ (p=NS) in age (30.0+-/9 vs 36.4+/-11 yrs); sex (6M/3F vs 10M/4F), pre-VAD EF (18.6+/-4 vs17.6+/-5%) or LVEDD (6.24+/-0.4 vs 6.54 +/- 0.8 cm). RNA was isolated from VAD-implant core and analyzed on Agilent GE60K arrays. After log2-transformation and cyclic LOESS normalization, expression analysis was performed (GeneSpring). Results: Uncorrected t-test revealed 302 transcripts that differed between R and D groups by &gt;1.5 fold (p&lt;0.05). Relative to D , R had 81 transcripts lower and 220 higher. Euclidean Ward’s clustering (Figure) of 45 transcripts with &gt;1.5X differential expression and p&lt;0.005 segregated most R (blue) from D (red) patients. Conclusions: In a small group of patients, gene expression analysis performed at the time of VAD placement showed potential differences between patients with eventual recovery versus those remaining VAD-dependent. The results may reflect differences in underlying in heart failure severity, and reveal those with potential for functional recovery. More cases will be required to confirm these preliminary observations.
Abstract 18985: Lentil-Based Diets Reduce Vascular Remodeling Through a p38 Mitogen-Activated Protein Kinase Dependant Mechanism in the Spontaneously Hypertensive Rat
Authors: Matthew Hanson, Peter Zahradka, Hope Anderson, Carla Taylor
Journal: Circulation (2013)

Hypertension is a major driving force behind arterial remodeling, which increases stiffness, and decreases compliance and function. Certain pharmaceuticals are capable of lowering high blood pressure, but most interventions are unable to also reverse remodeling. We have found that lentils are able to significantly attenuate the development of hypertension in the SHR, however the mechanism for this action remains unresolved. The current study examined the hypothesis that the positive actions of lentils on blood pressure are mediated through direct changes in arterial function that decrease remodeling and improve arterial compliance. Seventeen-week SHR were randomly assigned to groups (n=8/group) fed (i) 30% w/w green lentils, (ii) 30% w/w red lentils, (iii) 30% w/w mixed lentils (red and green), or (iv) no lentils. Normotensive WKY control rats were fed either mixed lentil or no lentil diets (n=8/group). BP and pulse wave velocity were measured weekly; pressure myography was performed at termination. Western Blotting was performed on aorta protein samples. There were no dietary related changes in pulse wave velocity, however, green lentils restored arterial compliance to a level better than control-fed WKY. All lentil fed animals exhibited arterial stiffness comparable to WKY control, with green lentils experiencing the largest improvement according to myography measurements. All lentils reduced the media:lumen ratio to a level between control fed SHR and WKY. Western blotting indicated a decrease in p38 MAPK activation in lentil-fed SHR with no change in ERK1/2 phosphorylation. Although both ERK1/2 and p38 MAPK are potent mediators of vascular remodeling, only p38MAPK phosphorylation is redox sensitive. These data would indicate that lentil-based diets are able to decrease vascular remodeling by ameliorating p38 MAPK-dependent redox-sensitive signaling cascades.
Abstract 13032: Evidence of Dimensional Adaptability of in vivo Tissue-engineered Allogenic “Biotube” Vascular Grafts in a Growing Canine Model
Authors: Maya Furukoshi, Yasuhide Nakayama
Journal: Circulation (2016)

Introduction: In pediatric surgery, size mismatch inducing between artificial vascular grafts and growing recipients vessels remains a serious problem to be solved. Biotubes are autologous connective tissue tubes, formed by in body tissue architecture technology (IBTA), which is a novel and practical approach of regenerative medicine based on the tissue encapsulation phenomenon. This study aimed to evaluate the growth potential of Biotubes by examining their caliber and length adaptation to growing native arteries after implantation. Allogenic implantation of Biotubes pre-prepared from adult beagles was performed to juvenile beagles. Methods and Results: IBTA-based Biotubes (internal diameter 3 mm, length 1 cm) were prepared in adult beagles (age, 1 year; weight ca. 10 kg) by subcutaneous embedding of silicone-based molds for 2 months. The obtained allogenic collagenous Biotubes (n=8) were implanted into the common carotid artery (internal diameter, 2 mm) of juvenile beagles (n=8, age 11 weeks, weight ca. 3 kg). In all cases, there was no aneurysm or stenosis formation with perfect patency for all observation periods. Almost complete vascular remodeling occurred only at 1 month of implantation. Follow-up angiogram showed that diameter of Biotubes was gradually expanded with that of the growing host arteries almost in the same way. In 1-year after implantation, there was little gap between them by ca.1.5-times of diameter expansion in Biotube. Interestingly, macroscopic observation showed elongation of Biotubes to ca 1.3 times in maximum. Conclusions: Even in allogenic manner, vascular reconstruction of Biotube to layered vascular tissue successfully occurred. After vascular reconstruction, Biotubes could be extended and expanded according to the growing native arteries. The growth potential of Biotubes was indicated in this animal experimental model for the first time. Biotubes have high potential usefulness in pediatric surgery.
Abstract 13644: The Effect of Computational Fluid Dynamics Modeling Assumptions in Endothelial Shear Stress Calculations derived From Coronary Computed Tomography Angiography
Authors: Andreas A Giannopoulos, Yiannis S Chatzizisis, Pal Maurovich-Horvat, Antonios P Antoniadis, Tianrun Cai, Udo Hoffmann, Michael L Steigner, Frank J Rybicki, Dimitrios Mitsouras
Journal: Circulation (2015)

Background: Low endothelial shear stress (ESS) is associated with coronary plaque progression and high-risk plaque features. Coronary ESS profiling requires the three-dimensional luminal geometry and Computational Fluid Dynamic (CFD) assumptions to successfully model coronary blood flow. Hypothesis: To examine whether two typical CFD modeling assumptions, namely the exclusion of side branches and the blood model used, alter the determination of those arterial regions that are exposed to low ESS. Methods: Five excised human hearts were imaged with 64-detector row CT. Coronary arteries &gt;1 mm in diameter were segmented and the coronary tree lumen was reconstructed with and without side branches. ESS was calculated for 3 models: a) the entire tree and a non-Newtonian blood model (reference standard) b) the entire tree and a Newtonian blood model and c) major coronaries only (no side branches) and a non-Newtonian blood model (Fig panel A). ESS was compared in each major coronary artery amongst models using Pearson’s correlation and via sensitivity and specificity to detect those 3 mm sections in the coronary circulation that contained the 10% of endoluminal surface with lowest ESS values. For sensitivity and specificity the first model (a) was considered the reference standard. Results: The Newtonian assumption for blood induced minimal change in ESS pattern other than a relative scaling of values. The exclusion of side branches however induced large, coronary-segment specific non-linear changes in both pattern and value. With no side branches, sensitivity and specificity to identify low ESS regions were 78% and 88%. With Newtonian blood and side branches, sensitivity and specificity were 89% and 98% (Fig panel B). Conclusion: Side branches are important for identifying areas of low ESS while the assumption that blood model behaves as a Newtonian fluid has negligible effect.
Abstract 13027: The Activation of Glucagon-Like Peptide-1 Improves the Mitochondrial Abnormalities in Skeletal Muscle and Exercise Intolerance in Heart Failure Mice
Authors: Takashi Katayama, Shingo Takada, Yoshihiro Masaki, Shintaro Kinugawa, Junichi Matsumoto, Takayuki Nakajima, Masaya Tsuda, Takaaki Furihata, Wataru Mizushima, Arata Fukushima, Takashi Yokota, Koichi Okita, Hiroyuki Tsutsui
Journal: Circulation (2016)

Introduction: In patients with heart failure (HF), exercise capacity is limited due to impaired energy metabolism and mitochondrial abnormalities in the skeletal muscle. Glucagon-like peptide-1 (GLP-1), one of the incretin hormones, has been indicated to improve exercise capacity in HF patients. We investigated the effects of the treatment of a dipeptidyl peptidase (DPP)-4 inhibitor on the limited exercise capacity and mitochondrial abnormalities in the skeletal muscle in HF mice after myocardial infarction (MI). Methods and Results: C57BL/6J male mice underwent surgery to ligate the left coronary artery or sham-operation. The mice were subsequently divided at random into groups with or without the treatment providing a DPP-4 inhibitor, MK-0626 (1 mg/kg body weight/day) in the diet. Four weeks after surgery, treadmill test and echocardiography were performed in 4 groups (n=14 each). The exercise capacity was limited in the MI mice, and it was improved in the MI+MK-0626 mice without affecting the infarct size, cardiac function, and skeletal muscle weight. The citrate synthase activity, mitochondrial oxidative phosphorylation capacity, fatty acid oxidation and their quantity were reduced in the skeletal muscle of the MI mice, and these decreases were normalized in the MI+MK-0626 group, in association with the improvement of mitochondrial biogenesis via phosphorylation of AMP-activated protein kinase (AMPK)-sirtuin1 (Sirt1)-peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling. Favorable effects of MK-0626 were significantly inhibited by treatment of GLP-1 antagonist, Excendin-(9-39) (150 pmol/kg body weight/min) with subcutaneous osmotic pumps in MI+MK-0626 mice. Similarly, exercise capacity and mitochondrial complex I activity were significantly improved by treatment of GLP-1 agonist, Excendin-4 (1 nmol/kg body weight/hour) with subcutaneous osmotic pumps in MI mice. Conclusions: The activation of GLP-1 receptor improves the reduced exercise capacity and mitochondrial abnormalities of skeletal muscle in HF mice after MI. The activation of GLP-1 receptor may be a novel therapeutic target against reduced exercise capacity and skeletal muscle dysfunction in HF.
Abstract 13016: Anticoagulation Control in Warfarin Treated Patients Undergoing Cardioversion for Atrial Fibrillation: A Pre-specified Ancillary Analysis From the ENSURE-AF Trial
Authors: Gregory Y Lip, Naab Al-Saady, James Jin, Ming Sun, Michael Melino, Shannon M Winters, Andreas Goette, Dmitry Zamoryakhin
Journal: Circulation (2016)

Background: In the ENSURE-AF study (NCT 02072434), the oral factor Xa inhibitor edoxaban was compared to warfarin in 2199 patients undergoing electrical cardioversion of nonvalvular AF. Ideal patient management requires optimization warfarin within a therapeutic range of INR 2.0-3.0. We determined aspects of anticoagulation control in the warfarin arm of this trial. Methods: In this multicenter, PROBE, parallel group Phase 3b clinical trial, we performed a pre-specified analysis of 1104 patients randomized to warfarin. We determined the Time to achieve Therapeutic Range (TtTR), Time in Therapeutic Range (TiTR), their clinical determinants and impact on outcomes. The primary safety endpoint was the composite of major + clinically relevant non-major (CRNM) bleeding from time of first administration of study drug to end of treatment +3 days. Patients were followed for 28 days on study drug after cardioversion + another 30 days to assess safety. Results: Among 1104 patients randomized to enoxaparin/warfarin, 27% were naïve to oral anticoagulants at randomization. Mean age was 64.2±11 years and mean CHA 2 DS 2 -VASc score was 2.6. Mean TtTR was 7.7 days (median 7 days) and mean TiTR after reaching INR 2.0-3.0 on warfarin was 70.8%. In 695 patients with INR &lt;2 prior to first dose and who reached therapeutic range of ≥2, 436 had a SAMe-TT 2 R 2 score ≤2 and 259 a score of &gt;2. Mean TtTR was 7.7 and 7.6 days, respectively. In 974 patients with INR in range of 2-3 post first dose, TiTR was 71.1% vs 70.3% for patients with SAMe-TT 2 R 2 score ≤2 and &gt;2, respectively. On multivariate regression, an independent predictor of extended TtTR was CrCl (P=0.02). Independent predictors of TiTR were prior VKA experience (P&lt;0.01) and low HAS-BLED score (P=0.02). TtTR was marginally related to stroke/SE/MI/CV mortality (P=0.06; OR [odds ratio]=0.23, CI 0.02-1.17) but not to any bleeding (P=0.53; OR=0.72, CI 0.28-1.80). TiTR was related to any bleeding (P=0.02; OR=0.39, CI 0.16-0.88), but not stroke/SE/MI/CV mortality (P=0.31; OR=0.42, CI 0.07-1.98). Conclusion: In this well-managed cohort of warfarin users in a clinical trial setting with a high TiTR (&gt;70%), the SAMe-TT 2 R 2 score did not discriminate between mean TtTR and TiTR. Even in this short term study, TiTR was related to bleeding events.
Abstract 13624: Effect of Electrical Therapy Using Biphasic Defibrillators in the 2010 CPR Guidelines for Patients With Out-of-Hospital Cardiac Arrest due to Nonshockable Rhythm
Authors: Tsukasa Yagi, Ken Nagao, Eizo Tachibana, Naohiro Yonemoto, Shinichi Shirai, Morimasa Takayama, Hiroshi Nonogi, Keijiro Saku, Sigemasa Tani, Naoya Matsumoto, Atsushi Hirayama
Journal: Circulation (2015)

Background: The 2005 guidelines for cardiopulmonary resuscitation (CPR) with electrical therapy recommended a single shock plus an immediate 2 minutes of CPR instead of 3-shock sequences recommended in the 2000 guidelines. The 2010 guidelines have stressed that it is necessary to improve CPR quality. Each set of guidelines recommended a timely shock when non-shockable patients were found to be in shockable rhythm. Few data are available concerning this electrical therapy. Methods: From the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest (OHCA), we included adult patients who had OHCA due to cardiac etiology, in whom non-shockable arrest were recorded as an initial rhythm, and who received shock using biphasic AEDs after conversion from non-shockable arrest to shockable arrest by emergency medical service (EMS) personnel. Study patients were divided into three groups based on the different CPR guidelines; 3-shock protocol in the 2000 guidelines (2000G), 1-shock protocol in the 2005 guidelines (2005G), and 1-shock protocol in the 2010 guidelines (2010G). The primary endpoint was favorable neurological outcome at 30 days after OHCA. Results: Of the 5066 patients who met the inclusion criteria (figure). The figure shows the comparison of favorable neurological using biphasic AEDs in the three groups. Adjusted odds ratios for favorable neurological outcome were 2.5 (95% CI, 1.3 to 4.7) after the 2005G group and the 2010G group as compared with the 2000G group, and 0.8 (95% CI, 0.6 to 1.1) after the 2010G group as compared with the 2005G group. ConclusioN: The single-shock protocol using biphasic AEDs of the 2005 and 2010 guidelines were superior to the 3-shock protocol of the 2000 guidelines, but the single-shock protocol using biphasic AEDs of the 2005 and 2010 guidelines had similar 30-day favorable neurological outcome in patients with non-shockable cardiac arrest.