tbuckley/cabot-search huggingface dataset:
Abstract 11955: Development of <i>in vivo</i> , Tissue-Engineered, Autologous, 3D Heart Valvular Tissue, Type SC Biovalve With Excellent Mechanical Properties, Valular Functions, and <i>in vivo</i> Performances
Authors: Yasuhide Nakayama, Yoshiaki Takewa, Takeshi Moriwaki, Hirohito Sumikura, Shinji Miyamoto, Keitaro Okamoto, Marina Funayama, Maya Furukoshi, Eisuke Tatsumi
Journal: Circulation (2015)

Background: Autologous pericardium is widely used for the reconstruction of intracardiac structures and pulmonary artery, and for aortic valve leaflets after fixation with glutaraldehyde for mechanical strengthening. We developed autologous prosthetic tissues by using in-body tissue architecture (IBTA) technology, which is a novel and practical approach of regenerative medicine based on the tissue encapsulation phenomenon of foreign materials in living bodies. In this study, IBTA-based heart valves with robust tissue wall [Biovalve (BV) Type SC] were prepared by using a novel caged mold. The mechanical properties of the valves were compared with human pericardium, and in vivo durability was evaluated in animal implantation study after in vitro evaluation using a pulsatile circulation circuit. Methods and Results: The BV preparation molds could be produced rapidly by using a 3D printing machine, based on the designed 3D-shape and size of native heart valves regardless of their type. Upon 1- or 2-month goat subcutaneous embedding of the molds aortic or pulmonary valve-shaped BVs (diameter 5-30 mm) were formed as type SC from completely autologous connective tissue with collagen and fibroblasts. All surfaces of the BVs that were in contact with blood were highly smooth and flat. The three leaflet tissues were seamlessly connected with the surrounding conduit tissue, and showed homogeneous wall thickness and excellent mechanical strength that was equivalent to or more than that of the human pericardium, with individual or regional differences. As an aortic valve, in vitro evaluation of the BV showed excellent valvular functions (regurgitation ratio 5.7% at 70 beats per minute). In a goat model, postoperative echocardiography after surgical replacement of the biovalves with stents showed smooth movement of the leaflets with little regurgitation under systemic circulation. In all implantation studies, the luminal surface after implantation was very smooth and fully covered with thin neointima, including endothelial cells without thrombus formation. Conclusion: Functional, completely autologous, robust, 3D aortic or pulmonary BVs showing the potential for clinical application were developed by in-body embedding of specially designed molds.
Abstract 18522: Echocardiogram in the Evaluation of Patients With Syncope and Normal Electrocardiogram: Do We Need It
Authors: Moustapha Atoui, Christian Gonzalez, Manoj Bhandari, Socrates Rosdan, Richard Peralta, Marin Nicu, Jonathan N Bella, Eduard Sklyar
Journal: Circulation (2013)

Background: Syncope is a major cause for emergency room visits and hospital admissions. The electrocardiogram (ECG) serves as an important and cheap diagnostic tool, but most patients undergo additional cardiac testing including echocardiogram. However, little is known about its benefit in patients with normal ECG. Hypothesis: We hypothesize that patients with syncope and normal ECG are likely to have normal echocardiogram. Methods: We conducted a retrospective chart review of adult patients admitted with syncope between Jan 2011 and Mar 2012. Demographics and cardiac testing were reviewed. Patients with positive drug screen or who didn’t meet our syncope definition were excluded. Study population was divided into two groups based on ECG. Abnormal ECG includes any arrhythmia, conduction delay, chamber hypertrophy and ST/T abnormalities. Abnormal echocardiogram includes any wall motion abnormality, decreased ejection fraction, significant valvular disease, pulmonary hypertension or chamber enlargement. Descriptive statistics with Confidence intervals (CIs), interquartile ranges (IQRs; 25%, 75%) and linear regression were done using SPSS 20. Results: We identified 497 adult patients admitted with syncope. Only 198 met our inclusion criteria. Mean age was 58 years (25%, 75% IQR 48, 70), 40% Men, 50% Hispanics, 30% Black, 71% Hypertensive, 29% Diabetics, 13% with Coronary artery disease and 3% with congestive heart failure. Normal ECG group consists of 110 (56%; 95% CI: 49-63) patients. Echocardiogram was performed on 177 (89%; 95% CI: 85-94) patients, from them 16 (8%; 95% CI: 4 to 12) were abnormal and only 2 (2%; 95% CI: -1 to 4) were in patients with normal ECG. A correlation was found between the patients with normal ECG and normal Echocardiogram (P&lt;0.001). On multiple linear regressions, predictors of abnormal echocardiogram were: Diabetes (β= - 0.145, p= 0.031), coronary artery disease (β= 4.32, p= &lt;0.001), congestive heart failure (β= 0.147 p= 0.027), and abnormal ECG (β= 0.185, p= 0.006). Conclusion: In conclusion, a normal ECG correlates with a normal echocardiogram in patients presented with syncope. Echocardiogram, frequently performed, may not be needed in this specific group of patients.
Abstract 12569: Relationship Between Neurodevelopmental Outcomes at 2 Years and 4 Years in Children With Congenital Heart Disease After Surgical Palliation
Authors: Cheryl L Brosig, Laurel Bear, Sydney Allen, Raymond G Hoffmann, Amy Pan, Michele Frommelt, Kathleen A Mussatto
Journal: Circulation (2016)

Introduction: Children with congenital heart disease (CHD) are at risk for neurodevelopmental (ND) delays. The American Heart Association (AHA) recommends serial ND evaluation for children with CHD. This study compares the ND testing results of children with CHD at 2 and 4 years of age. Methods: Children with CHD meeting the AHA high-risk criteria for ND delay were seen for longitudinal developmental evaluation. Testing included the Bayley Scales of Infant Development - III (BSID-III) at 2 years (±3 months) of age, and standardized neuropsychological measures at 4 years. Scores were compared to test norms and were classified as: average (within one SD of test mean); at risk (1-2 SDs from the test mean); and impaired (&gt;2SD from test mean). Spearman correlations and McNemar’s exact tests were performed to determine the relationship between test scores at the two times of assessment. Results: Of the 102 patients evaluated at 4 years of age, 73% (n=75) had a previous evaluation using the BSID-III; 48 (47%) completed the BSID-III at 24±3 months of age. Median age at first cardiac operation was 13 days. Patients had the following characteristics: single ventricle anatomy 33%; male 63%; prenatal diagnosis 53%; premature 18%; non-white/Hispanic race 13%; and comorbidities: medical 25%, genetic 17%. BSID-III cognitive, language, and motor scores were correlated with preschool IQ, language, and motor scores, r = 0.49 to 0.75, all p&lt;0.01. Of the patients who had average or above BSID-III cognitive scores at age 2, 29.7% scored in the at risk or delayed range on the preschool IQ test. Conclusion: BSID-III scores at 2 years are significantly associated with ND outcomes at 4 years. However, even though scores were related, many patients who scored in the average range at age 2 showed some deficits at age 4. Therefore, longitudinal ND assessment is recommended.
Abstract 18532: New Prognostic Factors in Heart Failure With Preserved Ejection Fraction: The KaRen Study
Authors: Donal Erwan, Lars H LUND, emmanuel oger, camilla Hage, jean-claude daubert, cecilia linde
Journal: Circulation (2013)

KaRen was a prospective multicentre study identifying predictors of outcome in patients with Heart Failure and preserved Ejection Fraction (HFpEF). Method: 539 patients were included following an acute HF presentation accompanied with BNP&gt; 100 pg/mL or NT-proBNP&gt;300 pg/mL and LVEF &gt; 45%. 438 patients were reassessed after 4 -8 weeks clinically, biologically and by ECG and echocardiography. ECG (18 variables) and echo (117 variables) were analysed in core centres. Patients were followed for vital status and hospitalisation every 6 months during a minimum of 18 months. The primary endpoint was time to all-cause death or first HF hospitalisation. A Cox proportional hazard modelling was applied. The multivariable model included univariable covariates at and below the significance level p=0.15 added by age and gender. Patients: The mean age was 76± 9 years and 57% were women. A history of HF was found in 40.4 %. Patients′ history included hypertension in 78.5%, atrial tachyarrhythmia in 58%, anemia in 47.2%, diabetes in 31.3%, renal dysfunction in 37.9%. At the acute event, LVEF was 56±7 %. Of the patients 6.1 % had first degree AV block and 14.9% had QRS width &gt; 120 ms. Right bundle branch block (BBB) was present in 6.6% and Left BBB in 3.7%. Results: During a mean follow-up time of 21.6 months a primary outcome event occurred in 204 patients (46.5%) , consisting of 101 deaths (23%) and 142 HF-hospitalizations (32.5%). Candidate predictors of outcome are: First degree AV block was the only dyssynchrony criteria independently predicting outcome (p=0.04); tricuspid regurgitation (mean±standard deviation = 2.87±0.64 m/s, p=0.0009) and mean e’ velocity &gt; 5.5cm/s (mean±standard deviation = 7.95±2.58, p=0.0009) were the two echocardiographic predictors. Ongoing ACE (ARB) treatment was the only positive predictor of outcome. CONCLUSION: The KaRen study recruited a representative population of HFpEF patients with a high rate of clinical events (23% deaths).First degree atrio-ventricular block and increased pulmonary arterial pressures and left ventricular diastolic dysfunction were independently associated with outcome. These novel data may provide new information improving the management of HFpEF patients.
Abstract 18487: Characteristics and Outcomes of Patients With Severe Aortic Stenosis (Peak Gradients &gt; 125 mm Hg)
Authors: Nishtha Sodhi, Kanhaiya Lal Poddar, Sachin Goel, Dhruv Modi, Navkaranbir Bajaj, Shiraz Rahim, E. Murat Tuzcu, Lars G Svensson, Brian P Griffin, Samir R Kapadia
Journal: Circulation (2013)

Background: Limited data exists about the unique echocardiographic characteristics of patients with very high gradient severe aortic stenosis (VHG-SAS). We sought to determine if there are differences in left ventricular hypertrophy severity, ejection fraction (EF), and coronary artery disease (CAD) status in patients with VHG-SAS compared to severe AS patients with lower gradients. Methods: We identified patients with greater than 125 mm Hg peak gradients defined as VHG-SAS and patients with peak gradients between 64-125 mm Hg defined as high gradient severe AS (HG-SAS) evaluated between 1994 and 2011from our echocardiographic database. We then propensity matched these patients based on age and gender and compared their echocardiographic characteristics. Results: 340 patients with HG-SAS and 212 patients with VHG-SAS were identified. Matched pairs of 212 patients were analyzed for a variety of baseline comorbidities and echocardiographic parameters (Table). Conclusions: Patients with VHG-SAS have fewer cardiac comorbidities (CAD, Mitral regurgitation, Depressed EF, Diabetes, Hypertension) compared to HG-SAS patients. Furthermore, patients with VHG-SAS have a smaller LV Size and greater wall thickness suggesting an adequate compensatory response to pressure overload.
Abstract 18609: MicroRNA-539 Upregulation Suppresses O-GlcNAcase in the Failing Heart
Authors: Senthilkumar Muthusamy, Lewis J Watson, Kyung U Hong, Steven P Jones
Journal: Circulation (2013)

Background: Cardiac metabolism and related signaling pathways are significantly altered in the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), represents an essential post-translational modification that modulates the function of many nuclear and cytoplasmic proteins, and, does so in a variety of diseases. O-GlcNAc modification is controlled by two antagonistic enzymes: O-GlcNAc transferase (OGT; adds O-GlcNAc) and O-GlcNAcase (OGA; removes O-GlcNAc). We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, mechanisms of OGA regulation during heart failure remain unknown. Methods and Results: Using miRNA microarray analysis, we observed changes of several miRNAs at 5 d and 28 d post-myocardial infarction in mice (n=4/group) and, specifically, that miR-539 is significantly (p&lt;0.05) elevated. Subsequent qRT-PCR analysis confirmed significant (p&lt;0.05) upregulation of miR-539 at both time points (4.8 fold at 5 d and 2.9 fold at 28 d) in infarcted hearts compared to sham hearts. TargetScan predicted OGA as a potential target of miR-539. Indeed, co-transfection of OGA-3’UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced the reporter activity compared to control in transiently transfected HEK 293 cells. To establish whether miR-539 suppresses OGA expression in cardiomyocytes, lentivirus based miR-539 overexpression system was used to transduce neonatal rat cardiomyocytes. Western blot analysis showed significant (~50%; p&lt;0.05) reduction of OGA protein expression. Conclusion: These results demonstrate that miR-539 is upregulated during heart failure, binds to OGA-3’UTR, and can significantly suppress OGA expression in cardiomyocytes. This work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel potential therapeutic target in the treatment of heart failure and other metabolic diseases.
Abstract 18557: Lipid Phenotypes at the Extremes of HDL Cholesterol: Very Large Database of Lipids Study 9
Authors: Mohammed Al-hijji, Seth S Martin, Michael Blaha, Parag H Joshi, Roger S Blumenthal, Peter P Toth, Steven R Jones
Journal: Circulation (2013)

Background: Patients with extreme levels of HDL-C may inform contemporary controversies in HDL metabolism and therapies. Aim: To characterize lipid phenotypes at extremes of HDL-C. Methods: We examined 136,746 U.S. adults and children from the Very Large Database of Lipids (Baltimore, MD; NCT01698489 ) who were clinically referred for a Vertical Auto Profile test (Birmingham, AL) of cholesterol subfractions from 2009 to 2011. We categorized patients at extreme levels of HDL-C into percentile categories (&lt;0.1 th , 0.1 th to &lt;1 st , 1 st to 5 th , 95 th to 99 th , &gt;99 th to 99.9 th , and &gt;99.9 th ). Within these groups, we examined HDL-C subclasses 2 and 3, LDL-C, LDL density, non-HDL-C, triglycerides, VLDL-C, and remnant lipoprotein cholesterol. Results: Patients had a mean age of 59±15 years and 52% were women. With increasing HDL-C percentile, there was monotonically rising HDL 2 -C/HDL 3 -C ratio, consistent with more cholesterol loaded HDL particles (Table, P&lt;0.0001). Triglycerides, VLDL-C, and remnant lipoprotein cholesterol levels decreased monotonically with rising HDL-C levels (P&lt;0.0001). LDL-C increased proportionally with VLDL-C decrease resulting in constant median non-HDL-C levels. There is a progressive increase in LDL density with decreasing HDL-C. In addition to these broad trends, there was within-group heterogeneity. Conclusion: Across a broad range of HDL-C, these findings illustrate the extensive interaction between HDL and triglyceride rich remnant lipoproteins, and LDL density, possibly mediating residual cardiovascular risk. Careful phenotyping will be crucial in selecting clinical trial populations for novel HDL-targeted therapies as patients with low and high HDL-C are not all one in the same.
Abstract 18384: Hypoxia-Induced FOXC2 Expression in Human Endothelial Cells is Dependent on the MEK and PI3K Pathways
Authors: Hyun-Young Koo, Kyoo S Shim, Ting Liu, Meredith Millay, William Dietz, Kathryn M Schultz, Christine Kamide, Sol Misener, Tsutomu Kume
Journal: Circulation (2013)

FoxC2, a member of the Forkhead box (Fox) transcription factor family, is critical for vascular formation during embryonic development and tumor progression; however, the role of Foxc2 in pathological neovascularization involving ischemic conditions remains largely unknown. To test the hypothesis that FoxC2 is induced and required for hypoxia-induced angiogenesis, in vitro culture of human umbilical vein endothelial cells (HUVECs) under hypoxia and a myocardial infarction (MI) mouse model were employed. FoxC2 expression in both experimental systems was subsequently assessed. Levels of FOXC2 mRNA were transiently increased in HUVECs after 1 hour of hypoxia. Treatment of a mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor (U0126) and a phosphatidylinositide 3-kinases inhibitor (LY 294002) significantly blocked hypoxia-induced FOXC2 expression, whereas culture with a MEK1 inhibitor (PD 98059) did not. Consistent with the in vitro observation, expression of Foxc2 was upregulated in ischemic myocardial tissue of murine hearts in a time-dependent manner from day 1 to day 7 after surgically induced MI. We next examined whether Foxc2 deficiency could influence neovascularization and cardiac repair after MI. Echocardiographic measurements of left ventricular ejection fractions and fractional shortening were reduced in heterozygous Foxc2 null mutant (Foxc2+/-) mice after MI compared to wild-type mice, whereas cardiac fibrosis was increased in Foxc2+/- mice. Most significantly, Foxc2+/- mice had a drastic reduction in capillary vessel formation in the ischemic border zone after MI compared to wild-type mice. Collectively, FoxC2 is transiently induced in vascular endothelial cells in vitro under hypoxia and in ischemic murine hearts after MI, and it is essential for neovascularization during ischemic cardiac repair after MI.
Abstract 12183: <i>SLCO1B1</i> Genotype-Guided Statin Therapy Lowers LDL Cholesterol in Patients With Statin-Intolerance- A Randomized Controlled Trial
Authors: Deepak Voora, Emily Perry, Kavisha Singh, Gloria Trujillo, Nicholas Milazzo, Dillon Savard, Susanne Haga, Michael D Musty, Yi-Ju Li, Bruce Peyser
Journal: Circulation (2016)

Introduction: Statin-intolerance is a barrier to reducing cardiovascular disease risk. A genetic variant (*5, rs4149056) in the SLCO1B1 statin hepatic transporter gene is well characterized and linked to higher statin concentrations, statin-intolerance, and statin non-adherence. SLCO1B1*5 has a high negative predictive value for severe simvastatin myopathy; Pravastatin[P]/ fluvastatin[F]/ rosuvastatin[R] are preferred statins in *5 carriers to minimize side effects. The effects of SLCO1B1 genotype-guided statin therapy or delivery of SLCO1B1 genetic risk information are unknown. Hypothesis: Genotype-guided statin therapy (GGST) is superior to usual care in patients with statin-intolerance for statin-related outcomes. Methods: We randomly assigned 159 primary care patients with statin intolerance not prescribed statins to either GGST vs. usual care. GGST patients and their providers received *5 genetic risk information about statin side effects and genotype-specific statin prescription recommendations. Patients in the usual care arm received general information regarding statin risk and prescriptions. The outcomes measured at 3 and 8 months were statin re-initiation, LDL cholesterol (LDLc), and statin adherence using the validated Morisky Medication Adherence Survey. Results: The median age was 64.0 years, 57% were female, 41% reported intolerance to &gt; 1 statin, 75% reported myalgia with statins, and 25% were *5 carriers. Follow up was complete for 144 patients (91%) at 3-months and 118 (74%) at 8-months. At 3-months, GGST was associated with a higher proportion of patients who restarted statin therapy (55.4% vs. 38.0%, p=0.037), and lower LDLc (131.9±42.0 vs. 144.4±43.0, p=0.041), but similar statin adherence scores (p=0.96). Effects at 8-months were consistent with 3-month results for statin prescriptions (54% vs. 37%, p=0.07) and LDLc (128.6±37.9 vs. 141.0±44.4, p=0.07). Use of P/F/R was higher in *5 carriers assigned to GGST versus usual care (92% vs. 67%, p=0.24). Conclusion: In primary care patients with statin-intolerance, SLCO1B1 genotype guided statin therapy is effective in lowering LDLc compared to usual care. GGST, however, did not improve statin adherence in those who re-initiated statin therapy.
Abstract 12269: Prognostic Role of Hemoconcentration in Acute Decompensated Heart Failure With Preserved and Reduced Ejection Fraction; an Analysis From Mode of Death
Authors: Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Takumi Kondo, Hideyuki Hakui, Masashi Ishimi, Tastsuhisa Ozaki, Yoshihiro Satoh, Iyo Ikeda, Eiji Fukuhara, Masatake Fukunami
Journal: Circulation (2015)

Backgrounds: Hemoconcentration (HC) during heart failure treatment is known to be associated with improved clinical outcome in patients with acute decompensated heart failure (ADHF). There is a difference in mode of death (cardiac [sudden vs pump failure death] vs non-cardiac death) between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF). However, there is no information available on the different impact of HC in the prediction of mode of death in ADHF patients, relating to HFpEF and HFrEF. Methods and Results: We studied 302 patients admitted with ADHF and discharged with survival (HFpEF(LVEF≥50%);n=139, HFrEF(LVEF&lt;50%); n=163). HC was defined as an increase in hemoglobin level from admission to discharge. During a follow-up period of 5.1±4.3 yrs, 65 patients had cardiac death (sudden cardiac death in 37 and pump failure death in 27 patients) and 56 patients had non-cardiac death. HC was significantly associated with cardiac death in patients with HFrEF (p=0.02) but not in those with HFpEF, while there were no associations between HC and non-cardiac death in both patients with HFpEF and HFrEF. In patients with HFrEF, although there was no association between HC and sudden cardiac death, HC was significantly associated with pump failure death (adjusted HR 0.31 [95%CI 0.10-0.91], p=0.04), independently of relevant covariates such as systolic blood pressure and BUN. On the other hand, there was no association between HC and sudden or pump failure death in patients with HFpEF. Conclusion: HC was related to improve pump failure death but not sudden cardiac death in hospitalized ADHF patients with HFrEF, not in those with HFpEF. This finding about clinical implication of HC might provide a new insight to decongestive therapy of ADHF in terms of LVEF.