tbuckley/cabot-search huggingface dataset:
Abstract 312: Outcomes After Therapeutic Hypothermia During Extracorporeal Membrane Oxygenation Following Out-of-Hospital Refractory Cardiac Arrest
Authors: Wook Jin Choi, Jung Seok Hong, Sun Hyu Kim, Ryeok Ahn, Eun Seog Hong, Jeong Won Kim, Jong Pil Jung, Eun Seok Shin, Sang Gon Lee, Jong Joon Ahn
Journal: Circulation (2012)

Background and Objective: For cardiac arrest patients who do not respond to conventional cardiopulmonary resuscitation, extracorporeal life-support (ELS) may represent an alternative therapeutic approach allowing significant survival rates. Following cardiac arrest, mild therapeutic hypothermia for 12-24 h is recommended. However, there is little clinical experience with good outcome in out-of-hospital refractory cardiac arrest. We present 5 cases of refractory cardiac arrest, who were treated with therapeutic hypothermia during extracorporeal membrane-oxygenation in the emergency department. Results: A retrospective review of 5 out-of-hospital cardiac arrest patients (4 male and 1 female; median age, 43), who were placed on therapeutic hypothermia during ELS, was performed. All patients were unresponsive to conventional CPR and advanced cardiac life support without return of spontaneous circulation beyond 30 min. ELS was initiated under continuous cardiac massage in the emergency department. Mild therapeutic hypothermia was induced and maintained successfully for 24 h via surface cooling methods. Three patients were fully recovered consciousness from being comatose after rewarming and cessation of sedatives. Two patients were discharged with no neurological sequelae (CPC 1). Conclusion: Mild therapeutic hypothermia during ELS in the ED can be beneficial in out-of-hospital cardiac arrest patients who are unresponsive to prolonged cardiac pulmonary resuscitation.
Abstract 19123: Brag2, An Arf6 Gef, Regulates Integrin-dependent Adhesion in Endothelial Cells and is Involved in Angiogenesis
Authors: Yosif Manavski, Guillaume Carmona, Katrin Bennewitz, Zhongshu Tang, Fan Zhang, Atsuko Sakurai, Silvio J Gutkind, Xuri Li, Jens Kroll, Stefanie Dimmeler, Emmanouil Chavakis
Journal: Circulation (2012)

β1-integrins are essential for angiogenesis. However, the mechanisms regulating integrin function in endothelial cells (EC) and their contribution to angiogenesis are unclear. Brag2 is a guanine nucleotide exchange factor for the small GTPase ARF6, which is involved in the traffic of receptors and in the regulation of actin cytoskeleton. Here, we demonstrate that siRNA-mediated silencing of Brag2 reduced basal and VEGF-induced activation of Arf6 and significantly blocked basal and VEGF-induced angiogenic sprouting (by 40 ± 7 %), tube formation and 3-dimensional migration of EC. Transfection with Brag2 siRNA increased focal adhesions and enhanced adhesion of EC on β1-integrin ligands, such as fibronectin and collagen. In line with these results, silencing of Brag2 significantly increased the surface expression of the α5β1-integrin. Moreover, silencing of Brag2 significantly reduced the endocytosis of β1-integrins and specifically of the active (matrix bound) α5β1-integrin present in focal adhesions, suggesting that Brag2 may contribute to the disassembly of focal adhesions during migration via β1-integrin-endocytosis. Strikingly, in vivo silencing of the Brag2 orthologues in zebrafish embryos with morpholinos perturbed vascular development by leading to defects of the parachordal vessels, the dorsal longitudinal anastomotic vessel and the intersomitic vessels. Beyond developmental angiogenesis, in vivo silencing of Brag2 with intravitreal injection of shRNA significantly reduced pathological retinal neovascularization in the model of retinopathy of prematurity (32 % inhibition) and pathological choroidal neovascularization in a model of laser-induced choroidal neovascularization. These data reveal that the Arf6 GEF, Brag2 is essential for developmental and pathological angiogenesis probably by mediating EC migration and angiogenic sprouting through regulation of adhesion by promoting integrin internalization.
Abstract 19465: Cardiac Gene Knockdown Using Small Inhibitory RNA-Loaded Microbubbles and Ultrasound
Authors: Andrew R Carson, Charles F McTiernan, Xucai Chen, Flordeliza S Villanueva
Journal: Circulation (2012)

Background RNA interference (RNAi) is a cellular process that regulates gene expression via sequence-specific mRNA degradation and translational blockage. The potent gene knockdown effects of RNAi could have broad therapeutic applications in cardiovascular disease, but is currently limited by inefficient delivery strategies, off-target effects, and nuclease activity which degrades RNAi molecules such as small inhibitory RNA (siRNA). We hypothesized that cardiac ultrasound (US)-targeted destruction of microbubbles (MB) bearing siRNA would selectively knock down target cardiac genes. Methods A transgenic mouse model of cardiac restricted luciferase expression was used. RNA binding-MBs were prepared by amalgamation of cationic and neutral lipids in the presence of siRNA specific to luciferase or negative control siRNA. RNA binding was confirmed by serial washing of loaded MBs followed by electrophoresis. RNAse resistance was determined by exposure of siRNA-loaded MBs to RNAseA, followed by electrophoresis. siRNA-loaded MBs (5 µg per 7x10 8 MBs) were infused through the internal jugular of transgenic mice over 15 min during concurrent MB-destructive transthoracic US (1.3 MHz, MI 1.6). The US pulse sequence was designed to allow complete myocardial MB replenishment between each destruction sequence, as confirmed by contrast-specific US imaging. Luciferase expression was determined 3 days later by luciferase assay and RT PCR. Results MBs bound ∼7 µg siRNA per 10 9 MBs and protected siRNA from RNAseA digestion at concentrations sufficient for digestion of siRNA in the absence of MBs. US-targeted cardiac delivery of MBs bearing luciferase siRNA resulted in significant knockdown of luciferase expression in transgenic mice 3 days after treatment compared to controls (53% knockdown vs. no treatment, p=0.03; 65% knockdown vs. control siRNA+MBs+US, p=0.02) and by RT PCR (68% knockdown vs. no treatment, p=0.05). Conclusion siRNA delivery using custom MBs and US silences cardiac reporter gene expression. These data establish general principles that can be extended to US-MB theranostic platforms for image-guided targeted gene knockdown in cardiovascular diseases for which specific gene silencing represents a therapeutic approach.
Abstract 9000: Long-term Outcomes After Sirolimus-Eluting Stent Implantation for Calcified Coronary Lesions: Insights From the j-Cypher Registry
Authors: Koji Nishida, Takeshi Kimura, Syuichi Seki, Syoichi Kubokawa, Kazuya Kawai, Naohisa Hamashige, Ichiro Miyano, Takeshi Morimoto, Kazuaki Mitsudou
Journal: Circulation (2012)

Background: The long-term clinical outcomes of drug-eluting stents for calcified coronary lesions in patients with and without dialysis have not yet been adequately addressed. Methods: Among 10,717 patients (16,947 lesions) who were exclusively treated with sirolimus-eluting stents (SES) in the j-Cypher registry, 5-year clinical outcome was compared between patients with at least 1 lesion with moderate to severe calcification (Calc group), and patients with non-calcified (no to mild calcification) lesions only (Non-calc group). Analyses were made separately according to dialysis status (non-dialysis stratum [Calc group: 3208 patients, and Non-calc group: 6919 patients], and dialysis stratum [Calc group: 419 patients, and Non-calc group: 171 patients]. Results: Cumulative incidence of adjusted risk for 5-year mortality was significantly higher in the Calc group than in the Non-calc group in both non-dialysis stratum (13.5% versus 8.3%: P&lt;0.0001, and hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.07-1.41, P=0.004) and dialysis stratum (49.4% versus 38.6%: P=0.016, and HR 1.53, CI 1.12-2.09, P=0.008). Regardless of dialysis status, the Calc group as compared with the Non-calc group had a significantly higher cumulative incidence of target lesion revascularization (TLR) (non-dialysis, 14.0% versus 11.2%, P&lt;0.0001; dialysis, 33.4% versus 18.7%, P&lt;0.0001) and major adverse cardiac events (MACE) (non-dialysis, 30.4% versus 22.9%, P&lt;0.0001; dialysis, 69.2% versus 53.8%, P&lt;0.0001). In non-dialysis stratum, the cumulative incidence of late TLR beyond 1 year was similar between the Calc and Non-calc groups (7.2% versus 7.0%, P=0.84). However, dialysis patients with calcified lesions had a significantly higher late TLR rate (17.2% versus 8.1%, P=0.014). Stent thrombosis was unrelated to both dialysis and calcification (non-dialysis, 1.5% versus 1.2%, P=0.23; dialysis, 2.6% versus 0.6%, P=0.076). Conclusion: Regardless of dialysis status, patients with calcified coronary artery lesions have an increased long-term risk for adverse events, such as mortality, TLR, and MACE, after SES implantation. Lesion calcification in dialysis patients was associated with higher risk for late TLR through 5 years.
Abstract 14316: Blue Again: Recurrent Cyanosis in a 30-Year-Old Man with Surgically Palliated Cyanotic Congenital Heart Disease
Authors: Janice Y. Chyou, Robert O Roswell, Michael Argilla, Muhamed Saric, Ralph Mosca, Stuart D Katz, Barry P Rosenzweig
Journal: Circulation (2012)

Janice Y. Chyou, 2012 Finalist and Presenting Author
Abstract 9102: Blood Transfusion is Associated with Increased Mortality in Myocardial Infarction-A Meta-analysis and Diversity-Adjusted Study Sequential Analysis
Authors: Saurav Chatterjee, Jorn Wetterslev, Abhishek Sharma, Edgar Lichstein, Wen-Chih Wu, Debabrata Mukherjee
Journal: Circulation (2012)

Introduction: The benefit of blood transfusion in patients with myocardial infarction is controversial and harm may be imminent. Hypothesis: To identify risk of mortality with blood transfusion in patients with myocardial infarction, through a meta-analysis of published data. Methods: A systematic search of studies published between 1966 and March, 2012 was conducted using MEDLINE, EMBASE, CINAHL, Scopus, the Web of Science and Cochrane CENTRAL databases. English-language studies comparing blood transfusion with no transfusion; or a liberal versus restricted transfusion strategy was identified. Two study authors independently reviewed the 729 titles and abstracts originally identified and selected 10 for analysis. Quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. Studies of transfusion strategies in anemia associated with myocardial infarction, and all-cause mortality rates at the longest available follow-up for the individual study, were abstracted. Pooled-effect estimates were calculated with random-effects models. Results: Analyses of transfusion in myocardial infarction revealed increased all-cause mortality with a strategy of transfusion during myocardial infarction-18.2% Vs 10.2% [RR 2.91 ( 95% CI 2.46-3.44); p&lt;0.001], with weighted absolute risk increase of 12 %, and a number needed to harm of 8 (95% CI 6-17). However, the mortality risk with transfusion was mitigated when restricted to STEMI patients and those having hematocrit below 30. Multivariate meta-regression revealed that transfusion was associated with higher risk of mortality, independent of baseline hemoglobin, nadir hemoglobin and change in hemoglobin. A higher risk with transfusion compared with no/restrictive transfusion was noted for subsequent myocardial infarction rates too. Conclusion: A strategy of blood transfusion/ liberal blood transfusion compared to no/restricted blood transfusion was associated with a higher incidence of all-cause mortality. A practice of routine/liberal blood transfusion in myocardial infarction should not be encouraged but investigated in a large trial with low risk of bias.
Abstract 8989: Left Atrial Appendage Volume as a Predictor of Left Atrial Appendage Thrombus and Sludge in Patients With Nonvalvular Atrial Fibrillation: A Three-Dimensional Transesophageal Echocardiographic Study
Authors: Kenji Harada, Jun Tanaka, Kirsten Tolstrup, Swaminatha V Gurudevan, Robert J Siegel, Takahiro Shiota
Journal: Circulation (2012)

Background: Clinical and echocardiographic predictors for detecting left atrial appendage (LAA) thrombus are well characterized. However, whether the size of LAA measured by two-dimensional transesophageal echocardiography (2D-TEE) predicts the risk of thrombus formation in LAA has been the subject of much controversy. Purpose: The aim of this study was to investigate the ability of LAA volume derived from real-time three-dimensional transesophageal echocardiography (RT3D-TEE) to predict LAA thrombus and/or sludge in patients with nonvalvular atrial fibrillation (NVAF). Methods and Results: A total of 71 patients with NVAF lasting ≥ 1 month and without severe valvular regurgitation, who underwent 2D-TEE and RT3D-TEE, were included in the study. They were divided into two groups according to the presence of LAA thrombus and/or sludge. LAA thrombus and/or sludge were detected in 28 patients (39%). In these patients, the prevalence of LAA thrombus and that of LAA sludge were 54% and 100%, respectively. All 2D and 3D measurements of LAA were performed at ventricular end-systole.A trend was only seen for a significant correlation between LAA volume measured by RT3D-TEE and LAA area in the longitudinal section imaged (usually between 60 and 90 dgrees) by 2D-TEE (r = 0.31, p = 0.08). On multivariable analysis, LAA volume and the ratio of early transmitral flow velocity to peak early diastolic mitral annular velocity (E/e') were found to be significantly predictive of LAA thrombus and/or sludge. Conversely, LAA emptying flow velocity predicted freedom from them (Table 1). Receiver operating characteristic analysis yielded an optimal cutoff value of 14.7 cm 3 for LAA volume to detect LAA thrombus and/or sludge (area under the curve 0.89). The sensitivity and specificity of this model were 79% and 89%, respectively. Conclusion: Our data suggest that increased LAA volume measurements by RT3D-TEE can assist in the detection of LAA thrombus and/or sludge in the patients with NVAF.
Abstract 8460: High-Sensitivity Cardiac Troponin T and the Risk of Incident Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Kristian B Filion, Sunil K Agarwal, Christie M Ballantyne, Ron C Hoogeveen, Rachel R Huxley, Laura R Loehr, Vijay Nambi, Elsayed Z Soliman, Alvaro Alonso
Journal: Circulation (2011)

Introduction: Structural changes in the heart, such as increased left atrial size and decreased ejection fraction, are known risk factors for atrial fibrillation (AF). An association between cardiac troponin T (hs-cTnT), a marker of myocardial cell damage measured with a high sensitivity assay, and the risk of AF could have implications for AF risk stratification. Objective: To estimate the association between hs-cTnT and the risk of incident AF in the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort of middle-aged adults from 4 U.S. communities. Methods: Study was restricted to 10,596 participants free of AF at the fourth clinic visit (1996-98). AF was defined using ICD codes from hospitalizations and death certificates. Cox proportional hazards models were used to estimate the association between hs-cTnT and the risk of AF adjusting for potential confounders (Table). Net reclassification index (NRI) was used to examine its discriminative ability for 10-year AF risk (&lt;5%, 5-15%, and &gt;15%). Results: We observed 920 incident AF cases over 109,607 person-years. The AF rate was lowest among participants with undetectable hs-cTnT levels and greatest among those with hs-cTnT &gt; 0.014 µg/L (Table). After adjustment for potential confounders, a 1 standard deviation difference in ln(hs-cTnT) was associated with a hazard ratio of 1.21 (95% CI = 1.13, 1.30). Addition of hs-cTnT to known AF predictors did not increase the area under the curve appreciably (without hs-cTnT: 0.755, 95% CI = 0.740, 0.771; with hs-cTnT: 0.759, 95% CI = 0.743, 0.774). Among those who developed AF, 3.2% had their risk increased by the inclusion hs-cTnT and 3.9% had their risk decreased (p=0.50). Among those who did not develop AF, 2.7% had their risk increased and 3.4% had their risk decreased (p=0.0001). There was no net improvement in risk stratification (NRI=0.36%, p=0.72). Conclusions: Hs-cTnT level is associated with an increased rate of AF but did not improve risk stratification.
Abstract 9693: Onset of Lone Atrial Fibrillation Before 40 Years is Associated with a High Prevalence of Mutations in the Cardiac Sodium Channel
Authors: Morten S Olesen, Lei Yuan, Jonas B Nielsen, Bo Liang, Anders Holst, Nicole Schmitt, Michael Christiansen, Søren-Peter Olesen, Stig Haunsø, Thomas Jespersen, Jesper H Svendsen
Journal: Circulation (2011)

Introduction Atrial Fibrillation (AF) is the most common sustained arrhythmia. Studies screening SCN5A, the gene encoding the α-subunit of the cardiac sodium channel, have reported that around 0-2 % of general AF patients have mutations in the gene. Hypothesis We tested the hypothesis that early onset lone AF is associated with a high prevalence of genetic variation in SCN5A and CAV3, both genes encoding important components of the cardiac sodium channel. Methods We sequenced the coding region and splice-site of SCN5A and CAV3 in 192 early onset lone AF patients. Only lone AF patients with onset of disease before the age of 40 years and without traditional risk factors for AF were included; patients with structural heart disease, diabetes or metabolic diseases or other disease were excluded. For electrophysiological patch clamp studies HEK cells were transiently co-transfected with pcDNA3-hSCN5A, and pcDNA3-eGFP as a reporter gene. Results Of 192 probands with early onset lone AF, nine non-synonymous mutations were found in ten probands: eight mutations in SCN5A; T220I, R340Q, T1304M, F1596I, R1626H (novel), D1819N, R1897W (novel), V1951M and one mutation in CAV3 (T78M in two patients). None of the mutations were present in public available databases and only V1951M has previously been reported in conjunction to AF. All other mutations affected evolutionarily conserved residues. All patient caring SCN5A mutations underwent a flecainide test, without inducing any sings of Brugada ECG pattern. SCN5A, T220I, T1304M and CAV3 T78M has been electrophysiologically investigated earlier and the mutations all significantly compromises sodium current. In vitro electrophysiological studies were conducted of the remaining mutations. R340Q, R1626H and R1897W showed loss-of-function while T1304M showed gain-of-function. F1596I did not affect the electrophysiologic function while V1951 showed both loss-of-function and gain of function. Conclusions Ten out of 192 patients with early-onset lone AF had a non-synonymous mutation in SCN5A and CAV3. All ten mutations either had been or were investigated electrophysiologically and of those, seven mutations compromised the sodium current and are therefore suspected to enhance the susceptibility to AF.
Abstract 19168: Effect of Endurance Exercise on Transgenic Arrhythomeginc Right Ventricular Cardiomyopathy Mice
Authors: Rahul Jain, Ruben Martherus, Ken Takagi, Jeanne James, Kristen Kramer, Enkhsaikhan Purevjav, Jeffrey A Towbin
Journal: Circulation (2012)

Rahul Jain, 2012 Finalist and Presenting Author
Abstract 309: An Electromyographic System for Guiding Tracheal Intubation
Authors: Christopher Levert, Robin Terry, Sarah Wagner, Michael Kosh, Joanna Nathan, Christopher Arevalos, Alan Brewer, Mehdi Razavi
Journal: Circulation (2012)

Introduction: When tracheal intubation is necessary outside the hospital setting, inadvertent esophageal intubation may occur due to lower levels of provider experience and less access to equipment that can verify tracheal intubation. Therefore, we created a simple, rapid method for guiding endotracheal tube insertion. Methods: We constructed a system that can differentiate between the esophagus (smooth muscle tissue) and the trachea (nonmuscular tissue) based on electromyographic signal-response characteristics. We modified an endotracheal tube by adding 4 electrodes (2 for stimulating tissue with applied voltage and 2 for recording the tissue response) and tested the tube in a warm porcine model. We recorded 9 samples in 3 different locations in both the esophagus and the trachea, for a total of 18 samples. Both the stimulating voltage and the tissue response were recorded. We then used computational tools to analyze the resulting data and to create an integrative algorithm for differentiating between esophageal and tracheal tissue, based on the response signal. We differentiated the tissue types by using 3 integrated methods to measure 1) baseline frequency components to determine the average magnitude of contraction of the esophageal muscle tissue; 2) the rate of rectification of the response signal after the stimulation period; and 3) the difference between the average response voltages before and directly after stimulation. Results: The average magnitude of contraction was 24.3±13.7 V for esophageal tissue and 6.7±2.7 V for tracheal tissue ( P =0.013). The average rate of rectification of the response signal was 22.7±15.6 mV/sec for esophageal tissue and -0.177±8.35 mV/sec for tracheal tissue ( P =0.021). The difference between the average response voltages before and after stimulation was 2.89±1.84 mV for esophageal tissue and 0.834±0.930 mV for tracheal tissue ( P =0.023). By integrating these 3 methods, our algorithm had a sensitivity of 87.5% and specificity of 100%. Conclusion: With our system, rapid differentiation of the endotracheal-tube tip location provides real-time feedback information that may facilitate tube insertion into the trachea.
Abstract 219: Prognostic Significance of Serum Albumin on Long-Term Mortality in Survivors of Out-of-Hospital Cardiac Arrest
Authors: In Won Park, Jae Hyuk Lee, Joonghee Kim, Kyuseok Kim, You Hwan Jo, Kyeongwon Kang, Changwoo Kang, Soohoon Lee, Joong Eui Rhee
Journal: Circulation (2012)

Introductions: Hypoalbuminemia is known as a reliable predictor of mortality in patients with various illnesses. However, the prognostic value of serum albumin on out of hospital cardiac arrest (OHCA) patients has not been established. The purpose of study is to investigate whether serum albumin concentration on hospital arrival may be useful in predicting the long-term mortality in survivors from OHCA. Methods: Retrospective analysis of emergency departments OHCA registry from January 2008 to December 2011 has been conducted. The individual medical records were reviewed for the data including Utstein predictors of OHCA, underlying disease, and initial laboratory finding including serum albumin. Primary outcome was survival at 6 months. The secondary outcome was CPC (Cerebral Performance Category) at 6 months. Albumin was categorized as quartiles as &lt; 2.7g/dL, 2.7 to 3.2g/dL, 3.2 to 3.9 g/dL and &gt; 3.9g/dL. Hazard ratios (HRs) were estimated using Cox-proportional hazard models in both univariate and multivariate analysis. All prognostic variables with their p value &lt; 0.1 in univariate analysis were used in multivariate analysis for adjustment. Results: Of 546 OHCA patients, 139 patients had sustained ROSC. Of those, 23 patients (16.5%) survived at 6 month and 16 patients (11.5%) had favorable neurological outcome (CPC 1,2). Survival rate at 6 months were significantly higher in patients with a higher albumin group and neurological outcomes were also more favorable in higher albumin group. In a Cox proportional hazard regression analysis for 6-month survival, patients with lower categories of albumin had increased mortality rates before and after multivariable adjustment. (p value for linear trend &lt; 0.05) Conclusion: Serum albumin is a robust predictor of long-term mortality and associated with neurological outcome in patients with sustained ROSC from OHCA