tbuckley/cabot-search huggingface dataset:
Abstract 10987: Minimally Invasive Percutaneous Pericardial ICD Placement in an Infant Piglet Model: Head-to-Head Comparison With an Open Surgical Thoracotomy Approach
Authors: Bradley C Clark, Tanya D Davis, Magdy M El-Sayed Ahmed, Nobuyuki Ishibashi, Christopher P Jordan, Timothy D Kane, Peter C Kim, Axel Krieger, Dilip S Nath, Justin D Opfermann, Charles I Berul
Journal: Circulation (2015)

Introduction: Epicardial ICD placement in infants, small children, and patients with complex cardiac anatomy requires an open thoracotomy and is associated with increased pain, longer length of stay, and higher cost. We compared a surgical epicardial approach with percutaneous pericardial placement of an ICD lead system in an infant piglet model. Methods: Animals were randomized to undergo either epicardial placement by direct suture fixation through a left mini-thoracotomy or minimally invasive pericardial insertion with thoracoscopic visualization. Pericardial access was achieved through sub-xiphoid insertion of a pericardiocentesis needle followed by 7-French sheath insertion over a guide wire. An ICD lead (Medtronic) was passed through the sheath and fixed to the epicardium. In both groups, the lead was connected to an ICD generator placed within a sub-rectus abdominal pocket. Lead testing and defibrillation threshold testing (DFT) were performed. All piglets underwent a 2 week survival period followed by repeat lead testing and DFT prior to euthanasia. Results: Minimally invasive pericardial placement was performed in 8 piglets and surgical epicardial placement in 7 piglets (3-4 kg) without procedural morbidity or mortality. Mean initial DFT was 10.5 Joules (range 3-28J) in the pericardial group and 10 Joules (range 5-35J) in the surgical group (p = N.S.). After the survival period, mean DFT was 12 Joules (range 3-20J) in the pericardial group and 12.3 Joules (range 3-35J) in the surgical group (p = N.S.). All lead and shock impedances, R-wave amplitudes, and ventricular pacing thresholds remained stable throughout the survival period and showed no significant difference between the two groups. Conclusions: Compared to surgically placed epicardial ICD leads, percutaneous pericardial placement shows a nearly identical ability to effectively defibrillate the heart and has demonstrated similar lead stability. This can provide a means of defibrillator implantation without the need for open chest approach and its attendant pain and morbidity. With continued operator experience, the minimally invasive method may provide a viable alternative to epicardial ICD lead placement in infants, children, and adults at risk for sudden cardiac death.
Abstract 10854: Ghrelin Promotes Functional Angiogenesis in a Mouse Model Of Critical Limb Ischemia Through Activation of Pro-angiogenic MicroRNAs
Authors: Rajesh Katare, Shruti Rawal, Pujika E Munasinghe, Parul Dixit, Hirotsugu Tsuchimochi, Tadakatsu Inagaki, Yutaka Fujii, Keiji Umetani, Kenji Kangawa, Mikiyasu Shirai, Daryl Schwenke
Journal: Circulation (2015)

Background: Current therapeutic strategies for the treatment of critical limb ischemia (CLI) have only limited success. Recent in vitro evidence in the literature, using cell lines, proposes that the peptide hormone ghrelin may have angiogenic properties. Objective: To investigate if ghrelin could promote post-ischemic angiogenesis in a mouse model of CLI and identify the mechanistic pathway(s) that underpin ghrelin’s pro-angiogenic properties. Methods and Results: CLI was induced in male CD1 mice by femoral artery ligation. Animals were then randomized to receive either vehicle or ghrelin (Ghr,150μg/kg/sc) for 14 consecutive days. Subsequently, Synchrotron Radiation microangiography was used to assess hindlimb perfusion. Ischemia alone stimulated the generation of new microvessels typically having an ID &lt; 80 μm, however, the magnitude of ‘angiogenesis’ was significantly augmented in ghrelin-treated mice (13.9 ± 1.3 vessels in CLI+Ghr mice vs. 7.6 ± 0.9 vessels in CLI+Vehicle mice, P &lt; 0.05). Moreover, the newly formed vessels of only the ghrelin-treated CLI mice were both structurally and functionally normal; evident by robust endothelium-dependent vasodilatory responses to acetylcholine. Histological analysis showed marked increase in the number of arterioles in Ghrelin treated group (81±8/mm 2 in vehicle treated group vs. 134±11/mm 2 in Ghrelin treated group, P&lt;0.01, n=5), confirming the angiography data. Molecular analysis revealed that ghrelin’s angiogenic properties were linked to activation of pro-survival Akt/VEGF/Bcl-2 signaling cascade, thus reducing the apoptotic cell death and subsequent fibrosis. Furtherstill, ghrelin treatment activated pro-angiogenic (miR-126, -132 and -27a) and anti-fibrotic (miR-30a) microRNAs while inhibiting anti-angiogenic (miR-92a and -206) microRNAs. Further, in vitro knockdown of miR-126 and miR-132 in human umblical vein endothelial cells markedly attenuated the angiogenic potential of ghrelin, as evaluated by decreased proliferation and tube forming capacity (P&lt;0.05). Conclusion: Ghrelin therapy significantly restored the blood flow to the ischemic hind limb by accelerating the formation of new functional arterioles through activation of pro-angiogenic microRNAs.
Abstract 10116: Polyunsaturated Fatty Acid Treatment and Post-discharge Outcomes Following Acute Myocardial Infarction
Authors: Stephen J Greene, Pier Luigi Temporelli, Umberto Campia, Muthiah Vaduganathan, Luca Degli Esposti, Stefano Buda, Chiara Veronesi, Javed Butler, Savina Nodari
Journal: Circulation (2015)

Introduction: Clinical trial data regarding efficacy of n-3 polyunsaturated fatty acids (PUFA) in improving outcomes following acute myocardial infarction (AMI) are mixed and large observational studies of non-trial populations are lacking. Methods: We collected data from 5 Italian Local Health Units for patients discharged with the primary diagnosis of AMI between January 1, 2010 and December 31, 2011. Using unique patient identifiers, patients were linked across government hospital discharge, medication prescription, and mortality databases and followed for 12 months post-discharge. Results: Overall, 2,425 (21.5%) of 11,269 patients received n-3 PUFA during follow-up at 1 g/day. Patients treated with n-3 PUFA tended to be younger, male, diabetic, and more likely to receive guideline medical therapy, including beta-blockers, ACE inhibitors/ARB, statins, and antiplatelet therapy (P&lt;0.001; Table). After adjustment for patient characteristics and concurrent therapies, n-3 PUFA treatment was associated with reduction in death (HR 0.76, 95% CI 0.59-0.97) and recurrent AMI (HR 0.65, 95% CI 0.49-0.87) through 12 months. Conclusions: In this large, contemporary, observational study of patients hospitalized for AMI, n-3 PUFA treatment was independently associated with robust reduction in post-discharge clinical events.
Abstract 18025: Greater Consumer Nutrition Environment Disparities Are Associated With Lower Levels of Neighborhood Wellness
Authors: Kristin N Culver, Kelly D Stephens, Sheryl Magzamen, Christina M Shay
Journal: Circulation (2013)

Introduction: Poor AHA Healthy Diet Scores are a major obstacle to the improvement of cardiovascular (CV) health in the U.S. population. Food accessibility and availability have been widely recognized to influence eating behaviors that lead to obesity and adversely influence CV health status. The purpose of this investigation is to examine associations between the consumer nutrition environment and level of community wellness in a Southwestern metropolitan area of the United States (U.S.). Methods: The Nutrition Environment Measures Survey in Stores (NEMS-S) was used to assess the availability, quality, and price of healthy food options in supermarkets located in Oklahoma County, Oklahoma. NEMS-S is a validated measure that assesses a variety of food products commonly purchased in the U.S., including low-fat milk, fruits, vegetables, lean meats, processed foods, whole grain breads, lower-calorie/-fat food options, and sugar-sweetened beverages. The Oklahoma County Wellness Score was calculated for all regional ZIP codes according to major health and socioeconomic indicators. NEMS-S scores were compared between ZIP codes with highest (n=11) and lowest (n=11) quartiles of Wellness Score. Results: High Wellness score ZIP codes exhibited significantly higher overall NEMS-S scores compared to those with low Wellness Scores (38.0 vs. 30.6, p=0.003). Although NEMS-S food quality and price scores were similar across ZIP code Wellness Scores, food availability score was significantly higher in high Wellness Score ZIP codes compared to ZIP codes with low Wellness Score (27.9 vs. 2.6, p&lt;0.001). ZIP codes with lower NEMS-S scores also had a higher percentage of households lacking access to a personal vehicle (6.1 vs. 16.0, p=0.001), higher proportion of minority population (50.9% vs. 20.7%, p=0.015), and lower median household income ($27,954 vs. $61,370, p&lt;0.0001) compared to high NEMS-S Score ZIP codes. Conclusions: Consumer nutrition environment disparities that limit access to healthy food options are negatively associated with regional indicators of health and socioeconomic status. Promoting healthy food availability in neighborhoods with low health status may be a successful strategy for improving the CV health of the U.S. population.
Abstract 18048: Early Termination of Cardiovascular Clinical Trials Registered in ClinicalTrials.gov: Where Do We Stand?
Authors: Sabrina B Pereira, Renato D Lopes, Maria Julia Carrion, Eliana V Santucci, Rafael M Soares, Matheus O Abreu, Ligia N Laranjeira, Dimas T Ikeoka, Ana Zazula, Frederico R Moreira, Alexandre B Cavalcanti, Evandro T Mesquita, Eric D Peterson, Robert M Califf, Otavio Berwanger
Journal: Circulation (2013)

Importance: Early termination of clinical trials represents a challenge in clinical research, yet little is known about the frequency and reasons for it. Objective: We aimed to describe reasons for termination, and identify the major predictors of early termination due to low recruitment.Study Selection: We reviewed all cardiovascular clinical trials registered in ClinicalTrials.gov from February 29, 2000 to January 17, 2013 and assessed information about trials that were completed and those that were terminated early.Data Extraction and Synthesis: The dataset was downloaded in XML containing all cardiovascular studies registered. The dataset was exported into R software to extract the values. Logistic regression models were developed to identify independent predictors of early termination due to low recruitment.Main Outcome Measure: Studies classified as completed or terminated prematurely, and reasons for termination. Results: Overall,684 of 6279 trials included (10.9%) were terminated prematurely. The main reason for early termination was lower than expected recruitment rates (278 trials; 53.6%); 24.1% of trials had no clear justification for premature termination. When comparing trials that terminated early due to low recruitment with those that were completed, we found that studies funded by the National Institutes of Health/ United States federal agencies (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.14-0.89), studies of behavior/diet intervention (OR 0.35, 95% CI 0.19-0.65), and single-arm design studies (OR 0.57, 95% CI 0.42-0.78) were associated with a lower risk of early termination. University/hospital (OR 1.52, 95% CI 1.10-2.10) and mixed-source funded studies (OR 2.14, 95% CI 1.52-3.01) were associated with a higher likelihood of early termination due to lower than expected recruitment rates. Conclusions and Relevance: Early termination of interventional cardiovascular trials is common and most frequently due to low recruitment. Funding source, type of intervention, and study design were factors associated with early termination due to low recruitment and might be good targets for the improvement of clinical trial conduct.
Abstract 18029: Copper Transporter ATP7A Protects Against Endothelial Barrier Dysfunction in Ischemic Injury in Diabetes
Authors: Sudhahar Varadarajan, Gin-Fu Chen, Norifumi Urao, Ronal D McKinney, Masuko Ushio-Fukai, Tohru Fukai
Journal: Circulation (2013)

Endothelial barrier dysfunction is the major vascular complications in inflammatory diseases such as diabetes mellitus (DM). Copper (Cu), an essential micronutrient, plays an important role in physiological repair processes. Since excess Cu has been implicated in various pathophysiologies such as DM, intracellular Cu levels are tightly controlled by Cu exporter ATP7A. In this study, we investigated a role of ATP7A in DM-induced endothelial barrier dysfunction using ischemic limb injury model. Here we show that ATP7A protein expression is markedly upregulated (&gt;2 folds) in ischemic injured tissue, which is significantly decreased in streptozotocin (STZ)-induced type1 DM mice. ATP7A dysfunctional mutant mice or DM mice show increased vascular permeability (assessed by Miles assay), excess macrophage infiltration, and tissue damage in ischemic tissue vs. control mice. In endothelial cells (ECs), ATP7A knockdown with siRNA or ECs derived from DM mice increases EC permeability (132%) as measured by transendothelial electric resistance in a Cu-dependent manner. This is due to decreased protein expression of VE-Cadherin (VE-Cad; 40% decrease), but not beta-catenin, thereby disrupting adherence junctions as visualized by beta-catenin staining. Mechanistically, ATP7A siRNA induces microRNA (miR)-125b (1.8 fold), which reduces VE-Cad protein, in a Cu-dependent manner. Of note, anti-miR125b rescues siATP7A-induced decrease in VE-Cad protein as well as increased EC permeability. ECs or ischemic tissues from DM mice show decreased ATP7A or VE-Cad protein expression and increased miR125b expression (P&lt;0.05). Moreover, ATP7A-depleted ECs exhibit disassembly of actin as visualized by phalloidin through activating Rac1 (1.4 fold), which is inhibited by Cu chelator TTM. Functionally, DM-induced vascular leakage and tissue damage in ischemic limbs is rescued in ATP7A overexpressing transgenic mice treated with STZ. In summary, Cu exporter ATP7A protects against endothelial barrier dysfunction in DM by suppressing miR-125b that downregulates VE-Cad as well as by inhibiting Rac1-mediated actin disassembly. Thus, ATP7A is a potential therapeutic target for promoting tissue repair in diabetic inflammatory ischemic disease.
Abstract 18032: Increased Late Sodium Current During Early Heart Failure Development Induced by Chronic Sympathetic Activation
Authors: Patrick Schoenleitner, Paulina Wakula, Stefan Engelhardt, Burkert M Pieske, Frank R Heinzel, Gudrun Antoons
Journal: Circulation (2013)

Chronic sympathetic activation promotes myocardial hypertrophy and heart failure. In mice overexpressing the human β1-adrenoreceptor (β1-OE), cytosolic [Na+]i increases during early stages of cardiac remodeling (8-12 weeks), thereby slowing relaxation and increasing diastolic [Ca2+]i due to increased Na+/Ca2+ exchanger (NCX) reverse mode activity. Here we investigate whether reduced Na+ efflux via Na+/K+ ATPase (NKA) regulation, or enhanced Na+ influx (voltage-dependent Na+ current or TRPC channel regulation) may account for increased [Na+]i in young β1-OE mice. In β1-OE mice (8-12 weeks) and their wild-type (WT) littermates protein expression of NKA and phospholemman (PLM) was determined by Western blot in ventricular homogenates or isolated ventricular myocytes (TRPC 1, 3, 6) and normalized to GAPDH. NKA current (Ipump, whole cell voltage clamp) was measured as the difference in outward current after rapid solution switch to 0 K+ external solution. The persistent component of the Na+ current, INa,late, was measured as the current sensitive to 30 μm Tetrodotoxin (TTX). In β1-OE, NKA α1 subunit expression was unchanged, whereas the α2 subunit was reduced (0.87±0.09 in β1-OE, n=5 vs. 1.24±0.08 in WT, n=4; p&lt;0.05; mean±s.e.). Phosphorylated PLM was increased (1.3±0.05 in β1-OE, n=5 vs. 0.748±0.06 in WT, n=4; p&lt;0.001), and total PLM was reduced in β1-OE mice (0.71±0.08 in β1-OE, n=5 vs. 1.23±0.18 in WT, n=4;p&lt;0.05). TRPC 1, 3 and 6 expression was unaltered. Maximal Ipump density (100 mM [Na+]i in the pipette) was unchanged. With 10 mM [Na+]i, Ipump was significantly increased, indicating a higher Na+ affinity of NKA in β1-OE myocytes. INa,late was increased in β1-OE myocytes: at the end of pulse amplitude was -0.149 ± 0.034 pA/pF in β1-OE, n=10 vs. -0.063± 0.018 pA/pF in WT, n=9; p&lt;0.05; integrated current was 138 ± 17 pC/pF in β1-OE, n=10 vs 85 ± 17 pC/pF in WT, n =9; p&lt;0.05. In conclusion, in β1-OE mice, increased INa,late contributes to elevated [Na+]i during chronic sympathetic activation. Higher Na+ affinity of NKA due to less inhibition by phospholemman only partially compensates increased Na+ influx at this early stage of heart failure development.
Abstract 10340: Multi-Center Experience With Endovascular Treatment of Aortic Coarctation and Post-Surgical Complications of Coarctation Repair in Adults
Authors: Young Erben, Gustavo S Oderich, Hence J Verhagen, Maarten Witsenburg, Allard T Van den Hoven, Eike S Debus, Tilo Kolbel, Frank R Arko, Giovanni B Torsello, Giovanni F Torsello, Peter F Lawrence, Michael P Harlander-Locke, J. Michael Bacharach, William D Jordan, Mark K Eskandari
Journal: Circulation (2015)

Objective: To evaluate outcomes of endovascular treatment of aortic coarctation in the adult, either newly diagnosed or due to recurrent coarctation and pseudoaneurysm formation Methods: Clinical data and imaging studies of 93 patients treated at nine institutions from 1999-2015 were reviewed. Primary end-points were morbidity and mortality. Secondary end-points were stent patency and need for re-intervention Results: There were 54 male and 39 female patients with a mean age of 44±17 years, including 32 with de novo coarctation (mean 48±16 years) and 61 with prior open repair during childhood, who required endovascular re-intervention (mean: 30±17 years after initial repair). Indications for treatment were: resistant hypertension (32%), left ventricular hypertrophy (23%) and claudication (20%). Imaging studies included: computed tomography angiography (CTA) (42%), CTA and magnetic resonance angiography (MRA) (37%), MRA (13%), angiography (5%) and ultrasound (2%). Endovascular treatment was performed using stent grafts (55%), balloon expandable bare metal in (28%) or covered stents (15%) and primary angioplasty alone (1%). Mean lesion length and diameter were 64±50mm and 20±7mm, respectively. Mean systolic pressure gradient decreased from 24±18mmHg to 5±8mmHg after treatment, (p&lt;0.001). Four patients had intraprocedural complications including: rupture in two, type 1A endoleak and access hemorrhage in one each. Perioperative complications occurred in six: aortic dissection in three, thrombus migration into renal artery, spinal headache requiring blood patch and lung hemorrhage in one patient each. Two patients died within 30-days from hemorrhage and cardiopulmonary arrest. After a mean follow up time of 7±21 years, nearly all patients (98%) had symptom improvement and all stents were patent. Re-intervention was needed in 11%. 2 patients died from coarctation related causes including rupture of an infected graft and visceral ischemia Conclusions: In this multi-center study, endovascular repair was a safe and effective treatment for de novo coarctation and post-surgical complications of coarctation repair in adults. Rate of procedural complications and re-interventions were low with high procedural and long-term clinical success
Abstract 18084: Diabetes Promotes Tissue Nitric Oxide (NO) Insufficiency in Critical Limb Ischemia Patients
Authors: David Polhemus, Traci Goodchild, David J Lefer, Luke P Brewster
Journal: Circulation (2013)

Background: Diabetic patients are 5 times more likely than non-diabetics to develop critical limb ischemia (CLI). The pathogenesis of CLI in diabetic patients remains poorly understood and at present there is a paucity of effective therapies to treat this devastating disease. Nitrite (NO2) and nitrosothiols (RSNO) have recently emerged as important storage forms of nitric oxide (NO) that modulate vascular reactivity and signaling. The purpose of this study was to investigate tissue NO bioavailability in muscle biopsies obtained from non-diabetic and diabetic (Db) patients following leg amputation. Methods: Gastrocnemius and tibialis anterior tissue was attained post-amputation from human non-diabetic patients with CLI (n=12) and diabetic patients with CLI (n=8). Nitrite concentrations were determined by ion chromatography methods. RSNO and NO-Heme levels were measured by chemiluminescence detection. Results: The CLI + Db group displayed reduced skeletal muscle (89.9 vs. 55.5 nM, p &lt; 0.05) nitrite levels compared to the CLI group without Db. Nitrosothiol (21.2 vs. 10.52 nM, p &lt; 0.05) concentrations and NO-Heme (27.61 vs. 13.0 nM, p &lt; 0.05) levels were also significantly attenuated in the CLI + Db group. Conclusion: These data clearly indicate significant reductions in NO bioavailability (nitrite, RSNO, and NO-heme) in diabetics with CLI. Future studies will evaluate the cellular mechanisms responsible for reduced NO levels in diabetic patients with CLI. Nitric oxide based therapeutics including sodium nitrite may be suitable to treat diabetic patients with CLI to attenuate the progression of this disease.
Abstract 11192: Correlation of the Predictive Ability of Early Warning Metrics and Mortality for Cardiac Arrest Patients Receiving in-Hospital Cardiopulmonary Resuscitation
Authors: Barbara DeVoe, Anita Roth, Gregory Maurer, Martin Lesser, Renee Pekmezaris, Michal Tamuz, Amgad N Makaryus, Alan Hartman, Paola DiMarzio
Journal: Circulation (2016)

Introduction: The Modified Early Warning System (MEWS) is a tool to help monitor patients and improve how quickly a patient experiencing a sudden decline in clinical status receives clinical care. Hypothesis/Aims: We assessed the risk factors that may be associated with hospital survival following cardiopulmonary resuscitation (CPR) in response to cardiac arrest (CA). In this study, we also examined the role of Modified Early Warning Score (MEWS) implementation on patients’ survival. Methods: Retrospective chart review of all patients who were treated with CPR after experiencing in-hospital CA (n=417) was conducted between January 2007 and December 2013, at a tertiary care hospital in the New York metropolitan area. The investigators determined survival rate for these patients and evaluated their MEWS on admission and during the 4 hours preceding the CA. Multivariable logistic regression was used to adjust for possible confounding factors. Specifically, we analyzed the relationship between MEWS and risk factors such as age, gender, type of electrographic cardiac rhythms, return of spontaneous circulation (ROSC) and MEWS using logistic regression. Results: Only 60% of the patient charts reviewed (256/417), indicated a return of spontaneous circulation (ROSC) following CPR. The overall survival rate, defined as survival to hospital discharge, was 21%. Strong predictors for survival were ventricular fibrillation (VF) (p&lt;.0001) and ventricular tachycardia (VT) rhythm (p&lt;.0001). MEWS values at hospital admission (p&lt;.005) and patients of younger age (p&lt;.005) were also significantly associated with survival to hospital discharge. In contrast, gender and MEWS prior to CA were not significantly associated with survival. Conclusions: Survival following CPR in response to in-hospital cardiac arrest is significantly associated with VF and VT rhythms and age. Moreover, MEWS at admission was significantly associated with survival, suggesting that higher MEWS scores at admission may be an important predictor of survival. MEWS monitoring may be an effective tool in identifying significant changes in a patient’s vital signs prior CA.