tbuckley/cabot-search huggingface dataset:
Abstract 18895: Freedom From Recurrent Ventricular Tachycardia After Ablation is Associated With Improved All-Cause Mortality
Authors: Roderick Tung, Ricky Yu, Marmar Vaseghi, Eric Buch, Jason Bradfield, Ravi Mandapati, Noel Boyle, Kalyanam Shivkumar
Journal: Circulation (2013)

Introduction: ICD therapy and recurrent VT have been shown to increase the risk for mortality. Catheter ablation of ventricular tachycardia has been demonstrated to reduce recurrent episodes of VT but no studies to date have demonstrated a reduction in all-cause mortality. Methods: Retrospective analysis of all patients referred for ablation of scar-mediated VT from 2004-2011 were reviewed. Acute procedural success and 1 year-freedom from VT recurrence were correlated with all-cause mortality at 1 year. Separate analyses were performed for patients with ICM and NICM and stratified by EF &lt;30%. Results: A total of 127 patients were included: 63±11 yrs, male 86%, ICM 56% (EF 28±12), NICM 44% (EF 31±15). Antiarrhythmic usage was 87%. Acute procedural success of noninducibility was achieved in 51% of patients with ICM and 38% with NICM. Acute procedural success predicted freedom from mortality for the NICM group (95% vs 67%, p=0.02), but not for the ICM group (76% vs 65%, p=0.43). Freedom from recurrent VT within the 1 year follow-up period was associated with a reduction in all-cause mortality for patients (ICM 82% vs 48%, p=0.005; NICM 100% vs 61%, p=0.006). However, the mean EF was significantly higher in patients who survived at 1 year (ICM 30±12 vs 23±8 ICM, p=0.007; NICM 33±15 vs 22±6, p&lt;0.001). When stratifying patients with EF≤30%, freedom from VT remained a predictor of 1 year survival (ICM 74% vs 42%, p=0.04; NICM 100% vs 50%, p=0.005). Conclusion: Freedom from VT at 1 year is associated with a reduction in all-cause mortality in patients with ICM and NICM who underwent catheter ablation of VT. EF is also a significant predictor of all-cause mortality, although the association between recurrent VT and mortality remains for when patients with EF&lt;30% are analyzed.
Abstract 13966: Left-sided Rib Fractures During Cardiopulmonary Resuscitation Are Associated With Better Coronary Perfusion Pressure in a Pig Model of Cardiac Arrest
Authors: Guillaume Debaty, Jason A Bartos, Timothy R Matsuura, Jennifer N Rees, Michael Lick, Scott H McKnite, Demetris Yannopoulos
Journal: Circulation (2015)

Introduction: Since its inception, concerns have been raised about the complications associated with cardiopulmonary resuscitation (CPR). To date, there is no evidence that these complications are linked to worsened outcomes. Hypothesis: The aim of this study was to describe the hemodynamic effect of rib fractures during automated mechanical CPR in a porcine model of cardiac arrest. Methods: We conducted a prospective observational study between November 2013 and November 2014. Animals were included if they developed rib fractures during CPR but prior to injection of any drugs. To determine the exact timing of the broken rib, only pigs with obvious thorax deformation were included. An autopsy was performed at the end of each study. A group of 11 control animals without broken ribs was also included to compare data between groups. Time points in the control group matched those in the broken rib group. Data are presented as mean ± standard error of mean. Results: Broken ribs were observed during CPR in 15 pigs at a mean time of 97 ± 10 sec after the start of CPR (12 with left chest deformation and 3 with right chest). The mean number of broken ribs was 4 ± 0.2. In the left-sided broken rib group, coronary perfusion pressure (CPP) and systolic blood pressure (SBP) increased after rib fractures (p for trend &lt;0.001). EtCO2 increased similarly in the left broken rib group from 31 ± 5 prior to rib fracture to 43 ± 3, 46 ± 4 and 49 ± 4 at 10, 30 and 60 seconds after rib fracture, respectively (p for trend &lt;0.001). This increase was not observed in the right-sided broken rib group (Fig 1). Return of spontaneous circulation was achieved in 12/12 animals with left broken ribs, 1/3 animals with right broken ribs and 6/11 animals in the control group (p=0.007). Conclusion: During CPR, left rib fractures improved CPP, SBP and EtCO2 compared to control animals. This may suggest direct cardiac compression as a means to the effect. Further studies are warranted to assess the impact on survival.
Abstract 13127: Catheter Ablation of Atrial Fibrillation: Midterm Outcome of Radiofrequency Catheter Ablation for Redo Procedures After Pulmonary Vein Isolation With the Cryoballoon First Versus Second Generation Cryoballoon)
Authors: Klaus Kettering, Felix Gramley
Journal: Circulation (2016)

Introduction: Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory AF. Cryoablation has been shown to be a safe and effective technique for PV isolation. However, there is a significant arrhythmia recurrence rate after cryoablation procedures and there are no established strategies for redo procedures in these patients. Therefore, we have summarized our experience with radiofrequency catheter ablation for redo procedures after pulmonary vein isolation with the cryoballoon technique (ater procedures performed with the first or second generation cryoballoon). Hypothesis / Methods: Sixty patients had to undergo a redo procedure after initially successful circumferential PV isolation with the cryoballoon technique (Arctic Front Balloon, Medtronic: 30 patients (group A); Arctic Front Advance, Medtronic: 30 patients (group B)). The redo ablation procedures were performed using a segmental approach or a circumferential ablation strategy (CARTO) depending on the intra-procedural findings. Results: During the redo procedure, a mean number of 1.9 re-conducting PVs were detected (group A: 2.5 re-conducting PVs, group B: 1.3 re-conducting PVs). In 26 patients in group A, a segmental approach was sufficient to eliminate the residual PV conduction because there were only a few recovered PV fibers (1-3 reconnected PVs; group A1). In the remaining 4 patients in group A, a circumferential ablation strategy was used because of a complete recovery of the PV-LA conduction of all four PVs (group A2). In group B, a segmental approach was sufficient in all patients because there was only a minor reconnection of 1-2 PVs. All recovered PVs could be isolated sucessfully again. At 6-month follow-up, 80.0 % of all patients were free from an arrhythmia recurrence (48/60 patients; group A: 23/30 patients (76.7 %), group B: 25/30 patients (83.3 %)). Conclusions: In patients with an initial circumferential PVI using the cryoballoon technique, a repeat ablation procedure can be performed safely and effectively using RF catheter ablation. In most cases only a few re-conducting PV fibers were found and therefore, a segmental re-ablation approach seems to be sufficient in the majority of patients.
Abstract 13125: FOXO1/Notch Signaling Modulates Ambient Ultrafine Particle Exposure-Impaired Vascular Development
Authors: Kyung In Baek, Tyler Beebe, Zhao Ma, Jon Gau, Arian Saffari, Constantinos Sioutas, Rongsong Li, Tzung Hsiai
Journal: Circulation (2016)

Introduction: Exposure to ultrafine particles (UFP, d &lt; 0.1 μm), redox-active components of particular matter (PM 2.5 ), promotes vascular inflammatory responses. Notch signaling in endothelial cells (EC) promotes differentiation and proliferation of vasculature. FOXO1, the dominant isoform of the forkhead box O subfamily (FOXO) in EC, interacts with Notch signaling via enhancing co-repressor clearance and assembly of activation complex during induction of Notch signaling. Whether a FOXO1/Notch signaling axis modulates UFP- impaired vascular development remains elusive. Hypothesis: We hypothesized that UFP impairs vascular repair by attenuating Notch signaling via inhibition on FOXO1. Methods and Results: Transgenic Tg(fli1:gfp) zebrafish at 3 days post fertilization (dpf) developed vascular regeneration at 3 days post amputation (dpa) of the tail, whereas exposure to UFP or treatment with ADAM10 inhibitor (inhibit Notch receptor activation to generate Notch intracellular cytoplasmic domain [NICD]) resulted in disrupted intersegmental vessels (ISV) and impaired tail regeneration ( P &lt; 0.05, n=20). Notch signaling was evidently visualized in the region of tail injury in the Notch responsive reporter fish Tg(tp1:gfp) crossed with Tg( flk1:mCherry) line at 3 dpa. UFP, ADAM10 inhibitor, and FOXO1 morpholino oligonucleotides (MO) micro-injection attenuated Notch activities at 3 dpa, respectively. NICD mRNA rescue partially restored Notch activity and vascular regeneration at 3 dpa, whereas combination of both NICD and FOXO1 mRNA rescue fully restored Notch activity and tail regeneration. As a corollary, UFP exposure induced a dose-dependent reduction in Notch reporter activity and FOXO1 mRNA expression in human aortic endothelial cells (HAEC). FOXO1 mRNA rescue restored Notch activity and Notch related gene expressions, including Dll4 and HES1( P &lt; 0.05, n=3) in fish exposed to UFP. Conclusions: UFP impairs vascular regeneration via Notch signaling. Notch/FOXO1 cooperation is implicated in promoting vascular development.
Abstract 18910: Deciphering and Exploiting Transcriptome-Wide MicroRNA Binding Profiles in Human Tissues
Authors: Ryan L Boudreau, Peng Jiang, Brian L Gilmore, Ryan M Spengler, Jay Nelson, Christopher A Ross, Yi Xing, Beverly L Davidson
Journal: Circulation (2013)

The orchestration of complex biological functions requires gene regulatory networks that are modulated, in part, by microRNAs (miRNAs). During the past decade, miRNAs have emerged as key biological effectors, and growing evidence indicates that miRNAs play critical roles in an array of human diseases, including neurological and cardiovascular conditions. These noncoding RNAs associate with Argonaute (Ago) proteins to direct post-transcriptional gene suppression via base-pairing with target transcripts. To better understand how miRNAs contribute to protective and pathogenic responses to disease, identifying their targets in affected tissues is of paramount importance. As an initial step towards addressing the latter, we profiled Ago2:RNA interactions using crosslinking immunoprecipitation coupled with high-throughput sequencing (CLIP-seq) to generate the first transcriptome-wide map of miRNA binding sites in a human primary tissue, the brain. We uncovered ~7000 stringent Ago2 binding sites which are highly enriched for conserved sequences corresponding to abundant brain miRNAs. This dataset points to functional miRNA:target pairs across more than 3000 genes and represents a valuable resource for accelerating our understanding of miRNA function in the central nervous system, and beyond. We explored this interactome for clinically-relevant miRNA binding sites and discovered sites overlapping single nucleotide polymorphisms linked to common and rare neuropsychiatric conditions, including Parkinson’s and Alzheimer’s. In addition, we identified nearly 50 miRNA target sites across 20 genes previously implicated in stroke and arterial disease. These findings provide clues which may facilitate the discovery of novel and refined pathogenic mechanisms and therapeutics for complex diseases of the brain and vasculature. Overall, this work lays the foundation for translating this methodology to characterize the diverse landscapes of miRNA:target interactions across normal and diseased human tissues, particularly heart, where miRNAs are well-established mediators of cardiac development and disease.
Abstract 13112: Benefit of Early Discharge Among Patients With Low-risk Pulmonary Embolism: Focus on Net Clinical Impact
Authors: Li Wang, Onur Baser, Phil Wells, W. F Peacock, Craig Coleman, Gregory J Fermann, Jeff Schein, Concetta Crivera
Journal: Circulation (2016)

Introduction: Clinical guidelines recommend early discharge of patients with Low Risk Pulmonary Embolism (LRPE). With increasing awareness of the risks of hospital acquired complications (HAC), we sought to measure the overall impact of early discharge of LRPE patients on clinical outcomes and costs within the Veterans Health Administration. Methods: Adult patients with ≥1 inpatient diagnosis for PE (index date) between 10/2011- 6/2015 and continuous enrollment for ≥12 months pre- and 3 months post-index date were included. PE risk stratification was done using the simplified Pulmonary Embolism Stratification Index (sPESI). Propensity score matching (PSM) was used to compare 90-day PE-related outcomes, HAC, healthcare utilization and costs among short versus long length of stay (LOS) LRPE patients. We defined short LOS as ≤2 days, adverse PE events (APE) as recurrent deep vein thrombosis, major bleed, or death, and net clinical benefit as 1 minus the combined rate of APE and HAC. Results: Among 6,746 PE patients, 95.4% were male, 67.7% were white, 22.0% were African American, and 1,918 had a LRPE. Among LRPE patients, only 688 (35.9%) had short LOS. After PSM, 784 LRPE patients were evaluated. There were no differences in APE, but short LOS had fewer HAC (1.5% vs. 13.3%; p&lt;0.0001) and bacterial pneumonias (5.9% vs. 11.7%, p&lt;0.005). Net clinical benefit was higher for short LOS patients (86.9% vs. 78.3%, p=0.0013). Among long LOS, the number of HAC (52) exceeded APE (14 recurrent DVT, 5 bleeds). Short LOS had lower inpatient costs ($2,164 vs. $5,100; p&lt;0.0001) and lower total costs ($9,056 vs. $12,544; p&lt;0.0001) versus long LOS. Conclusions: LRPE patients with short LOS had better net clinical outcomes at lower costs than those with long LOS. Providers should deploy risk stratification strategies and consider early discharge for LRPE patients.
Abstract 18908: Trends in Endocarditis Hospitalizations: Impact of the 2007 American Heart Association Guidelines on Adults With Congenital Heart Disease
Authors: Craig H Alexander, S. Kristen Sexson-Tejtel, Shaine A Morris, Keila N Lopez
Journal: Circulation (2013)

Introduction: In 2007, the American Heart Association (AHA) modified the recommendations for infective endocarditis (IE) antibiotic prophylaxis for all but the individuals at the highest risk of acquiring IE. The impact of these guidelines remains unclear, particularly for adults with congenital heart disease (CHD). Our objective was to evaluate the trend in IE hospitalization and mortality before and after implementation of the revised AHA guidelines. Hypothesis: We hypothesized no change in the overall trend in IE hospitalization and mortality, including those adults with CHD, in the period after adoption of the 2007 AHA endocarditis guidelines. Methods: We utilized the Texas Hospital Inpatient Discharge Public Use Data File to identify all patients hospitalized between 2001and 2011 with IE in Texas. We evaluated the trend over time of IE admission and the percentage of those with CHD. We also assessed mortality and need for surgery during the hospital admission. Results: We identified 29, 537 IE cases. There was a steady increase in IE hospitalizations over the 10-year period from 1515 cases in 2001 to 3009 in 2011, comprising an increasing proportion of total IE admissions (0.13% in 2001 to 0.17% in 2011, p for trend &lt;0.0001). Of the patients admitted with IE, 3.3% had CHD. While both IE and percentage with CHD increased overtime, neither had a significant change after the 2007 AHA guidelines (Figure 1). Overall CHD mortality decreased from 14.2% in 2001 to 13.7% in 2011 (p=0.09). Overall mortality for the 10-year period was 14.2% without CHD and 9.1% with CHD (p&lt;0.0001). Adults were three times more likely to undergo surgery if they had CHD (25.4% vs 8.1%; p&lt;0.0001). Conclusions: We found no evidence that the 2007 AHA antibiotic prophylaxis guidelines was associated with a significant change in IE admissions across Texas hospitals, even when accounting for adults with CHD. Overall IE admissions, including those with CHD have continued to increase steadily.
Abstract 18932: Pka is a Master Regulator of Cardiac Hypertrophy Induced by Pressure Overload
Authors: Xiaoying M Zhang, Mingxin Tang, Xiaojie Ai, Szeto Christopher, Xiongwen Chen
Journal: Circulation (2013)

Aims: Under pressure overload, the sympathetic nerve system is activated persistently leading to the overactivation of PKA. Conflicting roles of PKA in PCH have been reported. Also the roles of endogenous PKA inhibitor, PKI, in PCH have not been studied. This study aims to explore the role of PKI/PKA in PCH. Methods and results: 1. RT PCR and Western blot showed that PKIα and PKIγ were highly expressed in the heart but only the expression of PKIα was reduced by transaortic banding (TAB); TAB induced a significant increases in cardiac PKA activity at 1 week post TAB; 2. An adenovirus containing PKI-GFP and 4 transgenic mouse lines overexpressing PKI-GFP were established. AdPKI-GFP (MOI=100) infection of neonatal ventricular myocytes (NRVMs) was able to completely inhibit PKA activation induced by cAMP in the extract . Two transgenic mouse lines with high (HE) and very low (VLE) expression of PKI-GFP that inhibited maximum PKA activity by 95% and 10% were used; overexpressed PKI-GFP does not inhibit the activity of other kinases; 3. In the VLE PKI-GFP TG hearts, the expression of PKI-GFP was mosaic and isolated GFP- LVMs (3224.6±83.4μm2, n=500, N=5) had significantly larger surface area than GFP+ LVMs (2135.6±127.0μm2, n=500, N=5); 4. TAB for 8 weeks did not change HW/BW (5.0±0.4 vs. 5.1±0.6mg/g BW), myocyte cross-sectional area (CSA: 721.2±25.4 vs. 754.1±37.8μm2), myocardial fibrosis (1.0 ±0.3% vs. 1.1±0.4%) and cardiac fractional shortening (FS: 41.4±2.1% vs. 40.8±1.9%) in PKI HE mice (TAB N=12 vs. Sham N=11) but induced significant increases in HW/BW (8.4±0.9 vs. 5.0±0.6mg/gBW), MCSA (1152.9±108.4 vs. 712.4±65.2μm2, ), myocardial fibrosis (12.5 ±1.6% vs. 0.8±0.1%) and depressed FS (38.4±2.4% vs. 24.1±3.1%) in control (TAB, N=8 vs. Sham, N=10; p&lt;0.05) mice. 5. In cultured NRVMs, PKI-GFP prevented myocyte hypertrophy induced by isoproterenol (ISO), phenylephrine (PE) and angiotensin II, as evidenced by no significant increases in protein synthesis (protein/DNA ratio), myocyte surface area, sarcomere organization in AdPKI-GFP infected myocytes induced by these drugs; 6. PKI-GFP infection in NRVMs prevented the translocation of NFAT3 and HDAC5 induced by ISO and PE but increased ANF. Conclusions: PKA is a master regulator of PCH induced by pressure overload.
Abstract 18900: Impact of Acute and Chronic 5-Hour Energy Drink Consumption on Electrocardiographic Parameters
Authors: Sachin A Shah, Carolyn Lacey, Vicki Potts, Christopher M Lopez, Ian Riddock, Michael Lee, Nicholas Milazzo, Anthony E Dargush
Journal: Circulation (2013)

INTRODUCTION: The impact of energy drinks on the cardiac rhythm remains unknown. QT/QTc prolongation has been known to induce life threatening arrhythmias. We sought to determine the impact of 5-Hour Energy shot on the QTc interval after acute and chronic consumption. Methods: This was a randomized, placebo controlled, crossover study enrolling young healthy volunteers not on any medications. Subjects received the study drink (5 Hour Energy shot or placebo) twice daily separated by approximately 7 hours for the first 7 days. This was followed by a washout period of 6 days and the alternate study drink was consumed for the final 7 days. A 12-lead electrocardiogram was performed at baseline, 1, 3 and 5 hours on days 1, 7, 15 and 21. Automated ECG measurements were used for per-treatment and ITT analysis and analyzed using the paired student’s t-test. Results: A total of 24 subjects (29±5.8 years) were included for analysis. QTc values after consumption of a single placebo-dose were 414±18, 413±15, 413±19 and 417±19 milliseconds at baseline, 1, 3 and 5 hours respectively. Post consumption of a single 5 Hour Energy dose, QTc values were 415±17, 408±19, 410±20, and 413±17 milliseconds at baseline, 1, 3 and 5 hours, respectively (all time matched inter- group p-values &gt;0.291). QTc values after consumption of placebo for 7 days were 415±20, 413±18, 409±19, and 413±22 milliseconds at baseline, 1, 3 and 5 hours, respectively. Post consumption of 5 Hour Energy shots for 7 days, resulted in QTc values of 415±22, 413±24, 415±24, and 415±21 milliseconds at baseline, 1, 3 and 5 hours, respectively (all time matched inter- group p-values &gt;0.197 ). There was no difference between the PR interval, QRS duration, QT interval and heart rate between the two groups. CONCLUSION: 5-Hour Energy did not induce any significant changes in the QTc interval or other ECG parameters after single and multiple doses throughout a 7 day period. These results may vary between different energy drinks due to the varying ingredients within them. DISCLOSURE: The views expressed in this material are those of the authors and do not reflect the official policy or position of the U.S. government, the Department of Defense, or the Department of the Air Force.
Abstract 13977: Low Operative Mortality Achieved With Surgical Septal Myectomy: Role of Dedicated Hypertrophic Cardiomyopathy Centers in the Management of Dynamic Subaortic Obstruction
Authors: Barry J Maron, Joseph A Dearani, Steve R Ommen, Martin S Maron, Hartzell V Schaff, Rick A Nishimura, Anthony Ralph-Edwards, Mark V Sherrid, Daniel G Swistel, Sandhya Balaram, Hassan Rastegar, Ethan J Rowin, Nicholas G Smedira, Bruce W Lytle, Milind Y Desai, Harry M Lever
Journal: Circulation (2015)

Background: Treatment of progressive heart failure, due to left ventricular (LV) outflow tract obstruction has been a major component of hypertrophic cardiomyopathy (HCM) disease management for 50 years. Septal myectomy has been the primary treatment option to abolish gradients and relieve heart failure symptoms. The role of myectomy in HCM management has depended on effectiveness in relieving heart failure symptoms, but also an acceptable operative risk. Methods: Over the most recent 15-year period, we reviewed 3,700 consecutive isolated myectomy operations performed at major North American HCM institutions. Composite operative mortality (first 30 days) was only 0.4%. Seventeen operative deaths were at ages 24 to 82 (≥70 years), and only 6 occurred after 2010. Notably, 2 of the 4 Mayo Clinic deaths were in patients with prior alcohol septal ablation. Septal myectomy, when performed in experienced HCM centers, was much safer when compared to operative mortality with coronary artery bypass grafting (2.3%); valve replacement (3.5%); mitral valve replacement specifically (5.7%) (STS Database), similar to atrial or ventricular septal defect closure and 15-fold less than myectomy in community hospital or low volume surgical settings. Conclusions: Surgical myectomy performed in dedicated HCM centers with experienced surgeons and staff is one of the safest open-heart procedures currently practiced, with a mortality rate as low as 0.4%. The large mortality discrepancy for myectomy between community hospitals and dedicated HCM centers underscores that this operation should be considered a specialized procedure best performed in high volume HCM institutions.