bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16069: Low-Density Lipoprotein of Systemic Lupus Erythematosus Patients Contains Lysophosphatidylcholine-Rich Lipid That Induces Overexpression of CX3CL1 in Endothelial Cells
Authors: Chan Hua-Chen , Ke Liang-Yin , Chan Hsiu-Chuan , Su Hung , Lee An-Sheng , Lu Jonathan , Tsai Wen-Chan , Ou Tsan-Teng , Wu Cheng-Chin , Chu Chih-Sheng , Shiea Jentaie , Yen Jeng-Hsien , Chen Chu-Huang
Published: July 2021

Background:
Patients with systemic lupus erythematosus (SLE) are twice more likely to develop cardiovascular disease than the general population, even though their plasma LDL cholesterol (LDL-C) levels are usually not elevated. To delineate the mechanisms, we examined the chemical properties of their LDL.

Methods and Results:
LDL isolated from SLE patients (LDL-C, 105±33 mg/dL; n=24) exhibited greater mobility in agarose gel electrophoresis than LDL of healthy control subjects (LDL-C, 121±25 mg/dL; n=24), secondary to an increased distribution of L5 (2.30±1.3% vs. 0.7±0.3%;
P
<0.0001), the most electronegative subfraction of LDL identified by anion-exchange chromatography, in total LDL. CX3CL1 is a membrane-bound chemokine expressed in injured endothelial cells (ECs). CD16
+
monocytes are CX3CR1-expressing cells that recognize CX3CL1. Compared with control, SLE patients had a twofold (
P
<0.001) increase in CX3CL1 and a threefold (
P
<0.0001) increase in CD16
+
monocytes in the plasma. Moreover, there was a positive correlation between the CX3CL1 and L5 levels (R=0.45;
P
<0.018). MALDI/TOF mass spectrometry of the lipid extracted from SLE-LDL revealed a shift from phosphatidylcholines (PCs) to lyso-PCs (LPCs), including m/
z
496.33, 524.36, 537.01, 550.94, when compared with the lipid of control LDL (Figure). The shift was especially prominent in L5. Exposing human aortic ECs to L5 but not normal LDL resulted in a fivefold (
P
<0.0001) increase in CX3CL1 expression with concomitant apoptosis. These effects of L5 were significantly attenuated by blocking the platelet-activating receptor, confirming the role of phospholipids in L5’s bioactivity.

Conclusions:
The increased distribution of LPC-rich electronegative LDL, which induces CX3CL1-CX3CR1 interactions between vascular cells, may contribute to the increased cardiovascular disease prevalence in SLE in the absence of LDL-C elevation.
Abstract 16088: Comparison of Aspirin and Clopidogrel Therapy With Clopidogrel Alone Use Following Coronary Stent Implantation in Patients With Acute Myocardial Infarction
Authors: Park Jin Sup , Cha Kwang Soo , Shin Donghun , Lee Dae Sung , Lee Hye Won , Oh Jun-Hyok , Choi Jung Hyun , Lee Han Cheol , Hong Taek Jong
Published: July 2021

Introduction:
Dual antiplatelet (DAP) therapy with aspirin and a thienopyridine following coronary stenting is superior to aspirin alone use in reducing cardiovascular events in both acute coronary syndrome and stable angina. However, there is a doubt whether DAP therapy is more effective and safer than clopidogrel alone use in secondary prevention.

Hypothesis:
We assessed the hypothesis that we compared retrospectively clopidogrel alone use with DAP therapy in acute myocardial infarction (MI) patients treated with coronary stent.

Methods:
From the Korean MI registry, we selected a total of 13,348 patients who underwent coronary stent implantation and were discharged on clopidogrel alone use (n = 85, 0.6%) and DAP therapy (n = 13,263, 99.4%). Propensity score matching was used and two cohorts of 1:5 nearest neighbor matched patients were obtained to eliminate biased estimates. The primary endpoint was the composite of major adverse cardiac events (MACE; all-cause death, MI, or revascularization) at one-year.

Results:
In the two matched cohorts of clopidogrel alone use (n = 85) and DAP therapy (n = 425), there was no difference in all-cause death (3.1 vs. 3.5%, p = 0.82), cardiovascular death (2.1 vs. 2.4%, p = 0.892), MI (1.6 vs. 1.2%, p = 0.75), revascularization (6.6 vs. 8.2%, p = 0.583), and the composite of cumulative MACE (11.3 vs. 12.9%, p = 0.665) at median follow-up period of 11.8 months. Compared to DAP therapy, clopidogrel alone use was not associated with increased risk of all-cause death (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.314-3.93, p = 0.871), MI (HR 0.38, 95% CI 0.17-11.2, p = 0.763), revascularization (HR 0.808, 95% CI 0.353-1.851, p = 0.615), and the composite of MACE (HR 1.129, 95% CI 0.585-2.178, p = 0.717) at one-year.

Conclusions:
This observational study showed that clopidogrel alone use following coronary stenting was not associated with increased mortality and worse clinical outcomes at one-year compared to DAP therapy in patients with acute MI. Further studies are needed to support this observational result.
Abstract 16117: Clinical and Angiographic Scoring System to Predict the Probability of Successful First Attempt PCI in Patients With Coronary Chronic Total Occlusion
Authors: Alessandrino Giuseppe , Louvard Yves , Lefevre Thierry , Garot Philippe , Sanguineti Francesca , Unterseeh Thierry , Hovasse Thomas , Chevalier Bernard , Morice Marie-Claude
Published: July 2021

Background:
Coronary chronic total occlusion (CTO) remains the lesion subtype in which angioplasty has the lowest success rate. Although many independent predictors of final procedural success have been identified, no studies have yet analyzed their combined impact on final procedural outcome. In order to obtain a scoring model to predict final CTO-PCI success, we analyzed a population of patients who underwent a percutaneous coronary intervention for a chronic total occlusion (CTO-PCI) at our institution.

Methods:
We included 1,657 consecutive patients who underwent a first-attempt CTO-PCI at ICPS from January 2004 to December 2013. Clinical, angiographic procedural and technical characteristics were prospectively collected. A backword stepwise logistic regression including clinical and angiographic variables was used to create a multivariable model of independent predictors of CTO-PCI success. Independent variables were then scored.

Results:
Overall procedural success rate was 72.5%. The backward logistic regression model showed that two clinical variables: previous CABG (OR2.28, 95%CI1.53-3.4), previous MI (1.56, 95%CI 1.19-2.0) and four angiographic variables: severe lesion calcification (OR 2.95, 95%CI 2.08-4.2), longer CTOs (≥20 mm: OR 2.04, 95%CI 1.62-2.58), non LAD location (OR 1.58, 95%CI 1.21-2-06) and blunt stump morphology (OR 1.57, 95%CI 1.24-1.99) were independent predictors of CTO-PCI failure. The OR values of these variables were used to create the Clinical and Angiographic Scoring System (CL-SCORE). CL-Score values of 0, 1-3, >3 and ≤5 and >5 indentified subgroups at high (class 0), intermediate (class 1), low (class 2), very low (class 3) probability of CTO-PCI success (80.3%, 64.2%, 49.4 and 29% respectively; p<0,0001) Figure 1. The probability of CTO-PCI failure increased significantly from class 0 to class 1 (19.7% to 35.8%, p<0.0001), from class 1 to class 2 (35.8 to 50.6 p<0.0001) and from class 2 to class 3 (50.6% to 81% p=0.001), respectively.

Conclusion:
This clinical and angiographic score strongly predicted the final CTO-PCI procedural outcome of our study population. Further studies are required to validate this model.
Abstract 16141: Predictors of Death in Patients With Chagas Cardiomyopathy and Pacemaker - Preliminary Results of the PACINCHAGAS Study
Authors: Peixoto Giselle L , Madia Rodrigo O , Siqueira Sérgio F , Lensi Mariana M , Nishioka Silvana D , Pedrosa Anísio , Teixeira Ricardo A , Costa Roberto , Martinelli Martino
Published: July 2021

Introduction:
Chagas’ disease causes different clinical expressions in the heart and permanent pacing due to bradycardia is not uncommon.

Objective:
Predictors of death in patients with Chagas Cardiomyopathy requiring pacemaker (PM) are unknown. This is the aim of this study.

Methods:
We prospectively evaluated 529 patients included in the Pacinchagas Study - Risk Stratification in Pacemaker Patients with Chagas Cardiomyopathy, which primary objective is to create a risk score to predict death in this population. The patients are submitted to an extent questionnaire which included clinical (NYHA class, symptoms, comorbidities and medications) functional (electrocardiography, Holter and echocardiography) and electronic variables (burden of pacing and arrhythmias). Patients with at least 6 months of follow-up were included in this preliminar analysis.

Results:
The cohort included 337 (63.7%) females, the mean age was 62.3±11.9 years and 63.1% were in NYHA class I. Indication for PM implantation was atrioventricular block, sick sinus syndrome, atrial fibrillation with slow ventricular response and unknown in 72.0%; 20.4%; 5.1% and 2.5%, respectively. During a mean follow-up of 1.5±0.6 years, 62 (11.7%) patients died. The mean time of PM implantation was not different between the dead and the survivors (11.9±9.0years versus 11.1±8.6years, P=0.503). Twenty-five deaths (40.3%) were sudden, 22 (35.5%) were due to heart failure, 6 (9.7%) were due to other cardiovascular causes, and 7 (11.3%) were due to noncardiovascular causes. The cause of death could not be determined in two patients (3.2%). Cox proportional hazards identified three predictors of death: NYHA class III/IV (Hazard Ratio [HR] 5.661; 95% Confidence Interval [95%IC] 2.617-12.245; P<0.001); left ventricular ejection fraction (LVEF) ≤42% (HR 2.779; 95%IC 1.299-5.945; P=0.008) and chronic kidney disease (HR 2.635; 95%IC 1.167-5.948; P=0.020).

Conclusions:
This analysis of Pacinchagas study identified in a mean follow-up of one year and half, three predictors of death in PM users with Chagas Cardiomyopathy: NYHA class III/IV, LVEF≤42% and chronic kidney disease.
Abstract 16142: Grad 3-Ischemia (QRS Complex Distortion) as a Predictor of Myocardial Damage as Assessed by Cardiac Magnetic Resonance Imaging and Clinical Prognosis in Patients With ST-Elevation Myocardial Infarction
Authors: Rommel Karl-Philipp , Badarnih Hadil , Desch Steffen , Gutberlet Matthias , Schuler Gerhard , Thiele Holger , Eitel Ingo
Published: July 2021

Introduction:
Predicting the extent of myocardial damage on early electrocardiographic (ECG) findings could be helpful for improved risk stratification in patients with acute reperfused ST-elevation myocardial infarction (STEMI). Distortion in the terminal portion of the QRS complex (so called grade 3 ischemia, G3I) has been associated with adverse outcomes in STEMI patients. The correlation of G3I with infarct size and microvascular injury is not well defined.

Objective:
To studied the relation of G3I with myocardial damage as assessed by CMR and the association of G3I with adverse clinical outcomes in a STEMI population treated by primary percutaneous coronary intervention (PCI).

Methods:
We analyzed the ECGs of 572 consecutive STEMI patients regarding the presence or absence of G3I. G3I was defined as: 1) complete loss of S waves in 2 adjacent leads with typical Rs configuration (i.e. V1-V3), or 2) ST-J point to R wave amplitude ratio >0.5 in other leads with qR configuration. CMR was performed within 1 week after infarction for comprehensive assessment of myocardial damage using a standardised protocol. The primary clinical end-point was major adverse cardiac events (MACE) defined as death, reinfaction and readmission for congestive heart failure within 12 months after the index event.

Results:
G3I was present in 186 (32%) patients. The presence of G3I was associated with larger infarct size (18.3%LV [10.4 to 27.6] versus 16.5%LV (8.2 to 23.5), p=0.01), late microvascular obstruction (0.4%LV [0 to 2.7] versus 0%LV [0 to 1.5], p= 0.05, presence of intramyocardial hemorrhage (41 versus 32%, p=0.04) and less myocardial salvage (47 [28 to 64] versus 53 (35 to 68), p=0.01). G3I was associated with a significant higher incidence of MACE (p=0.01) and was identified as an independent predictor of MACE in Cox regression analysis (Hazard ratio 2.19 [1.10 to 4.38], p=0.03).

Conclusions:
This largest study to date correlating G3I on the admission ECG with CMR markers of myocardial damage demonstrates that G3I is significantly associated with infarct size, myocardial salvage and reperfusion injury in a STEMI population reperfused by primary PCI. Moreover, G3I was independently associated with MACE.
Abstract 16274: Identification of Novel CAD Genetic Loci by 1000 Genomes-Based Imputation and a Non-Additive Discovery Screen
Authors: Nikpay Majid , Goel Anuj , Won Hong-Hee ,   CARDIoGRAMplusC4D Consortium
Published: July 2021

Introduction:
Known common coronary artery disease (CAD) risk variants explain only 10% of the predicted genetic heritability of the disease, suggesting that important genetic signals remain to be discovered.

Hypothesis:
The 1000 Genomes imputation training set, and non-additive discovery screens, may allow detection of additional CAD-associated genetic variants that contribute to missing heritability.

Methods:
As part of the CARDIoGRAMplusC4D Consortium, we assembled 48 GWAS of CAD that included 1000 Genomes imputed data. These consisted of 60,801 CAD cases and 123,504 controls, 23% being of non-European ancestry. In each study, GWAS analysis was carried out by assuming an additive, dominant or recessive model of inheritance, and followed by meta-analysis to combine the GWAS results for each model.

Results:
After QC filtering, 9.4 million variants (91% SNPs, 9% INDELs) were available for meta-analysis. 29% of these were lower frequency variants (0.005 < MAF < 0.05). Novel associations (P < 5 x 10
-8
, and outside of known CAD genomic regions) under the additive model were detected for 38 variants (8% INDELs) with imputation info score of 0.94 [0.88-0.96] (median [IQR]). Of note, 34% of novel variants (N=13) were of low allele frequency (MAF < 0.05; median [IQR] = 0.03 [0.02-0.03]); these exhibited much larger effect sizes (P < 0.0001; Cohen’s d = 2.3) as compared to the common variants (MAF ≥ 0.05). The newly identified variants were mapped to 10 novel genomic loci for CAD. Together, these variants explained 2.5% of the heritability of CAD and majority (60%) were intronic. Three of these loci fit a dominant mode of inheritance. An additional two novel loci were identified by a recessive mode of inheritance. Among the newly identified loci, three had been previously reported at GWAS levels of significance for metabolic traits.

Conclusions:
These findings demonstrate the value of using a global imputation training set to enhance coverage of low allele frequency and incompletely tagged variants. Consideration of non-additive models of inheritance enabled identification of additional genetic variants associated with CAD.
Abstract 16341: Application of Genomic Markers to Predict Outcome in Patients Receiving Left Ventricular Assist Device (LVAD) Therapy
Authors: Mazhari Ramesh , Toma Ian , Konjedi Nahal , Murphy Claire , Moussavi Farzad , Sadri Maziar , Shah Palak , McCaffrey Timothy
Published: July 2021

Introduction:
LVADs are now used as a bridge to heart transplantation, or destination therapy in patients with advanced heart failure. LVAD therapy reverses left ventricular (LV) remodeling and improves survival in 50% of patients.

Hypothesis:
We hypothesize that patients with poor prognosis after LVAD therapy will have a different genomic profile as compared to patients with higher survival rate. We propose to use genome-wide expression analysis to determine the mRNA and microRNA profiling of LV tissue and peripheral blood and identify probes that predicts outcome in patients receiving LVAD therapy.

Methods:
Genome-wide RNA expression profiling of the LV apex core tissue, and blood samples of patients receiving LVAD were performed using Illumina HumanHT-12 v4 Expression BeadChip, to study the expression of 47000 mRNA and micro-RNA transcripts. Follow up echocardiographic parameters were used to determine the patients’ clinical response to LVAD therapy. We proposed that ≥10% reduction in LV end-diastolic diameter (LVEDD) at 3 months is considered a responder to LVAD therapy. The results of the gene expression analysis were integrated with clinical outcomes to identify RNA expression patterns that differentiate LVAD responders from non-responders.

Results:
The percent change in LVEDD at 3 months ranged from +12 to -44 (mean -12±0.21), and 45% of the patients were responders to LVAD therapy (n=35). We used GeneSpring GX12 to identify the differentially expressed transcripts, and filtered the probes by their correlation to % change in LVEDD as a continuous numerical measurement with correlation stringency of 0.85 <= r < =1.0. A total of 277 probes from LV samples were highly correlated with % change in LVEDD. The candidate mRNA, ncRNA, and microRNA transcripts (e.g. SOD1, 2, GPX1-4,TGF-β1, EGFR, AMPK, SRC) were categorized in 3 functional groups of oxidative stress, tissue fibrosis, and cellular energy depletion pathways using pathway studio. Profiling of blood samples did not reveal highly correlated probes.

Conclusions:
The myocardial transcriptome can predict the outcome in patients receiving LVAD therapy. The genetic markers, predictive of LV recovery after mechanical unloading, can help build new hypotheses for candidate pathways of LV remodeling.
Abstract 16348: Ecto-Nucleotidase-Derived Adenosine Promotes Mineralization Through A2a Receptor in Calcified Aortic Valves Disease
Authors: Abulajiang Maihemuti , Boulanger Marie-Chloé , Hadji Fayez , Bouchareb Rihab , Mathieu Patrick
Published: July 2021

Background:
Mineralization plays a crucial role in the development of calcific aortic valve disease (CAVD). The expression of ecto-nucleotidases may promote the mineralization of valve interstitial cells (VICs). We hypothesized that the expression of NPP1, which generates adenosine monophosphate (AMP), and 5’nucleotidase, an enzyme using AMP as a substrate to produce adenosine, may co-regulate the mineralization of the aortic valve.

Methods:
We have investigated the expression of NPP1 and 5’nucleotidase in CAVD tissues and determined the role of these ecto-nucleotidases on the mineralization of isolated VICs. The signaling pathway involving adenosine receptors was also studied.

Results:
In CAVD tissues, we documented that NPP1 and 5’nucleotidase enzyme activities were increased. NPP1 and 5’nucleotidase were co-expressed by VICs. In cell culture we found that mineralization induced by ATP was decreased by silencing NPP1 and 5’nucleotidase, suggesting a role for adenosine. Adenosine and specific A2a receptor agonist increased the calcification of VICs. Silencing of A2a receptor and the use of A2a-/- receptor mouse VICs abrogated adenosine-induced mineralization. Also, A2a receptor-mediated mineralization of VICs was negated by the transfection of a mutant dominant negative Gαs vector. Inhibition of the protein kinase A (PKA) pathway prevented adenosine-induced mineralization of VICs and expression of NPP1. We next showed that activation of PKA promoted in luciferase assay the activity of the NPP1 promoter. By using chromatin immunoprecipitation assay (ChIP) we documented that the cAMP response element binding protein (CREB), downstream of PKA, physically interacted with the NPP1 promoter region. Furthermore, the transfection of a mutant dominant active CREBDIEDML in isolated VICs increased the NPP1 promoter activity by 6.5-fold.

Conclusion:
The overexpression of NPP1 and 5’nucleotidase in CAVD promotes the mineralization of the aortic valve through A2a adenosine receptor, which signals through Gαs and the cAMP/PKA/CREB pathway. CREB is a positive regulator of NPP1 promoter activity in a positive feedback loop. The ecto-nucleotidases and/or A2a adenosine receptor could represent potential novel pharmaceutical targets in CAVD.
Abstract 16402: Feasibility and Safety of Uninterrupted Rivaroxaban in Patients Undergoing Radiofrequency Ablation for Long Standing Persistent Atrial Fibrillation
Authors: Di Biase Luigi , Trivedi Chintan , Mohanty Prasant , Mohanty Sanghamitra , Bai Rong , Santangeli Pasquale , Sanchez Javier , Horton Rodney , Gallinghouse G. Joseph , Zagrodzky Jason , Hao Steven , Hongo Richard , Beheiry Salwa , Lakkireddy Dhanujaya R. , Reddy Madhu , Viles-Gonzalez Juan F. , Burkhardt J. David , Natale Andrea
Published: July 2021

Introduction:
Periprocedural anticoagulation management is key to minimize bleeding and thromboembolic complications during and after radiofrequency catheter ablation. Uninterrupted strategies with warfarin in high risk patients have shown superiority over interrupted strategies.

We sought to assess the safety and feasibility uninterrupted rivaroxaban during atrial fibrillation (AF) ablation in patients with long standing persistent atrial fibrillation.

Methods:
One hundred and ninety six (196) consecutive patients undergoing AF ablation with uninterrupted rivaroxaban (last dose taken with food the night before the procedure and the following dose taken the night of the procedure) were matched by age and sex with an equal number of patients undergoing AF ablation with uninterrupted warfarin on a “therapeutic range”. All patients underwent pulmonary vein antrum isolation and ablation of non pulmonary vein triggers as disclosed by isoproterenol challenge test.

Results:
Baseline characteristics and procedural variables were similar between groups. Mean INR in warfarin group was 2.2 ± 0.5. CHADS2 Score was ≥ 2 in 141 (72%) in the rivaroxaban group and 130 (66%) in the warfarin patients (p=0.20). One pericardial tamponade and one groin hematoma occurred in rivaroxaban group while 2 patients in warfarin group developed groin hematoma. One TIA with positive MRI was present in the rivaroxaban group.

Conclusions:
Uninterrupted rivaroxaban therapy appears to be as safe and efficacious as uninterrupted warfarin strategy in preventing bleeding and thromboembolic events in patients undergoing long standing persistent AF ablation.
Abstract 16476: Safety Profile of Bivalirudin in the Treatment of ST-Segment Elevation Myocardial Infarction Patients in Clinical Practice - Results From the Bremen STEMI Registry
Authors: Zabrocki Robert , Fiehn Eduard , Wienbergen Harm , Seide Susanne , Schmucker Johannes , Garstka Daniela , Hambrecht Rainer
Published: July 2021

Introduction:
Previous studies demonstrated that treatment of patients (pts) being affected by ST-segment elevation myocardial infarction (STEMI) with bivalirudin (biv) instead of heparin (hep) reduced rates of major bleedings. Results regarding a reduction in all-cause mortality are inconclusive, stent thromboses however were slightly increased.

Real world data in pts with STEMI treated with biv in the era of new anti-thrombotic treatment are still spare. The aim of this study was to evaluate safety of biv for all-comers.

Methods:
All pts with STEMI from the metropolitan area of Bremen (Germany) are admitted to the Bremen heart center and documented in the Bremen STEMI-registry (BSR) since 2006. In May 2013 we adapted our anticoagulation strategy to the current guidelines from hep with glycoprotein IIb/IIIa inhibitors (GPI) to biv with provisional use of GPI. Pts receiving biv were compared to all pts until April 2013 in the BSR without chronic renal failure.

Results:
Baseline and interventional characteristics of 530 consecutive pts treated with biv and 5197 pts treated with hep are shown in table 1.

Despite a higher portion of pts after resuscitation (10.3% vs 8.6%; p<0.01) and a higher incidence of Killip class 3 or 4 (15% vs 8%; p<0.001) in the biv group inhospital all-cause mortality showed no difference (biv: 6.8% vs hep: 7.3%, p=0.66). However pts treated with biv demonstrated highly significant lower bleeding rates (TIMI major/minor bleedings: 0.8% vs 3.7%, p<.01). Stent-thromboses showed a trend towards an increased event rate with biv (1.3%, 7pts vs 1.0%, 52pts, p=0.07).

Conclusions:
In one of the largest all-comers registries treatment with biv was associated with significantly lower minor and major bleedings. There is only a trend for a higher rate of stent thromboses in the biv group. Therefore, data from our all-comers registry support the beneficial safety profile of biv observed in clinical studies.
Abstract 16576: The Role of Undetectable Cardiac High Sensitivity Troponin T and Copeptin for Prediction of 90 Day Outcomes in Low- to Intermediate-Risk Patients With Suspected ACS: A BIC-8 Biomarker Substudy
Authors: Vafaie Mehrshad , Slagman Anna , Searle Julia , Hamm Christian , Huber Kurt , Müller Christian , Vollert Jörn O , Blankenberg Stefan , Giannitsis Evangelos , Möckel Martin
Published: July 2021

Introduction:
The international randomized multicentre BIC-8 trial demonstrated that patients with suspected ACS and a negative baseline troponin, who also tested negative for copeptin, could safely be discharged and did not experience a higher rate of MACE within 30 days compared to patients managed according to current guidelines.

Objective:
This BIC8-substudy evaluates the usefulness of copeptin in patients with undetectable (below limit of detection (LOD)), compared to detectable (at or above LOD) high sensitivity troponin T (hsTnT) at presentation.

Methods:
In the original study, patients (n=902) were randomized 1:1 into standard and experimental arm. In the experimental arm, further patient care was based on copeptin levels at admission. After 30 and 90 days, a telephone follow-up was performed. Since hsTnT at LOD was evaluated in a post-randomization cohort, all analyses were executed on the entire study population.

For the hsTnT assay (Elecsys, Roche), LOD was defined as a value below 5 ng/l. Copeptin values were determined using the BRAHMS Copeptin us Kryptor assay (Thermo Scientific).

Results:
Of all patients enrolled in the original study (n=902), hsTnT at admission was available in 893 patients (99.0%). The majority of patients had detectable hsTnT values (65.4%, n=584). 34.6% (n=309) had no detectable hsTnT-values. In these patients, no myocardial infarctions (MIs) or deaths occurred within 90 days. In patients with detectable hsTnT-values, in 3.3% the combined endpoint of death or MI occurred within 90 days (table 1). In the subgroup of patients with a copeptin value ≥10 pmol/l the event-rate was 8.2% (10/122) and in patients below this value 2.0% (9/441), (RR = 4.02, p=0.003).

Conclusion:
In low-to-intermediate risk patients with suspected ACS, undetectable hsTnT values at admission allow a safe discharge without occurrence of death or MI within 90 days. In patients with detectable hsTnT, Copeptin is useful to stratify patients at higher risk for death/MI.
Abstract 16604: A Novel Endocardial Activation Analysis Software to Identify Rapid Activation Patterns During Atrial Fibrillation
Authors: Weiss Raul , Zeidan Ziad , Hummel John D , Kalbfleisch Steven J , Augostini Ralph , Houmsse Mahmoud , Daoud Emile G
Published: July 2021

Introduction:
The cornerstone of atrial fibrillation (AF) radiofrequency ablation (RFA) is pulmonary vein (PV) isolation. A recently described technique directs RFA to electrical rotors identified by computational analyses of 64-electrode basket catheter (BC) endocardial recordings of AF.

Hypothesis:
The purpose of this study was to develop and then to assess the ability of a novel analysis method, CartoFinder™ (CF), incorporated into a 3D mapping system, CARTO (Biosense Webster, CA, USA) to identify rapid activation patterns (RAP).

Methods:
20 patients who were undergoing RFA AF utilizing CARTO mapping and who consented were enrolled. 1 minute BC maps of the right (RA) and left (LA) were obtained after creation of a 3D virtual anatomic shell prior to and after RFA around the PV. In each atria, 2 BC recordings were obtained at the same location, separated by 5 minutes.

Results:
Unipolar signals from the BC were recorded by CARTO and analyzed offline. The signal was processed to filter out far-field ventricular activity and the remaining signals were analyzed to create dynamic 3D activation maps and visually identify RAP. CF labels the leading edge of activation with a red color. Of these 20 patients, CF recordings were complete in 14 pts (mean age 59; 12 with persistent AF). There were 2.8 RAP / pt. (mean 1.3 RA; 1.6 LA). No RAP were recorded in 2 pts. The correlation of the BC separated by 5 minutes to identify the same RAP was 12/15 in RA and 15/18 in LA (total: 27/33, 82%).

Conclusions:
CF is a newly developed online technique to identify RAP incorporated into a conventional 3D mapping system. RAPs can be identified in the majority of patients undergoing RFA AF with approximately 80% reproducibility.
Abstract 16612: Efficacy and Safety of Edoxaban for the Management of Elderly Patients With Atrial Fibrillation: Engage AF-TIMI 48
Authors: Toda Kato Eri , Giugliano Robert P , Ruff Christian T , Murphy Sabina A , Nordio Francesco , Kimura Tetsuya , Jin James , Lanz Hans , Mercuri Michele , Braunwald Eugene , Antman Elliott M
Published: July 2021

Background:
Elderly patients with atrial fibrillation (AF) treated with anticoagulants are at higher risk of both ischemic and bleeding events compared to younger patients. Intracranial bleeding (ICH) remains one of the most concerning complications of anticoagulation therapy, and risk is strongly related to age. The ENGAGE AF-TIMI 48 trial showed that both the high (HD) and low dose (LD) regimens of the once daily oral factor Xa inhibitor edoxaban were non-inferior to well-managed warfarin (TTR 68.4%) in preventing stroke and systemic embolic events (SEE) while reducing major bleeding.

Methods:
21,105 patients were enrolled in ENGAGE-TIMI 48 trial and stratified into pre-specified age categories: <65 (n=5,497), 65 to 74 (n=7,134), ≥75 (n=8,474) years. The primary endpoints were stroke/SEE and major bleeding as defined by the ISTH and outcomes over 2.8 years of median follow-up compared by age and treatment.

Results:
Regardless of treatment, the risk of major bleeding and stroke/SEE increased with age (p<0.001), but more markedly so for major bleeding. Both edoxaban regimens were similar to warfarin in effect on stroke/SEE across the age categories (HD vs. warfarin: <65yr HR 0.94, 65-74yr HR 0.89, ≥75yr HR 0.83; LD vs. warfarin: <65yr HR 1.42, 65-74yr HR 1.0, ≥75yr HR 1.12; P-int both NS). When comparing edoxaban with warfarin, a major impact was seen on absolute risk reduction for major bleeding, including ICH (figure). The edoxaban treatment benefits were consistent across ages (P-int NS for both).

Conclusion:
The efficacy and safety of edoxaban compared to well-managed warfarin are consistent regardless of age in patients with AF. Due to the higher risk of bleeding with increasing age, the absolute benefits of edoxaban are greater in the elderly.
Abstract 16637: Antioxidant-1, a Novel Cu-Dependent Transcription Factor for NADPH Oxidase p47phox, Promotes Wound Healing by Regulating Inflammation and Angiogenesis
Authors: Das Archita , Chen Gin-Fu , Kim Ha Won , Youn Seock-Won , Varadarajan Sudhahar , McKinney Ronald D , Finney Lydia , Ushio-Fukai Masuko , Fukai Tohru
Published: July 2021

Background:
Wound healing is important repair process after injury associated with inflammation and angiogenesis. Copper (Cu) plays an important role in wound healing and angiogenesis; however, underlying mechanism is unknown. Bioavailability of Cu is tightly controlled by transport proteins (Cu importer CTR1 and Cu exporter ATP7A) and chaperone (antioxidant-1, Atox1) which transfers Cu to ATP7A. We reported that Atox1 also functions as a Cu-dependent transcription factor; however, its role in wound healing is unclear.

Results:
Using mouse skin puncture model, here we show that, Atox 1 protein (8 fold) and Cu level (by X-ray Fluorescence Microscope; 2.5 fold) increased in skin after wounding in WT mice at day 7 when Atox1 was localised in the nucleus of dermis endothelial cell (ECs) and ATP7A was markedly decreased. ATP7A transgenic mice showed impaired wound healing. Atox1 knockout (KO) mice exhibited decrease in wound repair (40% inhibition vs. WT, day 7) which was rescued by Atox1 gene transfer by lentivirus. Macrophage which secrets angiogenic cytokines/chemokines was significantly reduced which resulted in decreased VEGF and SDF-1α protein and angiogenesis at day 7. In cultured human ECs, inflammatory cytokine TNF-stimulation significantly decreased ATP7A protein (80%) and increased intracellular Cu and Atox1 in nucleus. ATP7A knockdown with siRNA in ECs increased intracellular Cu and promoted nuclear Atox1, which were rescued by Cu importer CTR1 siRNA or Cu chelator BCS, indicating ATP7A downregulation-induced Cu accumulation is required for Atox1 nuclear translocation. By screening Atox1 target genes, we found that NADPH oxidase p47phox promoter contains Atox1 binding responsible element. p47phox protein expression was significantly increased by wounding or overexpression of nuclear-targeted Atox1, which was markedly decreased in Atox1 KO mice with its downstream VCAM1/ICAM1.

Conclusions:
Cu chaperone Atox1 functions as a transcription factor by sensing ATP7A downregulation-induced intracellular Cu to upregulate NADPH oxidase p47phox and its downstream redox-sensitive VCAM1/ICAM1 expression in response to injury. This in turn promotes inflammatory cell recruitment and angiogenesis, and thus stimulating wound repair.
Abstract 16662: GDF-15: Association With Pulmonary Hemodynamic Indices and Reduction With Serelaxin in Acute Heart Failure
Authors: Prescott Margaret F , Ponikowski Piotr , Mitrovic Veselin , Ruda Mikhail , Fernandez Alberto , Voors Adriaan A , Metra Marco , Cotter Gad , Zhang Yiming , Dahlke Marion
Published: July 2021

Background:
Growth differentiation factor 15 (GDF-15) appears to have a role in regulating inflammation and apoptosis and is up-regulated following injury to the liver, kidney, heart and lung. Elevated baseline (BL) levels of GDF-15 and increases over time have been shown to be associated with adverse events in heart failure (HF). GDF-15 was decreased following LVAD implantation and cardiac unloading in end stage HF. As previously reported, serelaxin improved Pulmonary Capillary Wedge Pressure (PCWP), mean Pulmonary Artery Pressure (mPAP), and Pulmonary Vascular Resistance (PVR) during a 20 h infusion period (all p<0.005 vs. placebo [PBO]). A post-hoc analysis was performed to explore serelaxin effects on GDF-15 in acute HF (AHF) and whether GDF-15 is associated with pulmonary hemodynamics.

Methods:
Following serelaxin (30 ug/kg/d) or PBO infusion for 20 h in AHF patients, PCWP, mPAP, PVR, NTproBNP (Roche Diagnostics) and GDF-15 (pre-commercial kit, Roche Diagnostics) were measured in 32 serelaxin and 31 PBO treated patients. The effect of serelaxin on GDF-15 and NTproBNP was analyzed and the potential association of GDF-15 or NTproBNP with selected hemodynamic indices was explored combining treatment data from the two treatment arms.

Results:
Following the 20 h infusion period, serelaxin reduced GDF-15 vs BL (BL median 3192 pg/ml) by 16% (serelaxin vs PBO p=0.021) and reduced NTproBNP (BL median 3262 pg/ml) by 13% (serelaxin vs PBO p=0.021). GDF-15 at BL and 20 h was significantly associated with BL and 20 h NTproBNP (both p<0.001), mPAP (both p<0.025), and PVR (both p<0.001). At 20 h GDF-15 and PCWP were significantly associated (p<0.02) but their association at BL was not statistically significant (p=0.70). The association of NTproBNP at BL and 20 h was not statistically significant for BL or 20 h PCWP, mPAP or PVR (all p >0.05).

Conclusions:
In this small invasive hemodynamic study in patients with AHF, serelaxin significantly reduced GDF-15 and NTproBNP and had favorable effects on pulmonary hemodynamics. GDF-15 levels at BL and 20 h showed a strong correlation with BL and 20 h values of mPAP and PVR. Additional studies measuring GDF-15 levels in acute HF patients with pulmonary congestion appear warranted.
Abstract 16668: The Effects of Dabigatran on Fibrin Network Structure and Lysis: A Simple Technique to Monitor Efficacy of Treatment?
Authors: Franchi Francesco , King Rhodri , Phoenix Fladia , Rollini Fabiana , Cho Jung Rae , Bhatti Mona , DeGroat Christopher , Tello-Montoliu Antonio , Duarte Valeria , Thano Estela , Faz Gabriel , Zenni Martin M , Guzman Luis A , Bass Theodore A , Angiolillo Dominick J , Ajjan Ramzi
Published: July 2021

Background:
Thrombus formation represent the final step in the atherothrombotic process and occurs secondary to a complex interaction between platelets and coagulation factors. Increased platelet reactivity and enhanced clot formation can both determine predisposition to vascular events. Direct platelet inhibition by modern antiplatelet therapy is now effective at controlling the cellular component of coagulation but the fibrin network is not generally targeted in arterial disease. Our aim was to investigate the effects of dabigatran on fibrin network characteristics in individuals dual antiplatelet therapy (DAPT).

Methods:
This was a prospective, randomized, double-blind study conducted in 30 patients on maintenance (at least 30 days) DAPT with aspirin (81mg/day) and clopidogrel (75mg/day). Patients were randomized to receive either dabigatran 150mg bid or matching placebo for 7 days. Fibrin clot properties were studied using a validated turbidimetric assay and the following parameters were recorded: lag phase and time to full clot formation, both of which measure clotting potential; clot maximum absorbance, representing fibrin network density and fibre thickness; clot lysis time to assess fibrinolytic efficiency.

Results:
Dabigatran treatment was associated with an increase in lag phase, compared with baseline, of 1013±167 sec , whereas no difference was detected in placebo treated patients (-17±14 sec, p<0.001 for dabigatran vs placebo). Similar results were obtained for clot formation time with an increase of 240±37 sec in dabigatran treated patients with no change following placebo treatment (-24±18 sec; p<0.001 comparing the two groups). The change in clot maximum absorbance after dabigatran and placebo treatment showed no differences (-0.02±0.01 and 0.00±0.01 au, respectively; p=0.2) and clot lysis time was similar.

Conclusions:
In patients on DAPT with aspirin and clopidogrel, additional treatment with dabigatran delays fibrin clot formation without affecting fibrinolysis. Therefore, triple therapy with dabigatran may be one option to reduce thrombosis potential in high risk individuals. Moreover, our assay, which can be conducted on stored samples, offers the opportunity to monitor response to dabigatran therapy.
Abstract 16688: Trans-Satellite Wireless 12 Lead ECG Transmission From the Ambulance to the Primary PCI Facility as Part of Nationwide Primary PCI Program for ST-Elevation Myocardial Infarction
Authors: Gehani Abdurrazzak , Al Suwaidi Jassim , Tamimi Omer , Arafa Salah , Al Qahtani Awad , Arabi Abdulrahman , Rafie Ihsan , Nabti Abdulrahman , ABujalala Salem , Yacoub Magdi
Published: July 2021

Introduction:
Time is recognized as a crucial factor in the success of Primary PCI (PPCI). We have installed a “Nationwide” Trans-Satellite Wireless ECG Transfer (W-ECG) which enables swift identification of STEMI and direct transfer to the PPCI facility in Heart Hospital (HH). It also initiates PPCI staff to be ready even before patient arrives, and eliminates delays in Emergency rooms.

Methods:
Of 510 patients who had PPCI for STEMI, 282 (55%) were transferred directly to the Heart Hospital (HH). These were compared with 228 patients (45%) who went to other hospitals first (OH) before transfer to the HH. Age was similar 50.2 vs 50 years and there was no Ethnic difference (73% Asians and 26% Arabs) in both groups. We compared the two with regard to achieving the optimal Door to Balloon Time (DBT) of 90min for PPCI facility (HH), versus 120min for the OH group, as per guidelines.

Results:
The DBT was 53±23min for HH group vs 104±55min in OH group (p<0.001). However, while 88% achieved <90min in HH group, only 70% achieved <120min in OH group, p<0.001. Furthermore, Out of Hospital Delay (
OHD
i.e delay from symptoms until arrival to hospital) was also different. Patients who had W-ECG arrived faster to HH and thus had shorter OHD (198±183min) than those using own transport to HH (287±276min). Although OHD was longer in HH group (216±212) than OH group (201±172min), the combined OHD+DBT= (Total delay from symptoms to Balloon) was still shorter in HH (W-ECG) group (269min) than similar group going to OH (305min), thus saving 36 vital minutes.

Although initial TIMI-0 flow was similar (HH 46% vs OH 44%), TIMI-III flow was achieved more often in HH (97%) than in OH group (92%). Peak Troponin (ng/ml) was also higher in OH group (71251) vs (6576) in HH, p<0.05. While Ejection fraction was similar (HH 45% vs OH 43%), in-hospital mortality was higher in OH group (3.5%) vs (2.5%) in HH, p=0.05. Length of stay was also longer in OH (4.3±4.7) compared to 3.4±3.1 in HH group, p=0.005.

Conclusion:
Trans-satellite wireless ECG from the ambulance to Primary PCI facility results in significantly shorter DBT, total symptoms to balloon time, and length of stay, as well lower peak Troponin and a trend towards lower in-hospital mortality. Continued study and wider use will further confirm the impact of this technology.
Abstract 16720: Cytoglobin Regulates Cardiovascular Function and Vessel Tone by Controlling the Rate of Vascular Nitric Oxide Metabolism
Authors: Liu Xiaoping , El-Mahdy Mohamed A , Ismail Raed S , Little Sean , Thuy Le T , Kawada Norifumi , Zweier Jay L
Published: July 2021

Cytoglobin (Cygb) can effectively metabolize nitric oxide (NO), a potent vasodilator, in the presence of oxygen and reductants. Cygb in the vascular wall may affect cardiovascular functions by changing the rate of NO metabolism. In this study, we directly tested the vascular role of Cygb using Cygb knockout (Cygb-/-) mice. The mean blood pressure of Cygb-/- and C57BL/6 wild type (WT) mice was 65.3 ± 1.9 mmHg and 93.7 ± 1.5 mmHg, respectively (n=10). Using echocardiography, we observed that cardiac output (CO) was increased in Cygb-/- mice compared to WT with values of 29.8 ± 3.9 vs 17.7 ± 0.9 ml/min. The systemic vascular resistance (SVR) of Cygb-/- mice was decreased by ~60% vs that of WT mice (Fig. 1). Further, the inner diameter (id) of aorta of Cygb-/- mice was dilated compared to WT with values of 2.2 ± 0.1 mm vs 1.5 ± 0.05 mm (n=5), respectively. After treatment with the NO synthase inhibitor L-NAME, no difference in the aortic id remained between Cygb-/- (1.55 ± 0.03 mm) and WT (1.49 ± 0.02 mm) mice, indicating that the NO pathway is responsible for the difference in vascular inner diameters and tone. Myograph experiments show that the aortic vasodilation response of Cygb-/- mice is much more sensitive to acetylcholine (Ach) or the NO donor nitroprusside (SNP) (EC50 shifts from 13 nM and 2.9 nM (WT mice) to 0.33 nM and 0.16 nM (Cygb-/-) for Ach and SNP, respectively). Using NO electrodes to measure the rate of NO consumption by SMCs and quantitative imunoblotting to estimate Cygb content in RSMCs-AR and Cygb knockdown RSMCs, we observed that 90% of NO consumption by RSMCs-AR is caused by the intracellular Cygb. Our results indicate that Cygb deficiency in the vascular wall of Cygb-/- mice greatly reduces the rate of NO metabolism and increases vascular NO concentration, resulting in vasodilation, increase in vessel lumen diameter, and decrease in SVR. These results demonstrate that Cygb regulates cardiac function and vessel tone by controlling the rate of vascular NO metabolism.
Abstract 16741: The Cost-Effectiveness of Apixaban versus Warfarin in Patients With Atrial Fibrillation: Insights From the ARISTOTLE Study Group
Authors: Cowper Patricia A , Sheng Shubin , Anstrom Kevin J , Stafford Judith A , Lopes Renato D , Davidson-Ray Linda , Wallentin Lars , Phatak Hemant M , Ansell Jack , Dorian Paul , Husted Steen , McMurray John J , Steg P. Gabriel , Alexander John H , Granger Christopher B , Mark Daniel B
Published: July 2021

Background:
In Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE), apixaban (vs. warfarin) significantly reduced stroke, death, and major bleeding in 18,201 patients with atrial fibrillation (AF). We assessed the cost-effectiveness of apixaban vs. warfarin from the perspective of the US health care system.

Methods:
Resource use (service dates, intensive care days, days on drug) was obtained from ARISTOTLE case report forms. Unit costs for components of hospital-based care of AF patients were estimated with generalized linear models using the national Premier database. Daily cost of anticoagulants was based on current acquisition cost (apixaban=$9.49; warfarin=$0.09) for 10 years, after which time apixaban was valued at projected costs of generic substitutes ($1.89). Physician services and anticoagulant monitoring were valued using Medicare fees. Within-trial costs were estimated using inverse probability weighting for differential follow-up. Survival was modeled with patient-level ARISTOTLE data using a two stage approach that combined a time-based Cox model for the within-trial period and an age-based Cox model for extrapolation. Uncertainty surrounding estimates of cost, life expectancy and cost/per life year gained was characterized with bootstraps and sensitivity analyses.

Results:
After 2 years, costs in the US cohort (n=3417) excluding study drug and monitoring averaged $306 less with apixaban than warfarin ($6257 vs. $6563). This difference was more than offset by higher apixaban anticoagulation costs ($6160 vs. $1181), resulting in an overall increase of $4673/patient. Over a lifetime, gains in life expectancy with apixaban (9.92 vs. 9.69; p<.001) were achieved at an additional cost of $17,564 ($29,447 vs. $11,883; p<.001), yielding a cost-effectiveness ratio (ICER) of $76,365/life year gained (85% likelihood of meeting $110,000 willingness to pay threshold). Cost-effectiveness was most sensitive to cost of apixaban.

Conclusions:
Reductions in mortality, stroke, and bleeding observed in ARISTOTLE translate to significant increases in life expectancy. At an estimated ICER of $76,365/life year gained, apixaban is a cost-effective alternative to warfarin.
Abstract 16748: Application and Utility of iPads in Pediatric Tele-Echocardiography
Authors: Colombo Jamie N , Seckeler Michael D , Barber Brent J , Krupinski Elizabeth , Weinstein Ronald S , Sisk Dave , Lax Daniela
Published: July 2021

The remote acquisition and interpretation of medical information (telemedicine) is an integral part of health care. Radiologic images (eg CT scans) can be accurately interpreted on tablet devices with high display resolution. To date, there have been no published studies on the use of iPads for interpretation of pediatric echocardiograms (echo).

OBJECTIVES:
We evaluated and compared the quality of echo images, diagnostic accuracy, and review time for pediatric echos using 3 different modalities: remote access on an iPad Air (iPad), remote access via computer (Remote), and direct access on computer Ethernet linked to the server (Direct).

METHODS:
Fifty archived pediatric echos were re-interpreted using the 3 modalities. Studies were analyzed blindly and independently by two pediatric cardiologists. Outcome measures included: time to review, diagnoses and discrepancies, image quality, sharpness, and jitter.

Diagnostic accuracy was assessed by comparing the study diagnoses with the original interpretation in patient’s chart. Discrepancies were rated as none, minor (one grade difference in severity of lesion, patient management not affected), or major (> one grade difference in severity of lesion, management affected). Remote desktop, Wi-Fi, Verizon, and Ethernet were used.

RESULTS:
Combining data from both reviewers, there were no major discrepancies, and 9.77% minor discrepancies. There were no significant differences in discrepancies as a function of device (iPad, Remote, Direct). Remote yielded significantly (p < 0.001) worse ratings for image quality, sharpness and jitter with iPad next and Direct yielding the best ratings (Table). Overall interpretation times were different (p < 0.0001) between viewing modes, (iPad longer vs remote vs direct).

CONCLUSIONS:
Remote echo review on iPads is possible, yields very good-to-excellent image quality, and allows for convenient, and reliable interpretation of pediatric echos.