tbuckley/cabot-search huggingface dataset:
Abstract 12860: Enhanced Expression and PKCδ-mediated Hyperphosphorylation Underlie the Proarrhythmic Increase in Na <sup>+</sup> -Ca <sup>2+</sup> Exchanger Activity in Patients With Chronic Atrial Fibrillation
Authors: Shokoufeh Ghezelbash, Cristina Espinosa Molina, Lina Badimon, Markus Kamler, Jordi Heijman, Dobromir Dobrev
Journal: Circulation (2016)

Background: Enhanced Na + -Ca 2+ exchanger type-1 (NCX1) function is implicated in triggering and maintaining atrial fibrillation (AF), but the molecular mechanisms of dysfunctional NCX in AF patients are unknown and were the main subject of this study. Methods: We used perforated patch-clamp technique to measure transient inward currents (I ti ) in atrial cardiomyocytes from sinus rhythm (Ctl) and chronic AF (cAF) patients. Co-immunoprecipitation (co-IP) and Western blot in atrial tissue lysates and membrane fractions and in-cell co-IP (DuoLink ® ) in human atrial cardiomyocytes were employed to identify regulatory partners of NCX1 and potential differences in their expression in Ctl versus cAF patients. Results: Frequency of spontaneous NCX-mediated I ti and amplitude of caffeine-induced peak I ti were higher in cAF than Ctl patients, with no change in SR Ca 2+ content (Fig A), validating the increased NCX function in cAF. Expression of the functional 160 kDa full-length NCX1 protein was strongly increased in cAF membrane fractions and was responsible for more than 90% of total membranous NCX1 (Fig B). Co-IPs followed by immunoblotting identified two protein kinase-C isoforms (PKCα and PKCδ), protein phosphatase-type-1α (PP1α), phospholemman (PLM) and AMP-activated protein kinase-α (AMPKα) as parts of the NCX1 complex, whereas calcineurin-Aβ (CnAβ) and protein phosphatase type-2A (PP2A) were absent (Fig C). Although expression levels of PKCδ were 50% lower in cAF lysates, attachment of PKCδ to NCX1 was 875% higher in cAF vs. Ctl (Fig D). The positive interaction between NCX1 and PKCδ in the plasma membrane of human atrial cardiomyocytes was shown using Duolink (red dots in Fig E), but was absent in fibroblasts. Conclusions: We identified PKCα, PKCδ, PP1α, PLM and AMPKα as part of the human atrial NCX1 protein complex. Increased membranous NCX1 protein and a stronger PKCδ-mediated NCX1 phosphorylation (Fig F) may underlie the proarrhythmic NCX dysfunction in cAF.
Abstract 12836: Usefulness of Serum Levels of Adipocytokines and Estimated Δ-5 Desaturase Activity as Biomarkers Predicting Hepatic Steatosis in Patients With Coronary Artery Disease on Statin Therapy
Authors: Morihiro Matsuda, Ritsu Tamura
Journal: Circulation (2016)

Introduction: Nonalcoholic fatty liver disease (NAFLD) is closely linked to obesity or type 2 diabetes mellitus, which are risk factors for coronary artery disease (CAD), and also includes non-alcoholic steatohepatitis that often develops life-threatening liver cirrhosis. Imaging tests for NAFLD are more sensitive than liver biochemistries, but expensive and cumbersome as screening tests. An establishment of biomarkers for NAFLD is important for prevention of fatal liver diseases in CAD patients. Hypothesis: Serum levels of adipocytokines/adipokines and estimated Δ-5 desaturase (D5D) activity may be useful biomarkers predicting NAFLD in patients with CAD. Methods: A cross-sectional study was conducted on 127 patients with CAD on statin therapy. Dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) in serum total lipids were measured by gas chromatography, and D5D activity was estimated by AA to DGLA ratio. Serum levels of adiponectin (Apn), leptin, resistin, visfatin and plasminogen activator inhibitor (PAI)-1, were determined by the respective ELISA. Abdominal computed tomography (CT) measured CT attenuation for liver (L-CTA) to estimate lipid content, and subjects with L-CTA &lt;50 HU were defined as NAFLD. Results: Simple linear regressions revealed that L-CTA was significantly correlated with serum levels of Apn, leptin and D5D activity (p &lt; 0.01, p = 0.03 and p &lt; 0.001, respectively), but not with those of resistin, visfatin or PAI-1. In multivariate logistic analysis among three factors consisting of a low Apn level: &lt; 6.8 μg/mL, a high leptin level: ≥ 3.4 ng/mL and a low D5D activity: ≤ 5.2 (the cutoff points were defined via ROC analysis against NAFLD), NAFLD was significantly associated with a high leptin level and a low D5D activity (adjusted odds ratio [OR]: 4.9, 95% confidence interval [CI]: 1.5-20) and OR: 15.6, 95%CI: 2.9-290, respectively), but weakly with a low Apn level (OR: 1.9, 95%CI: 0.6-6.5). A combination of these factors showed a strong association with NAFLD (area under the ROC curve: 0.84, p &lt; 0.0001). Conclusions: Serum levels of Apn, leptin and estimated D5D activity were significantly correlated with hepatic lipid content, and incrementally predict the presence of NAFLD in patients with CAD on statin therapy.
Abstract 13398: Impact of CREST on Carotid Artery Stenting and CEA Utilization in the Dallas/Fort Worth Area
Authors: Robert M McCurdy
Journal: Circulation (2015)

Introduction: Carotid endarterectomy (CEA) is a safe and effective way to reduce the ischemic stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. Following the North American Symptomatic Carotid Endarterectomy Trial and the Asymptomatic Carotid Atherosclerosis Study in the early 1990s, the number of CEAs performed annually surged. An alternative to this procedure is carotid angioplasty and stenting, which was introduced in 1994. In May 2010, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) compared the overall effectiveness of carotid artery stenting (CAS) versus CEA. CREST is currently considered the definitive study demonstrating the therapeutic equivalence of CEA and CAS. The goal of our study is to compare the incidence of CEA before and after the CREST study in the Dallas-Fort Worth (DFW) area. We hypothesize that the number of CAS procedures has increased since the CREST study. This is the first report to determine the effect of CREST on CAS utilization. Methods: Consecutive cases of intervention for carotid artery stenosis were reviewed before and after CREST using data from the DFW Hospital Council from 7/1/07-7/1/13. The primary endpoint of the study was the number of CEA and CAS performed during Pre-CREST (7/1/07-6/30/10) and Post-CREST (7/1/10-7/1/13). Results: A total of 12021 interventions on patients with carotid stenosis were identified. Pre-CREST there were 4575 CEA and 1060 CAS performed. Post-CREST there were 5250 CEA and 1136 CAS performed. The adjusted p-value comparing the likelihood of undergoing CAS between the two study periods was 0.305. Conclusions: In contrast to previous carotid treatment trials the CREST study has not impacted the utilization CAS in the DFW area. Possible reasons for this include the higher rate of stroke with CAS compared with CEA in CREST, the CMS restrictions on re-imbursement for CAS compared with CEA, limitations in the physician workforce performing CAS, and non-malleable referral patterns that favor the status quo for these two procedures.
Abstract 18714: Arterial Stiffness and Subclinical Inflammation in the General Population: The Asklepios Study
Authors: Julio Chirinos, Thierry Gillebert, Marc De Buyzere, Diana Chirinos, Patrick Segers, Dirk De Bacquer, Ernst Rietzschel
Journal: Circulation (2013)

Background: Chronic subclinical inflammation is a potentially treatable process that may contribute to arterial stiffening. However, previous studies assessing this relationship have used single inflammatory markers and have not assessed potential gender differences in this relationship. Methods: We assessed the relationship between arterial stiffness and inflammation among 2,430 middle-aged adults (51.8% female) enrolled in the population-based Asklepios study in Belgium. Using confirmatory factor analysis, we built a measurement model for inflammation, a latent factor contributing to shared variability in multiple acute-phase reactants (C-reactive protein, interleukin-6, white blood cell count and fibrinogen). We used structural equation modeling to characterize the relationship between inflammation and carotid-femoral pulse wave velocity (CF-PWV), a measure of large artery stiffness. Results: Our measurement model demonstrated adequate fit (Comparative fit index=0.996; root mean square error of approximation=0.029; standardized root mean square residual=0.012). In unadjusted models, inflammation was significantly related to arterial stiffness in both men (β=0.26; P &lt;0.0001) and women (β=0.21; P &lt;0.0001). After adjustment for age, current smoking, body mass index, mean arterial pressure, diabetes mellitus, triglycerides, LDL- and HDL-cholesterol, inflammation was independently related to arterial stiffness in men (β=0.13; P =0.007) but not in women (β=0.017; P =0.7585). This was true for both pre- and post-menopausal women and regardless of oral contraceptive use. Conclusions: Important gender differences exist in the association between inflammation and large artery stiffness. Inflammation is independently associated with large artery stiffness in middle age in men, but not in women.
Abstract 18733: Evaluation of a Super-Sensitivity Cardiac Troponin I Assay for Diagnosing Non ST-Segment Elevation Myocardial Infarction
Authors: Niklas Schofer, Fabian Brunner, Michael Schlueter, Ojeda Francisco, Tanja Zeller, Stephan Baldus, Christoph Bickel, Karl Lackner, Thomas MÜnzel, Till Keller, Stefan Blankenberg, Britta Goldmann
Journal: Circulation (2013)

Introduction: Acute myocardial infarction (AMI) is defined by cardiac troponin (cTn) elevation. According to current guidelines the diagnosis of AMI requires a rise or fall of cTn (delta) with at least one value above the diagnostic cutoff, i.e. the 99th percentile (P99) of a reference population. Lately, cTn assays with high analytical precision have become available. Use of high-sensitivity cTn showed improved diagnostic accuracy with absolute deltas being superior compared to relative deltas. The diagnostic utility of super-sensitivity cTn assays, that are capable of cTn detection in &gt;95% of the general population, has not been sufficiently elucidated. Hypothesis: We assessed the hypothesis that a super-sensitivity cTnI assay combined with a diagnostic algorithm that incorporates an absolute delta provides sufficient detection of non ST-segment elevation myocardial infarction (NSTEMI). Methods: The study comprised 1566 patients with new-onset chest pain (246 with NSTEMI, 222 with unstable angina pectoris, 1097 with non-coronary chest pain). On admission and 3 hours later cTnI was measured by a super-sensitivity assay (Erenna® cTnI immunoassay, Singulex, Inc., Alameda, CA, USA). Diagnostic performance was assessed via a two-step algorithm: First, 3h-cTnI had to exceed a certain cutoff concentration (P99 as well as arbitrarily chosen cTnI concentrations) and, when this criterion was fulfilled, secondly, an absolute delta criterion was applied. Results: A 3h-cTnI cutoff concentration of 40 ng/l provided a negative predictive value of 99.1% and a sensitivity of 95.5% indicating confident rule-out of NSTEMI, when this criterion was not fulfilled (n=1256). For patients with 3h-cTnI &gt;40 ng/l (n=310) an absolute delta of ≥50 ng/l resulted in a positive predictive value, i.e. diagnostic certainty for ruling in NSTEMI, of 84.2%. Application of this algorithm to the overall study population yielded a negative predictive value of 96.1%, positive predictive value of 84.2%, sensitivity of 81.8% and a specificity of 97.1%. Conclusion: In conclusion, the super-sensitivity cTnI assay showed a clinically acceptable performance in diagnosing NSTEMI by use of an algorithm that is P99-independent and includes an absolute delta.
Abstract 18728: Patterns of Antiplatelet Use in Patients With Stable Atherosclerosis: Insights From the Tra 2°P-timi 50 Trial
Authors: Giulia Magnani, David A Morrow, Benjamin M Scirica, Marc S Sabatine, Sabina A Murphy, Marc P Bonaca
Journal: Circulation (2013)

Background: Oral antiplatelet (AP) therapy is broadly supported as preventive therapy for patients with established atherosclerotic vascular disease; however, emerging evidence for specific agents show heterogeneous outcomes by symptomatic vascular bed. Patterns of use may vary by symptomatic territory. Methods: We examined patterns of AP use at baseline in 26,449 stable outpatients randomized in the TRA 2° P-TIMI 50 trial including 17,779 with history of myocardial infarction (MI), 4,883 with history of ischemic stroke (CVD), and 3,787 with peripheral artery disease (PAD). Results: Overall 24,734 (94%) of patients were on aspirin (ASA). In the MI cohort 17448 (98%) were treated with aspirin and the majority (76%) were treated with dual AP therapy with aspirin and a thienopyridine (DAPT) (fig). Within the CVD group overall AP use was frequent (98%) with the majority on monotherapy (70%) with either ASA (54%) or thienopyrdine (16%) (fig). Of those on multi-agent therapy (28%) the combination of ASA and dipyridamole was more frequent then DAPT (19% vs 7%). Within the PAD group AP therapy was also frequent (97%) with a similar proportion on monotherapy (69%) with either ASA (60%) or thienopyridine (9%). In those on multi-agent therapy, DAPT was the most frequent (28%) followed by the combination of ASA and cilostazol (11%) (fig). Conclusions: Although atherosclerosis is a systemic disease and data supporting the use of antiplatelet therapy has often evaluated benefit broadly, in practice the distribution of agent and the intensity vary by symptomatic vascular territory. These patterns reflect emerging heterogeneity in outcomes trials evaluating specific therapies by symptomatic bed and support further evaluation of the risks and benefits in these specific populations.
Abstract 18737: Prevalence and Outcome of Patients With Idiopathic QT Prolongation Identified Through an Institution-Wide QT-Alert System
Authors: Johan M Bos, Kristina H Haugaa, Robert F Tarrell, Bruce W Morlan, Pedro J Caraballo, Michael J Ackerman
Journal: Circulation (2013)

Background: Since QT prolongation is a risk factor for sudden death, stroke, and all-cause mortality, we developed an electronic, institution-wide QT alert system to identify patients with significant QT prolongation (i.e. QTc≥500 ms if QRS &lt;120 ms). These patients encountered a significant increased mortality within 1 year, and nearly 40% of patients with ≥4 QTc inciting factors have died. Herein, we examined the patients with ≤1 identifiable QTc inciting factor. Methods: Between November 2010 and June 2011, 53,732 patients underwent ECG-evaluation, 1,145 QT-alerts (2.1%) were triggered, and 470 of the QT-alerted patients had ECG-isolated QT prolongation. Clinical, laboratory, and therapeutic information were collected. Excluding female gender and bradycardia, other potential QT inciting factors (drugs, electrolyte disturbances, and co-morbidities) were synthesized into a pro-QT score and patients with a score of ≤1 were compared to patients with a pro-QT score &gt;1. Results: About one-third (N=150, 59% female) of this QT-alerted cohort had a pro-QT score of ≤1 including 42 patients with an established diagnosis of congenital long QT syndrome (LQTS). Excluding LQTS patients, the remaining 108 patients (60 female, age 59±25 years) were significantly more likely to have a QT prolonging cardiovascular co-morbidity (44%) than those with a QT-score &gt;1 (29%; p=0.006). However, mortality was similar between those with a QT-score ≤1 (19%) and those with a QT-score &gt;1 (27%, p=0.09). Fourteen patients (9 female; age 64±22 years; QTc 507±14 ms) had no discernible QT inciting factors (i.e. pro-QT score=0) including 6 patients with previously documented QT prolongation. Conclusions: Only a minority of patients with ECG-isolated QT-prolongation (~3%) had no discernible QT-inciting factors other than female gender in 9. Careful scrutiny of these patients with seemingly idiopathic QT prolongation may identify novel QT provoking conditions. Alternatively, considering that 14 of 53,732 patients (1 in 3888) activated the alert system without obvious QT inciting factors and that congenital LQTS has an estimated prevalence of 1 in 2000, it is possible that this universal QT alert system has caught patients with yet to be diagnosed LQTS.
Abstract 18707: The Baseline Image Intensity Ratio, a Surrogate for Pre-existing Left Atrial Fibrosis, is Associated With Recurrence of Atrial Fibrillation Following Pulmonary Vein Isolation
Authors: Jane Dewire, Irfan Khurram, Vadim Zipunnikov, Roy Beinart, David Spragg, Joseph Marine, Ronald Berger, Henry Halperin, Stefan Zimmerman, Hugh Calkins, Saman Nazarian
Journal: Circulation (2013)

Introduction: Catheter ablation of AF is beneficial for many patients, but it is associated with a high AF recurrence rate that previously has been correlated with left atrial (LA) fibrosis on late gadolinium enhanced (LGE) MRI. We sought to test the association of LA fibrosis with recurrent post-ablation AF, using the image intensity ratio (IIR), a novel and standardized measure for quantification and inter-patient comparisons of LA fibrosis. Methods: Fifty consecutive AF patients (59.2±9.0 years, 74% men, 44% persistent AF) were enrolled and underwent LGE-MRI prior to initial AF ablation procedure. The local IIR was defined as the LA myocardial signal intensity of each sector in axial plane divided by the mean LA blood pool image intensity. The cohort was divided into four groups using mean IIR thresholds of 0.95. The mean follow-up was 9.0±4.6 months, and recurrences were documented with routine follow-up and symptom-prompted electrocardiography as well as phone calls. Results: Of 50 total patients, 11 (22%) experienced AF recurrence (4/28 paroxysmal AF (14.3%), and 7/ 22 persistent AF (31.8%)). The baseline IIR was higher in paroxysmal AF patients that experienced recurrence (1.0±0.18 vs. 0.81±0.08, p=0.001), but was similar in persistent AF patients with or without recurrence (0.84±0.12 vs. 0.88±0.14, p=NS). The Figure illustrates Kaplan-Meier survival analyses based upon baseline IIR derived patient groups. Conclusions: Baseline left atrial fibrosis is strongly associated with AF recurrence in patients with paroxysmal AF, but is unassociated with outcomes in patients with persistent AF.
Abstract 18709: Older Former Smokers with &lt;32 Pack-Years of Prior Smoking and &lt;15 Years of Abstinence Have Lower Risk of Incident Heart Failure and Cardiovascular Mortality But Not of All-Cause Mortality: Findings From a Prospective Population Study
Authors: Amiya A Ahmed, Charity J Morgan, Gregg C Fonarow, Sumanth Prabhu, Vera Bittner, Kanan Patel, Prakash Deedwania, Gerasimos Filippatos, Stefan D Anker, Richard M Allman, Wilbert Aronow, Ali Ahmed
Journal: Circulation (2013)

Background: According to the US Surgeon General, the cardiovascular (CV) risk of former-smokers may become similar to that of never-smokers after 15 years of abstinence. We have previously demonstrated that former heavy smokers (≥32 pack-years) may still be at increased risk of incident heart failure (HF) despite &gt;15 years of abstinence (Circulation 2010; 122: A17788 and Circulation 2011; 124: A18263 ). In the current study, we examined the risk of incident HF and mortality in former light and heavy smokers who quit ≤15 years ago. Methods: Of the 3410 community-dwelling adults, age ≥65 yrs, free of baseline HF, in the Cardiovascular Health Study, 2557 were never-smokers and 853 were former-smokers who quit ≤15 (median, 8) years ago. Heavy smoking was defined as ≥32 PY of smoking. Cox regression models were adjusted for age, sex and race only as other baseline confounders were likely affected by prior smoking and acted as mediators. Results: Unadjusted and age-sex-race adjusted associations of former smoking with outcomes during 13 years of follow-up are displayed in the Table . Conclusions: We found no evidence of higher risk for incident HF and CV mortality among former light smokers who quit 15 or fewer (median, 8) years ago when compared with never smokers, although the risk for all-cause and non-CV mortality was higher. Former heavy smokers had significantly higher risk for all outcomes.
Abstract 12833: Can We Predict the Probability of ROSC by the Change in Cerebral rSO <sub>2</sub> Value?
Authors: Ryosuke Takegawa, Tadahiko Shiozaki, Tomoya Hirose, Nobuto Mori, Tomohiko Sakai, Mitsuo Ohnishi, Takeshi Shimazu
Journal: Circulation (2016)

Introduction: There is no consensus on how long we should continue cardiopulmonary resuscitation (CPR). When determining this, it is important to assess the probability of return of spontaneous circulation (ROSC). We have been evaluating the usefulness of regional cerebral oxygen saturation (rSO 2 ) during resuscitation since 2007. At the 2014 AHA congress, we reported that the probability of ROSC would be low if the rSO 2 was less than 55%. In the present study, we focused on the relation between the rate of rSO 2 increase and the occurrence of ROSC from the time of hospital arrival. Methods: This was a retrospective study of out-of-hospital cardiac arrest (OHCA) patients with successful measurement of rSO 2 from December 2012 to December 2015. During CPR, rSO 2 was recorded continuously from the forehead of the patients by a TOS-OR (TOSTEC, Japan). CPR for patients with OHCA was performed according to the 2010 JRC guidelines. Results: Ninety patients with OHCA (59 men, 31 women; mean age 74.8 years) were included in this study, of whom 35 had ROSC. The baseline value of rSO 2 was determined as the mean value of the initial 1 minute of rSO 2 . The rate of change in rSO 2 was calculated as the ratio of the maximum rSO 2 value at 4, 8, 12, 16, and 20 minutes to the baseline value. Receiver operating characteristic curve analysis showed that the area under the curve was 0.72 with the cut-off value set at 14.5%. The specificity and sensitivity of ROSC were 68.6% and 68.6%, respectively. Although this cut-off value is not a criterion for stopping CPR, the probability of ROSC would be low if the rate of change in rSO 2 is less than 14.5%. Conclusions: The rate of change in the rSO 2 value during CPR might be a new index for the prediction of ROSC.