tbuckley/cabot-search huggingface dataset:
Abstract 9899: Effect of Renal Sympathetic Denervation on Atrial Fibrillation
Authors: Qingyan Zhao, Zixuan Dai, Shengbo Yu, Xule Wang, Jinping Xiao, Congxin Huang
Journal: Circulation (2012)

Introduction - The fundamental mechanisms underlying atrial fibrillation (AF) have not been elucidated. Much attention has been devoted to assess the role of renin-angiotensin-aldosterone system (RAAS) in AF. Hypothesis - We assessed the hypothesis that renal sympathetic denervation had effect on atrial substrate remodeling and inhibited inducilibity of AF by preventing RAAS. Methods - Thirteen dogs were randomly divided into control group (7 dogs) and renal artery ablation (RAA) group (6 dogs). In control group, at first, AF was induced by anterior right ganglionated plexi (ARGP) stimulation. Then, rapid atrial pacing was performed for 7 hours and atrial effective refractory period (AERP) was measured. Subsequently, pacing was stopped and AF was induced again by atrial burst pacing. In RAA group, dogs were raised for 6 weeks after each renal artery ablation. After that, the procedure of pacing and electrophysiological measurement was nearly same as in the control group. Densities of autonomic nerve, Cx43 and ANP in pulmonary veins (PVs) and atrial tissues were measured and levels of TGF-β, Ang II and aldosterone in blood were studied. Results - There was a persistent decrease in AERP in both the two groups. The voltage in the sinus rate slowing response and the threshold for AF inducilibity increased during ARGP stimulation after renal sympathetic denervation (3.5±1.6V vs 1.6±0.3V, P=0.03; 5.1V±1.0V vs 2.1V±0.7V, P=0.03). Induced number of times and duration of AF was higher in control group than that in RAA group after rapid pacing. The plasma Ang II and aldosterone concentration increased in control group while decreased in RAA group after rapid pacing. Furthermore, levels of ANP in right atrium and densities of Cx43 in PVs were lower in RAA group than that in control group (ANP: 220.5±37.6 pg/ml vs 164.4±22.0 pg/ml, P=0.02; Cx43: 1.91 vs 0.92, P[[Unable to Display Character: ]]0.01). There was no significant difference in the densities of autonomic nerve and TGF-β between the two groups. Conclusions [[Unable to Display Character: ]]Renal sympathetic denervation results in atrial substrate remodeling and markedly decrease the inducilibity of AF by inhibiting activity of RAA.
Abstract 9907: Exposure to Oxidized LDL Converts Early Endothelial Progenitors Into Dendritic/Antigen Presenting Cells
Authors: Maria Cristina Vinci, Gianluca Polvani, Maurizio Pesce
Journal: Circulation (2012)

Background- “Early” endothelial progenitor cells (eEPCs) derive from circulating monocytes in the presence of angiogenic factors. While eEPCs number and ability to form angiogenic cell clusters in culture are reduced by risk conditions, changes in their function have not been yet reported. Specific aims and Results - In the present work, we assessed whether eEPCs are functionally converted into dendritic cells (DCs) by exposure to oxidized LDL (Ox-LDL), a lipoprotein abundant in atherosclerotic plaques. eEPCs were derived by culturing mononuclear cells (MNCs) purified from buffy-coats of healthy blood donors into EGM-2 medium for 7 days. They were then primed for 3 days with a cytokine cocktail containing GM-CSF and IL4 (10 ng/ml) in 10% FBS containing medium. To promote DCs maturation, primed eEPCs were cultured for 2 further days with OxLDL (100μg/ml) in 1% FBS-containing medium. In these conditions, eEPCs showed a typical DCs morphology, acquired DC-specific markers CD80 and CD83 (both &lt;1% vs. 88.1±3.5 and 30.0±5.8; C vs. Ox-LDL, P &lt;.05, t-test, n=5) and underwent a robust upregulation of CD86 (48.6±10.1 vs. 81.9±5.1, C vs. Ox-LDL; P &lt; .05, t-test, n=5), another DC-specific antigen. Mixed lymphocyte reaction (MLR) experiments revealed high levels of BrdU incorporation in CD3 + T-cells mixed in a 10:1 ratio with eEPCs-derived DCs. The percentage of BrdU + CD3 + cells was comparable to that of T-cells cocultured with control CD14 + cells-derived DCs (44.7±1.7 vs. 43.9±6.7, P &gt; .05, t-test, n=3). Analysis of 30 cytokines released in the culture supernatant revealed a substantially overlapping secretome profile in eEPCs-derived and CD14 + -derived DCs. In addition, they showed an angiogenic “fingerprint”, as witnessed by significantly ( P &lt; .05, t-test, n=3) higher expression of PDGF-BB (790±185 vs. 192±18, pg/ml), IL-8 (25.5±4.4 vs. 3.4±1.1 ng/ml), bFGF (3.5±0.7 vs. 1.0±0.43 pg/ml) and VEGF (535±19 vs 7.8±1.3 pg/ml), compared with CD14 + -derived DCs. Conclusions - The present data show an unexpected pro -inflammatory conversion of human eEPCs in response to a potent "auto-antigen" such as OxLDL. This unravels a possible specific immune modulator role of these cells in patients with risk factors, thus contributing to progression of coronary artery disease.
Abstract 9473: Prognostic Significance of Temporal Increase in QRS Duration and Morphological Development of QRS Complex
Authors: Tamiro Kawaguchi, Hideki Hayashi, Akashi Miyamoto, Tomohide Yoshino, Nobu Naiki, Atsushi Taniguchi, Yoshihisa Sugimoto, Makoto Itoh, Yoshitaka Murakami, Minoru Horie
Journal: Circulation (2012)

Background: QRS duration and morphology provide an opportunity to derive useful prognostic information. But, prognostic value of temporal increase in QRS duration in relation to the morphological development is yet to be determined. Methods: From among a database containing 359,737 ECGs, digital analysis of 12-lead ECG was performed to select patients whose QRS duration increased from &lt;110 ms to ≥120 ms over time. The long-term prognosis was assessed according to QRS morphology. Hospitalization for heart failure was the primary end point, and the cardiovascular composite events of hospitalization for heart failure, device implantation, or cardiovascular death were the secondary end point. Results: We enrolled 143 patients (100 males; mean age, 58.9±11.1 years). During follow-up (mean, 12.0±5.3 years), QRS duration increased by 46.4±13.8 ms (49.6%), resulting in the development of right bundle branch block (RBBB) in 99 (69.2%) patients and non-RBBB (i.e., left bundle branch block,RBBB with left anterior hemiblock, or intraventricular conduction disturbance) in 44 (30.8%) patients. During a mean follow-up of 16.6±5.3 years, 44(30.3%),15(10.3%), and 6(4.1%) patients resulted in heart failure hospitalization,device implantation, and cardiovascular death, respectively. Cox proportional -hazards model showed that 1) the temporal increment of QRS duration was significantly associated with the primary end point (HR 1.98; 95% CI 1.05-3.80; P=0.04 for QRS duration ≥4 ms/year versus &lt;4 ms/year) and the secondary end point (HR 2.79;95% CI 1.55-5.00; P=0.0001 for QRS duration ≥5 ms/year versus &lt;5 ms/year),2) QRS morphology was significantly associated with the primary end point (HR 3.02;95% CI 1.59-5.73; P=0.0001 for non-RBBB versus RBBB) and the secondary end point (HR 2.82; 95% CI 1.57-3.09; P=0.001 for non-RBBB versus RBBB), and 3) the temporal increment of QRS duration and the QRS morphology of non-RBBB potentiated each other, leading to the higher primary end point rate (HR 7.73; 95% CI 2.90-22.74;P&lt;0.0001) and the higher secondary end point rate (HR 8.25; 95% CI 3.39-19.85; P&lt;0.0001). Conclusion: Newly developed wide QRS complex excluding RBBB played a significant role in heart failure hospitalization and cardiovascular events.
Abstract 9504: Phosphodiesterase Modulation of Cardiomyopathy in Murine and Canine Models of Muscular Dystrophy Treated With Sildenafil and Tadalafil
Authors: Chonyang L Albert, Meg Sleeper, H. Lee Sweeney
Journal: Circulation (2012)

Patients with Duchenne muscular dystrophy (DMD) suffer from a myriad of musculoskeletal, respiratory, and cardiac symptoms.Cardiomyopathy is the second most common cause of death in DMD patients. The development of cardiomyopathy in these patients is often insidious, but untreated, many patients progress to overt heart failure. Current therapies used to treat the cardiomyopathy of DMD have been poorly studied since many of the same medications are used empirically from patients with congestive heart failure, despite the different underlying mechanical causes of heart failure in DMD patients. Using a well-established murine model of DMD, we treated mdx mice with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil or tadalafil) for a duration of 1 month and 8 months. Treatment response was measured by dobutamine stress echocardiography parameters, proteomic expression, and histologic studies. We saw an increase in protein kinase G (PKG) levels in the sildenafil and tadalafil treated mice hearts, afterboth 1 month and 8 months of treatment, which suggests that the PDE-5 inhibitors’ mechanism of action is active in the heart. This was accompanied by a low level of atrial natriuretic peptide in the treated hearts compared to the untreated hearts at 8 months. Our results suggest that PDE-5 inhibition modulates and down-regulates the pro-fibrotic and pro-inflammatory cascade in the dystrophic mdx heart through TGF beta and SMAD2/3 pathways in an ERK-independent manner. Moreover, in a canine study in which dogs affected with golden retriever muscular dystrophy were treated with one of these 2 drugs for one month, both PDE-5 inhibitors resulted in improved left ventricular strain as measured with cardiac magnetic resonance imaging. There are some differences between the effects of the two PDE-5 inhibitors which is likely attributable to differences in the potency and specificity of these two agents at PDE5 inhibition. Further studies will continue to elucidate the role of PDE-5 inhibitors in the treatment of the dilated cardiomyopathy of DMD. Supported by Parent Project Muscular Dystrophy
Abstract 9521: Ventricular Dyssynchrony at Baseline Predicts Transplant-Free Long-Term Survival in Patients Treated by Cardiac Resynchronization Therapy
Authors: Christian Prinz, Cinthia D Felice, Roman Lehmann, Maria Schwarz, Eva-Maria Prinz, Thomas Bitter, Júrgen Vogt, Dieter Horstkotte, Barbara Lamp, Lothar Faber
Journal: Circulation (2012)

Aim s: To analyze whether left ventricular dyssynchrony (LVD) at baseline is predictive for long-term outcome in heart failure (CHF) patients with left ventricular (LV) dysfunction and conduction disturbances treated with cardiac resynchronization therapy (CRT). Methods: In 504 consecutive individuals with CHF scheduled for implantation of a CRT device, LVD was assessed by tissue Doppler imaging (TDI), defined as an electromechanical delay (EMD) difference of ≥40 ms in 2 opposed left ventricular wall regions (septal vs. lateral, anterior vs. inferior). All-cause mortality, heart transplantation, or assist device implantation was defined as combined primary end point. Secondary end points were measures of reverse LV remodeling and of symptomatic improvement. Results: Mean follow-up was 68±36 months. LVD at baseline was present in 308 patients (61%). Of these, 24% reached the combined primary endpoint in contrast to 58% of patients without LVD (p&lt;0.001). Furthermore, patients with LVD showed pronounced improvement of all secondary end point parameters. An independent association was found between outcome, LVD (β-coefficient in the final model 0.4, p&lt;0.001), and gender (β-coefficient in the final model 0.2, p=0.002). Conclusions: LVD at baseline as assessed by TDI is associated with more pronounced reverse LV remodeling and seems to be a predictor for transplant-free long-term survival in CRT recipients.
Abstract 9471: Reverse Left Atrial Remodeling, Contraction and Compliance after Radiofrequency Catheter Ablation in Patients with Fixed Atrial Fibrillation
Authors: Sou Takenaka, Takashi Nakashima, Takahiro Gunji, Yukihiro Ozaki, Mitsuchika Nakamura, Masato Otsuka, Yukio Tsurumi
Journal: Circulation (2012)

Background &amp; Objectives: Restoration and maintenance of regular rhythm can be achieved by radiofrequency catheter ablation (RFCA) in patients with fixed atrial fibrillation (AF). However, it still remains undetermined whether this reversal is accompanied with amelioration of atrial function, which is associated with reduced risk of subsequent thromboembolic events. Methods: We studied 35 consecutive patients (age: 63±10 years) who had received RFCA for fixed AF. Serial changes in left atrial (LA) size and function were evaluated with echocardiography at baseline, 2 weeks, 3 months and 12 months after the procedure. Results: Thirty-one of 35 patients had recovered and maintained regular rhythm over 12 months following RFCA. Of these 31 patients, 7 patients required second or third sessions. LA size and biplane volume index significantly and progressively reduced over the time during 12-month follow-up periods (p&lt;0.001 and p&lt;0.001, respectively). Atrial contractibility, assessed by time-velocity integral of atrial wave and atrial filling fraction (p&lt;0.001 and p&lt;0.001, respectively), was improved after the procedure. In addition, atrial compliance, assessed by peak systolic strain of LA inferior and septal wall (p&lt;0.001 and p&lt;0.001, respectively), was also improved over the time. LA active contraction, assessed by LA late diastolic strain of LA inferior and septal wall, was appeared at 2 weeks after the procedure, and preserved during the follow-up periods. In addition, this improvement of atrial function was accompanied with that of left “ ventricular ” ejection fraction (p&lt;0.001). Conclusion: Restoration and maintenance of regular rhythm achieved by RFCA was associated with reduction in atrial size and volume as well as improvement in contraction and compliance. Our findings may encourage usefulness of RFCA for fixed AF, expecting risk of reduction of subsequent thlomboembolic events.
Abstract 9481: The Response of the Qt Interval and the T-wave Morphology to Sudden Tachycardia Provoked by Standing in Young Athletes
Authors: Andrea Menafoglio, Marcello Di Valentino, Augusto Gallino
Journal: Circulation (2012)

Background: the response of the QT interval to the sudden tachycardia provoked by standing can aid in the diagnosis of the long QT syndrome (LQTS). It is therefore important to know what is the normal response to this maneuver. The aim of this study was to characterise the response of the QT interval and the T-wave morphology following this provocation test in young healthy athletes. Methods: ECG was analysed as part of a prospective study about the impact of cardiovascular screening with ECG in young (14-35 years) athletes. ECG was performed after 5 minute of supine resting. Athletes without cardiac abnormalities, not taking drugs and with normal ECG (QTc for men &lt; 450 msec, for women &lt; 460 msec) were asked to stand up quickly with continuous ECG monitoring for 30”. Heart rate, QT, QTc (Bazett) and T-wave morphology [normal, biphasic, notched G1 (T2&gt;T1), notched G2 (T2&gt;&gt;T1)] were analysed at baseline and at maximal tachycardia. Results: ECG of 289 athletes was analysed (76 % men, mean age 18.4 ± 5.6 years). Baseline parameters were following: heart rate 69 ± 11/min, QT 378 ± 27 msec, QTc 401 ± 21 msec. After standing, the maximal heart rate was 101 ± 13/min. QT was 361 ± 28 msec (shortening by 17 ±11 msec). In 4 % of athletes QT increased by 10-20 msec. QTc was 466 ± 30 msec (lengthening of 65 ± 24 msec). In 12 % of athletes QTc was ≥ 500 msec. T-wave morphology during tachycardia were notched G2 in 6% of athletes. During tachycardia, 15 % of athletes displayed a QTc ≥ 500 msec or QT lengthening or notched G2 morphology of T waves. Conclusions: During sudden tachycardia, a significant proportion of healthy young athletes demonstrated QTc interval and changes of T-wave morphology in the magnitude observed in patients with the LQTS. Caution should be applied in interpreting these parameters in ECG tracing and Holter monitoring displaying sudden oscillations of heart rate in this population.
Abstract 9485: Translocation of miRNA from Mesenchymal Stem Cells Protects Cardiomyocytes against Ischemic Injury in vitro
Authors: Bin Yu, Zeeshan Pasha, Yueting Yang, Yigang Wang, Ronald W Millard, Muhammad Ashraf, Meifeng Xu
Journal: Circulation (2012)

microRNAs (miR) play an important role in cell survival. In this study, we investigated whether mesenchymal stem cells (MSC) mediated cardioprotection was associated with the regulation of miR as well as their targeted proteins. Methods: MSC were harvested from rat bone marrow. Cardiomyocytes (CM) were obtained from neonatal rat ventricles. In vitro cardioprotection by MSC was assayed by lactate dehydrogenase (LDH) release, Annexin-V staining, and DNA fragmentation following cells exposure to hypoxia for 48 hours. The expression of miR in MSC and CM was assessed by quantitative real-time PCR. miR targeted proteins were evaluated using a luciferase reporter assay and western blotting. To further investigate the role of miR, pre-miR precursor molecules were introduced into MSC using Lipofectamine 2000. Results: miR-221 was expressed 12-fold more in MSC than in CM (p&lt;0.05). The p53-upregulated modulator of apoptosis (PUMA), one of miR-221 targeted proteins, was lower in MSC than in CM (Fig. A). When co-cultured with CM in a dual-chamber system, MSC markedly reduced LDH release and the number of annoxin-V positive CM, and increased CM survival in hypoxic culture. Transfection of miR-221 into MSC significantly increased MSC mediated cardioprotection compared to MSC transfected with negative control miR. In CM co-cultures with MSC, miR-221 transferred from MSC to CM was confirmed by using fluorescence in situ hybridization (FISH) and immunostaining. Moreover, less PUMA protein was found in CM co-cultured with MSC than in CM cultured alone (Fig. B). Conclusions: Cardioprotective effects of MSC are putatively associated with intercellular translocation of specific miR and regulation of their targeted proteins such as PUMA in CM.
Abstract 9501: Gender Differences in Mortality Associated with Implantable Cardioverter-Defibrillator Infections
Authors: Muhammad R Sohail, Charles A Henrikson, Mary Jo Braid-Forbes, Kevin Forbes, Daniel J Lerner
Journal: Circulation (2012)

Introduction: Implantable cardioverter-defibrillators (ICDs) reduce morbidity and mortality in appropriately selected patients, but device-related infections are associated with significant mortality that can mitigate this benefit. Women are at higher risk for adverse events during ICD procedure admissions, but there are limited data on the mortality associated ICD infection in women. Objective: To compare the clinical characteristics and mortality rate of men and women who have an infection associated with ICD procedure. Methods: Retrospective cohort study of 64,903 Medicare fee-for-service patients admitted for ICD generator implantation, replacement, or revision from January 1, 2007 to December 31, 2007. Primary outcome measures were unadjusted and risk-adjusted longer-term mortality associated with ICD infection. Results: There were a total of 1,855 (2.89%) admissions with an ICD infection. Longer-term mortality (death during admission quarter and subsequent 4 quarters) was significantly higher with ICD infection than without (28.4% vs. 16.7%, P&lt;0.001). While longer-term mortality without ICD infection was significantly lower for women (hazard ratio=0.89 [95%CI 0.85-0.93]), longer-term mortality with ICD infection was significantly higher for women, compared to men (hazard ratio=1.20 [95%CI 1.03-1.41]. Multivariate regression analysis adjusting for age, gender, race/ethnicity and 28 comorbidities demonstrated a significant interaction between gender and ICD infection associated short and, and longer-term mortality. The risk-adjusted longer-term mortality with ICD infection was significantly higher for women compared to men (hazard ratio = 1.25 [95% CI 1.02-1.53]). Conclusions: Women have significantly higher rate of death, compared to men, following infection associated with ICD procedures. Further studies to determine the underlying causes of this disparity are warranted.
Abstract 9461: Circulating CD14 <sup>+</sup> CD16 <sup>+</sup> Monocyte Subsets as Biomarkers for Severity of Coronary Artery Disease in Patients With Stable Angina Pectoris
Authors: Yuichi Ozaki, Toshio Imanishi, Hirishi Aoki, Makoto Orii, Yasutsugu Shiono, Kunihiro Shimamura, Kohei Ishibashi, Takashi Tanimoto, Takashi Yamano, Yasushi Ino, Tomoyuki Yamaguchi, Takashi Kubo, Takashi Akasaka
Journal: Circulation (2012)

Background: Circulating monocytes can be divided into two subsets typically identified by the expression of CD14 and CD16. Although previous studies have shown that circulating monocytes contribute to the progression of coronary atherosclerotic lesions, the relationship between the severity of coronary artery disease (CAD) and the two distinct monocyte subsets has not previously been evaluated. We investigated the relationship between monocyte subsets and severity of CAD assessed by coronary angiography (CAG) in patients with stable angina pectoris (SAP). Methods: We enrolled 125 patients who underwent diagnostic CAG. Patients were divided into three groups; those without CAD, those with single-vessel disease (SVD), and those with multiple-vessel disease (MVD), according to diagnostic CAG findings. In addition, severity of CAD was evaluated by Gensini score. Two monocyte subsets (CD14 + CD16 - and CD14 + CD16 + ) were measured by flow cytometry. Results: Circulating CD14 + CD16 + monocytes were more frequently observed in patients with MVD (24.4 [18.5 to 29.8] %) than in those with SVD (vs. 12.8 [10.0 to 16.2] %, p&lt;0.001) or without CAD (vs. 8.9 [7.6 to 10.2] %, p&lt;0.001). High-sensitivity C-reactive protein and soluble CD40 ligand were not significantly different among the three groups. The proportion of CD14 + CD16 + monocytes was positively correlated with Gensini score (r=0.618, p&lt;0.001). Multivariate logistic regression analysis revealed that the preferential increase of CD14 + CD16 + monocytes was an independent predictor of MVD ((odds ratio: 1.475; 95% confidence interval: 1.273 to 1.708, p&lt;0.001). Conclusions: Our results revealed that the increased proportion of CD14 + CD16 + monocytes associated with severity of CAD in patients with SAP. Preferential increase in peripheral CD14 + CD16 + monocytes might closely relate to the pathophysiology of CAD progression.