bluuebunny/crossref_metadata_2025_split huggingface dataset:
The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: Roles of white blood cell count and body weight
Authors: El Ghannudi Soraya , Hess Sebastien , Reydel Antje , Crimizade Ulun , Jesel Laurence , Radulescu Bogdan , Wiesel Marie L. , Gachet Christian , Ohlmann Patrick , Morel Olivier 
Published: June 2012

SummaryIt was the study objective to determine whether glycaemic control affects the extent of platelet inhibition by thienopyridines as assessed by vasodilator-stimulated phosphoprotein flow cytometry (VASP-FCT) in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) during acute coronary syndrome (ACS). Although the proportion of high on-treatment residual platelet reactivity is higher in DM, the contributions of glycaemic control and other factors associated with DM, such as excess body weight and inflammation, to this impaired platelet inhibition by thienopyridines have not yet been fully characterised. In this study, the extent of P2Y12 ADP receptor pathway inhibition was evaluated by the VASP-FCT. Platelet activation was expressed as the platelet reactivity index (PRI). Low response to clopidogrel (LR) was defined as a PRI of >61%. Four hundred forty-five consecutive ACS patients (DM = 160, NDM = 285) were enrolled. The proportion of LR was higher in DM patients (50 vs. 37.5%). In DM, PRI was not correlated with glycosylated haemoglobin (HbA1c) or glycaemia. In a univariate analysis, LR was associated with age, male sex, overweight, and white blood cell count (WBC). In a multivariate analysis, WBC >10,000 and body weight >80 kg were the sole independent predictors of LR to clopidogrel (hazard ratio (HR) 3.02 [1.36–6.68], p=0.006 and HR 2.47 [1.14–5.35], p = 0.021, respectively). Conversely, in non-DM patients, ST-elevation myocardial infarction was the sole independent predictor of LR. In conclusion, in ACS DM patients undergoing PCI, the extent of P2Y12 inhibition by clopidogrel is not related to glycaemic control but is related to body weight and inflammatory status as assessed by the WBC.
An indirect comparison of dabigatran, rivaroxaban and apixaban for atrial fibrillation
Authors: Ansell Jack , Mantha Simon 
Published: June 2012

SummaryNew oral anticoagulant drugs are emerging as alternatives to warfarin for the prevention of stroke in patients with non-valvular atrial fibrillation. Two agents are direct factor Xa inhibitors (rivaroxaban and apixaban), and the third is a direct thrombin inhibitor (dabigatran). They have been separately compared to warfarin in large randomised trials. Our objective was to indirectly compare the three agents to each other for major efficacy and safety outcomes. Studies were assessed for comparability and the odds ratios of selected outcomes for each anticoagulant versus one another were estimated indirectly. The three cohorts differed significantly in terms of CHADS2 score and the number of individuals with a past history of stroke, transient ischemic attack or systemic embolism. The estimated odds ratio of stroke or systemic embolism was 1.35 for rivaroxaban vs dabigatran 150 mg (p=0.04), 0.97 for rivaroxaban versus dabigatran 110 mg (p=0.81), 1.22 for apixaban versus dabigatran 150 mg (p=0.18), 0.88 for apixaban versus dabigatran 110 mg (p=0.34) and 0.90 for apixaban versus rivaroxaban (p=0.43). The estimated odds ratio of major bleeding was 1.10 for rivaroxaban versus dabigatran 150 mg (p=0.36), 1.28 for rivaroxaban versus dabigatran 110 mg (p=0.02), 0.74 for apixaban versus dabigatran 150 mg (p=0.004), 0.87 for apixaban versus dabigatran 110 mg (p=0.17) and 0.68 for apixaban versus rivaroxaban (p<0.001). In conclusion, the available data indicate no significant difference in efficacy between dabigatran 150 mg and apixaban for the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. It appears however that apixaban is associated with less major bleeding than dabigatran 150 mg or rivaroxaban and that rivaroxaban is less effective than dabigatran 150 mg in preventing stroke or systemic embolism. Such an indirect comparison should be used only to generate hypotheses which need to be tested in a dedicated randomised trial comparing the three drugs directly.
An innovative flow cytometric approach for small-size platelet microparticles: Influence of calcium
Authors: Montoro-García Silvia , Shantsila Eduard , Orenes-Piñero Esteban , Lozano María , Lip Gregory Y. H. 
Published: June 2012

SummaryMicroparticles (MPs) are small submicron membrane-derived vesicles shed from a variety of cells and they have been implicated in different disorders. Accordingly, understanding of physiological characteristics of MPs and improvement of methods of their quantification are important for further advance in the field. Although flow cytometry is the most widely applied technique for MP analysis, it is limited by lack of adequate standardisation. Annexin V (AnV), which binds surface phos-phatidylserine (PS) with high affinity, has been long regarded as a marker of MPs, but AnV binding is Ca2+-dependent and it is unclear how [Ca2+] concentrations could affect AnV binding to MPs and its enumeration. MPs from citrated and heparinised plasma were labelled with AnV, anti-CD42b and quantified using an Apogee A50 flow cytometer. The small-size MP gate was defined with the use of size beads (from 0.1 to 0.5 μm) and confirmed with an in vitro assessment of platelet stimulation. Biotinylated anti-CD42b antibodies were then bound to streptavidin conjugated with different fluorochromes, leading to an amplified signal of platelet MPs (PMPs). Moderate increase of [Ca2+] concentrations in the annexin V staining buffer allows initial plasma recalcification and more accurate MP quantification in citrated plasma. Thrombin stimulation of platelet-free plasma containing only MPs did not produce any changes in the concentration of AnV+ MPs, but decreased the anti-CD42b binding. The results also indicate that prolonged storage and thrombin induce the release of AnV+ MPs whereas PS exposure in pre-existent MPs is not affected by thrombin. In conclusion, we present a sensitive protocol for the analysis of circulating and in vitro induced small-size PMPs that might contribute to future cardiovascular and clinical research.Note: The editorial process for this article was fully handled by Prof. Christian Weber, Editor-in-Chief.
Predictive Value of Beat-to-Beat QT Variability Index Across the Continuum of Left Ventricular Dysfunction
Authors: Tereshchenko Larisa G. , Cygankiewicz Iwona , McNitt Scott , Vazquez Rafael , Bayes-Genis Antoni , Han Lichy , Sur Sanjoli , Couderc Jean-Philippe , Berger Ronald D. , de Luna Antoni Bayes , Zareba Wojciech 
Published: June 2012

Background—
The goal of the present study was to determine the predictive value of beat-to-beat QT variability in heart failure patients across the continuum of left ventricular dysfunction.

Methods and Results—

Beat-to-beat QT variability index (QTVI), log-transformed heart rate variance, normalized QT variance, and coherence between heart rate variability and QT variability have been measured at rest during sinus rhythm in 533 participants of the Muerte Subita en Insuficiencia Cardiaca heart failure study (mean age, 63.1±11.7; men, 70.6%; left ventricular ejection fraction >35% in 254 [48%]) and in 181 healthy participants from the Intercity Digital Electrocardiogram Alliance database. During a median of 3.7 years of follow-up, 116 patients died, 52 from sudden cardiac death (SCD). In multivariate competing risk analyses, the highest QTVI quartile was associated with cardiovascular death (subhazard ratio, 1.67 [95% CI, 1.14–2.47];
P
=0.009) and, in particular, with non-SCD (subhazard ratio, 2.91 [1.69–5.01];
P
<0.001). Elevated QTVI separated 97.5% of healthy individuals from subjects at risk for cardiovascular (subhazard ratio, 1.57 [1.04–2.35];
P
=0.031) and non-SCD in multivariate competing risk model (subhazard ratio, 2.58 [1.13–3.78];
P
=0.001). No interaction between QTVI and left ventricular ejection fraction was found. QTVI predicted neither noncardiac death (
P
=0.546) nor SCD (
P
=0.945). Decreased heart rate variability rather than increased QT variability was the reason for increased QTVI in the present study.

Conclusions—
Increased QTVI because of depressed heart rate variability predicts cardiovascular mortality and non-SCD but neither SCD nor extracardiac mortality in heart failure across the continuum of left ventricular dysfunction. Abnormally augmented QTVI separates 97.5% of healthy individuals from heart failure patients at risk.
Differential Effects of Adenosine on Pulmonary Vein Ectopy After Pulmonary Vein Isolation
Authors: Cheung Jim W. , Ip James E. , Chung Jeffrey H. , Markowitz Steven M. , Liu Christopher F. , Thomas George , Lee Joseph M. , Lessner Seth J. , Lerman Bruce B. 
Published: June 2012

Background—
The mechanism of pulmonary vein (PV) triggers of atrial fibrillation remains unclear. We performed adenosine (ADO) testing after PV isolation to characterize spontaneous dissociated PV rhythm and ADO-induced PV ectopy.

Methods and Results—
Seventy-four patients (61 men; age, 61±10 years) undergoing PV isolation for atrial fibrillation were studied. For each isolated PV, dissociated ectopy was recorded and ADO was administered. After isolation of 270 PVs, 50 PVs with dissociated ectopy were identified. In 42 PVs exhibiting PV rhythm, ADO resulted in PV rhythm suppression in 35 (83%) PVs, with all occurring during ADO-induced bradycardia, and in PV rhythm acceleration in 13 (31%) PVs, with all occurring after resolution of ADO-induced bradycardia. In 11 PVs, both ADO-induced PV rhythm acceleration and suppression were seen. Among 220 electrically silent PVs, ADO induced PV ectopy in 28 (13%) veins. The timing of ADO-induced PV ectopy with respect to ADO effects on heart rate varied. ADO induced PV ectopy during the early phase of ADO effect only in 12 PVs, during the late phase of ADO effect only in 8 PVs, and during both early and late phases of ADO effect in 8 PVs.

Conclusions—
The mechanism of spontaneous PV rhythm after isolation is likely automaticity, given the close association of ADO effects on PV rhythm with its chronotropic and dromotropic effects. However, ADO can induce PV ectopy in electrically silent PVs in a manner not closely tied to its effects on heart rate and may be because of the activation of autonomic triggers.
Ascending Aortic and Main Pulmonary Artery Areas Derived From Cardiovascular Magnetic Resonance as Reference Values for Normal Subjects and Repaired Tetralogy of Fallot
Authors: Kutty Shelby , Kuehne Titus , Gribben Paul , Reed Eric , Li Ling , Danford David A. , Beerbaum Philipp B.J. , Sarikouch Samir 
Published: June 2012

Background—
Cardiac magnetic resonance (CMR) imaging is an important clinical tool for serial follow-up of patients with congenital heart disease, but normative data for great vessel dimensions in pediatric subjects are scarce. We investigated the ascending aortic (AO) and main pulmonary artery dimensions in normal children and young adults in comparison with a cohort of patients with repaired tetralogy of Fallot (TOF).

Methods and Results—

Subjects were prospectively enrolled for cardiac magnetic resonance after a standardized protocol in 14 participating centers of the German Competence Network for Congenital Heart Defects. All studies were performed in 1.5-T scanners and used single-slice multiphase acquisitions steady-state free precession and velocity-encoded cine. AO and main pulmonary artery areas were measured. The cohort consisted of 483 subjects: 105 normal controls (55 men; 50 women; and median age, 14 years) and 378 patients with repaired TOF (210 men; 168 women; and median age, 16 years). Among TOF, 35 (9%) had pulmonary atresia, 98 (26%) had a palliative procedure before repair, the mean age at repair was 2.9 years, and 82 (23%) used a transannular patch repair. Great vessel areas correlated well with body surface area and age in controls and reference Z-score values were derived. Z scores for ascending AO areas were larger in TOF compared with controls (mean Z score =1.95,
P
=0.001). In TOF, pulmonary atresia (
P
=0.003), male sex (
P
=0.01) and previous palliations (
P
=0.046) were associated with larger AO areas. Main pulmonary artery area Z scores in surgically modified TOF were smaller on an average than controls (mean Z score =−0.293
P
=0.001) but not small to the same extent as the AO was large.

Conclusions—
This study provides cardiac magnetic resonance reference Z scores for great vessel areas in normal children and adolescents in comparison with a large contemporary cohort of repaired TOF. Male sex, pulmonary atresia, and previous palliations emerged as predictors for larger AO dimensions in TOF.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00266188.
Bicuspid Aortic Valve Is Associated With Altered Wall Shear Stress in the Ascending Aorta
Authors: Barker Alex J. , Markl Michael , Bürk Jonas , Lorenz Ramona , Bock Jelena , Bauer Simon , Schulz-Menger Jeanette , von Knobelsdorff-Brenkenhoff Florian 
Published: June 2012

Background—
Hemodynamics may play a role contributing to the progression of bicuspid aortic valve (BAV) aortopathy. This study measured the impact of BAV on the distribution of regional aortic wall shear stress (WSS) compared with control cohorts.

Methods and Results—

Local WSS distribution was measured in the thoracic aorta of 60 subjects using 4-dimensional (4D) flow-sensitive magnetic resonance imaging. WSS analysis included 15 BAV patients: 12 with fusion of the right-left coronary cusp (6 stenotic) and 3 with fusion of the right and noncoronary cusp. The right-left BAV cohort was compared with healthy subjects (n=15), age-appropriate subjects (n=15), and age-/aorta size–controlled subjects (n=15). Compared with the age-appropriate and age-/aorta size–matched controls, WSS patterns in the right-left BAV ascending aorta were significantly elevated, independent of stenosis severity (peak WSS=0.9±0.3 N/m
2
compared with 0.4±0.3 N/m
2
in age-/aorta size–controlled subjects;
P
<0.001). Time-resolved (cine) 2D images of the bicuspid valves were coregistered with 4D flow data, directly linking cusp fusion pattern to a distinct ascending aortic flow jet pattern. The observation of right-anterior ascending aorta wall/jet impingement in right-left BAV patients corresponded to regions with statistically elevated WSS. Alternative jetting patterns were observed in the right and noncoronary cusp fusion patients.

Conclusions—
The results of this study demonstrate that bicuspid valves induced significantly altered ascending aorta hemodynamics compared with age- and size-matched controls with tricuspid valves. Specifically, the expression of increased and asymmetric WSS at the aorta wall was related to ascending aortic flow jet patterns, which were influenced by the BAV fusion pattern.
Left Ventricular Remodeling and Improvement in Diastolic Function After Balloon Aortic Valvuloplasty for Congenital Aortic Stenosis
Authors: Friedman Kevin G. , McElhinney Doff B. , Colan Steven D. , Porras Diego , Powell Andrew J. , Lock James E. , Brown David W. 
Published: June 2012

Background—
In congenital aortic stenosis, chronic pressure load has detrimental effects on left ventricular (LV) systolic and diastolic function. Reduction in LV pressure load with balloon aortic valvuloplasty (BAVP) may improve diastolic function.

Methods and Results—

Echocardiographic and catheterization data for 25 consecutive patients undergoing BAVP for congenital aortic stenosis were retrospectively analyzed. Median age at BAVP was 11.5 years (3.2–40.1). LV end-diastolic pressure was elevated (≥15 mm Hg) in 72% of patients, with a median of 17 mm Hg (range, 9–24). With BAVP, median aortic stenosis gradient was reduced from 63 mm Hg (range, 44–105) to 30 mm Hg (range, 10–43). Aortic regurgitation increased from trivial (none to mild) to mild (trivial to moderate). Pre-BAVP early diastolic mitral inflow velocity/tissue Doppler early diastolic velocity (E/E´) correlated with LV end-diastolic pressure (
r
=0.52,
P
=0.007). On follow-up echocardiography (median, 11 months after BAVP), aortic stenosis gradient was lower (
P
<0.001) and degree of AR was higher (
P
=0.01) compared with pre-BAVP echocardiograms. LV end-diastolic volume
z
-score increased (
P
=0.02), LV mass was unchanged, and LV mass:volume decreased (
P
=0.002). Mitral annular and septal E´ (
P
<0.001) were higher and E/E´ was lower after dilation (10.8 versus 14.2,
P
<0.001). Lower pre-BAVP E/E´ and lower pre-BAVP LV mass
z
-score were associated with lower post-BAVP E/E.

Conclusion—

After BAVP, LV remodeling characterized by an increase in EDV and decrease in LV mass:volume occurs and echocardiographic measures of diastolic function and LV end-diastolic pressure improve in most patients. Risk factors for persistent diastolic dysfunction include higher pre-BAVP LV mass
z
-score and worse pre-BAVP diastolic function.
Adult Bone Marrow Cell Therapy Improves Survival and Induces Long-Term Improvement in Cardiac Parameters
Authors: Jeevanantham Vinodh , Butler Matthew , Saad Andre , Abdel-Latif Ahmed , Zuba-Surma Ewa K. , Dawn Buddhadeb 
Published: June 2012

Background—
Despite rapid clinical translation and widespread enthusiasm, the therapeutic benefits of adult bone marrow cell (BMC) transplantation in patients with ischemic heart disease continue to remain controversial. A synthesis of the available data is critical to appreciate and underscore the true impact of this promising approach.

Methods and Results—

A total of 50 studies (enrolling 2625 patients) identified by database searches through January 2012 were included. Weighted mean differences for changes in left ventricular (LV) ejection fraction, infarct size, LV end-systolic volume, and LV end-diastolic volume were estimated with random-effects meta-analysis. Compared with control subjects, BMC-treated patients exhibited greater LV ejection fraction (3.96%; 95% confidence interval, 2.90–5.02;
P
<0.00001) and smaller infarct size (−4.03%, 95% confidence interval, −5.47 to −2.59;
P
<0.00001), LV end-systolic volume (−8.91 mL; 95% confidence interval, −11.57 to −6.25;
P
<0.00001), and LV end-diastolic volume (−5.23 mL; 95% confidence interval, −7.60 to −2.86;
P
<0.0001). These benefits were noted regardless of the study design (randomized controlled study versus cohort study) and the type of ischemic heart disease (acute myocardial infarction versus chronic ischemic heart disease) and persisted during long-term follow-up. Importantly, all-cause mortality, cardiac mortality, and the incidence of recurrent myocardial infarction and stent thrombosis were significantly lower in BMC-treated patients compared with control subjects.

Conclusions—
Transplantation of adult BMCs improves LV function, infarct size, and remodeling in patients with ischemic heart disease compared with standard therapy, and these benefits persist during long-term follow-up. BMC transplantation also reduces the incidence of death, recurrent myocardial infarction, and stent thrombosis in patients with ischemic heart disease.
Evolution of the study coordinator role: The 28-year experience in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC)
Authors: Larkin Mary E , Lorenzi Gayle M , Bayless Meg , Cleary Patricia A , Barnie Annette , Golden Ellen , Hitt Susan , Genuth Saul 
Published: June 2012

Background The role of the study coordinator (SC) in multicenter studies of long duration has received limited attention. Purpose To describe the evolution of the SC’s role during the 28-year Diabetes Control and Complications Trial (DCCT) and its follow-up study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Methods The evolution of the SC’s position from the traditional role of protocol implementation to that of research collaborator and co-investigator, based on personal experience and observation, is described in detail. Findings from a survey regarding professional demographics and job satisfaction, completed by all 28 SCs in 2010, provided additional information. We used dimensions of the SC’s role specific to DCCT/EDIC to construct a classification schema of functions and responsibilities that describe the SC’s role. Results Among the 28 SCs, 24 were nurses, 12 held bachelor’s degrees, 11 had a master’s degree, 19 were certified diabetes educators (CDEs), 12 had worked with DCCT/EDIC for more than 20 years, and 5 had been with the study since its inception (>26 years). Responses confirmed a high degree of functional consistency across sites with data acquisition, performing study procedures, recruitment and consent for additional ancillary studies, regulatory management, scheduling, clinical consultation, and ongoing contact with study participants frequently reported. Study-wide leadership activities, a category not generally included in the usual SC role, were reported by approximately 30% of the SCs. The level of professional satisfaction was high with two-thirds being very satisfied, one-third moderately to quite satisfied, and none dissatisfied. Limitations The limitations include a relatively small sample size, self-reported data, and a single long-term multicenter trial and observational follow-up study on which we based our findings and conclusions. Conclusions By optimizing their organizational and scientific contributions to the overall research endeavor, SCs in DCCT/EDIC have made major contributions to the unprecedented success of the study and report high job satisfaction. The efforts of the SCs have been integral to the remarkably high participant retention and data completion rates. The DCCT/EDIC experience may serve as a model for the role of the SC in future diabetes and other multicenter clinical trials.
Pharmacokinetics, Safety, and Tolerability Following the Administration of a Single Dose of a Combination Tablet Containing Sumatriptan and Naproxen Sodium in Adolescent Patients With Migraine and in Healthy Adult Volunteers
Authors: Berges Alienor , Robertson Jonathan , Upward James , Meyers Scott , Chen Chao 
Published: June 2012

AbstractObjective: The objective was to compare the pharmacokinetics of sumatriptan and naproxen in adolescent migraineurs and healthy adults after administration of sumatriptan/naproxen sodium combination tablets. Design: The design was an open‐label, randomized, parallel group study. Adolescent migraineurs (12–17 years) and healthy adults received 1 dose of sumatriptan/naproxen: 10 mg/60 mg, 30 mg/180 mg, or 85 mg/500 mg. Pharmacokinetic and safety assessments were conducted. Results: Sumatriptan achieved Cmax rapidly (median tmax: 0.8–1.5 hours for adolescents, 0.5–2.0 hours for adults); elimination was also rapid (geometric mean t½: <2 hours for adolescents, 1.9–2.4 hours for adults). Compared with sumatriptan, naproxen was absorbed and eliminated more slowly (median tmax: 1.0–4.0 hours for adolescents, 1.0–3.0 hours for adults; geometric mean t½: 13.4–16.3 hours for adolescents, 14.3–16.6 hours for adults). Sumatriptan Cmax and AUC were similar for adolescents and adults for the 85 mg/500 mg dose; exposure for the 2 lower doses showed slight differences (not significant). Naproxen Cmax and AUC were comparable between the 2 groups at all doses. Increases in sumatriptan Cmax and AUC were dose proportional; for naproxen, slightly less than proportional. The tablets were generally well tolerated. Conclusion: Sumatriptan and naproxen pharmacokinetics were not dissimilar between adolescent migraineurs and healthy adults.