Objective Carotid magnetic resonance imaging (MRI) may be a useful tool in characterizing carotid plaque vulnerability, but large studies are still lacking. The purpose of this study was to assess ...carotid MRI features of vulnerable plaque in a large study and the changes in carotid plaque morphology with respect to time since the neurological event. Methods We included 161 patients with carotid plaque more than 3 mm thick. All patients underwent carotid MRI to obtain 3-T high-resolution magnetic resonance sequences. Large lipid core, intraplaque hemorrhage (IPH), fibrous cap rupture (FCR), and gadolinium enhancement (GE) were assessed and classified as present or absent. Prevalences of these features were then compared between symptomatic and asymptomatic patients and time since stroke. Results Seven patients were excluded because of poor image quality. Of the remaining 154 patients, 52 were symptomatic and 102 were asymptomatic. The prevalences of IPH (39 vs 16%; P = .002), FCR (30 vs 9%; P = .001), and GE (75 vs 55%; P = .015) were significantly higher in symptomatic than asymptomatic patients. After multivariate analysis, the prevalences of IPH (odds ratio, 2.6; P = .023) and FCR (odds ratio, 2.8; P = .038) were still significantly higher. The prevalence of IPH was significantly higher in symptomatic patients with plaque regardless of the time since the neurological event. For FCR, the difference between symptomatic and asymptomatic patients was significant only during the first 15 days after the neurological event. Conclusions Carotid MRI can identify plaque features that are associated with symptomatic presentation and may be indicative of plaque vulnerability. These features may ultimately be used in the management of extracranial carotid stenosis.
It has been previously demonstrated that a new index of aortic stenosis (AS) severity derived from dobutamine stress echocardiography (DSE), the projected aortic valve area (AVA) at a normal ...transvalvular flow rate (AVA(proj)), is superior to traditional Doppler echocardiographic indices to discriminate true severe from pseudosevere low-gradient AS. The objectives of this study were to prospectively validate the diagnostic and prognostic value of AVA(proj) in a large series of patients and to propose a new clinically applicable simplified method to estimate AVA(proj).
AVA(proj) was calculated in 142 patients with low-flow AS using 2 methods. In the conventional method, AVA was plotted against mean transvalvular flow (Q) at each stage of DSE, and AVA at a standardized flow rate of 250 ml/s was projected from the slope of the regression line fitting the plot of AVA versus Q: AVA(proj) = AVA(rest) + slope x (250 - Q(rest)). In the simplified method, using this equation, the slope of the regression line was estimated by dividing the DSE-induced change in AVA from baseline to the peak stage of DSE by the change in Q.
There was a strong correlation between AVA(proj) calculated by the two methods (r = 0.95, P < .0001). Among the 142 patients, 52 underwent aortic valve replacement and had underlying AS severity assessed by the surgeon. Conventional and simplified AVA(proj) demonstrated similar performance in discriminating true severe from pseudosevere AS (percentage of correct classification of AVA(proj) < or = 1 cm(2), 94% and 92%, respectively) and were superior to traditional dobutamine stress echocardiographic indices (percentage of correct classification, 60%-77%). Both conventional and simplified AVA(proj) correlated well with valve weight (r = 0.52 and r = 0.58, respectively), whereas traditional dobutamine stress echocardiographic indices did not. In the 84 patients who were treated medically, conventional AVA(proj) < or = 1.2 cm(2) (hazard ratio, 1.65; P = .02) and simplified AVA(proj) < or = 1.2 cm(2) (hazard ratio, 2.70; P < .0001) were independent predictors of mortality. Traditional dobutamine stress echocardiographic indices were not predictive.
In patients with low-flow AS, AVA(proj) better predicts underlying AS severity and patient outcomes than traditional dobutamine stress echocardiographic indices. Simplified AVA(proj) is easier to calculate than conventional AVA(proj), facilitating the use of AVA(proj) in clinical practice.
Background Elderly patients are at high risk for both ischemic and bleeding events. Platelet monitoring offers the opportunity to individualized antiplatelet therapy to optimize the therapeutic ...risk/benefit ratio. Study design The ANTARCTIC study is designed to demonstrate the superiority of a strategy of platelet function monitoring with dose and drug adjustment in patients initially on prasugrel 5 mg as compared with a more conventional strategy using prasugrel 5 mg without monitoring and without adjustment (Conventional Treatment Arm) to reduce the primary end point evaluated 1 year after stent percutaneous coronary intervention in elderly patients presenting with an acute coronary syndrome (ACS). ANTARCTIC is a multicenter, prospective, open-label study with 2 parallel arms. A total of 852 elderly patients (≥75 years) undergoing stent percutaneous coronary intervention for ACS are to be enrolled. The primary end point is the time to first occurrence of cardiovascular death, myocardial infarction, stroke, definite stent thrombosis, urgent revascularization, and bleeding complications (Bleeding Academic Research Consortium definition 2, 3, or 5). Platelet function analyses will be performed 14 days after randomization and repeated 14 days later in patients who require a change in treatment. Conclusion ANTARCTIC is a nationwide, prospective, open-label study testing a strategy of platelet function monitoring with dose and drug adjustment to reduce ischemic and bleeding complications in elderly ACS patients undergoing coronary stenting.
Previous coronary artery bypass grafting (CABG) increases operative risk in conventional valve replacement. Transcatheter aortic valve implantation (TAVI) has been shown to be successful in high-risk ...patient subgroups. The present study compared outcome and overall survival in patients who underwent TAVI with and without history of CABG. From January 2010 to December 2011, 683 of the 3,761 patients selected for TAVI in 34 French centers (18%) had a history of CABG. Outcomes (mortality and complications) were collected prospectively according to the Valve Academic Research Consortium (VARC) criteria. Patients with previous CABG were younger, with higher rates of diabetes and vascular disease and higher logistic European System for Cardiac Operative Risk Evaluation (29.8 ± 16.4 vs 20.1 ± 13.0, p <0.001) but lower rates of pulmonary disease. Two types of valve (Edwards SAPIEN and Medtronic CoreValve) were implanted in equal proportions in the 2 groups. The 30-day and 1-year mortality rates from all causes on Kaplan-Meier analysis (9.2% vs 9.7%, p = 0.71; and 19.0% vs 20.2%, p = 0.49, respectively) did not differ according to the history of CABG. There were no significant differences in the Valve Academic Research Consortium complications (myocardial infarction, stroke or vascular, and bleeding complications). On multivariate analysis, CABG was not associated with greater 1-year post-TAVI mortality. In conclusion, previous CABG did not adversely affect outcome in patients who underwent TAVI, which may be an alternative to surgery in high-risk patients with severe aortic stenosis and history of CABG.
Aims The management of asymptomatic severe mitral regurgitation remains controversial. The aim of the study was to assess the long-term survival, incidence of cardiac complications, factors that ...predict outcome, and effect of mitral surgery on the long-term prognosis of patients with asymptomatic severe mitral regurgitation amenable to valve repair. Methods One hundred ninety-two asymptomatic patients (mean age, 63 ± 13 years) with severe degenerative mitral regurgitation diagnosed by 2-dimensional echocardiography between 1990 and 2001 were prospectively followed for a median of 8.5 years. Results Overall, cardiovascular, and event-free survival was evaluated in 2 groups of patients: a “conservative approach” group (n = 67) and an “early surgery” group (n = 125). Outcomes were also analyzed among patients with atrial fibrillation, pulmonary hypertension, or both, as well as in patients free of any mitral regurgitation complications. In the whole population, 10-year overall survival was significantly lower with the conservative approach than early surgery (50% ± 7% vs 86% ± 4%, log-rank < 0.0001). Similar results were obtained in the subgroups with atrial fibrillation and/or pulmonary hypertension. The 10-year propensity-matched score-adjusted hazards ratio for overall mortality, cardiac mortality, and cardiovascular events for the conservative treatment were 5.21, 4.83, and 4.40, respectively. Conclusion Our results show that the outcome of asymptomatic patients with severe degenerative mitral regurgitation is better with an early surgical approach rather than a more conservative treatment strategy.
Summary Children younger than 18 years account for a substantial proportion of patients with tuberculosis worldwide. Available treatments for paediatric drug-susceptible and drug-resistant ...tuberculosis, albeit generally effective, are hampered by high pill burden, long duration of treatment, coexistent toxic effects, and an overall scarcity of suitable child-friendly formulations. Several new drugs and regimens with promising activity against both drug-susceptible and drug-resistant strains have entered clinical development and are either in various phases of clinical investigation or have received marketing authorisation for adults; however, none have data on their use in children. This consensus statement, generated from an international panel of opinion leaders on childhood tuberculosis and incorporating reviews of published literature from January, 2004, to May, 2014, addressed four key questions: what drugs or regimens should be prioritised for clinical trials in children? Which populations of children are high priorities for study? When can phase 1 or 2 studies be initiated in children? What are the relevant elements of clinical trial design? The consensus panel found that children can be included in studies at the early phases of drug development and should be an integral part of the clinical development plan, rather than studied after regulatory approval in adults is obtained.
Metabolic Syndrome Increases Operative Mortality in Patients Undergoing Coronary Artery Bypass Grafting Surgery Najmedine Echahidi, Philippe Pibarot, Jean-Pierre Després, Jean-Marc Daigle, Dania ...Mohty, Pierre Voisine, Richard Baillot, Patrick Mathieu We hypothesized that metabolic syndrome (MS) could increase operative mortality associated with coronary artery bypass grafting surgery (CABG). In a series of 5,304 patients undergoing isolated CABG, operative mortality was markedly increased among the 2,411 (46%) patients with MS defined according to the National Cholesterol Education Program—Adult Treatment Panel III guidelines. On multivariate analysis, MS was found to be a strong independent predictor of operative mortality irrespective of diabetes status. This is the first study to report that MS is a strong independent risk factor for operative mortality after CABG surgery.
Background Low-grade inflammation may potentially explain the relationship between obstructive sleep apnea syndrome (OSA) and cardiovascular events. However, the respective contribution of ...intermittent hypoxia and confounders, such as obesity, is still debated. Objectives To monitor urinary leukotriene E4 (U-LTE4 ), a validated marker of proinflammatory cysteinyl leukotriene production, in OSA; to determine the influence of obesity and other confounders on U-LTE4 concentrations; to examine the mechanisms involved through transcriptional profiling of the leukotriene pathway in peripheral blood mononuclear cells (PBMCs); and to investigate the effect of continuous positive air pressure (CPAP) on U-LTE4 concentrations. Methods We measured U-LTE4 by liquid chromatography–tandem mass spectrometry. Results The U-LTE4 concentrations were increased ( P = .019) in 40 nonobese patients with OSA carefully matched for age, sex, and body mass index (BMI) to 25 control subjects, and correlated ( r = 0.0312; P = .017) to the percentage of time spent with mean oxygen saturation (SaO2 ) less than 90%. In a larger cohort of patients with OSA (n = 72), U-LTE4 increased as a function of BMI ( r = 0.445; P = .0002). In those patients, the expression levels of 5-lipoxygenase activating protein mRNA in mononuclear cells exhibited a similar pattern. A stepwise multiple linear regression analysis performed in this cohort identified BMI ( P = .001; regression coefficient, 3.33) and percentage of time spent with SaO2 <90% ( P = .001; regression coefficient, 1.01) as independent predictors of U-LTE4 concentrations. Compared with baseline, CPAP reduced by 22% ( P = .006) U-LTE4 concentrations only in patients with OSA with normal BMI. Conclusion Obesity, and to a lesser extent hypoxia severity, are determinant of U-LTE4 production in patients with OSA.
Aims The aims of the study are to compare the outcome with and without major bleeding and to identify the independent correlates of major bleeding complications and mortality in patients described in ...the ATOLL study. Methods The ATOLL study included 910 patients randomly assigned to either 0.5 mg/kg intravenous enoxaparin or unfractionated heparin before primary percutaneous coronary intervention. Incidence of major bleeding and ischemic end points was assessed at 1 month, and mortality, at 1 and 6 months. Patients with and without major bleeding complication were compared. A multivariate model of bleeding complications at 1 month and mortality at 6 months was realized. Intention-to-treat and per-protocol analyses were performed. Results The most frequent bleeding site appears to be the gastrointestinal tract. Age >75 years, cardiac arrest, and the use of insulin or >1 heparin emerged as independent correlates of major bleeding at 1 month. Patients presenting with major bleeding had significantly higher rates of adverse ischemic complications. Mortality at 6 months was higher in bleeders. Major bleeding was found to be one of the independent correlates of 6-month mortality. The addition or mixing of several anticoagulant drugs was an independent factor of major bleeding despite the predominant use of radial access. Conclusions This study shows that major bleeding is independently associated with poor outcome, increasing ischemic events, and mortality in primary percutaneous coronary intervention performed mostly with radial access.
Summary Background Revaccination with double-dose hepatitis B vaccine has been recommended in HIV-infected patients who do not respond to standard vaccination, but has not yet been assessed. We aimed ...to compare the safety and immunogenicity of a reinforced hepatitis B revaccination protocol with the standard revaccination schedule in HIV-infected patients not responding to primary vaccination. Methods We did this multicentre, open-label, randomised controlled trial, at 53 centres in France. HIV-infected adults (aged ≥18 years), with CD4 counts of 200 cells per μL or more and no response to a previous hepatitis B vaccination or a 20 μg booster dose, were randomly assigned (1:1), according to a computer-generated randomisation list with permuted blocks (block sizes of two to six), to receive either standard-dose (20 μg) or double-dose (40 μg) recombinant hepatitis B vaccine at weeks 0, 4, and 24. Randomisation was stratified by baseline CD4 count (200–349 vs ≥350 cells per μL). Patients and treating physicians were not masked to treatment allocation, but the randomisation list was concealed from the investigators who assigned participants to the vaccination groups. The primary endpoint was the proportion of responders, defined as patients with hepatitis B surface antibody (anti-HBs) titres of 10 mIU/mL or more, at week 28. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov , number NCT00670839. Findings Between May 19, 2008, and May 8, 2011, 178 participants were randomly assigned to the standard-dose group (n=90) or the double-dose group (n=88), of whom 176 (98%) participants were included in the primary efficacy analysis. At week 28, we recorded a response in 60 patients (67%, 95% CI 57–77) in the standard-dose group versus 64 patients (74%, 63–82) in the double-dose group (p=0·334). Except for more frequent local reactions in the double-dose group than the standard-dose group (13 15% vs four 4% patients; p=0·020), there was no difference in safety between groups. Interpretation In adults with HIV-1 who have not responded to previous hepatitis B vaccination, double-dose revaccination did not achieve a higher response rate than did revaccination with standard single-dose regimen. However, the safety profile was similar between treatment groups. Our results should be assessed in future studies before double-dose vaccine can be considered for the standard of care of vaccine non-responders. Funding French National Institute for Medical Research–French National Agency for Research on AIDS and Viral Hepatitis.
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