The additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress cardiac MRI for the detection of myocardial ischemia

Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 μg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6–20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation

Performance of adenosine “stress-only” perfusion MRI in patients without a history of myocardial infarction: a clinical outcome study

To assess the diagnostic value of adenosine “stress-only” myocardial perfusion MR for ischemia detection as an indicator for coronary angiography in patients without a prior myocardial infarction and a necessity to exclude ischemia. Adenosine perfusion MRI was performed at 1.5 T in 139 patients with a suspicion of ischemia and no prior myocardial infarction. After 3 min of adenosine infusion a perfusion sequence was started. Patients with a perfusion defect were referred to coronary angiography (CAG). Patients with a normal perfusion were enrolled in follow-up. Fourteen out of 139 patients (10.1%) had a perfusion defect indicative of ischemia. These patients underwent a coronary angiogram, which showed complete agreement with the perfusion images. 125 patients with a normal myocardial perfusion entered follow-up (median 672 days, range 333–1287 days). In the first year of follow-up one Major Adverse Coronary Event (MACE) occurred and one patient had new onset chest pain with a confirmed coronary stenosis. Reaching a negative predictive value for MACE of 99.2% and for any coronary event of 98.4%. At 2 year follow-up no additional MACE occurred. Sensitivity of adenosine perfusion MR for MACE is 93.3% and specificity and positive predictive value are 100%. Adenosine myocardial perfusion MR for the detection of myocardial ischemia in a “stress-only” protocol in patients without prior myocardial infarctions, has a high diagnostic accuracy. This fast examination can play an important role in the evaluation of patients without prior myocardial infarctions and a necessity to exclude ischemia

Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

Background: Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design: The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome. Implications: The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease. Trial registration: Clinicaltrials.gov NCT0018911

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies

European visa cooperation: interest politics and regional imagined communities

Since the early 1990s the European Union has struggled to increase integration in the sovereignty sensitive areas of justice and home affairs and foreign policy. The aim of this paper is to enhance our understanding of what patterns of cooperation have been established between the member states, and why. I do so by analysing the case of short-stay visa policy. Visas are a corner stone of EU's border control, regulating access to the Union's area of freedom, security and justice. It is moreover an instrument used in foreign and diplomatic relations. As a field where the member states' cooperation is particularly intense it is an 'extreme case' well-suited for drawing out empirical patterns and developing theoretical concepts. The paper is based on a network analytical approach and a new dataset of all the EU/Schengen member states' mutual consular visa assistance agreements. This I use to document the extent and pattern of cooperation from 2005 to 2010. I show that the member states rely intensively on each other's consular services. They mainly share sovereignty in four distinct regional clusters – a Nordic, Benelux, Southern European and an emerging Central Eastern. France and Germany are at the centre of the network. To explain this structure of cooperation I discuss the relative merits of realist, liberal intergovernmentalist and constructivist approaches. I show how they each identify important dynamics but emphasise the relative merits of a constructivist perspective. I put forward a new concept of 'regional imagined communities' which explains cooperation by the existence of shared identities owing to regional commonalities in language and state-building histories. I argue that the concept improves our understanding of European integration in visa policy, and suggest it might hold wider potential for explaining dynamics of collaboration in other sovereignty sensitive policy areas

Influence of the Choice of Software Package on the Outcome of Semiquantitative MR Myocardial Perfusion Analysis

<p>Purpose: To assess the repeatability and reproducibility of semi-quantitative magnetic resonance (MR) perfusion analysis performed by using different software packages.</p><p>Materials and Methods: The study protocol was approved by the institutional ethics committee. Informed consent was obtained from each patient. Semi-quantitative perfusion analysis was performed twice by two independent observers using four dedicated software packages. MR perfusion datasets originated from eight patients with known single-vessel disease who were scheduled for percutaneous coronary intervention (PCI) on the basis of coronary angiography findings. Each patient underwent two examinations: 1 day before and 1 day after PCI. Repeatability (intra- and inter-observer agreements) and reproducibility (intersoftware agreement) were evaluated for perfusion upslope and myocardial perfusion reserve index with Student t test and Bland-Altman analyses.</p><p>Results: Intra- and interobserver agreements were good and comparable for repeated measurements within each individual software platform (mean differences, <6%, intraclass correlation coefficient [ICC] >= 0.68). However, the intersoftware variability was significant (limits of agreement. 65%, ICC.</p><p>Conclusion: The results indicate high repeatability within individual software but low reproducibility between different software packages, suggesting that within-group and/or sequential observation of semiquantitative perfusion parameters must be performed with the same software platform. Before semiquantitative perfusion analysis can be incorporated reliably into clinical studies, it is important to resolve the differences between the software packages. (C) RSNA, 2012</p>

Parallel imaging for first-pass myocardial perfusion

Two parallel imaging methods used for first-pass myocardial perfusion imaging were compared in terms of signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and image artifacts. One used adaptive Time-adaptive SENSitivity Encoding (TSENSE) and the other used GeneRalized Autocalibrating Partially Parallel Acquisition (GRAPPA), which are both applied to a gradient-echo sequence. Both methods were tested on 12 patients with coronary artery disease. The order of perfusion sequences was inverted in every other patient. Image acquisition was started during the administration of a contrast bolus followed by a 20-ml saline flush (3 ml/s), and the next perfusion was started at least 15 min thereafter using an identical bolus. An acceleration rate of 2 was used in both methods, and acquisition was performed during breath-holding. Significantly higher SNR, CNP, and image quality were obtained with GRAPPA images than with TSENSE images. GRAPPA, however, did not yield a higher CNR when applied after the second bolus. GRAPPA perfusion imaging produced larger differences between subjects than did TSENSE. Compared to TSENSE, GRAPPA produced significantly better CNR on the first bolus. More consistent SNR and CNR were obtained from TSENSE images than from GRAPPA images, indicating that the diagnostic value of TSENSE may be better. (c) 2007 Elsevier Inc. All rights reserved

Evaluation of global left ventricular function assessment by dual-source computed tomography compared with MRI

Left ventricular (LV) function assessment by dual-source computed tomography (DSCT) was compared with the reference standard method using magnetic resonance imaging (MRI). Accurate assessment of LV function is essential for the prediction of prognosis in cardiac disease. Thirty-four patients undergoing DSCT examination of the heart for various clinical indications underwent MRI after DSCT. Short-axis cine images were reconstructed from the DSCT datasets and were analyzed using a dedicated post-processing software-tool to generate global left ventricular function parameters. Five DSCT datasets were considered to be of insufficient image quality. DSCT showed a small overestimation of end-diastolic and end-systolic volumes of 11.0 ml and 3.5 ml, nrespectively. Myocardial mass assessed by DSCT showed an average underestimation of 0.2 g. DSCT showed a small overestimation of LV ejection fraction (LVEF) of 0.4%-point with a Bland-Altman interval of [-8.67 (0.40) 9.48]. Global LV functional parameters calculated from DSCT datasets acquired in daily clinical practice correlated well with MRI and may be considered interchangeable. However, visual assessment of the image quality of the short-axis cine slices should be performed to detect any artifacts in the DSCT data which could influence accuracy

Assessment of global left ventricular functional parameters: analysis of every second short-axis magnetic resonance imaging slices is as accurate as analysis of consecutive slices

The purpose of this study was to assess whether accurate global left-ventricular (LV) functional parameters can be obtained by analyzing every second short-axis magnetic resonance imaging cine series instead of consecutive slices, in order to reduce post-processing time. Forty patients, were scanned on a 1.5 T MRI-system (Magnetom Sonata, Siemens Medical Systems, Erlangen, Germany) using a steady-state free precession (SSFP) sequence. A stack of short-axis cine series from above the mitral valve through the apex was acquired. Post-processing was started at the most basal slice of the left ventricle, in which at least 50% of the circumference was myocardium. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF) and LV mass (LVM), were calculated. Data analysis was repeated, but now only every second slice was analyzed. Bland-Altman analysis showed slightly lower values for all LV parameters when only every second slice was analyzed, ranging from 1.7% difference for EF (limits of agreement -3.5 to 5.0) to 4.6% for SV (limits of agreement -7.2 to 15.0). Analysis of every second slice for quantification of global LV function is time-saving and as accurate as analysis of consecutive slices