Changes in anticoagulant prescription in Dutch patients with recent-onset atrial fibrillation: observations from the GARFIELD-AF registry.

BACKGROUND: For the improvement of AF care, it is important to gain insight into current anticoagulation prescription practices and guideline adherence. This report focuses on the largest Dutch subset of AF-patients, derived from the GARFIELD-AF registry. METHODS: Across 35 countries worldwide, patients with newly diagnosed 'non-valvular' atrial fibrillation (AF) with at least one additional risk factor for stroke were included. Dutch patients were enrolled in five, independent, consecutive cohorts from 2010 until 2016. RESULTS: In the Netherlands, 1189 AF-patients were enrolled. The prescription of non-vitamin K antagonist oral anticoagulants (NOAC) has increased sharply, and as per 2016, more patients were initiated on NOACs instead of vitamin K antagonists (VKA). In patients with a class I recommendation for anticoagulation, only 7.5% compared to 30.0% globally received no anticoagulation. Reasons for withholding anticoagulation in these patients were unfortunately often unclear. CONCLUSIONS: The data from the GARFIELD-AF registry shows the rapidly changing anticoagulation preference of Dutch physicians in newly diagnosed AF. Adherence to European AF guidelines in terms of anticoagulant regimen would appear to be appropriate. In absence of structured follow up of AF patients on NOAC, the impact of these rapid practice changes in anticoagulation prescription in the Netherlands remains to be established.

Functional neuroanatomy of non-verbal semantic sound processing in humans.

Environmental sounds convey specific meanings and the neural circuitry for their recognition may have preceded language. To dissociate semantic mnemonic from sensory perceptual processing of non-verbal sound stimuli we systematically altered the inherent semantic properties of non-verbal sounds from natural and man-made sources while keeping their acoustic characteristics closely matched. We hypothesized that acoustic analysis of complex non-verbal sounds would be right lateralized in auditory cortex regardless of meaning content and that left hemisphere regions would be engaged when meaningful concept could be extracted. Using H(2) (15)O-PET imaging and SPM data analysis, we demonstrated that activation of the left superior temporal and left parahippocampal gyrus along with left inferior frontal regions was specifically associated with listening to meaningful sounds. In contrast, for both types of sounds, acoustic analysis was associated with activation of right auditory cortices. We conclude that left hemisphere brain regions are engaged when sounds are meaningful or intelligible.

[Taxonomy of sheep (genus Ovis, Linnaeus, 1758)]. / De taxonomie van het schaap (genus Ovis, Linnaeus, 1758).

Until recently, mainly comparative morphology was used to classify animals into species, but this method has not led to consensus about the genus sheep (Ovis). However, advanced research techniques, such as cytodiagnosis, provide greater certainty and it is anticipated that these techniques will enable agreement to be reached about the taxonomy of the sheep.

[The European mouflon, Ovis musimon]. / De Europese moeflon, Ovis musimon.

Until a couple of decades ago, the European mouflon found on the islands of Corsica, Sardinia, and Cyprus was considered an independent wild species and last representative of the European wild sheep. However, recent research has shown that there have not been wild sheep in Europe since the late Pleistocene. Archeological investigation in Corsica has shown that the mouflon is not a wild sheep but a primitive domestic sheep brought to the islands by farmers from the Near East and which then became wild (feral).

Evaluation of performance characteristics of automated measurement systems for allergy testing.

Reliability of test results, convenient handling and flexibility are major requirements on automated immunoassays systems. To investigate to what extent these requirements were met by the Pharmacia CAP and DPC IMMULITE and DPC Microplate Systems, we evaluated several performance characteristics of assays of specific IgE against some common inhalant allergens as well as the atopy tests Phadiatop (Pharmacia CAP System) and AlaTOP (DPC IMMULITE and Microplate System). Comparing Phadiatop and AlaTOP results (n = 95) to clinical data, the sensitivity was found to be 97% in the Pharmacia CAP System and 82% in the AlaTOP-DPC Microplate System and 88% with AlaTOP-IMMULITE. Specificity was in all cases higher than 90%. The pooled total variation was more than twice as high with the DPC Microplate System as compared to the Pharmacia CAP System in our first investigation. A second investigation showed similar values. The investigation of systematic differences showed that the error contribution of sample related differences between the systems was even larger and far exceeded the analytical variation. Thus the two methods do not seem to be measuring the same specific IgE antibodies. In 8 out of 8 cases with the Pharmacia CAP System positive and DPC negative results and in 2 out of 2 cases with DPC positive and Pharmacia CAP System negative results, the presence of IgE antibodies could be confirmed by IgE immunoblotting. Serum dilutions showed very irregular O/E patterns for the DPC Microplate System. There was no effect when adding non-specific IgE to serum samples. Addition of competing IgG antibodies showed a moderate decrease in binding of specific IgE in the Pharmacia CAP System when increasing amounts of IgG were added. The effect in the DPC Microplate System was more pronounced with large decreases, or increases of measured values even at lower concentration of the competing antibody. The results may indicate insufficient allergen concentration in the DPC assay and draw attention to the risk for undesirable complex formation between allergen and antibody in solution. The combination of the two DPC systems did not offer any advantages over Pharmacia CAP System from the handling or work flow point of view.

Evaluation of the Abbott automated random, immediate and continuous access immunoassay analyser, the AxSYM.

The new Abbott automated immunoassay analyser called AxSYM was evaluated in our laboratories. The AxSYM is a completely automated system that allows random access in combination with immediate and continuous access. Here we describe the evaluation of the AxSYM on three panels of analytes, thyroid, fertility and tumour markers. We observed good within-run reproducibility (ranging from %CV = 3.15 to 11.37 for low assay control to %CV = 1.18 to 6.38 for high controls) as well as between-day and between-laboratory precision (low controls 3.44 to 14.6% CV and high controls 2.56 to 8.9% CV). The analytical sensitivity of the assays ranged from very sensitive to acceptable, but always better than claimed by the manufacturer. The throughput of the AxSYM in our hands was 68 tests per hour. Correlation between the AxSYM assays and other Abbott assays (IMx) was excellent (slopes ranging from 0.965 to 1.071, correlation, r = 0.964 to 0.999). Compared to the Tosoh AIA 1200, good correlation was observed (slopes ranging from 0.964 to 1.111, correlation, r = 0.740 to 1.000), except for thyrotropin (slope = 0.689, r = 0.998) and carcinoembryonic antigen (slope = 0.737, r = 0.949). We concluded that the AxSYM represents a new generation of random access automated immuno analysers with very good performance in a daily routine use. We also concluded that the AxSYM was very technician friendly compared to the Tosoh AIA 1200.

Morphologic changes during follow-up after successful percutaneous transluminal coronary balloon angioplasty: quantitative angiographic analysis in 778 lesions--further evidence for the restenosis paradox. MERCATOR Study Group (Multicenter European Research trial with Cilazapril after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis).

The purpose of this study was to determine if there are any morphologic characteristics of lesions that renarrow (that is, restenotic lesions) following successful coronary balloon angioplasty that are different from their appearance pretreatment or from the appearance of nonrestenotic lesions that might provide some new insight into the restenosis phenomenon. The study population consisted of 653 patients (778 lesions) with 6 months of angiographic follow-up (94% angiographic follow-up rate) who were participating in the Multicenter European Research trial with Cilazapril after Angioplasty to prevent Transluminal coronary Obstruction and Restenosis (MERCATOR) study. Detailed quantitative angiographic measurements, including the mean diameter of the vessel segment (in millimeters) that was subjected to balloon dilation, were performed preangioplasty, postangioplasty, and at follow-up using the cardiovascular angiographic analysis system to provide some objective measurement of the actual extent of luminal changes in the months following coronary balloon angioplasty. Two different approaches for restenosis were used: (1) static criterion of > 50% diameter stenosis at follow-up and (2) dynamic criteria of > or = 0.40 or > or = 0.72 mm change in minimal lumen diameter between postangioplasty and follow-up. Both approaches identified more severe stenosis to be a typical feature for restenotic lesions before angioplasty compared with nonrestenotic lesions. No differences were observed in lesion length, balloon-inflated vessel segment, or roughness index before angioplasty between the groups. Conflicting data were found for the amount of atherosclerotic plaque, symmetry index, and curvature index. The restenotic lesion at follow-up compared with its initial appearance gave conflicting results depending on which approach was used. The dynamic criteria illustrate that the reference diameter and the mean diameter of the entire segment dilated are reduced during follow-up. Two messages emerge from the study: (1) the restenosis process clearly involves the apparent normal vessel wall adjacent to the actual lesion, probably in response to the unavoidable injury caused by balloon dilatation and (2) the use of percentage diameter stenosis measurements depending on the assumptions of normality for a reference segment will therefore underestimate the true extent of the restenosis process and should be replaced in clinical angiographic studies by absolute luminal measurements.

Quantitative angiography during coronary angioplasty with a single angiographic view: a comparison of automated edge detection and videodensitometric techniques.

Little information is available on the reliability of coronary luminal measurements obtained from quantitative analysis of a single angiographic view, an approach that is central to the practical use of on-line quantitative angiography. In the present study we investigated the contribution of two different techniques of quantitative angiography, edge detection (ED) and videodensitometry (VD), to the application of this concept during coronary angioplasty. Forty-six balloon angioplasty procedures were included in this study, all of them performed in a stenosis located in the mid right coronary segment. This coronary location was chosen to optimize data collection on luminal morphology and to minimize the number of factors that may adversely affect quantitative analysis with both techniques. In all cases two orthogonal angiographic projections were obtained before, after balloon dilatation, and at follow-up. Correlation coefficients and differences between orthogonal measurements obtained with each technique were used to evaluate the agreement between orthogonal readings at every stage of the procedure. The obtained correlation coefficients and mean differences (MD) between orthogonal measurements were as follows: before percutaneous transluminal coronary angiography (PTCA), 0.67 (MD 0.01 +/- 0.47 mm2) and 0.57 (MD 0.05 +/- 0.64 mm2) for ED and VD, respectively (Pitman's test for SD, p < 0.05); after balloon dilatation, 0.32 (MD -0.56 +/- 1.53 mm2) and 0.53 (MD -0.15 +/- 1.43 mm2) for ED and VD, respectively (paired t test for MD, p < 0.05); and at follow-up 0.79 (MD -0.15 +/- 0.97 mm2) and 0.73 (MD 0.17 +/- 1.16 mm2) for ED and VD, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Coronary Artery Restenosis Prevention on Repeated Thromboxane Antagonism (CARPORT) Study Group.

BACKGROUND: The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure-related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies. METHODS AND RESULTS: Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina < 2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length > or = 6.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< or = -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively). CONCLUSIONS: Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics.

Pharmacological approaches to the prevention of restenosis following angioplasty. The search for the Holy Grail? (Part II).

Part I of this article reviewed the results of studies investigating the effectiveness of antithrombotic, antiplatelet, antiproliferative, anti-inflammatory, calcium channel blocker and lipid-lowering drugs in preventing or reducing restenosis after angioplasty. However, despite 15 years of clinical experience and research in the field of restenosis prevention, this has not yet resulted in the revelation of unequivocal beneficial effects of any particular drug. Other newer approaches likely to receive more attention in the future include antibodies to growth factors, gene transfer therapy and antisense oligonucleotides. Whether there is a feasible monotherapy, whether we have to focus on a drug combination, or whether we are only searching for 'the Holy Grail' remain to be answered.

Usefulness of quantitative and qualitative angiographic lesion morphology, and clinical characteristics in predicting major adverse cardiac events during and after native coronary balloon angioplasty. CARPORT and MERCATOR Study Groups.

Major, adverse cardiac events (death, myocardial infarction, bypass surgery and reintervention) occur in 4 to 7% of all patients undergoing coronary balloon angioplasty. Prospectively collected clinical data, and angiographic quantitative and qualitative lesion morphologic assessment and procedural factors were examined to determine whether the occurrence of these events could be predicted. Of 1,442 patients undergoing balloon angioplasty for native primary coronary disease in 2 European multicenter trials, 69 had major, adverse cardiac procedural or in-hospital complications after > or = 1 balloon inflation and were randomly matched with patients who completed an uncomplicated in-hospital course after successful angioplasty. No quantitative angiographic variable was associated with major adverse cardiac events in univariate and multivariate analyses. Univariate analysis showed that major adverse cardiac events were associated with the following preprocedural variables: (1) unstable angina (odds ratio [OR] 3.11; p < 0.0001), (2) type C lesion (OR 2.53; p < 0.004), (3) lesion location at a bend > 45 degrees (OR 2.34; p < 0.004), and (4) stenosis located in the middle segment of the artery dilated (OR 1.88; p < 0.03); and with the following postprocedural variable: angiographically visible dissection (OR 5.39; p < 0.0001). Multivariate logistic analysis was performed to identify variables independently correlated with the occurrence of major adverse cardiac events. The preprocedural multivariate model entered unstable angina (OR 3.77; p < 0.0003), lesions located at a bend > 45 degrees (OR 2.87; p < 0.0005), and stenosis located in the middle portion of the artery dilated (OR 1.95; p < 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological approaches to the prevention of restenosis following angioplasty. The search for the Holy Grail? (Part I).

Luminal renarrowing after balloon angioplasty still hampers the long term vessel patency in a substantial percentage of patients. Morphologically, the restenotic lesion comprises hyperplasia of intimal tissue, which is mainly characterised by proliferation of smooth muscle cells of the synthetic type with abundant extracellular matrix production, chiefly composed of proteoglycans. Unravelling the underlying pathophysiological process enables more specific intervention in basic interactions and cell responses. Critical events in the development of restenotic tissue are platelet aggregation and thrombus formation, while the release of several mediators promotes proliferation and migration of various cell types. All of these steps give access for a diversity of pharmacological interventions. With this in mind, antithrombotic, antiplatelet, antiproliferative, antiinflammatory, calcium channel blocking and lipid-lowering drugs have been investigated in the prevention of restenosis. Part II of this article reviews newer approaches, such as antibodies to growth factors, gene transfer and antisense oligonucleotides.

Restenosis after directional coronary atherectomy and balloon angioplasty: comparative analysis based on matched lesions.

OBJECTIVES: Late lumen narrowing after directional coronary atherectomy was assessed by quantitative coronary angiography and compared with that after balloon angioplasty. BACKGROUND: Directional coronary atherectomy has been introduced as an alternative technique for balloon angioplasty and may reduce the incidence of restenosis. METHODS: A prospectively collected consecutive series of 87 native coronary artery lesions successfully treated with atherectomy were matched with 87 coronary artery lesions selected from a consecutive series of lesions that had been successfully dilated by balloon angioplasty. Late angiographic analysis was performed in 158 lesions. The net gain index represents the ultimate gain in minimal lumen diameter at follow-up study, normalized for the vessel size. This index is the result of the relative gain attained during the procedure (the ratio of the change in minimal lumen diameter and reference diameter) and the relative loss observed during the follow-up period (the ratio of the change in minimal lumen diameter during the follow-up period and the reference diameter). RESULTS: Matching for clinical and angiographic variables resulted in two comparable groups with similar baseline stenosis characteristics. Atherectomy resulted in a more pronounced increase in minimal lumen diameter than did balloon angioplasty (mean +/- SD 1.17 +/- 0.29 to 2.44 +/- 0.42 mm vs. 1.21 +/- 0.38 to 2.00 +/- 0.36 mm, p < 0.001). However, this favorable immediate result was subsequently lost during late angiographic follow-up, so that the minimal lumen diameter at follow-up and the net gain index did not differ significantly between the two groups (1.76 +/- 0.62 vs. 1.77 +/- 0.59 mm, p = 0.93, and 0.18 +/- 0.19 vs. 0.17 +/- 0.17, p = 0.70). Consequently, the relative gain and relative loss were higher in the atherectomy group. For both techniques, the relative gain was linearly related to the relative loss but the slope of the regression line was steeper for atherectomy, suggesting that the relative loss in the atherectomy group is proportionally even larger for a given relative gain compared with that in the angioplasty group. CONCLUSIONS: In matched groups of patients, atherectomy induces a greater initial gain in minimal lumen diameter than does balloon angioplasty. However, the vascular wall injury induced by the device is of a different nature (debulking vs. dilating) that leads to more relative loss over the follow-up period in the atherectomy group.

Matching based on quantitative coronary angiography as a surrogate for randomized studies: comparison between stent implantation and balloon angioplasty of native coronary artery lesions.

Although intracoronary stenting has been advocated as an adjunct to balloon angioplasty to circumvent late restenosis, its effectiveness has not yet been verified. Therefore the aim of this study was to determine the differences in the immediate and long-term changes in stenosis geometry between Wallstent implantation and balloon angioplasty in native coronary artery lesions. To obtain two study populations with identical baseline stenosis characteristics, patients were matched for lesion site, vessel size, and minimal luminal diameter. Only patients undergoing elective and successful coronary intervention of a native coronary artery, in whom a control angiographic study had been performed, were included. A total of 186 patients (93 in each group) were selected. The coronary angiograms were analyzed with the computer-assisted cardiovascular angiographic analysis system. Matching was considered adequate, since there was an equal number of lesion sites in each study population and there were no differences in baseline reference diameter and minimal luminal diameter. Wallstent implantation resulted in a significantly greater increase in minimal luminal diameter (from 1.22 +/- 0.34 mm to 2.49 +/- 0.40 mm, p < 0.00001) compared with balloon angioplasty (from 1.21 +/- 0.29 mm to 1.92 +/- 0.35 mm, p < 0.00001). Despite a greater decrease in minimal luminal diameter after Wallstent implantation (0.48 +/- 0.74 mm) than after balloon angioplasty (0.20 +/- 0.46 mm), the minimal luminal diameter at follow-up was significantly greater after stent implantation (2.01 +/- 0.75 mm vs 1.72 +/- 0.54, p < 0.0001). It was concluded that Wallstent implantation results in a superior immediate and long-term increase in minimal luminal diameter compared with balloon angioplasty. The larger initial gain after stent implantation compensates for the late loss, and thus an improved initial result and not lessened neointimal hyperplasia is responsible for a reduced incidence of restenosis. Studies based on matching of angiographic variables are a surrogate for randomized studies, forecasting their results and offering insight into the effects of different interventional techniques. Moreover, these studies yield statistical information that may be helpful for the proper design of a randomized study (sample size, type II error).

Which angiographic variable best describes functional status 6 months after successful single-vessel coronary balloon angioplasty?

OBJECTIVES: The aim of this study was to determine which quantitative angiographic variable best describes functional status 6 months after coronary balloon angioplasty. BACKGROUND: Several angiographic restenosis criteria have been developed. These can be divided into those that describe the change in lesion severity and those that merely describe lesion severity at follow-up angiography. The functional significance of these criteria is unknown. METHODS: We studied 350 patients with single-vessel coronary artery disease who underwent a single-site balloon dilation. Sensitivity and specificity curves were constructed for the prediction of anginal status and exercise electrocardiography of four quantitative angiographic variables that describe restenosis. The point of highest diagnostic accuracy for the variables was determined at the intersection of the sensitivity and specificity curves. Results of exercise electrocardiography were considered indicative for ischemia 6 months after angioplasty if horizontal or downsloping ST segment depression > or = 1 mm occurred. RESULTS: The points of highest diagnostic accuracy of the angiographic variables were similar for both anginal status and exercise electrocardiography: 1.45 and 1.46 mm for the minimal lumen diameter measurements, 45.5% and 46.5% for the percent diameter stenosis measurements at follow-up, -0.30 and -0.32 mm for change in minimal lumen diameter and -10% and -10% for the change in percent diameter stenosis at follow-up. CONCLUSIONS: Angiographic variables reflecting a change in lesion severity at follow-up angiography were only slightly less accurate than variables that describe lesion severity at follow-up. The large study group and the fact that the same optimal values for diagnostic accuracy of the various quantitative angiographic variables were obtained for the prediction of two different markers of ischemia suggests that these values reflect the lesion severity or increase in lesion severity in major epicardial vessels at which coronary flow reserve is unable to meet myocardial demands.

Patient, lesion, and procedural variables as risk factors for luminal re-narrowing after successful coronary angioplasty: a quantitative analysis in 653 patients with 778 lesions. Multicenter European Research Trial with Cilazapril after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) Study Group.

Follow-up angiography at 6 months was obtained in 94% of the 693 patients (778 successfully dilated coronary lesions) enrolled in the Multicenter European Research trial with Cilazapril after Angioplasty to prevent Transluminal Coronary Obstruction and Restenosis (MERCATOR) trial--a double-blind, placebo-controlled trial--to study the effects of cilazapril 5 mg b.i.d. on restenosis [defined as the mean loss in minimal luminal diameter during follow-up, assessed by an interpolated edge detection technique (coronary angiography analysis system)] and long-term clinical outcome. No statistically significant difference could be detected between treatment and placebo groups with regard to clinical outcome or restenosis. The purpose of this ancillary study was to determine which, if any, patient, lesion, or procedural factors were predictive of restenosis. The identification of such factors could be helpful in the selection of lesions suitable for angioplasty and, if modifiable or controllable, potentially reduce restenosis. A stepwise multiple linear regression analysis was performed to identify independent predictors of restenosis. The following variables were retained in the model in order of significance: (a) relative gain (difference between the minimal luminal diameter pre- and post-percutaneous transluminal coronary angioplasty (PTCA), normalized for vessel size), (b) minimal luminal diameter post-PTCA, and (c) dilatation of another vessel than right coronary artery. The fit of the model was poor; where the predicted change in minimal luminal diameter was < 0.1 mm, 0.1-0.3 mm, > 0.3 mm, the corresponding percent correct classification was 30, 52, and 55%. The present study illustrates that the restenosis phenomenon cannot accurately be predicted by patient, lesion, and procedural variables.