Frederik J. A. Beek

Accuracy of Computed Tomographic Angiography and Magnetic Resonance Angiography for Diagnosing Renal Artery Stenosis

Context Physicians sometimes use computed tomographic angiography (CTA) or magnetic resonance angiography (MRA) to diagnose renal artery stenosis. Contribution This prospective multicenter study compared CTA and MRA with digital subtraction angiography (the reference standard) in 402 hypertensive patients with suspected renal artery stenosis. Multiple experienced physicians sometimes disagreed about whether the CTA and MRA tests showed renal artery stenosis. The sensitivity estimates of CTA and MRA for detecting renal artery stenosis were 64% and 62%. Implications In this study, even trained physicians had difficulty interpreting some CTA and MRA tests, and neither test was sensitive enough to rule out renal artery stenosis. Renal artery stenosis may cause renovascular hypertension and renal impairment. Accurate detection and treatment of clinically relevant stenoses may cure or improve hypertension and preserve renal function. Current treatment options include surgery, percutaneous transluminal renal angioplasty with or without stent placement, and medical therapy. Despite the availability of several other diagnostic tests, intra-arterial digital subtraction angiography (DSA) remains the reference standard for anatomic diagnosis of renal artery stenosis. This test, however, is an invasive procedure that carries a risk for serious complications and is burdensome for patients (1, 2). For this reason, less invasive diagnostic alternatives, such as computed tomographic angiography (CTA) and 3-dimensional contrast-enhanced magnetic resonance angiography (MRA), are widely used for diagnostic work-up in patients with suspected renal artery stenosis. A recent meta-analysis (3) found that CTA and MRA were significantly better than non-contrast-enhanced magnetic resonance angiographic techniques, ultrasonography, captopril renal scintigraphy, and the captopril test at identifying renal artery stenosis when DSA was used as the reference standard. To date, however, only a limited number of small, well-designed studies have been published on the diagnostic accuracy of either CTA or MRA for detection of renal artery stenosis in patients with suspected renovascular hypertension (4-14). Because CTA and MRA seemed to be promising techniques with the potential to reduce the number of patients requiring conventional angiography, we set up a large-scale multicenter study to investigate the diagnostic performance of these tests, using DSA as reference standard, in hypertensive patients clinically deemed at risk for renal artery stenosis. The purpose of our study was to determine the interobserver agreement and diagnostic accuracy of CTA and MRA in comparison with DSA and to examine whether CTA or MRA can be used as an initial test for detection of renal artery stenosis. Methods We performed a prospective comparative study among CTA, MRA, and the reference standard, DSA, for the detection of renal artery stenosis. Each included patient underwent all 3 diagnostic tests. Participants Over a 3-year period, patients were prospectively recruited from the internal medicine outpatient clinics of 3 large teaching hospitals and 3 university hospitals in the Netherlands. The ethical review board of each hospital approved the study, and written informed consent was obtained from all participants. At the 2 hospitals that recruited most of the participating patients, enrollment was consecutive; the other participating hospitals included patients by using nonsystematic convenience samples. At the 6 participating centers, all hypertensive patients between 18 and 75 years of age with a diastolic blood pressure greater than 95 mm Hg were routinely screened for predefined clinical clues indicating renal artery stenosis, as described by the Working Group on Renovascular Hypertension (15) and others (16, 17). Patients were eligible for participation in the study if they exhibited at least 1 clinical clue. Exclusion criteria were known allergy to iodinated contrast agents; pregnancy; contraindications to MRA, CTA, or DSA (18, 19); contraindications to intervention; or previous participation in the study. All included patients were scheduled to have CTA, MRA, and DSA within a 3-month window. At the coordinating center (Maastricht University Hospital), included patients were scheduled to undergo CTA and MRA on the same day, followed by DSA the next day. At the other centers, the tests were performed on the basis of availability. No treatments that could affect the test results were allowed before all tests were completed. The case record forms for all patients were collected at the coordinating center, and the information was entered into a database. Imaging Techniques Each participating hospital was equipped with state-of-the art magnetic resonance scanners (1.0 or 1.5 Tesla), helical computed tomography scanners (single- or multi-detector row systems), and DSA equipment. In addition, hospitals were allowed to optimize scan protocols during the study when new insights emerged or when equipment was upgraded, an approach that conforms to usual clinical practice. Changes in scan protocols occurred twice (Appendix Table 1). To ensure state-of-the art magnetic resonance imaging, all scan protocols had to meet minimal quality standards in terms of spatial resolution and scan duration. The quality standards were defined by the coordinating center and were based on the protocols that were published at the start of the study. During the entire study, the coordinating center continuously monitored the quality of all images. Information about manufacturers, scan protocols, and contrast agents is shown in Appendix Table 1. All imaging was performed or supervised by experienced radiologists and radiologic technologists. Renal CTA, MRA, and DSA had already been part of clinical routine before the start of the study. Image Evaluation At the conclusion of study enrollment, 2 panels of 3 observers evaluated the CTA and MRA image data at the coordinating center. All observers had more than 3 years of experience evaluating such data on a regular basis, and for each method 1 observer had more than 6 years of experience. Each observer independently performed the evaluations and was blinded to all other results, including clinical information and DSA results. Digital image data for all CTA and MRA examinations were evaluated by using a work station equipped with all commonly used image-processing tools (EasyVision, release 4.2.1, Philips Medical Systems, Best, the Netherlands). Source images had to be examined in all cases before a final diagnosis could be made. The DSA images were evaluated by 4 vascular radiologists, all with more than 10 years of experience in this particular field. The first observer was the radiologist who actually performed the test; the evaluation took place during the DSA procedure. The second and third observers who judged each DSA examination knew the first observers judgment. If discrepancies existed among the first 3 observers with respect to the number of renal arteries involved or the nature, location, or severity of disease (differences of >10% in the degree of stenosis), a fourth radiologist, who had access to the diagnoses of the other observers, made the final diagnosis. This consensus approach has been used in several other CTA and MRA studies (6, 7, 12-14). All DSA observers were blinded to the results of CTA and MRA. To determine the degree of stenosis, the diameter of the most severely affected part of a renal artery was measured and related to the reference diameter, which was defined as the diameter of a representative nonaffected portion of the artery, preferably immediately distal to the stenosis (that is, beyond the site of poststenotic dilatation, if present). Fibromuscular dysplasia was diagnosed when multiple aneurysms separated by focal narrowing (string-of-beads sign) were observed. For CTA, MRA, and DSA, luminal narrowing of at least 50%, as well as all cases of fibromuscular dysplasia, was defined as clinically relevant renal artery stenosis (3). For each patient, the observers first recorded the number of renal arteries. Subsequently, these arteries were judged with respect to the presence or absence of stenosis (expressed as percentage of luminal narrowing), the nature of the stenosis (atherosclerotic or fibromuscular dysplasia), the location of the stenosis (ostial or truncal), and the level of confidence in the diagnosis (high, moderate, or poor) (6). Inconclusive examination results were noted on the standardized form used to collect all relevant data. Statistical Analysis The severity of the stenoses as seen on CTA and MRA was categorized on a 5-point scale (grade 1, 0% to 19%; grade 2, 20% to 49%; grade 3, 50% to 74% or fibromuscular dysplasia; grade 4, 75% to 99%; and grade 5, total occlusion [100% stenosis]). The Cohen weighted analysis was used to test for agreement beyond that of chance among the 3 observers of MRA and among the 3 observers of CTA (20). Unless stated otherwise, all analyses on the diagnostic accuracy of CTA and MRA (sensitivity, specificity, and receiver-operating curve [ROC] analysis) compared with DSA are based on patients as the unit of analysis. In the by-patient analysis, a patient was classified as having positive results if 1 or more renal arteries were found to be stenotic ( 50%) on DSA. The most severe stenosis per patient was used for analysis. Inconclusive CTA and MRA results were considered as positive test results because further diagnostic work-up would be required in clinical practice and these patients would be referred for DSA. Exact 2-sided 95% CIs for proportions were calculated by using a binomial distribution. Overall estimates of sensitivity, specificity, positive predictive value, and negative predictive value for all observers per method, including 95% CIs, were calculated by using the cluster option of Stata, version 8.2 (Stata Corp., College Station, Texas) (21). This

Long-term outcome of individualized prophylactic treatment of children with severe haemophilia.

The development of arthropathy is a serious complication of severe haemophilia. With the use of prophylaxis, bleeds can be prevented and arthropathy delayed. We investigated whether an individually tailored prophylactic regimen can prevent arthropathy and whether it had a similar effect on orthopaedic outcome compared with that of a high‐dose regimen. Efficacy was determined clinically and by radiographs of six major joints. Prophylaxis was started in 70 patients at a mean age of 4·1 years. Mean follow‐up was 15·6 years (range 8–24·5 years). The mean factor VIII consumption was 2319 IU/kg/year. The mean number of joint bleeds was 3·5/year and the mean clinical score (maximum score 90) was 1·0, with a mean Pettersson joint score (maximum score 78) of 3·0 at a mean age of 13·5 years. In conclusion, long‐term, early‐onset, individualized prophylaxis in haemophilia is feasible and prevents arthropathy.

Transluminal vascular stents for ostial atherosclerotic renal artery stenosis

We implanted transluminal stents in 24 hypertensive patients with a critical atherosclerotic ostial renal artery stenosis (28 arteries). Immediate revascularisation was successful in all. Follow-up angiography at 6 months, available in 18 patients, revealed restenosis twice. In another patient restenosis was suspected and confirmed by angiography at 2 months. Hence, the total restenosis rate was 3 of 19 patients (16%) and 3 of 23 arteries (13%). Two patients developed renal insufficiency due to cholesterol embolism. In the remaining 22 patients renal function improved (n = 8) or stabilised (n = 14). Although all had to resume antihypertensive treatment, blood pressure normalised in 15 patients, improved in one, remained unchanged in five and worsened in one.

Whole-body MRI, including diffusion-weighted imaging, for the initial staging of malignant lymphoma: comparison to computed tomography.

Purpose:To assess the value of whole-body magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), for the initial staging of malignant lymphoma, compared with computed tomography (CT). Materials and Methods:Thirty-one consecutive patients with newly diagnosed malignant lymphoma prospectively underwent whole-body MRI (T1-weighted and short inversion time inversion recovery [n = 31], and DWI [n = 28]) and CT. Ann Arbor stages were assigned by 1 radiologist according to whole-body MRI findings, and by another radiologist according to CT findings. Differences in staging between whole-body MRI (without and with DWI) and CT were resolved using other (imaging) studies (including 18F-fluoro-2-deoxyglucose positron emission tomography and bone marrow biopsy) and follow-up studies as reference standard. Results:Staging results of whole-body MRI without DWI were equal to those of CT in 74% (23/31), higher in 26% (8/31), and lower in 0% (0/31) of patients, with correct/incorrect/unresolved overstaging relative to CT in 3, 2, and 2 patients, respectively, and incorrect staging of both modalities in 1 patient. Staging results of whole-body MRI with DWI were equal to those of CT in 75% (21/28), higher in 25% (7/28), and lower in 0% (0/28) of patients, with correct/incorrect overstaging relative to CT in 6 and 1 patient(s), respectively. Conclusion:Our results suggest that initial staging of malignant lymphoma using whole-body MRI (without DWI and with DWI) equals staging using CT in the majority of patients, whereas whole-body MRI never understaged relative to CT. Furthermore, whole-body MRI mostly correctly overstaged relative to CT, with a possible advantage of using DWI.

Newly Diagnosed Lymphoma: Initial Results With Whole-Body T1-Weighted, STIR, and Diffusion-Weighted MRI Compared With 18F-FDG PET/CT

OBJECTIVE The purpose of this study was to compare whole-body MRI including diffusion-weighted imaging (DWI) with (18)F-FDG PET/CT in the staging of newly diagnosed lymphoma. SUBJECTS AND METHODS Twenty-two consecutively registered patients with newly diagnosed lymphoma prospectively underwent whole-body MRI (22 with T1-weighted, STIR, and DWI sequences and 21 with T1-weighted and STIR sequences but not DWI) and FDG PET/CT. Whole-body MRI-DWI was independently evaluated by two blinded observers. Interobserver agreement was assessed, and whole-body MRI-DWI was compared with FDG PET/CT. RESULTS The kappa values for interobserver agreement on whole-body MRI-DWI for all nodal regions together and for all extranodal regions together were 0.676 and 0.452. The kappa values for agreement between whole-body MRI-DWI and FDG PET/CT for all nodal regions together and for all extranodal regions together were 0.597 and 0.507. Ann Arbor stage according to whole-body MRI-DWI findings was concordant with that of FDG PET/CT findings in 77% (17/22) of patients. Understaging and overstaging relative to the findings with FDG PET/CT occurred in 0% (0/22) and 23% (5/22) of cases. In the care of 9% (2/22) of patients, overstaging with whole-body MRI-DWI relative to staging with FDG PET/CT would have had therapeutic consequences. CONCLUSION Our early results indicate that overall interobserver agreement on whole-body MRI-DWI findings is moderate to good. Overall agreement between whole-body MRI-DWI and FDG PET/CT is moderate. In the care of patients with newly diagnosed lymphoma, staging with whole-body MRI-DWI does not result in underestimation of stage relative to the results with FDG PET/CT. In a minority of patients, reliance on whole-body MRI-DWI leads to clinically important overstaging relative to the results with FDG PET/CT. FDG PET/CT remains the reference standard for lymphoma staging until larger-scale studies show that use of whole-body MRI-DWI results in correct staging in this minority of cases.

Complications during renal artery stent placement for atherosclerotic ostial stenosis.

PurposeTo describe short-term complications during stent placement for atherosclerotic renal artery ostial stenosis.MethodsSixty-one arteries in 50 patients were treated with Palmaz stents. Nineteen patients had a single functioning kidney, 23 had a bilateral stenosis, which was stented bilaterally in 11, and 8 had a unilateral stenosis. The complications were grouped as those related to the catheterization procedure, those related to stent placement, and those possibly related to either category. The complications were divided into those with severe clinical significance (SCS), those with minor clinical significance (MCS), and radiological-technical complications (RTC). The stent placement procedures were ordered chronologically according to examination date and the complications were tabulated per group of 10 patients.ResultsFive (10%) SCS, 5 (10%) MCS, and 8 (16%) RTC occurred in 50 patients. The catheterization procedure led to 2 SCS, 3 MCS, and 1 RTC. Stent placement gave rise to 7 RTC. Three SCS and 2 MCS could have been related to either catheterization or stent placement. More SCS occurred in the first group of 10 patients than in the following groups.ConclusionRenal artery stent placement for atherosclerotic ostial stenosis has a considerable complication rate and a learning curve is present. The complications related to the actual stent placement were without clinical consequences.

Repeated Intervention for In-Stent Restenosis of the Renal Arteries

PURPOSE To assess the long-term technical success of repeated endovascular intervention in stenosed renal artery stents. MATERIALS AND METHODS Fifteen patients with stenoses >or=50% in a renal stent placed because of an ostial atherosclerotic renal artery stenosis were included in this study. In the presence of increased blood pressure or decreased renal function, the in-stent restenosis was treated with percutaneous transluminal angioplasty (PTA) in the stent or placement of a second stent if the stenosis was located too distally in the stent. The results of these repeat interventions were evaluated by angiography. RESULTS The 15 patients had a total of 20 stenosed stents. Eighteen of these in-stent stenoses were treated with PTA and two were treated with placement of a second stent. Angiographic follow-up was available in 16 arteries, showing in-stent restenosis in four (25%; mean follow-up, 11 mo). The cumulative patency rates after repeat endoluminal intervention were 93% (95% CI: 80%-106%) and 76% (95% CI: 52%-101%) after 6 and 12 months, respectively. Renal function remained stable or improved in most patients (80%) after repeated intervention in the stent, and hypertension was classified as improved or cured in 47% of patients after 1 year. CONCLUSION Patients with stenosed renal artery stents can be treated successfully with PTA in a majority of cases, with a long-term success rate of 75% and stable renal function 1 year after repeated intervention.

Duplex Ultrasonography in Assessing Restenosis of Renal Artery Stents

Purpose: To determine the accuracy and optimal threshold values of duplex ultrasonography (US) in assessing restenosis of renal artery stents.Methods: Twenty-four consecutive patients with 33 renal arteries that had previously been treated with placement of a Palmaz stent underwent duplex US prior to intraarterial digital subtraction angiography (DSA), which was the reference standard. Diagnostic accuracy of in-stent peak systolic velocity (PSV) and reno-aortic ratio (RAR=PSV renal stent/PSV aorta) in detecting τ; 50% in-stent restenosis were evaluated by the receiver operating characteristic curve. Sensitivity and specificity were determined using the optimal threshold values, and using published threshold values: RAR τ; 3.5 and in-stent PSV τ; 180 cm/sec.Results: Six examinations were technically inadequate. Nine stents had residual or restenosis τ; 50% at DSA. The two duplex parameters were equally accurate since areas under the curves were similar (0.943). With optimal threshold values of 226 cm/sec for PSV and 2.7 for RAR, sensitivities and specificities were 100% and 90%, and 100% and 84%, respectively. Using the published duplex criteria resulted in sensitivities and specificities of 100% and 74% for PSV, and 50% and 89% for RAR.Conclusion: Duplex US is a sensitive modality for detecting in-stent restenosis if laboratory-specific threshold values are used.

Whole-body MRI, including diffusion-weighted imaging, for staging lymphoma: Comparison with CT in a prospective multicenter study

To compare whole‐body magnetic resonance imaging (MRI), including diffusion‐weighted imaging (DWI), to computed tomography (CT) for staging newly diagnosed lymphoma.

Iliac artery stenoses after percutaneous transluminal angioplasty: Follow-up with duplex ultrasonography

PURPOSE To assess iliac artery stenosis before and up to 1 year after percutaneous transluminal angioplasty (PTA) with duplex ultrasound (DUS) to determine the incidence of residual and recurrent stenoses and correlate these findings to clinical outcome. PATIENTS AND METHODS Sixty-one patients with 70 iliac artery segments treated with PTA were examined. The peak systolic velocity (PSV) ratio (PSV ratio = PSV in stenosis divided by PSV proximal or distal to stenosis) was determined by DUS before PTA and 1 day, 3 months and 1 year after PTA. Three categories of results were identified by using PSV ratios at the site of the treated stenosis 1 day and 1 year after PTA (good result, residual stenosis, and recurrent stenosis). The DUS-determined anatomic result was correlated with the clinical outcome at 1 year. Clinical outcome was classified according to Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) criteria. RESULTS Good results with DUS (PSV ratio 1 day and 1 year after PTA > or = to 2.5) were found in 45 of 70 segments (64.3%), residual stenoses (PSV ratio > or .5 1 day after PTA) in 15 of 70 segments (21.4%), and recurrent stenosis (PSV ratio 1 day after PTA < 2.5 and 1 year after PTA > or = 2.5) in 10 of 70 segments (14.3%). PSV ratios of residual stenoses decreased significantly between 1 day and 1 year after PTA because some residual stenoses improved hemodynamically in time. Clinical results were significantly better in patients with a good result compared with other patients. However, the clinical outcome of patients with residual stenoses was not significantly different from the patients with good DUS results. CONCLUSION Some residual stenoses improved sonographically after PTA. Clinical results at 1 year are highly variable within different groups. Clinical outcome of patients with residual stenoses did not differ from patients with good DUS results, whereas clinical outcome in patients with recurrent stenoses was worse than in the other groups.