M.W. de Haan

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

Contemporary imaging techniques for the diagnosis of renal artery stenosis

Renal artery stenosis (RAS) is a potentially curable cause of renovascular hypertension (RVH) and is caused by either atherosclerosis or fibromuscular dysplasia (FMD) in the vast majority of patients. Although intra-arterial digital subtraction angiography (IA-DSA) is still considered the standard of reference test for the anatomical diagnosis of RAS, noninvasive techniques such as MR angiography, CT angiography, and color-aided duplex ultrasonography are promising alternatives that also allow functional characterization of RAS. We provide an overview of these techniques and discuss their relative merits and shortcomings. Analysis of high-quality studies shows that both MR and CT angiography are significantly more accurate for the diagnosis of at least 50% atherosclerotic RAS than ultrasonographic techniques. The primary strength of ultrasonography at present is its suggested ability to predict functional recovery based on preinterventional resistance index measurements. A still unresolved issue is the detection of FMD. Because missing RVH may have serious consequences the most important requirement for a screening test is that it has high sensitivity.

Renovascular disease in patients with hypertension: detection with duplex ultrasound.

The aim of this study was to evaluate the accuracy of duplex ultrasound for the diagnosis of renovascular disease in a cohort of hypertensive patients. In 78 patients suspected of renovascular hypertension on clinical grounds duplex ultrasound examination of the renal arteries was performed. Renal angiography was used as the standard of reference. Duplex ultrasound was inconclusive in 11 kidneys (7%). None of the supernumerary renal arteries was detected with duplex ultrasound. The overall prevalence of significant renovascular disease (⩾50% stenosis) was 20%. Based on the combination of parameters at thresholds commonly applied in current literature: ie PSVmax >180 cm/sec and RAR >3.5 the overall sensitivity of duplex ultrasound for detection of haemodynamically significant renovascular disease was 50.0% with a specificity of 91.3% (PPV: 87.9%; NPV: 59.1). Lowering the thresholds for both parameters improved the test results at the cost of a significant increase of false positive examinations. In a population of hypertensive patients clinically suspected of renovascular hypertension, only limited results for duplex ultrasound could be acquired in the detection of renovascular disease. This result, in combination with the wide range of sensitivities and specificities published in international literature and the relatively large number of incomplete examinations does not support the general application of duplex ultrasound as a screening procedure for detection and assessment of renovascular disease.

Renal artery blood flow: quantification with breath-hold or respiratory triggered phase-contrast MR imaging

Abstract. The aim of this study was to evaluate the validity and reproducibility of breath-hold and respiratory triggered phase-contrast (PC) MR imaging techniques in the measurement of renal artery blood flow. In 12 healthy subjects cardiac-gated PC flow measurements were obtained in the renal arteries using a breath-hold and a respiratory-triggered technique. The flow measurements were repeated in each renal artery separately. Comparison between the sum of flow measurements in the renal arteries and the difference in aortic flow measurements above and below the renal arteries served as an internal control. The flow measurements showed a good reproducibility both with the breath-hold (r = 0.92, p < 0.0001) and with the respiratory-triggered (r = 0.91, p < 0.0001) technique. The validity of both methods was good and there was no statistically significant difference. Reproducible quantitative measurements of renal artery blood flow are possible with respiratory controlled, cardiac-gated, PC MR imaging.

The cost-effectiveness of the diagnosis of renal artery stenosis

The objective of this study was to assess the cost effectiveness of eight strategies to diagnose renovascular hypertension (RVHT) followed by treatment with percutaneous transluminal angioplasty (PTRA) with or without stent placement. The eight diagnostic strategies were compared with a reference strategy, i.e. antihypertensive medication. The diagnostic imaging techniques under consideration were captopril renography, spiral computed tomography angiography (CTA), magnetic resonance angiography (MRA) and conventional angiography. Cost-effectiveness analysis was carried out from the perspective of the health care system, based on data from the literature. A model was developed to predict the reduction in 10-year morbidity and 10-year mortality owing to myocardial infarction, stroke and chronic renal failure achieved after PTRA compared with the reference strategy. Life-years gained over a 10-year follow-up period and the incremental cost-effectiveness ratio per life-year saved were the outcome measures. The strategy CTA followed by angiography was more effective, but more costly, than captopril renography followed by angiography, with an incremental cost-effectiveness ratio per life-year gained of Dfl 64700. Combining captopril renography with CTA was even more effective, but the incremental cost-effectiveness ratio per life-year gained was Dfl 236400. Strategies including MRA were not cost-effective. The results suggest that diagnostic strategies that include CTA are more effective than captopril renography in detecting renal artery stenosis (> 50%) and cost saving due to prevented myocardial infarction, stroke or chronic renal failure. MRA is even more effective, but in order to achieve an acceptable cost-effectiveness ratio, the costs would need to be reduced. The cost-effectiveness of the diagnostic strategies is sensitive to the pre-test probability of RVHT. So, careful clinical evaluation, in order to achieve a pre-test probability of at least 20%, is an essential component of the complete workup strategy in patients suspected to have RVHT.

Current techniques for assessment of upper extremity vasculature prior to hemodialysis vascular access creation

Vascular access problems lead to increased patient morbidity and mortality and place a large burden on care facilities, manpower and costs. Autogenous arteriovenous fistulas (AVF) are preferred over arteriovenous grafts (AVG) because of a lower incidence of vascular access related complications. An aggressive increase in the utilization of AVF, however, results in an increased incidence of AVF early failure and non-maturation. Increasing evidence suggests that routine preoperative assessment results in an increased utilization of functioning AVF by better selection of adequate vessels. To date, the reproducibility and standardization of assessment protocols are lacking and assessment of a single morphological parameter has not enabled adequate prediction of postoperative AVF function for individual patients. In this paper, we provide an overview of available diagnostic modalities and parameters that potentially enable better selection of adequate vessels for successful AVF creation.

Surgical Desobstruction of the Common Femoral Vein in Deep Venous Occlusive Disease.

thrombomodulin (TM), plays an integral role in clot formation by catalyzing the conversion of fibrinogen to fibrin. Plasmin, which is formed by the action of urokinase and tissue plasminogen activator (uPA and tPA), is responsible for the enzymatic degradation of the fibrin clot, a process known as fibrinolysis. The goal of this study was to determine the thrombotic reactivity of the pulmonary artery and iliac vein endothelial beds. Methods: Human iliac vein endothelial cells (HIVEC) and human pulmonary artery endothelial cells (HPAEC) were incubated at 37 C in the presence or absence of thrombin (1 nM, 10 nM, 25 nM, and 100 nM) for 24 hours. Plasminogen activator inhibitor-1 (PAI-1), uPA, tPA, EPCR, PAR-1, and TM expression in cell lysates were evaluated by Western blot analysis. Results: While thrombin had no effect on the expression of uPA in HPAEC, there was a w20% decrease in uPA expression in HIVEC in the presence of both 1 nM and 100 nM thrombin. Similarly, when tPA expression was examined, there was no change in HPAEC and a marked increase in HIVEC in response to thrombin. In contrast, thrombin stimulation caused a decrease in PAI-1 expression in HPAEC while having no effect on HIVEC. There was no change in EPCR expression in HPAEC; however, after stimulation with 25 nM and 100 nM thrombin, there was >20% decrease in expression of EPCR in HIVEC. HPAEC demonstrated decreased expression of PAR1 in the presence of 25 nM and 100 nM thrombin, and, in contrast, an almost 40% increase in PAR1 expression was observed in HIVEC. Thrombin produced no change in HIVEC recombinant TM expression; however, 10 nM and 100 nM thrombin produced >20% increased expression of recombinant TM in HPAEC. In addition, there was also w20% increase in the expression of pre-cursor TM in both HPAEC and HIVEC after stimulation with 25 nM thrombin. Conclusions: Endothelial cells from the deep vein and pulmonary artery venous beds differentially express markers of the fibrinolytic and coagulation pathways, and this variance in expression may play a role in the thrombotic reactivity of these vascular beds. This data may aide in the prevention and treatment of patients with pulmonary emboli.