A Randomized Trial of Intravenous Alteplase before Endovascular Treatment for Stroke.

BACKGROUND: The value of administering intravenous alteplase before endovascular treatment (EVT) for acute ischemic stroke has not been studied extensively, particularly in non-Asian populations. METHODS: We performed an open-label, multicenter, randomized trial in Europe involving patients with stroke who presented directly to a hospital that was capable of providing EVT and who were eligible for intravenous alteplase and EVT. Patients were randomly assigned in a 1:1 ratio to receive EVT alone or intravenous alteplase followed by EVT (the standard of care). The primary end point was functional outcome on the modified Rankin scale (range, 0 [no disability] to 6 [death]) at 90 days. We assessed the superiority of EVT alone over alteplase plus EVT, as well as noninferiority by a margin of 0.8 for the lower boundary of the 95% confidence interval for the odds ratio of the two trial groups. Death from any cause and symptomatic intracerebral hemorrhage were the main safety end points. RESULTS: The analysis included 539 patients. The median score on the modified Rankin scale at 90 days was 3 (interquartile range, 2 to 5) with EVT alone and 2 (interquartile range, 2 to 5) with alteplase plus EVT. The adjusted common odds ratio was 0.84 (95% confidence interval [CI], 0.62 to 1.15; P = 0.28), which showed neither superiority nor noninferiority of EVT alone. Mortality was 20.5% with EVT alone and 15.8% with alteplase plus EVT (adjusted odds ratio, 1.39; 95% CI, 0.84 to 2.30). Symptomatic intracerebral hemorrhage occurred in 5.9% and 5.3% of the patients in the respective groups (adjusted odds ratio, 1.30; 95% CI, 0.60 to 2.81). CONCLUSIONS: In a randomized trial involving European patients, EVT alone was neither superior nor noninferior to intravenous alteplase followed by EVT with regard to disability outcome at 90 days after stroke. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by the Collaboration for New Treatments of Acute Stroke consortium and others; MR CLEAN-NO IV ISRCTN number, ISRCTN80619088.).

Predictive Factors for Sustained Pain after (sub)acute Osteoporotic Vertebral Fractures. Combined Results from the VERTOS II and VERTOS IV Trial.

PURPOSE: Osteoporotic vertebral compression fractures are treated conservatively or in selected cases with percutaneous vertebroplasty (PV). The purpose of this retrospective analysis is to determine predictive factors for a high visual analogue scale (VAS) pain score after conservative, sham or PV and is based on previously published randomized trials. METHODS: The VERTOS II compared conservative versus PV, and VERTOS IV compared sham versus PV treatment. The conservative group received pain medication. The sham and PV group received subcutaneous lidocaine/bupivacaine. In addition, the PV group received cementation, which was simulated in the sham group. Nineteen different predictors of high (≥ 5) versus low (< 5) VAS pain score at 12 months were investigated. RESULTS: 20.7% of patients in the PV group demonstrated a VAS ≥ 5 at the 12-month, compared to 40.1% in the conservative or sham group, with a significant difference (χ2(1) = 15.26, p < 0.0001, OR = 2.57, 95% CI = 1.59 to 4.15). In the subgroup analysis, we detected five predictors for the risk of high pain scores (VAS ≥ 5 after 12 months follow-up), namely: female, baseline VAS > 8, long-term baseline pain, mild/severe Genant and new fractures. CONCLUSIONS: Statistically significant more patients had a high pain score at 12 months in the sham and conservative group when compared with the PV group. Five predictors were identified for sustained high local back pain, regardless of the received treatment. Patients with moderate fracture deformity were less likely to have high pain scores at 12 months if they received PV than if they had sham or conservative therapy.

Vertebroplasty versus conservative treatment in acute osteoporotic vertebral compression fractures (Vertos II): an open-label randomised trial.

BACKGROUND: Percutaneous vertebroplasty is increasingly used for treatment of pain in patients with osteoporotic vertebral compression fractures, but the efficacy, cost-effectiveness, and safety of the procedure remain uncertain. We aimed to clarify whether vertebroplasty has additional value compared with optimum pain treatment in patients with acute vertebral fractures. METHODS: Patients were recruited to this open-label prospective randomised trial from the radiology departments of six hospitals in the Netherlands and Belgium. Patients were aged 50 years or older, had vertebral compression fractures on spine radiograph (minimum 15% height loss; level of fracture at Th5 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 5 or more. Patients were randomly allocated to percutaneous vertebroplasty or conservative treatment by computer-generated randomisation codes with a block size of six. Masking was not possible for participants, physicians, and outcome assessors. The primary outcome was pain relief at 1 month and 1 year as measured by VAS score. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00232466. FINDINGS: Between Oct 1, 2005, and June 30, 2008, we identified 431 patients who were eligible for randomisation. 229 (53%) patients had spontaneous pain relief during assessment, and 202 patients with persistent pain were randomly allocated to treatment (101 vertebroplasty, 101 conservative treatment). Vertebroplasty resulted in greater pain relief than did conservative treatment; difference in mean VAS score between baseline and 1 month was -5·2 (95% CI -5·88 to -4·72) after vertebroplasty and -2·7 (-3·22 to -1·98) after conservative treatment, and between baseline and 1 year was -5·7 (-6·22 to -4·98) after vertebroplasty and -3·7 (-4·35 to -3·05) after conservative treatment. The difference between groups in reduction of mean VAS score from baseline was 2·6 (95% CI 1·74-3·37, p<0·0001) at 1 month and 2·0 (1·13-2·80, p<0·0001) at 1 year. No serious complications or adverse events were reported. INTERPRETATION: In a subgroup of patients with acute osteoporotic vertebral compression fractures and persistent pain, percutaneous vertebroplasty is effective and safe. Pain relief after vertebroplasty is immediate, is sustained for at least a year, and is significantly greater than that achieved with conservative treatment, at an acceptable cost. FUNDING: ZonMw; COOK Medical.

Percutaneous Vertebroplasty is no Risk Factor for New Vertebral Fractures and Protects Against Further Height Loss (VERTOS IV).

BACKGROUND: Percutaneous vertebroplasty (PV) is an alternative option to treat pain after an osteoporotic vertebral compression fracture (OVCF). Controversy exists as to whether PV increases the risk of new OVCFs or prevents further vertebral height loss in treated levels. We assessed both during 1-year follow-up in patients with acute OVCF randomised to PV or a sham procedure. METHODS: VERTOS IV is a prospective, multicentre, randomised controlled trial comparing PV with sham therapy in 180 patients. New OVCFs and further vertebral height loss were assessed at 3, 6, and 12 months. RESULTS: After a median follow-up of 12 months (interquartile range (IQR) = 12-12) 31 new fractures were reported in 15 patients from the PV group and 28 new fractures in 19 patients from the sham group. The occurrence of new vertebral fractures did not significantly differ between the groups (χ2(1) = 0.83, p = 0.36, OR = .71, 95%CI = 0.33-1.50). There was no higher fracture risk of adjacent versus distant vertebrae. After sham procedure, further height loss of treated vertebrae occurred more frequently (7 patients (8%) in the PV group and 39 (45%) in the sham group (χ2(1) = 28.85, p < 0.001, OR = 9.84, 95%CI = 4.08-23.73)) and was more severe (p < .001) than after PV. CONCLUSIONS: The risk of further vertebral height loss is significantly lower after PV compared to a sham intervention, i.e. PV protects against progressive vertebral height loss. In addition, PV does not increase the risk of new adjacent and distant OVCFs. LEVEL OF EVIDENCE: Level 1a, therapeutic study. ClinicalTrials.gov number, NCT01200277.

Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): randomised sham controlled clinical trial.

OBJECTIVE: To assess whether percutaneous vertebroplasty results in more pain relief than a sham procedure in patients with acute osteoporotic compression fractures of the vertebral body. DESIGN: Randomised, double blind, sham controlled clinical trial. SETTING: Four community hospitals in the Netherlands, 2011-15. PARTICIPANTS: 180 participants requiring treatment for acute osteoporotic vertebral compression fractures were randomised to either vertebroplasty (n=91) or a sham procedure (n=89). INTERVENTIONS: Participants received local subcutaneous lidocaine (lignocaine) and bupivacaine at each pedicle. The vertebroplasty group also received cementation, which was simulated in the sham procedure group. MAIN OUTCOME MEASURES: Main outcome measure was mean reduction in visual analogue scale (VAS) scores at one day, one week, and one, three, six, and 12 months. Clinically significant pain relief was defined as a decrease of 1.5 points in VAS scores from baseline. Secondary outcome measures were the differences between groups for changes in the quality of life for osteoporosis and Roland-Morris disability questionnaire scores during 12 months' follow-up. RESULTS: The mean reduction in VAS score was statistically significant in the vertebroplasty and sham procedure groups at all follow-up points after the procedure compared with baseline. The mean difference in VAS scores between groups was 0.20 (95% confidence interval -0.53 to 0.94) at baseline, -0.43 (-1.17 to 0.31) at one day, -0.11 (-0.85 to 0.63) at one week, 0.41 (-0.33 to 1.15) at one month, 0.21 (-0.54 to 0.96) at three months, 0.39 (-0.37 to 1.15) at six months, and 0.45 (-0.37 to 1.24) at 12 months. These changes in VAS scores did not, however, differ statistically significantly between the groups during 12 months' follow-up. The results for secondary outcomes were not statistically significant. Use of analgesics (non-opioids, weak opioids, strong opioids) decreased statistically significantly in both groups at all time points, with no statistically significant differences between groups. Two adverse events occurred in the vertebroplasty group: one respiratory insufficiency and one vasovagal reaction. CONCLUSIONS: Percutaneous vertebroplasty did not result in statistically significantly greater pain relief than a sham procedure during 12 months' follow-up among patients with acute osteoporotic vertebral compression fractures. TRIAL REGISTRATION: ClinicalTrials.gov NCT01200277.

Preoperative diagnosis of carotid artery stenosis: accuracy of noninvasive testing.

BACKGROUND AND PURPOSE: Carotid endarterectomy has been shown to be beneficial in symptomatic patients with a severe stenosis (70% to 99%) of the internal carotid artery (ICA). Digital subtraction angiography (DSA) is the standard of reference in the diagnosis of carotid artery stenosis but has a relatively high complication rate. In a diagnostic study we investigated the accuracy of noninvasive testing compared with DSA. METHODS: In a prospective diagnostic study we performed duplex ultrasound (DUS), magnetic resonance angiography (MRA), and DSA on 350 consecutive symptomatic patients. Stenoses were measured with the observers blinded for clinical information and other test results. Separate and combined test results of DUS and MRA were compared with the reference standard DSA. Only the stenosis measurements of the arteries on the symptomatic side were included in the analyses. RESULTS: DUS analyzed with previously defined criteria resulted in a sensitivity of 87.5% (95% CI, 82.1% to 92.9%) and a specificity of 75.7% (95% CI, 69.3% to 82.2%) in identifying severe ICA stenosis (70% to 99%). Stenosis measurements on MRA yielded a sensitivity of 92.2% (95% CI, 86.2% to 96.2%) and a specificity of 75.7% (95% CI, 68.6% to 82.5%). When we combined MRA and DUS results, agreement between these 2 modalities (84% of patients) gave a sensitivity of 96.3% (95% CI, 90.8% to 99.0%) and a specificity of 80.2% (95% CI, 73.1% to 87.3%) for identifying severe stenosis. CONCLUSIONS: MRA showed a slightly better accuracy than DUS in the diagnosis of carotid artery stenosis. To achieve the best accuracy, however, both tests should be performed subsequently.

Evaluation of semiautomated internal carotid artery stenosis quantification from 3-dimensional contrast-enhanced magnetic resonance angiograms.

RATIONALE AND OBJECTIVES: The performance of a semiautomatic technique for internal carotid artery (ICA) stenosis quantification of the internal carotid artery in contrast-enhanced magnetic resonance angiography was evaluated. MATERIALS AND METHODS: The degree of stenosis of 52 ICAs was quantified by measuring the cross-sectional area along the center lumen line. This was performed both by 3 independent observers and the semiautomated method. The degree of stenosis was defined as the amount of cross-sectional lumen reduction. RESULTS: Agreement between the method and observers was good (weighted-kappa, kappaW = 0.89). Reproducibility of measurements of the semiautomated technique was better (kappaW = 0.97) than that of the observers (kappaW = 0.76), and the evaluated technique was considerably less time-consuming. CONCLUSIONS: Because the user interaction is limited, this technique can be used to replace an expert observer in 3-dimensional stenosis quantification of the ICA at CE-MRA in clinical practice.

Iatrogenic subtotal stenosis of the right subclavian artery treated with percutaneous transluminal angioplasty.

This report describes a rare vascular complication of surgical placement of a marking clip and a possible approach to problem solving. A 55-year-old patient presented with loss of sensation in the fingers and loss of peripheral pulsations in the right arm 4 days after right upper lobectomy for a pT2N1 moderately differentiated adenocarcinoma of the lung. Duplex examination and computed tomography were performed the same day and showed a subtotal stenosis of the right subclavian artery, which was caused by the surgical placement of a metal clip to mark the surgical boundary. Selective angiography was subsequently performed. Percutaneous transluminal angioplasty (PTA) successfully dilated the stenosis and pushed the clip off. Flow in the right subclavian artery (RSA) was completely restored as were neurology and peripheral pulses. In conclusion, arterial stenosis by a surgical (marking) clip may be feasibly treated with PTA.

Cryoplasty for occlusive disease of the femoropopliteal arteries: 1-year follow-up.

Atherosclerosis of femoropopliteal arteries is an important cause of morbidity and mortality. Percutaneous transluminal angioplasty (PTA) has only limited success in treating these arteries, mainly because of the high rate of recurrent stenosis. Cryoplasty has been proposed as a technique which might improve treatment outcome. This study reports our single-center experience with cryoplasty. Thirty-two claudicants, 33 arteries, in whom conservative therapy failed, were consecutively included. Duplex ultrasound (US), angiography, and ankle-brachial index (ABI) measurement were performed before the procedure; ABI and duplex US, 2 weeks and 3, 6, and 12 months after the procedure. Patients' symptoms were categorized according to the Rutherford classification. Lesions were classified as TASC A, B, or C according to angiographic appearance. Differences in ABI before and after the procedure were defined as significant at p < 0.05 by paired t-test. Patency was evaluated using duplex US by determining the peak systolic velocity ratio. Sixteen TASC A lesions, 13 TASC B lesions, and 4 TASC C lesions were included. ABI improved significantly for TASC A lesions 2 weeks and 3 months postprocedure. Patency after 2 weeks, 6 months, and 12 months was 93%, 67%, and 64% for TASC A lesions, 83%, 31%, and 31% for TASC B lesions, and 100%, 50%, and 33% for TASC C lesions, respectively. In conclusion, cryoplasty has good immediate success rates and patency rates similar to the results of conventional PTA in the literature.

Carotid artery stenosis: accuracy of contrast-enhanced MR angiography for diagnosis.

PURPOSE: To assess accuracy of contrast material-enhanced magnetic resonance (MR) angiography as compared with three-dimensional (3D) time-of-flight (TOF) MR angiography and reference digital subtraction angiography (DSA) in diagnosis of carotid artery stenosis. MATERIALS AND METHODS: Enhanced and 3D TOF MR angiography and DSA were performed in 51 consecutive patients suspected of having carotid artery stenosis at duplex ultrasonography. Stenoses were measured by two independent observers blinded to clinical information and other test results. Pearson correlation coefficients were used, and kappa for interobserver variabilities was estimated. Sensitivity and specificity of enhanced and 3D TOF MR angiography were calculated and compared with those of DSA. RESULTS: Pearson correlation coefficients were 0.94 (P <.01) for enhanced angiography versus DSA, 0.92 (P <.01) for 3D TOF angiography versus DSA, and 0.93 (P <.01) for enhanced versus 3D TOF angiography for observer 1 and 0.94 (P <.01), 0.95 (P <.01), and 0.94 (P <.01), respectively, for observer 2. kappa statistics were 0.81 for enhanced angiography, 0.79 for 3D TOF angiography, and 0.78 for DSA. Stenosis measurements of observer 1 at enhanced MR angiography, with inclusion of carotid arteries on the symptomatic side only, compared with those of DSA yielded a sensitivity of 90% (95% CI: 68%, 99%) and a specificity of 77% (95% CI: 55%, 92%). 3D TOF angiography yielded a sensitivity of 86% (95% CI: 67%, 97%) and a specificity of 73% (95% CI: 50%, 89%) compared with those of DSA. For observer 2, sensitivity and specificity for enhanced angiography were 91% (95% CI: 70%, 99%) and 76% (95% CI: 52%, 91%), respectively, and 90% (95% CI: 68%, 99%) and 77% (95% CI: 51%, 92%), respectively, for 3D TOF angiography. CONCLUSION: Accuracy of enhanced MR angiography in diagnosis of severe stenosis is similar to that of 3D TOF MR angiography.

Overestimation of carotid artery stenosis with magnetic resonance angiography compared with digital subtraction angiography.

BACKGROUND AND PURPOSE: Three-dimensional time-of-flight (3D TOF) magnetic resonance angiography (MRA) is generally considered to overestimate the degree of stenosis in the internal carotid artery (ICA) in comparison with the reference standard intraarterial digital subtraction angiography (DSA). We evaluated whether the degree of stenosis was more accurately assessed with 3D TOF MRA if corresponding projections on MRA and DSA were compared instead of comparison of maximal stenosis at MRA with maximal stenosis at DSA. METHODS: From February 1997 to December 1999, we included 186 symptomatic and 17 asymptomatic consecutive patients suspected of having carotid artery stenosis on the basis of clinical presentation and screening with duplex ultrasound scan examination. All patients subsequently underwent DSA and MRA imaging. From each ICA, 12 maximum intensity projections with 3D TOF MRA and two or three projections with DSA were obtained. First, we compared the maximal stenosis at MRA with the maximal stenosis at DSA. Subsequently, we used the stenosis at MRA measured on the projection corresponding with the DSA projection that showed the maximal stenosis. For both strategies, the mean differences in stenosis and sensitivity and specificity for assessment of severe stenosis (70% to 99%) were calculated and compared. RESULTS: The MRA and DSA images of 354 ICAs could be compared. The sensitivity and specificity of MRA with the projection that showed the maximal stenosis were 92.6% (95% CI, 85.3% to 97.0%) and 82.7% (95% CI, 78.1% to 87.3%), respectively. The sensitivity and specificity with the MRA projection, corresponding with the DSA projection showing the maximal stenosis, were 88.3% (95% CI, 81.8% to 94.8%) and 89.6% (95% CI, 85.9% to 93.3%), respectively. The mean difference between maximal stenosis at MRA and DSA was 7.5% (95% CI, 5.2% to 9.9%). The mean difference between stenosis at MRA and DSA in corresponding projections was 0.4% (95% CI, -2.0% to 2.7%). CONCLUSION: If corresponding MRA and intraarterial DSA projections are compared, 3D TOF MRA does not overestimate carotid stenosis.

Hemodialysis access imaging: comparison of flow-interrupted contrast-enhanced MR angiography and digital subtraction angiography.

PURPOSE: To compare flow-interrupted contrast material-enhanced magnetic resonance (MR) angiography with conventional digital subtraction angiography (DSA) for hemodialysis access imaging. MATERIALS AND METHODS: Twenty-two accesses (14 arteriovenous grafts [AVGs], eight arteriovenous fistulas [AVFs]) in 18 consecutive patients were imaged with flow-interrupted contrast-enhanced MR angiography and subsequent conventional DSA. MR image quality was assessed as excellent, good, or nondiagnostic. Anastomotic diameters in AVGs and postanastomotic diameters in AVFs were measured in consideration of an adjacent normal segment. Reductions in the diameter of the lumen and interobserver differences were analyzed with method comparison as described by Bland and Altman and expressed as the mean difference with its 95% confidence limits (CLs) (mean +/- 2 SDs). RESULTS: Image quality obtained with flow-interrupted contrast-enhanced MR angiography was considered excellent in 73% (16 of 22) and good in 23% (5 of 22). Method comparison analysis between MR angiography and DSA indicated a mean difference of 3.2% (95% CLs: -26.7%, 33.1%) for observer 1 and 4.1% (95% CLs: -23.8%, 32.1%) for observer 2. Interobserver analysis at MR angiography indicated a mean difference of 3.2% (95% CLs: -28.8%, 35.2%), and that at DSA indicated a mean difference of 3.6% (95% CLs: -9.4%, 16.7%). CONCLUSION: Image quality and anatomic depiction with flow-interrupted contrast-enhanced MR angiography and with DSA were comparable.