Agreement between site-reported and ultrasound core laboratory results for duplex ultrasound velocity measurements in the Carotid Revascularization Endarterectomy versus Stenting Trial.

OBJECTIVE: Patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) had duplex ultrasound (DU) scans prior to treatment and during follow-up to document the severity of carotid disease and the anatomic outcome of carotid endarterectomy (CEA) or carotid artery stenting (CAS). An ultrasound core laboratory (UCL) reviewed DU data from the clinical sites. This analysis was done to determine the agreement between site-reported and UCL-verified DU velocity measurements. METHODS: Clinical site DU worksheets, B-mode images, and Doppler velocity waveforms for the treated carotid arteries were reviewed at the UCL. The highest internal carotid artery peak systolic velocity (PSV) and associated Doppler angle were verified. If the angle was misaligned by >3 degrees, it was remeasured at the UCL and the PSV was recalculated. Agreement for PSV was defined as site-reported PSV within ± 5% of UCL-verified PSV. Transcription errors were corrected by the UCL but were not considered as disagreements. Follow-up analysis was limited to patients who received the assigned treatment. RESULTS: The UCL reviewed 1702 prior-to-treatment and 1743 12-month follow-up DU scans (873 CEA, 870 CAS) from 111 clinical sites. Site-reported and UCL-verified PSV agreed in 1124 (66%) of the prior-to-treatment scans and 1200 (69%) of the follow-up scans. In those cases with a disagreement, Doppler angle accounted for disagreement in 339 (59%) of the prior-to-treatment scans and 277 (51%) of the follow-up scans. Based on a threshold PSV for ≥ 70% stenosis of ≥ 230 cm/s on the prior-to-treatment scans and ≥ 300 cm/s on the follow-up scans, UCL review resulted in reclassification of stenosis severity in 75 (4.4%) of the prior-to-treatment scans and 13 (0.75%) of the follow-up scans. There is evidence that the proportion of reclassification at follow-up was greater for CAS (10 scans; 1.2%) than for CEA (three scans; 0.34%) (P = .057). CONCLUSIONS: There was a high rate of agreement between site-reported and UCL-verified DU results in CREST, and UCL review was associated with a low rate of stenosis reclassification. However, angle alignment errors were quite common and prompted recalculation of velocity in 20% of prior-to-treatment scans and 18% of follow-up scans. The use of a UCL provides a uniform process for DU interpretation and can identify sources of error and suggest technical improvements for future studies.

Restenosis after carotid artery stenting and endarterectomy: a secondary analysis of CREST, a randomised controlled trial.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3·0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6·0%) and 62 who had carotid endarterectomy (6·3%) had restenosis or occlusion (hazard ratio [HR] 0·90, 95% CI 0·63-1·29; p=0·58). Female sex (1·79, 1·25-2·56), diabetes (2·31, 1·61-3·31), and dyslipidaemia (2·07, 1·01-4·26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2·26, 1·34-3·77) but not after carotid artery stenting (0·77, 0·41-1·42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

Standardized ultrasound evaluation of carotid stenosis for clinical trials: University of Washington Ultrasound Reading Center.

INTRODUCTION: Serial monitoring of patients participating in clinical trials of carotid artery therapy requires noninvasive precision methods that are inexpensive, safe and widely available. Noninvasive ultrasonic duplex Doppler velocimetry provides a precision method that can be used for recruitment qualification, pre-treatment classification and post treatment surveillance for remodeling and restenosis. The University of Washington Ultrasound Reading Center (UWURC) provides a uniform examination protocol and interpretation of duplex Doppler velocity measurements. METHODS: Doppler waveforms from 6 locations along the common carotid and internal carotid artery path to the brain plus the external carotid and vertebral arteries on each side using a Doppler examination angle of 60 degrees are evaluated. The UWURC verifies all measurements against the images and waveforms for the database, which includes pre-procedure, post-procedure and annual follow-up examinations. Doppler angle alignment errors greater than 3 degrees and Doppler velocity measurement errors greater than 0.05 m/s are corrected. RESULTS: Angle adjusted Doppler velocity measurements produce higher values when higher Doppler examination angles are used. The definition of peak systolic velocity varies between examiners when spectral broadening due to turbulence is present. Examples of measurements are shown. DISCUSSION: Although ultrasonic duplex Doppler methods are widely used in carotid artery diagnosis, there is disagreement about how the examinations should be performed and how the results should be validated. In clinical trails, a centralized reading center can unify the methods. Because the goals of research examinations are different from those of clinical examinations, screening and diagnostic clinical examinations may require fewer velocity measurements.

Measurement of anastomosis geometry in lower extremity bypass grafts with 3-D ultrasound imaging.

The attachment sites of lower extremity bypass grafts are known to exhibit a wide range of geometries. Factors that determine the geometry of a given anastomosis include graft material, graft site, native vessel size, graft size and individual patient anatomy. Therefore, it is difficult to specify a standard anastomosis geometry before surgery and difficult to predict the effect of the geometry on long-term graft patency. We have used 3-D ultrasound imaging to study 46 proximal anastomoses of lower limb bypass grafts. We have developed methods to characterize the 3-D geometry of the anastomosis in terms of component sizes and angles. These detailed geometric measurements describe a range of anastomosis geometries and establish standardized parameters across cases that can be used to relate anastomosis geometry to outcome.

Display of spatially-registered Doppler spectral waveforms and three-dimensional vein graft geometry.

A method has been developed to display Doppler spectral waveforms in lower extremity vein grafts in conjunction with 3-D vessel geometry. Doppler spectral waveforms and cross-sectional images of the vein graft are collected with a custom 3-D ultrasound imaging system. Computer processing generates a display of the Doppler sample volumes registered in 3-D space with a surface reconstruction of the vein graft lumen. An interactive computer interface displays spectral waveforms at user-selected sites in the graft. Summary displays combining spectral waveforms, maximum velocity and cross-sectional area provide a pictorial record of the state of the vein graft along its full length. The method is demonstrated for two patient studies, each at two time points after graft revisions. The graphic display of both hemodynamics and geometry allows rapid assessment of vein graft changes over time.

Remodeling in peripheral vein graft revisions: serial study with three-dimensional ultrasound imaging.

OBJECTIVE: Remodeling of vein grafts in the lower limb can lead to stenotic lesions that threaten long-term graft patency. Progressive changes in vein graft geometry were measured at sites of repaired stenoses with three-dimensional (3D) ultrasound imaging. METHODS: Ten vein graft revisions with patch angioplasty were followed up for 31 to 47 weeks. Four revisions were at valve sites, and six were at sites of diffuse intimal hyperplasia. Sets of spatially registered two-dimensional (2D) cross-sectional ultrasound images were assembled to create 3D computer models of each vein graft. Cross-sectional area measurements in planes normal to the vessel center axis were calculated from the 3D surface reconstructions. Data sets from serial studies were registered in a common coordinate system, and cross-sectional area measurements were compared at matched sites. RESULTS: Three of the four vein graft revisions at valve sites changed by less than 18%, and one decreased in cross-sectional area by 61%. Five of the six revisions at sites of diffuse intimal hyperplasia demonstrated significant decreases in lumen area ranging from 26% to 61%, and one revision exhibited no significant change in cross-sectional area. Reproducibility of the cross-sectional area measurements derived from the 3D imaging technique was 6.9%. CONCLUSIONS: Sequential area measurements from 3D ultrasound scans demonstrated different remodeling patterns and rates of change among revision sites within the vein grafts. Lumen narrowing documented with 3D scanning was not associated with consistent flow velocity changes on conventional duplex graft surveillance scans.

Coagulation, fibrinolysis, and recanalization after acute deep venous thrombosis.

OBJECTIVE: Recanalization is common after acute deep venous thrombosis, but the factors that contribute to its variable extent are unknown. The purpose of this study was to examine the relationship between recanalization and plasma markers of coagulation and fibrinolysis. METHODS: Subjects with an ultrasound-confirmed deep venous thrombosis had prothrombin fragment 1+2 (F 1+2), tissue plasminogen activator (t-PA) activity, plasminogen activator inhibitor (PAI-1) activity, and t-PA antigen levels determined before anticoagulation therapy. Ultrasound and plasma studies were repeated at 14 days, 1 month, and every 3 months for 1 year. RESULTS: Among 71 enrolled subjects, F 1+2 levels normalized within 14 days. The mean t-PA activity was within the normal range at all follow-up intervals. However, the mean t-PA antigen (10.7 plus minus 10.5 to 13.6 plus minus 13.5 ng/mL; P =.04) and PAI-1 (9.0 plus minus 8.1 to 13.2 plus minus 17.3 U/mL; P =.05) levels increased between the time of presentation and day 14. The mean reduction in thrombus score among 44 patients who completed 9 months of follow-up was 60.9% (plus minus 42.1%). Percent recanalization was directly associated with initial t-PA activity levels (R =.4; P =.006) and inversely related to F 1+2 (R = minus sign. 5; P =.004), t-PA antigen (R = minus sign.5, P =.002), and PAI-1 (r = minus sign. 5, P =.001) levels. However, only initial F 1+2 (P =.0009) and t-PA antigen (P =.004) levels were independent predictors of the degree of recanalization. CONCLUSION: Although the mechanisms by which the venous lumen is restored are still being elucidated, recanalization is inversely related to levels of activated coagulation (F 1+2) and fibrinolytic inhibition (t-PA antigen) at the time of presentation.