Bleeding increases the risk of ischemic events in patients with peripheral arterial disease.

BACKGROUND: Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease. METHODS AND RESULTS: All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7). CONCLUSIONS: In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.

Effect of carotid endarterectomy on primary collateral blood flow in patients with severe carotid artery lesions.

BACKGROUND AND PURPOSE: In patients with severe obstruction of the internal carotid artery (ICA), it is recognized that the preoperative failure to visualize collaterals of the circle of Willis increases the risk of hemispheric ischemia before, during, and after carotid endarterectomy (CEA). The purpose of the present study was to assess the effect of CEA on the anatomy and function of the circle of Willis. METHODS: Time-of-flight and phase-contrast MR angiography were used to study changes in vessel diameter and collateral flow of the circle of Willis in 48 patients with 70% to 99% ICA stenosis before and after CEA. RESULTS: In patients with unilateral ICA stenosis, all preoperative vessel diameters on both sides of the circle of Willis were larger than in control subjects. All demonstrated a significant diameter decrease to reach normal values after CEA. Furthermore, preoperative collateral flow patterns normalized after CEA (P=0.03). In patients with stenosis and contralateral ICA occlusion, CEA resulted in a significant increase in the prevalence of collateral flow via the anterior communicating artery (33% to 83%, P<0.01) and a significant increase in diameter of both A1 segments (P<0.05) in patients in whom collateral flow developed after CEA. CONCLUSIONS: CEA reduces the caliber of compensatory collateral channels to normal levels by MR angiography measurements in the presence of severe unilateral stenosis; when the opposite side is occluded and the stenosis is removed ipsilaterally, a greater amount of compensatory collateral circulation can be measured on both the occluded side and the fully opened side.

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.

Increased pregnancy loss in young women with aortoiliac disease.

BACKGROUND: During clinical evaluation of young women with peripheral arterial occlusive disease, we were surprised by the high prevalence of pregnancy loss in women with segmental stenosis confined to the aortoiliac segment. We wondered if increased occurrence of miscarriage is the result of high expression of vascular and obstetrical risk factors in these patients, or if it is related to localization of disease. In a case-control study designed to investigate risk factors for peripheral arterial occlusive disease in young women, we assessed the risk of miscarriage in these patients according to level of obstruction. METHODS: A total of 202 female patients, aged 18-49 years and 466 healthy control women from a population based case-control study, donated venous blood samples and filled out a structured questionnaire concerning classical cardiovascular risk factors and obstetrical history. In all patients, diagnosis of peripheral arterial occlusive disease was confirmed by intra-arterial angiography. Patients were classified into two groups: those with and those without stenosis of the aortoiliac segment (aortoiliac disease). RESULTS: In 77 of the 202 patients (38%) with peripheral arterial occlusive disease, the obstruction was confined to the aortoiliac segment. The occurrence of miscarriage was high (42%) in young women with aortoiliac disease. Compared to healthy controls, the risk of miscarriage increased 3-fold (OR 3.1; 95% CI 1.8-5.6) in these patients. Adjustment for obstetrical and vascular risk factors did not affect the risk estimate. CONCLUSION: This is the first study that identifies aortoiliac disease as a risk factor for pregnancy loss in young women. The risk of miscarriage is increased 3-fold in women with aortoiliac disease. The presence of vascular and obstetrical risk factors did not affect the strength of the association. Pregnancy loss could be the first sign of insufficient aortic circulation in these patients.

Time-of-flight MR angiography of carotid artery stenosis: does a flow void represent severe stenosis?

BACKGROUND AND PURPOSE: Time-of-flight (TOF) magnetic resonance angiography (MRA) is commonly used to visualize the carotid arteries; however, flow void artifacts can appear. Our purpose was to determine the frequency and diagnostic meaning of flow voids by using real patient data, as part of a larger study of MRA compared with the criterion standard, digital subtraction angiography (DSA). METHODS: In 1997-2000, 390 consecutive patients with sonographic findings suggestive of carotid artery stenosis were included in this study. All patients subsequently underwent three-dimensional (3D) TOF MRA and conventional DSA. The frequency of flow void artifacts on 3D TOF MRA images were compared with stenosis measurements on DSA images. RESULTS: We recorded 107 flow voids (16%) during 3D TOF MRA of 662 carotid arteries. DSA images were available for comparison in 102 cases. The median percentage of stenosis in this subgroup of flow voids on MRA images was 80%, compared with measurements on DSA images according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria. Stenoses ranged from 36% to 100% (occlusion). Three flow voids (2.9%) were in the 0-49% range; 11 (10.8%), in the 50-69% range; and 86 (84.3%), in the 70-99% range. Two flow voids (2.0%) represented occlusions. The positive predictive value of a flow void artifact for the presence of severe (70-99%) stenosis was 84.3% (95% CI: 77.3%, 91.4%). CONCLUSION: Flow void artifacts represented severe stenosis in most of the arteries. According to our data, the assumption that flow voids on 3D TOF MRA images represent severe stenosis is justified.

Closure of the arteriotomy after carotid endarterectomy: patch type is related to intraoperative microemboli and restenosis rate.

OBJECTIVE: Patch closure after carotid endarterectomy (CEA) improves clinical outcome compared with primary closure. Whether there are differences in outcome between various patch materials is still not clear. The objective of this retrospective study was to investigate whether a relationship exists between the patch type and the number of microemboli as registered during CEA by transcranial Doppler imaging, the clinical outcome (transient ischemic attack and cerebrovascular accident), and the occurrence of restenosis. METHODS: We included 319 patients who underwent CEA. Intraoperative microembolus registration was performed in 205 procedures. Microembolization was recorded during four different periods: dissection, shunting, clamp release, and wound closure. The decision to perform primary closure or to use a patch for the closure of the arteriotomy was made by the surgeon, and Dacron patches were used when venous material was insufficient. Cerebral events were recorded within the first month after CEA, and duplex scanning was performed at 3 months (n = 319) and 1 year (n = 166) after CEA. A diameter reduction of more than 70% was defined as restenosis. RESULTS: Primary, venous, and Dacron patch closures were performed in 83 (26.0%), 171 (53.6%), and 65 (20.4%) patients, respectively. Primary closure was significantly related to sex (Dacron patch, 35 men and 30 women; venous patch, 108 men and 63 women; primary closure, 72 men and 11 women; P < .001). The occurrence of microemboli during wound closure was also related to sex (women, 2.5 +/- 0.6; men, 1.0 +/- 0.2; P = .01). Additionally, during clamp release, Dacron patches were associated with significantly more microemboli than venous patches (11.1 +/- 3.4 vs 4.0 +/- 0.9; P < .01), and this difference was also noted during wound closure (3.1 +/- 0.9 vs 1.4 +/- 0.4; P < .05). Transient ischemic attacks and minor strokes after CEA occurred in 5 (2.4%) of 205 and 6 (2.9%) of 205 procedures, respectively, and the degree of microembolization during dissection was related to adverse cerebral events (P = .003). In contrast, the type of closure was not related to immediate clinical adverse events. However, primary closure and Dacron patches were associated with an increase in the restenosis rate compared with venous patches: after 400 days, the restenosis rate for Primary closure was 11%, Dacron patch 16%, and venous patch 7% (P = .05; Kaplan-Meier estimates). CONCLUSIONS: Microemboli are more prevalent during clamp releases and wound closure when Dacron patches are used. Additionally, the observed differences in embolization noted by patch type were mainly evident in women. However, the use of Dacron patches was not related to immediate ischemic cerebral events but was associated with a higher restenosis rate compared with venous patch closure. This suggests that venous patch closure may be preferred for CEA.

Magnetic resonance angiography of collateral compensation in asymptomatic and symptomatic internal carotid artery stenosis.

OBJECTIVE: In patients with stenosis of the internal carotid artery (ICA), the presence of collateral circulatory pathways may be crucial to maintain cerebral perfusion pressure, metabolism, and function. The purpose of the present study was to determine whether patients with asymptomatic stenosis of the ICA have a better collateral ability of the circle of Willis when compared with patients with symptomatic ICA stenosis. METHOD: Magnetic resonance angiography consisting of the circle of Willis was performed in 19 patients with severe asymptomatic ICA stenosis and in 21 patients with severe symptomatic ICA stenosis prior to carotid endarterectomy and in 53 control subjects. Between group comparisons were made for function (directional flow) and anatomy (diameter). RESULTS: In patients with asymptomatic ICA stenosis, the prevalence of collateral flow via the anterior communicating artery was significantly increased (37%, 7 of 19) compared with symptomatic patients (10%, 2 of 21) and control subjects (0%; P <.001). Patients with asymptomatic ICA stenosis demonstrated the largest mean diameter of the anterior communicating artery (1.33 +/- 0.18 mm) compared with patients with symptomatic ICA stenosis (1.22 +/- 0.18 mm) and control subjects (1.06 +/- 0.10 mm, P <.05). No differences in collateral flow pattern or diameter were found for the posterior communicating artery between the groups. CONCLUSIONS: The present cross-sectional study demonstrates the importance of an adequate hemodynamic compensation via the circle of Willis in patients with ICA stenosis. Whether differences in collateral compensation can be used to select patients for CEA has yet to be determined.

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.

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.

Imaging of carotid arteries in symptomatic patients: cost-effectiveness of diagnostic strategies.

PURPOSE: To assess the cost-effectiveness of noninvasive imaging strategies in patients who have had a transient ischemic attack (TIA) or minor stroke and are suspected of having significant carotid artery stenosis. MATERIALS AND METHODS: From 1997 through 2000, 350 patients were included in a multicenter blinded consecutive cohort study. The sensitivities and specificities of duplex ultrasonography (US), magnetic resonance (MR) angiography, and these two examinations combined were estimated by using digital subtraction angiography (DSA) as the reference standard. The actual costs (from a societal perspective) of performing imaging and endarterectomy were estimated. The survival, quality of life, and costs associated with stroke were based on data reported in the literature. Markov modeling was used to predict long-term outcomes. Subsequently, a decision model was used to calculate costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained for 62 examination-treatment strategies. Extensive sensitivity analyses were performed. RESULTS: Duplex US had 88% sensitivity and 76% specificity with use of conventional cutoff criteria. MR angiography had comparable values: 92% sensitivity and 76% specificity. Combined concordant duplex US and MR angiography had superior diagnostic performance: 96% sensitivity and 80% specificity. Duplex US alone was the most efficient strategy. Adding MR angiography led to a marginal increase in QALYs gained but at prohibitive costs (cost-effectiveness ratio > 1 500 000 per QALY gained). Performing DSA owing to discordant duplex US and MR angiographic findings and to confirm duplex US and MR angiographic findings led to extra costs and QALY loss owing to complications. Sensitivity analyses revealed that duplex US as a stand-alone examination remained the preferred strategy while estimates and assumptions were varied across plausible ranges. CONCLUSION: Duplex US performed without additional imaging is cost-effective in the selection of symptomatic patients suitable for endarterectomy. Adding MR angiography increases effectiveness slightly at disproportionately high costs, whereas DSA is inferior because of associated complications.