Risk factors associated with major cerebrovascular complications after intracranial stenting.

BACKGROUND: There are limited data on the relationship between patient and site characteristics and clinical outcomes after intracranial stenting. METHODS: We performed a multivariable analysis that correlated patient and site characteristics with the occurrence of the primary endpoint (any stroke or death within 30 days of stenting or stroke in the territory of the stented artery beyond 30 days) in 160 patients enrolled in this stenting registry. All patients presented with an ischemic stroke, TIA, or other cerebral ischemic event (e.g., vertebrobasilar insufficiency) in the territory of a suspected 50-99% stenosis of a major intracranial artery while on antithrombotic therapy. RESULTS: Cerebral angiography confirmed that 99% (158/160) of patients had a 50-99% stenosis. In multivariable analysis, the primary endpoint was associated with posterior circulation stenosis (vs anterior circulation) (hazard ratio [HR] 3.4, 95% confidence interval [CI] 1.2-9.3, p = 0.018), stenting at low enrollment sites (< 10 patients each) (vs high enrollment site) (HR 2.8, 95% CI 1.1-7.6, p = 0.038), < or = 10 days from qualifying event to stenting (vs > or = 10 days) (HR 2.7, 95% CI 1.0-7.8, p = 0.058), and stroke as a qualifying event (vs TIA/other) (HR 3.2, 95% CI 0.9-11.2, p = 0.064). There was no significant difference in the primary endpoint based on age, gender, race, or percent stenosis (50-69% vs 70-99%). CONCLUSIONS: Major cerebrovascular complications after intracranial stenting may be associated with posterior circulation stenosis, low volume sites, stenting soon after a qualifying event, and stroke as the qualifying event. These factors will need to be monitored in future trials of intracranial stenting.

Current status of the management of symptomatic intracranial atherosclerotic disease: the rationale for a randomized trial of medical therapy and intracranial stenting.

Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) is a randomized trial comparing aggressive medical management alone with aggressive medical management in combination with angioplasty and stenting using the Gateway-Wingspan system in patients with symptomatic, high-grade, intracranial stenosis. This trial represents a landmark in the maturation of the field of neurointervention, establishing a foundation for evidenced-based practice. We review the natural history of symptomatic intracranial stenosis when treated medically, the available interventional therapies and the rationale for the design of the SAMMPRIS trial.

The NIH registry on use of the Wingspan stent for symptomatic 70-99% intracranial arterial stenosis.

BACKGROUND: The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial showed that patients with symptomatic 70% to 99% intracranial arterial stenosis are at particularly high risk of ipsilateral stroke on medical therapy: 18% at 1 year (95% CI = 3% to 24%). The Wingspan intracranial stent is another therapeutic option but there are limited data on the technical success of stenting and outcome of patients with 70% to 99% stenosis treated with a Wingspan stent. METHODS: Sixteen medical centers enrolled consecutive patients treated with a Wingspan stent in this registry between November 2005 and October 2006. Data on stenting indication, severity of stenosis, technical success (stent placement across the target lesion with <50% residual stenosis), follow-up angiography, and outcome were collected. RESULTS: A total of 129 patients with symptomatic 70% to 99% intracranial stenosis were enrolled. The technical success rate was 96.7%. The mean pre and post-stent stenoses were 82% and 20%. The frequency of any stroke, intracerebral hemorrhage, or death within 30 days or ipsilateral stroke beyond 30 days was 14.0% at 6 months (95% CI = 8.7% to 22.1%). The frequency of >or=50% restenosis on follow-up angiography was 13/52 (25%). CONCLUSION: The use of a Wingspan stent in patients with severe intracranial stenosis is relatively safe with high rate of technical success with moderately high rate of restenosis. Comparison of the event rates in high-risk patients in Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) vs this registry do not rule out either that stenting could be associated with a substantial relative risk reduction (e.g., 50%) or has no advantage compared with medical therapy. A randomized trial comparing stenting with medical therapy is needed.

Risk factor status and vascular events in patients with symptomatic intracranial stenosis.

BACKGROUND: There are limited data on the relationship between control of vascular risk factors and vascular events in patients with symptomatic intracranial arterial stenosis. METHODS: We utilized the Warfarin Aspirin Symptomatic Intracranial Disease study database to analyze vascular and lifestyle risk factors at baseline and averaged over the course of the trial. Cutoff levels defining good control for each factor were prespecified based on national guidelines. Endpoints evaluated included 1) ischemic stroke, myocardial infarction, or vascular death or 2) ischemic stroke alone. Univariate associations were assessed using the log-rank test and multivariable analysis was done using Cox proportional hazards regression. RESULTS: From baseline until year 2 follow-up, there was not a significant improvement in blood pressure control. During the same period, there were improvements in patients with total cholesterol <200 mg/dL (54.6% to 79.2%, p < 0.001) or low-density lipoprotein <100 mg/dL (28.7% to 55.9%, p < 0.001). Multivariable analysis showed that systolic blood pressure >or=140 mm Hg (HR = 1.79, p = 0.0009, 95% confidence limits 1.27 to 2.52), no alcohol consumption (HR 1.69, 1.21 to 2.39, p = 0.002), and cholesterol >or=200 mg/dL (HR 1.44, 1.004 to 2.07, p = 0.048) were associated with an increased risk of stroke, myocardial infarction, or vascular death. The same risk factors were predictors of ischemic stroke alone in multivariable analysis. CONCLUSIONS: Elevated blood pressure and cholesterol levels in symptomatic patients with intracranial stenosis are associated with an increased risk of stroke and other major vascular events.

The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial.

BACKGROUND: Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography. STUDY DESIGN: SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography. RESULTS: SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained. CONCLUSIONS: Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.

Warfarin vs aspirin for symptomatic intracranial stenosis: subgroup analyses from WASID.

The WASID trial showed no advantage of warfarin over aspirin for preventing the primary endpoint of ischemic stroke, brain hemorrhage, or vascular death. In analyses of selected subgroups, there was no definite benefit from warfarin. Warfarin reduced the risk of the primary endpoint among patients with basilar artery stenosis, but there was no reduction in stroke in the basilar artery territory or benefit for vertebral artery stenosis or posterior circulation disease in general.

A standardized method for measuring intracranial arterial stenosis.

BACKGROUND AND PURPOSE: Atherosclerosis of the major intracranial arteries is an important cause of ischemic stroke. We established measurement criteria to assess percent stenosis of a major intracranial artery (carotid, middle cerebral, vertebral, basilar) and determined the interobserver/intraobserver agreements and interclass/intraclass correlations of these measurements. METHODS: We defined percent stenosis of an intracranial artery as follows: percent stenosis = [(1 - (D(stenosis)/D(normal)))] x 100, where D(stenosis) = the diameter of the artery at the site of the most severe stenosis and D(normal) = the diameter of the proximal normal artery. If the proximal segment was diseased, contingency sites were chosen to measure D(normal): distal artery (second choice), feeding artery (third choice). Using a hand-held digital caliper, three neuroradiologists independently measured D(stenosis) and D(normal) of 24 stenotic intracranial arteries. Each observer repeated the readings 4 weeks later. We determined how frequently two observers' measurements of percent stenosis of each of the 24 diseased arteries differed by 10% or less. RESULTS: Among the three pairs of observers, interobserver agreements were 88% (observer 1 versus observer 2), 79% (observer 1 versus observer 3), 75% (observer 2 versus observer 3) for the first reading and were 75% (observer 1 versus observer 2), 100% (observer 1 versus observer 3), and 71% (observer 2 versus observer 3) for the second reading. Intraobserver agreement for each of the observers was 88%, 83%, and 100%. Interclass correlation was 85% (first reading) and 87% (second reading). Intraclass correlation was 92% (first and second readings combined). CONCLUSION: This method shows good interobserver and intraobserver agreements for the measurement of intracranial stenosis of a major artery. If validated in subsequent studies, this method may serve as a standard for the measurement of percent stenosis of an intracranial artery.

Frequency and severity of asymptomatic coronary disease in patients with different causes of stroke.

BACKGROUND AND PURPOSE: We sought (1) to compare the frequency and severity of asymptomatic coronary artery disease (CAD) in patients with different causes of brain ischemia and (2) to determine profiles of patients with brain ischemia who are at highest risk of asymptomatic CAD. METHODS: Sixty-nine patients with transient ischemic attack or stroke and without overt CAD underwent a cardiac stress test and a diagnostic evaluation to determine the cause of brain ischemia. The frequency of abnormal cardiac stress tests was compared in patients with large-artery cerebrovascular disease versus other causes of brain ischemia (90% of whom had penetrating artery disease or cryptogenic stroke). Additionally, the frequencies of vascular risk factors, resting electrocardiographic abnormalities, and cause of stroke (large-artery disease versus other causes) were compared in patients with abnormal stress tests versus patients with normal stress tests. RESULTS: The frequency of abnormal stress tests was 50% (15 of 30) in patients with large-artery cerebrovascular disease versus 23% (9 of 39) in patients with other causes of brain ischemia (P = .04). Moreover, 60% of abnormal stress tests (9 of 15) in patients with large-artery cerebrovascular disease suggested severe underlying CAD that was confirmed in 7 of 7 patients who underwent coronary angiography. On the other hand, less than 25% of abnormal stress tests (2 of 9) in patients with other causes of brain ischemia suggested severe underlying CAD. Features that were more common in patients with abnormal stress tests were smoking (P = .006), large-artery cerebrovascular disease (P = .02), veteran status (P = .02), and left ventricular hypertrophy (P = .07). CONCLUSIONS: Patients with penetrating artery disease or cryptogenic stroke have a significantly lower frequency of asymptomatic CAD than patients with large-artery cerebrovascular disease. Large-artery cerebrovascular disease, smoking, veteran status, and possibly left ventricular hypertrophy may be useful features for identifying patients with transient ischemic attack or stroke who are at highest risk of harboring asymptomatic CAD.

The Warfarin-Aspirin Symptomatic Intracranial Disease Study.

We conducted a retrospective, multicenter study to compare the efficacy of warfarin with aspirin for the prevention of major vascular events (ischemic stroke, myocardial infarction, or sudden death) in patients with symptomatic stenosis of a major intracranial artery. Patients with 50 to 99% stenosis of an intracranial artery (carotid; anterior, middle, or posterior cerebral; vertebral; or basilar) were identified by reviewing the results of consecutive angiograms performed at participating centers between 1985 and 1991. Only patients with TIA or stroke in the territory of the stenotic artery qualified for inclusion in the study. Patients were prescribed warfarin or aspirin according to local physician preference and were followed by chart review and personal or telephone interview. Seven centers enrolled 151 patients; 88 were treated with warfarin and 63 were treated with aspirin. Median follow-up was 14.7 months (warfarin group) and 19.3 months (aspirin group). Vascular risk factors and mean percent stenosis of the symptomatic artery were similar in the two groups, yet the rates of major vascular events were 18.1 per 100 patient-years of follow-up in the aspirin group (stroke rate, 10.4/100 patient-years; myocardial infarction or sudden death rate, 7.7/100 patient-years) compared with 8.4 per 100 patient-years of follow-up in the warfarin group (stroke rate, 3.6/100 patient-years; myocardial infarction or sudden death rate, 4.8/100 patient-years). Kaplan-Meier analysis showed a significantly higher percentage of patients free of major vascular events among patients treated with warfarin (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Right atrial spontaneous contrast: echocardiographic and clinical features.

We describe the clinical and echocardiographic findings in eight patients with right atrial spontaneous echo contrast who were identified from 648 consecutive patients undergoing transesophageal echocardiography. Common findings in these patients were right atrial enlargement (8 patients), tricuspid regurgitation (7 patients), atrial fibrillation or flutter (6 patients), elevated right ventricular pressure (5 patients), moderate or severe mitral valve disease (5 patients), and right to left interatrial shunts (3 patients). Right heart catheterization in three patients showed markedly elevated right atrial, right ventricular, and pulmonary artery pressures. Two patients had thromboembolic events-one patient had recurrent pulmonary emboli, and another patient with an atrial septal aneurysm had recurrent transient ischemic attacks. Right atrial echo contrast is an uncommon finding at echocardiography that is associated with severe right heart dysfunction. It may also be associated with paradoxical or pulmonary embolism.

Ischemic stroke and TIA: clinical clues to common causes.

Establishing the cause of a transient ischemic attack (TIA) or minor stroke enables you to institute effective therapy to prevent major stroke. Clinical and radiologic features that help to clarify the cause of cerebrovascular ischemia include characteristics of prior TIAs, temporal progression and nature of the neurologic deficit, and appearance of infarction on CT and MRI of the brain. Carotid and transcranial Doppler ultrasound, magnetic resonance angiography, arterial angiography, and echocardiography are used to confirm the cause of cerebral ischemia. We provide three case studies to illustrate our approach to stroke diagnosis.

Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167.

BACKGROUND AND PURPOSE: Patients with carotid stenosis have a high frequency of asymptomatic coronary artery disease (CAD). The purpose of this study of patients with asymptomatic carotid stenosis was to test the hypothesis that patients without a history of CAD have the same cardiac prognosis as patients with a history of CAD. METHODS: Men enrolled in the Department of Veterans Affairs study on the efficacy of carotid endarterectomy for asymptomatic carotid stenosis underwent a baseline cardiac evaluation (history, physical examination, and electrocardiogram) to document previous angina or myocardial infarction. Patients were randomized to medical therapy alone or medical therapy and carotid endarterectomy. Medical therapy consisted of aspirin 650 mg twice daily and treatment of risk factors. All episodes of angina, myocardial infarction, or sudden death during follow-up (average of 47.9 months) were recorded. RESULTS: Of 444 men enrolled in the study, 200 (45%) had a history of CAD. During the study 86 (43%) of 200 patients with CAD and 81 (33%) of 244 patients without a history of CAD had cardiac ischemic events (P = .03). In patients without a history of CAD, the first cardiac event was myocardial infarction or sudden death in 45 patients (56%). Factors that were independently associated with cardiac events in patients without a history of CAD were diabetes (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.15 to 3.97), intracranial occlusive disease (OR, 2.13; 95% CI, 1.13 to 4.02), and peripheral vascular disease (OR, 2.04; 95% CI, 1.14 to 3.66). Forty-two percent of patients with two of these factors and 69% of patients with all three factors had cardiac events. CONCLUSIONS: Men with carotid stenosis and no history of CAD have a lower rate of cardiac events than men with carotid stenosis who have a history of CAD. However, a subgroup of patients with carotid stenosis and no history of CAD who have coexistent intracranial occlusive disease, diabetes, or peripheral vascular disease have a risk of cardiac events similar to that of patients with a history of CAD.

Contralateral reperfusion injury after carotid endarterectomy.

Reperfusion brain edema occurs infrequently after carotid endarterectomy and has been reported only ipsilateral to the side of surgery. We report a 51-year-old woman who presented with transient right arm weakness followed by left hemiparesis. Angiography showed occlusion of the left internal carotid artery, 90% stenosis of the right internal carotid artery, filling of the left anterior cerebral artery from the right carotid circulation only, and filling of the left middle cerebral artery branches by pial collaterals from the left anterior cerebral and posterior cerebral arteries. The patient had a right carotid endarterectomy and 1 day postoperatively developed a severe headache but had no new focal neurologic findings. Computed tomography showed effacement of sulci and scattered areas of high attenuation in the left parietal lobe, consistent with cerebral edema and petechial hemorrhage or vascular engorgement. Magnetic resonance imaging 2 days later did not show a lesion in the left hemisphere, suggesting resolution of the edema. This report suggests that reperfusion brain edema can occur contralateral to carotid endarterectomy.

Death associated with asymptomatic carotid artery stenosis: long-term clinical evaluation. VA Cooperative Study 167 Group.

PURPOSE: As part of a prospective clinical trial on the efficacy of carotid endarterectomy in patients with asymptomatic carotid artery stenosis, we studied the risk factors for death in 444 male patients. METHODS: At entry to the trial, patients were judged to be healthy enough to be randomized to operative intervention and were judged to be free of any disease that would preclude a minimal 5-year life expectancy after randomization. RESULTS: Patients were treated with aspirin and optimal medical care and were monitored for an average of 4 years. Combined mortality rate was 37% (9% per year) for the medical group (38%) and surgical group (35%). Eight factors were identified that were significantly associated with increased mortality rates: coronary artery disease (p = 0.044), history of angina (p = 0.047), congestive heart failure (CHF) (p = 0.012), abnormal electrocardiography results at entry (p = 0.005), peripheral vascular disease (p = 0.019), claudication (p = 0.044), diabetes (p = 0.008), and history of hypertension (p = 0.044). The increase in risk indicated by the odds ratios (OR) were moderate (OR < 2.00) for each of the clinical risk factors except for CHF. Sixteen of 27 patients (59%) with a history of CHF at entry to the study died during follow-up (OR = 2.67). Arteriographic predictors of increased mortality rates included bilateral carotid artery stenosis and intracranial vascular disease (ICVD). With bilateral stenosis, 42% (80 of 190 patients) died compared with 33% (83 of 252 patients) with unilateral stenosis (p = 0.062). With ICVD, 43% (56 of 130 patients) died compared with 34% (107 of 314 patients) of those without ICVD (p = 0.073). Multivariate analysis demonstrated that three risk factors were significantly associated with an increased risk of death: diabetes, abnormal electrocardiography results, and claudication. Patients with two or three of these risk factors demonstrated annual mortality rates of 11.3% and 13%, respectively. This was significantly higher than patients with none of these risks (OR = 2.95 and OR = 4.06, respectively). CONCLUSION: Adult male patients with high-grade asymptomatic carotid artery stenosis demonstrate a mortality rate of 37% at a mean follow-up of 4 years. Although age was not a risk for increased mortality rates in this population, diabetes, abnormal electrocardiography results, and claudication were significant. Patients with two or three of these risk factors were at high risk of death and may require aggressive treatment of their concurrent medical diseases.

Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis.

BACKGROUND AND PURPOSE: Spontaneous echo contrast is a dynamic smokelike signal that is detected by transesophageal echocardiography in patients with stasis of blood in the left atrium. We designed this study to determine if spontaneous echo contrast is associated with an increased risk of previous stroke or peripheral embolism. METHODS: Forty-two patients with spontaneous echo contrast were identified (34 had atrial fibrillation or mitral stenosis; 8 had neither). Control subjects comprised 40 patients randomly selected from patients with atrial fibrillation or mitral stenosis who did not have spontaneous echo contrast at transesophageal echocardiography. The frequency of vascular risk factors, echocardiographic features, and stroke or peripheral embolism within 1 year of echocardiography were compared in the two groups. RESULTS: The frequency of traditional risk factors for stroke were the same in both groups, yet 9 of 42 patients with spontaneous contrast had stroke or peripheral embolism compared with only 1 of 40 control subjects (P < .02; relative risk, 10.6; 95% confidence interval, 1.3 to 88.4). In patients with nonvalvular atrial fibrillation, 6 of 12 patients with spontaneous contrast had a stroke or peripheral embolism compared with 1 of 28 patients without spontaneous contrast (P < .001; relative risk, 27.0; 95% confidence interval, 2.7 to 267.8). CONCLUSIONS: Spontaneous echo contrast is highly associated with previous stroke or peripheral embolism in patients with atrial fibrillation or mitral stenosis. Transesophageal echocardiography may enable stratification of cardioembolic risk in patients with nonvalvular atrial fibrillation.

Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction.

Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to-side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to-side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke.

Further observations on the pathology of subcortical lesions identified on magnetic resonance imaging.

We performed postmortem magnetic resonance imaging and pathologic examinations on the brains of seven consecutive patients older than 50 years of age who died of non-neurologic causes. Multiple hyperintense subcortical lesions were identified in each patient, and a total of 29 lesions were examined histologically (eight rims, six caps, six punctate lesions, and nine patches). Rims were characterized by subependymal gliosis and loss of the ependymal lining; caps were associated with myelin pallor, gliosis, and arteriosclerosis; punctate lesions were characterized by dilated perivascular spaces and perivascular gliosis; and patches were associated with myelin pallor and dilated perivascular spaces. The pattern of myelin pallor defined the size and shape of caps and patches. Arteriosclerosis was identified in six of six caps, three of six punctate lesions, and in three of nine patches. These data indicate that (1) each type of hyperintense subcortical lesion has a distinct pathologic correlate; (2) arteriosclerosis is not invariably associated with all types of hyperintense subcortical lesions on magnetic resonance imaging; and (3) myelin pallor appears to contribute to the magnetic resonance imaging signal at 1.5 tesla.