Linda Rose-Finnell

Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke study (VERiTAS): Rationale and design

Background Over one-third of ischaemic strokes occur in the posterior circulation, and a leading cause is atherosclerotic vertebrobasilar disease. Symptomatic vertebrobasilar disease carries a high annual recurrent stroke risk, averaging 10–15% per year. Endovascular angioplasty and stenting are increasingly used but carry risks, and the benefit remains unproven. Determining stroke predictors in this population is critical to identifying high-risk patients for future trials of intervention. Preliminary studies indicate that stroke risk in vertebrobasilar disease is strongly related to haemodynamic compromise, which can be measured noninvasively using quantitative magnetic resonance angiography. Methods/study design The Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke (VERiTAS) study, a prospective multicentre NIH-funded observational study of symptomatic vertebrobasilar stenosis (≥50%) or occlusion, is designed to test the hypothesis that patients demonstrating compromised blood flow as assessed by quantitative magnetic resonance angiography are at higher stroke risk. The study will recruit 80 patients at six sites in North America over 4-years. Upon enrollment, subjects will undergo haemodynamic assessment with blinded quantitative magnetic resonance angiography to assess large vessel flow in the vertebrobasilar territory, and be prospectively designated as compromised or normal flow. Patients will be re-imaged with quantitative magnetic resonance angiography at 6-, 12-, and 24-months, and followed for 12–24-months for the primary end-point of stroke in the vertebrobasilar territory. Conclusion The VERiTAS study is the first prospective study of haemodynamics and stroke risk in the posterior circulation. The results may impact the selection criteria for interventional candidates and also define a low-risk population in whom the risks of invasive interventions would be unnecessary.

Effect of Hemodynamics on Stroke Risk in Symptomatic Atherosclerotic Vertebrobasilar Occlusive Disease

IMPORTANCE Atherosclerotic vertebrobasilar (VB) occlusive disease is a significant etiology of posterior circulation stroke, with regional hypoperfusion as an important potential contributor to stroke risk. OBJECTIVE To test the hypothesis that, among patients with symptomatic VB stenosis or occlusion, those with distal blood flow compromise as measured by large-vessel quantitative magnetic resonance angiography (QMRA) are at higher risk of subsequent posterior circulation stroke. DESIGN, SETTING, AND PARTICIPANTS A prospective, blinded, longitudinal cohort study was conducted at 5 academic hospital-based centers in the United States and Canada; 82 patients from inpatient and outpatient settings were enrolled. Participants with recent VB transient ischemic attack or stroke and 50% or more atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries underwent large-vessel flow measurement in the VB territory using QMRA. Physicians performing follow-up assessments were blinded to QMRA flow status. Follow-up included monthly telephone calls for 12 months and biannual clinical visits (for a minimum of 12 months, and up to 24 months or the final visit). Enrollment took place from July 1, 2008, to July 31, 2013, with study completion on June 30, 2014; data analysis was performed from October 1, 2014, to April 10, 2015. EXPOSURE Standard medical management of stroke risk factors. MAIN OUTCOMES AND MEASURES The primary outcome was VB-territory stroke. RESULTS Of the 82 enrolled patients, 72 remained eligible after central review of their angiograms. Sixty-nine of 72 patients completed the minimum 12-month follow-up; median follow-up was 23 (interquartile range, 14-25) months. Distal flow status was low in 18 of the 72 participants (25%) included in the analysis and was significantly associated with risk for a subsequent VB stroke (P = .04), with 12- and 24-month event-free survival rates of 78% and 70%, respectively, in the low-flow group vs 96% and 87%, respectively, in the normal-flow group. The hazard ratio, adjusted for age and stroke risk factors, in the low distal flow status group was 11.55 (95% CI, 1.88-71.00; P = .008). Medical risk factor management at 6-month intervals was similar between patients with low and normal distal flow. Distal flow status remained significantly associated with risk even when controlling for the degree of stenosis and location. CONCLUSIONS AND RELEVANCE Distal flow status determined using a noninvasive and practical imaging tool is robustly associated with risk for subsequent stroke in patients with symptomatic atherosclerotic VB occlusive disease. Identification of high-risk patients has important implications for future investigation of more aggressive interventional or medical therapies.

Hemodynamic Features of Symptomatic Vertebrobasilar Disease

Background and Purpose— Atherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort. Methods— Patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was assessed using quantitative MRA. Results— The cohort (n=72; 44% women) had a mean age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows correlated negatively with percentage stenosis in the affected vessel and positively to the minimal diameter at the stenosis site (P<0.01). A relative threshold effect was evident, with flows dropping most significantly with ≥80% stenosis/occlusion (P<0.05). Tandem disease involving the BA and either/both vertebral arteries had the greatest negative impact on immediate downstream flow in the BA (43 mL/min versus 71 mL/min; P=0.01). Distal flow status assessment, based on an algorithm incorporating collateral flow by examining distal vessels (BA and posterior cerebral arteries), correlated neither with multifocality of disease nor with severity of the maximal stenosis. Conclusions— Flow in stenotic posterior circulation vessels correlates with residual diameter and drops significantly with tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease.

Higher Stroke Risk with Lower Blood Pressure in Hemodynamic Vertebrobasilar Disease: Analysis from the VERiTAS Study.

BACKGROUND Despite concerns regarding hypoperfusion in patients with large-artery occlusive disease, strict blood pressure (BP) control has become adopted as a safe strategy for risk reduction of stroke. We examined the relationship between BP control, blood flow, and risk of subsequent stroke in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS The VERiTAS study enrolled patients with recent vertebrobasilar (VB) transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion of vertebral or basilar arteries. Hemodynamic status was designated as low or normal based on quantitative magnetic resonance angiography. Patients underwent standard medical management and follow-up for primary outcome event of VB territory stroke. Mean BP during follow-up (<140/90 versus ≥140/90 mm Hg) and flow status were examined relative to subsequent stroke risk using Cox proportional hazards analysis. RESULTS The 72 subjects had an average of 3.8 ± 1.2 BP recordings over 20 ± 8 months of follow-up; 39 (54%) had mean BP of<140/90 mm Hg. The BP groups were largely comparable for baseline demographics, risk factors, and stenosis severity. Comparing subgroups stratified by BP and hemodynamic status, we found that patients with both low flow and BP <140/90 mm Hg (n = 10) had the highest risk of subsequent stroke, with hazard ratio of 4.5 (confidence interval 1.3-16.0, P = .02), compared with the other subgroups combined. CONCLUSIONS Among a subgroup of patients with VB disease and low flow, strict BP control (BP <140/90) may increase the risk of subsequent stroke.