Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Optimized Hemodynamic Assessment to Predict Stroke Risk in Vertebrobasilar Disease: Analysis From the VERiTAS Study.

Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We sought to compare predictive models using thresholds for posterior circulation vessel flows standardized to age and vascular anatomy to optimize risk prediction. Methods and Results VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis/occlusion in vertebral and/or basilar arteries. Quantitative magnetic resonance angiography measured large-vessel vertebrobasilar territory flow, and patients were designated as low or normal flow based on a prespecified empiric algorithm considering distal territory regional flow and collateral capacity. For the present study, post hoc analysis was performed to generate additional predictive models using age-specific normalized flow measurements. Sensitivity, specificity, and time-to-event analyses were compared between the algorithms. The original prespecified algorithm had 50% sensitivity and 79% specificity for future stroke risk prediction; using a predictive model based on age-normalized flows in the basilar and posterior cerebral arteries, standardized to vascular anatomy, optimized flow status thresholds were identified. The optimized algorithm maintained sensitivity and increased specificity to 84%, while demonstrating a larger and more significant hazard ratio for stroke on time-to-event analysis. Conclusions These results indicate that flow remains a strong predictor of stroke across different predictive models, and suggest that prediction of future stroke risk can be optimized by use of vascular anatomy and age-specific normalized flows.

Infarct Patterns in Patients with Atherosclerotic Vertebrobasilar Disease in Relation to Hemodynamics.

INTRODUCTION: Distal territory blood flow is independently associated with subsequent strokes in symptomatic vertebrobasilar atherosclerotic disease. We aimed to assess infarct patterns in relation to hemodynamic status in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS: Distal territory blood flow was measured using quantitative magnetic resonance angiography (MRA) in 72 patients with symptomatic atherosclerotic vertebrobasilar disease, and then dichotomized into normal (n = 54) and low (n = 18) flow. Patients were followed longitudinally on standard medical management. Two observers blinded to flow status independently reviewed the imaging performed at the time of subsequent strokes, in order to adjudicate the likely mechanism based on infarct patterns. The frequency of stroke mechanisms was qualitatively compared based on flow status. RESULTS: During a median follow-up period of 23 months, 10/72 patients had a subsequent stroke; 5 of these had low distal flow. Infarct patterns were adjudicated to be consistent with hemodynamic (n = 2), embolic (n = 4), and junctional plaque/perforator (n = 4) infarcts. Hemodynamic infarcts were seen in 40% (2/5) low-flow patients, in comparison to 0% (0/5) normal-flow patients. CONCLUSION: In contrast to normal-flow patients, those with low distal flow seem to be uniquely susceptible to hemodynamic infarctions, although other patterns of infarction can also be seen in these hemodynamically impaired patients.

Hypoperfusion Symptoms Poorly Predict Hemodynamic Compromise and Stroke Risk in Vertebrobasilar Disease.

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods- VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results- Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P=0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P=0.87, log-rank test). Conclusions- These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

Cost-Effectiveness of Quantitative Magnetic Resonance Angiography Screening and Submaximal Angioplasty for Symptomatic Vertebrobasilar Disease.

Background and Purpose- The VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated posterior circulation distal flow status, determined by quantitative magnetic resonance angiography, is a robust predictor of vertebrobasilar stroke risk in patients with symptomatic atherosclerotic vertebrobasilar disease. Flow-compromised high-risk patients may benefit from flow-restoring endovascular procedures, such as submaximal angioplasty. In this study, we examine the cost-effectiveness of quantitative magnetic resonance angiography screening to identify patients who may benefit from submaximal angioplasty to restore vertebrobasilar flow. Methods- A Markov model was created comparing a no screening strategy with standard medical management alone and a screening strategy involving quantitative magnetic resonance angiography imaging and submaximal angioplasty for treatable patients with low vertebrobasilar flow for a 30-year time horizon. Outcomes included quality-adjusted life years (QALY) and lifetime costs. Rates of stroke and death were obtained from VERiTAS data, and disability rates and costs were derived from VERiTAS and the literature. A sensitivity analysis was performed with periprocedural stroke rate from angioplasty the primary variable of interest. Results- At a 6% periprocedural stroke risk, the screening strategy saved an average of 0.364 QALYs per patient and a lifetime cost savings of $7312 versus the no screening strategy. Among patients with low flow suitable for intervention, the benefit was substantially higher, averaging 1.485 QALYs saved and lifetime cost savings of $21 294. Across the entire cohort, QALY savings were observed at the end of the first year and economic savings at year 6. The benefit of screening declined at higher periprocedural risk. Conclusions- Quantitative magnetic resonance angiography screening and submaximal angioplasty with 6% periprocedural risk in suitable patients are cost effective both in terms of QALY and lifetime costs for patients with symptomatic vertebrobasilar occlusive disease. With potential health and economic savings, a clinical trial examining the periprocedural risk of submaximal angioplasty is warranted. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00590980.

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.

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.

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.