Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS)

Approximately 700,000 strokes occur annually in the U.S. making it the third leading cause of
death and the leading cause of permanent disability among adults. Over one third of strokes
occur in the posterior circulation, the leading cause of which is vertebrobasilar occlusive
disease secondary to atherosclerosis. Symptomatic vertebrobasilar disease (VBD) carries a
high annual risk of stroke, averaging 10-15% per year despite medical therapy. This
represents a potentially treatable high risk stroke etiology. Advances in endovascular
angioplasty and stenting have created new treatment options, but these interventions carry
significant risks, and the selection criteria for appropriate candidates remains uncertain.
Determining predictors of stroke in this population is the first step toward identifying
those high risk patients most suitable for consideration of intervention. Our preliminary
studies suggest that the risk of stroke in VBD is strongly related to the extent to which
intracranial blood flow is compromised.

The objective is to conduct a longitudinal study of patients with symptomatic VBD. Our
central hypothesis is that patients with symptomatic VBD who demonstrate limitation of blood
flow on quantitative magnetic resonance angiography (QMRA) are at higher risk of stroke.The
primary aim of this proposal is to test the hypothesis that among patients with VBD, those
with distal blood flow compromise are at higher risk of subsequent posterior circulation
stroke than those with normal flow.

Secondary exploratory aims of the proposal are to determine:the correlation between large
vessel flow measured by QMRA and tissue level perfusion measured by MR perfusion in the
posterior circulation, and the predictive value of each; other predictive factors for stroke
in this population; hemodynamic effects of varying degrees of vertebrobasilar stenosis;
changes in hemodynamic status of patients on medical therapy over time; utility of QMRA as a
non-invasive screening and monitoring tool in VBD.

The study is a prospective multi-center observational cohort study of patients with
symptomatic angiographically confirmed vertebrobasilar atherostenosis (≥ 50%), or occlusion).
Upon enrollment, patients will undergo hemodynamic assessment with noninvasive MR imaging
(including QMRA and MR perfusion), the results of which will be kept blinded from treating
physicians and the patients. Patients will be prospectively designated as demonstrating
compromised or normal distal cerebral flow based upon an existing validated algorithm of
individual posterior circulation vessel flow measurements. Baseline demographic, clinical and
laboratory data will be gathered. Subsequently, patients will have monthly clinical follow-up
and be re-imaged with QMRA at 6 month intervals for a minimum of 12 months. The primary
endpoint will be stroke incidence in the vertebrobasilar territory at one year. Survival
analysis methods, with censoring of patients not achieving endpoint at the end of the study
period, will be used for comparison of patients with compromised versus normal blood flow.

The overall goal of the study is to define the population of patients with symptomatic VBD at
highest risk of recurrent ischemic events. The information gained can significantly impact
the selection criteria and likelihood for success of future clinical trials aimed at
assessing the efficacy of endovascular or surgical interventions for the treatment of VBD.
Moreover, the ability to define a low risk population in whom the risks of expensive invasive
interventions would be unnecessary will have an equally important impact on the management of
the disease both from a clinical and cost perspective. Data regarding the hemodynamic effects
and changes over time of vertebrobasilar occlusive disease may also enhance our understanding
of the basic pathophysiology and mechanisms of stroke in this morbid disease entity.

Inclusion Criteria:

- Stroke or TIA in the vertebrobasilar territory

- Conventional or CT angiographic demonstration of ≥50% stenosis or occlusion of
extracranial or intracranial vertebrobasilar artery

- Symptoms within 60 days of enrollment

- Age 18 and above

- Able to provide informed consent

Exclusion Criteria:

Neurologic criteria:

- Major disabling stroke prohibiting the ability to return for follow-up assessment

- Any neurological disease which would confound follow-up assessment

Medical criteria:

- Any severe co-morbidity condition with less than 12 month life expectancy

- Known cardiac disease associated with cardioembolic risk specifically atrial
fibrillation, prosthetic valves, endocarditis, left atrial/ventricular thrombus,
cardiomyopathy with EF<25%, cardiac myxoma

- Blood dyscrasias, specifically polycythemia vera, essential thrombocytosis, sickle
cell disease

Disease criteria:

- Non-atherosclerotic disease vertebrobasilar disease including dissection,
fibromuscular dysplasia, vasculitis, radiation induced vasculopathy

- Unilateral vertebral stenosis or occlusion

Patient criteria:

- Unable or unwilling to undergo MRI or cerebral angiography or CTA

- Pregnancy concurrent participation in an interventional trial for treatment of
vertebrobasilar disease.

- Renal dysfunction will be exclusionary if it precludes angiography. No subjects will
be excluded based upon gender, race, ethnic group, religion or socioeconomic status.
Children will not be recruited as atherosclerotic VBD is a condition that affects
adults primarily in later life and is not a disease that occurs or is relevant in
children.