Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity

Christiaan H B van Niftrik; Martina Sebök; Menno R Germans; Matthias Halter; Thomas Pokorny; Vittorio Stumpo; Jacopo Bellomo; Marco Piccirelli; Athina Pangalu; Mira Katan; Susanne Wegener; Michael Tymianski; Zsolt Kulcsár; Andreas R Luft; Joseph A Fisher; David J Mikulis; Luca Regli; Jorn Fierstra

doi:10.1161/STROKEAHA.123.044259

Increased Risk of Recurrent Stroke in Symptomatic Large Vessel Disease With Impaired BOLD Cerebrovascular Reactivity

Stroke. 2024 Mar;55(3):613-621. doi: 10.1161/STROKEAHA.123.044259. Epub 2024 Feb 8.

Authors

Christiaan H B van Niftrik^#^{1

2}, Martina Sebök^#^{1

2}, Menno R Germans^{1

2}, Matthias Halter^{1

2}, Thomas Pokorny^{2

3}, Vittorio Stumpo^{1

2}, Jacopo Bellomo^{1

2}, Marco Piccirelli^{2

4}, Athina Pangalu^{2

4}, Mira Katan^{2

3}, Susanne Wegener^{2

3}, Michael Tymianski⁵, Zsolt Kulcsár^{2

4}, Andreas R Luft^{2

3}, Joseph A Fisher^{6

7}, David J Mikulis⁸, Luca Regli^{1

2}, Jorn Fierstra^{1

2

5}

Affiliations

¹ Department of Neurosurgery (C.H.B.v.N., M.S., M.R.G., M.H., V.S., J.B., L.R., J.F.), University Hospital of Zürich, University of Zürich, Switzerland.
² Clinical Neuroscience Center (C.H.B.v.N., M.S., M.R.G., M.H., T.P., V.S., J.B., M.P., A.P., M.K., S.W., Z.K., A.R.L., L.R., J.F.), University Hospital of Zürich, University of Zürich, Switzerland.
³ Department of Neurology (T.P., M.K., S.W., A.R.L.), University Hospital of Zürich, University of Zürich, Switzerland.
⁴ Department of Neurology (M.P., A.P., Z.K.), University Hospital of Zürich, University of Zürich, Switzerland.
⁵ Division of Neurosurgery, Toronto Western Hospital (M.T., J.F.), University of Toronto, ON, Canada.
⁶ Institute of Medical Science (J.A.F.), University of Toronto, ON, Canada.
⁷ Department of Anesthesia and Pain Management (J.A.F.), University Health Network, Toronto, ON, Canada.
⁸ Joint Department of Medical Imaging and Functional Neuroimaging Laboratory (D.J.M.), University Health Network, Toronto, ON, Canada.

^# Contributed equally.

PMID: 38328926
DOI: 10.1161/STROKEAHA.123.044259

Abstract

Background: Impaired cerebrovascular reactivity (CVR) has been correlated with recurrent ischemic stroke. However, for clinical purposes, most CVR techniques are rather complex, time-consuming, and lack validation for quantitative measurements. The recent adaptation of a standardized hypercapnic stimulus in combination with a blood-oxygenation-level-dependent (BOLD) magnetic resonance imaging signal as a surrogate for cerebral blood flow offers a potential universally comparable CVR assessment. We investigated the association between impaired BOLD-CVR and risk for recurrent ischemic events.

Methods: We conducted a retrospective analysis of patients with symptomatic cerebrovascular large vessel disease who had undergone a prospective hypercapnic-challenged BOLD-CVR protocol at a single tertiary stroke referral center between June 2014 and April 2020. These patients were followed up for recurrent acute ischemic events for up to 3 years. BOLD-CVR (%BOLD signal change per mm Hg CO₂) was calculated on a voxel-by-voxel basis. Impaired BOLD-CVR of the affected (ipsilateral to the vascular pathology) hemisphere was defined as an average BOLD-CVR, falling 2 SD below the mean BOLD-CVR of the right hemisphere in a healthy age-matched reference cohort (n=20). Using a multivariate Cox proportional hazards model, the association between impaired BOLD-CVR and ischemic stroke recurrence was assessed and Kaplan-Meier survival curves to visualize the acute ischemic stroke event rate.

Results: Of 130 eligible patients, 28 experienced recurrent strokes (median, 85 days, interquartile range, 5-166 days). Risk factors associated with an increased recurrent stroke rate included impaired BOLD-CVR, a history of atrial fibrillation, and heart insufficiency. After adjusting for sex, age group, and atrial fibrillation, impaired BOLD-CVR exhibited a hazard ratio of 10.73 (95% CI, 4.14-27.81; P<0.001) for recurrent ischemic stroke.

Conclusions: Among patients with symptomatic cerebrovascular large vessel disease, those exhibiting impaired BOLD-CVR in the affected hemisphere had a 10.7-fold higher risk of recurrent ischemic stroke events compared with individuals with nonimpaired BOLD-CVR.

Keywords: biomarkers; cerebral blood flow; ischemic stroke; odds ratio.

MeSH terms

Atrial Fibrillation*
Cerebral Infarction
Cerebrovascular Circulation / physiology
Cerebrovascular Disorders*
Humans
Hypercapnia / diagnostic imaging
Ischemic Stroke*
Magnetic Resonance Imaging / methods
Prospective Studies
Retrospective Studies
Stroke* / diagnostic imaging