BCS Conference 2022 Highlights: Improving embolic stroke risk prediction by left atrial 4D flow

By Dr. Oliver Jones

Key Points:

  • AF is a major risk factor for embolic stroke, but CHA2DS2VASc performs only modestly as a predictor of stroke – low risk patients are not routinely recommended OAC, but incident ischaemic stroke events range from 0.2% to 6.6% in this group.
  • Additionally, up to 20% of embolic strokes occur in the absence of AF or any other identifiable cause/
  • LA vorticity, a novel imaging biomarker of LA stasis using CMR 4D flow, was shown at the BCS Conference 2022 to be associated with increased risk of embolic stroke in a cross-sectional study
  • LA vorticity may help reclassify patients into higher risk groups, therefore identifying patients who would benefit from OAC

Atrial fibrillation, blood flow velocity, and embolic stroke

Atrial fibrillation (AF) is a major risk factor for embolic stroke. Low blood flow velocities within the fibrillating left atrium (LA) are thought to predispose to activation of the coagulation cascade and local thrombus formation, with consequent higher risk of cardioembolic stroke.

However, not all patients with AF are at risk of developing a stroke. International guidelines recommend oral anticoagulation (OAC) for patients in AF based on the presence of clinical risk factors including heart failure, hypertension, age, diabetes mellitus, prior stroke, vascular disease, and sex category, which are the components of the CHA2DS2VASc score. Patients in AF with a non-sex CHA2DS2VASc score < 2 are not routinely recommended OAC, although there are reports of incident ischaemic stroke events in this subgroup ranging from 0.2% to 6.6% in published cohort studies. The main reason behind this seems to be the relatively modest performance of CHA2DS2VASc score alone as a risk-predictor. This implies that novel biomarkers of stroke risk are needed.

Furthermore, up to 20% of embolic strokes occur in the absence of AF or any other identifiable cause. There is a possibility that patients without AF may have pro-thrombotic LA flow changes which may lead to embolic brain infarcts even in the absence of AF.

A novel imaging biomarker

For the 2022 BCS Conference Young Investigators Award Competition, Dr Marco Spartera presented a novel risk-prediction imaging biomarker using cardiac magnetic resonance (CMR) 4D flow as a predictor of LA stasis and embolic stroke risk.

CMR 4D flow was instrumented to quantify LA vorticity, a mathematical function which expresses in radians/second the tendency of blood flow to rotate within the LA. This novel biomarker stems from five years of technical development work at the University of Oxford, where Dr Spartera led the development of a LA 4D flow post-processing tool which is now open source and available on the Oxford Research Archive website. Previously published technical work from the same group has shown LA vorticity to be a temporally stable imaging biomarker with a good reproducibility profile.

Improving prediction of embolic stroke

In this latest cross-sectional study, a total of 134 patients underwent a CMR and brain magnetic resonance imaging (MRI), and 29% of patients displayed at least 1 embolic brain infarct on the brain MRI. The principal finding was that, in both AF and sinus rhythm, the risk of embolic brain infarct roughly doubled for each standard deviation reduction in LA vorticity. This relationship was preserved even after adjusting for rhythm, CHA2DS2VASc score, and other clinical and imaging factors.

Dr Spartera also pointed out that this finding is biologically plausible, as the typical LA flow pattern is vortical and a disruption of this pattern may impact the biomechanical function of platelets, but study of this had been neglected so far because of the lack of technology to study these phenomena.

Dr Spartera explained that in patients with low CHA2DS2VASc score, who are not routinely recommended for oral OAC, LA vorticity may help reclassify these patients into higher risk groups, therefore identifying otherwise untreated patients who would benefit from OAC.
An equally notable finding is that reduced LA vorticity also appeared to be associated with increased risk of embolic infarct in patients in sinus rhythm without AF. This raises the question of whether such patients could benefit from OAC – 20% of patients in sinus rhythm with embolic infarct have no identifiable embolic source.

Discussing his exciting findings, Dr Spartera outlined future research avenues, including randomised controlled trials of OAC in patients with reduced LA vorticity, who do not currently have a full indication for OAC.

Read more

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  2. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. European heart journal. 2012 Jun 1;33(12):1500-10.
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  4. Spartera MS. 2020. [updated 2020; cited 2022 June 7]. Available from: https://ora.ox.ac.uk/objects/uuid:8f2910d9-44ed-4479-85b1-dbd4f06ea54c
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