Predicting atrial fibrillation risk following embolic stroke of unknown source using cardiac magnetic resonance imaging
Authors: Kotadia I , O'dowling R , Aboagye A , Crawley R , Plein S , Sztriha L , Scott P , Masci P G , Harrison J , Birns J , Sommerville P , Bhalla A , Niederer S , O'neill M , Williams S E 
Published: May 2024

Abstract

Background
Approximately 25% of embolic strokes of unknown source (ESUS) are attributed to undiagnosed atrial fibrillation (AF).1 The European Stroke Organisation (ESO) recommends implantable loop recorder (ILR) monitoring to identify ESUS patients with AF, permit the initiation of anticoagulation and reduce risk of recurrent stroke.2 However, this approach delays treatment and carries significant cost and resource implications. An alternative approach, where early anticoagulation is initiated in the absence of AF has failed to reduce recurrent stroke in four randomised controlled trials (NAVIGATE ESUS, RE-SPECT ESUS, ATTICUS and ARCADIA).3-6 An urgent need exists for new strategies to identify ESUS patients with undiagnosed AF that are at high risk of future thromboembolism.

Purpose
The primary objective of this study was to produce a substrate-based predictive model for AF in ESUS patients using atrial cardiac magnetic resonance imaging (CMRi).

Method
The Atrial CARdiac Magnetic resonance imaging in patients with embolic stroke of unknown source without documented AF (CARM-AF) Study is a prospective, multi-centre, observational study. All patients underwent CMRi and ILR insertion for AF detection within 3 months of ESUS. The main inclusion criteria were expected survival &gt;12 months, CHA2DS2VASc≥3 and eGFR &gt;30ml/min. Patients were allocated to the study group if AF &gt;30 seconds was detected by ILR during the first year of follow-up and control group if no AF detected (Figure 1). Univariable analysis was used to identify clinical, echocardiographic and CMR parameters associated with AF diagnosis. Parameters with p&lt;0.2 and no co-linearity were used to develop multivariable logistic regression models for AF prediction.

Results
From September 2020 to September 2022, 102 patients were enrolled and 91 were included in the final analysis. AF was detected in 17 patients during the first year of follow-up (18.6%). In univariable analysis, patients with AF were more likely to be female (p=0.02), but there were no significant differences in age, race, body mass index (BMI) or CHA2DS2VASc score (p=0.06, 0.272, 0.195, 0.211) between groups. Increased left atrial (LA) volume, surface area and reduced LA ejection fraction were associated with increased risk of AF detection at 1 year (p=0.006, 0.044, 0.008). LA fibrosis and sphericity were not associated with AF (p=0.84, 0.98).
Logistic regression models for AF risk prediction were developed using patient, echocardiographic and CMR parameters. A combined model of patient and CMR parameters outperformed assessment of patient characteristics alone, achieving an AUC of 0.85 for predicting AF occurrence (p&lt;0.005). Pseudo R2 of 0.30 (McFadden) indicated excellent model fit (Figure 2).

Conclusion
CARM-AF is the first study to demonstrate feasibility and utility of CMR imaging to predict AF risk following ESUS. A randomised controlled trial initiating anticoagulation using the developed model is recommended.Study DesignModel Comparison (ROC Curves)