Atrial fibrosis in embolic stroke of undetermined source: A multicenter study

Abstract

Background and purpose Left atrial (LA) cardiac disease is a suspected cause of embolic stroke of undetermined source (ESUS). We tested the hypothesis that LA fibrosis, quantified using late‐gadolinium‐enhancement magnetic resonance imaging (LGE‐MRI), predicts recurrent stroke or atrial fibrillation (AF) in patients with ESUS. Methods We compared atrial fibrosis in healthy controls and patients with lacunar stroke, ESUS, and known AF with or without prior stroke. We followed patients with ESUS prospectively for the primary outcome of recurrent ischemic stroke, incident AF, or both. Results We enrolled 203 patients from three centers: 103 patients without AF (35 healthy controls, 15 with lacunar strokes, 53 with ESUS) and 100 patients with AF (50 with and 50 without prior stroke). Patients with ESUS had significantly higher atrial fibrosis (15.0 ± 6.2%) compared to healthy controls (8.1 ± 7.9%; <0.0001) and compared to lacunar stroke patients (10.8 ± 8.4; p = 0.02), but had comparable fibrosis to patients with AF with (17.9 ± 11.4%) or without prior stroke (16.6 ± 9.2%; p = NS for both). Over a mean follow‐up of 19 months, nine of 53 patients (16.9%) with ESUS experienced the combined primary outcome, which included six patients (11.3%) with recurrent ischemic stroke and five patients with incident AF (9.4%). Patients with ESUS with fibrosis ≥12% had a higher proportion of the combined outcome: 25.0% vs. 4.8%; p = 0.039. Conclusions Patients with ESUS demonstrate atrial fibrosis comparable to that seen in AF. Atrial fibrosis ≥12% was associated with recurrent stroke, incident AF or both. This subgroup of ESUS patients may benefit from anticoagulation for secondary prevention of ischemic stroke.

Fibrosis: A nexus between atrial fibrillation and left atrial appendage thrombosis

“…Tandon et al studied atrial fibrosis in patients with ESUS and demonstrated a high LGE‐MRI quantified fibrosis burden, similar to that seen in age‐ and sex‐matched AF patients 6 . A similar finding was demonstrated by Fonseca et al in a nonmatched cohort, 7 whereas Kühnlein et al also showed a higher fibrosis burden in ESUS patients and higher risk of new‐onset AF or recurrent stroke in ESUS patients with higher LGE‐MRI quantified atrial fibrosis 8 …”

“…6 A similar finding was demonstrated by Fonseca et al in a nonmatched cohort, 7 whereas Kühnlein et al also showed a higher fibrosis burden in ESUS patients and higher risk of new-onset AF or recurrent stroke in ESUS patients with higher LGE-MRI quantified atrial fibrosis. 8 In this issue of the Journal of Cardiovascular Electrophysiology,…”

Atrial Fibrosis, Ischaemic Stroke and Atrial Fibrillation

“…[ 46 ] In a larger study, atrial fibrosis was found to be significantly higher in patients with ESUS than in lacunar stroke patients and control subjects and comparable to that seen in patients with known AF ( Figure 1 ). [ 47 ]…”

“…In a prospective study, patients with ESUS underwent LGE-MRI quantification of left atrial fibrosis and were followed prospectively for recurrent stroke or incident AF. [ 47 ] Those with atrial fibrosis ≥12% were found to have a 4.3-fold increase in the risk of the combined outcome of recurrent stroke or new-onset AF compared to those with fibrosis <12%, after an average follow-up period of 19 months ( Figure 2 ). The potential implications of this study may be significant in patients with ESUS, as atrial fibrosis could be a patient selection tool for oral anticoagulation for secondary prevention.…”

Atrial CARdiac Magnetic resonance imaging in patients with embolic stroke of unknown source without documented Atrial Fibrillation (CARM-AF): Study design and clinical protocol

“… 21 Although atrial CMR imaging has frequently been used for substrate assessment in patients with known AF, few studies have published data regarding atrial substrate assessment in ESUS patients, highlighting a key knowledge gap. 22 Identifying ESUS patients displaying these structural changes in the absence of AF may arguably identify patients at higher risk of developing AF and who may benefit from early anticoagulation poststroke.…”