Atrial fibrosis predicts poor outcomes in embolic stroke of undetermined source
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In patients with embolic stroke of undetermined source, atrial fibrosis predicted recurrent stroke or new atrial fibrillation, according to data presented at the virtual Heart Rhythm Society Annual Scientific Sessions.
Embolic stroke of undetermined source (ESUS) accounts for as many as 25% of ischemic strokes, but implantable loop recorders indicate AF as a cause for approximately 30% of ESUS incidents, meaning another hypothesis may be necessary for the remainder of patients, Nazem Akoum, MD, MS, FACC, FAHA, FHRS, associate professor of medicine and director of the atrial fibrillation program at the University of Washington School of Medicine, said during a press conference.
Akoum and colleagues enrolled 201 patients, of whom 50 had known AF with a history of stroke (mean age, 72 years; 64% women), 50 had known AF but no history of stroke (mean age, 62 years; 33% women), 51 had ESUS but no known AF (mean age, 60 years; 44% women), 15 had lacunar stroke but no known AF (mean age, 55 years; 47% women) and 35 had no stroke or AF (mean age, 51 years; 34% women).
Atrial fibrosis burden as assessed by MRI was lowest in healthy controls (8.1%), then progressively higher in lacunar stroke/no known AF (10.8%), ESUS/no known AF (14.7%), AF without prior stroke (16.6%) and AF with prior stroke (17.9%), Akoum said during a press conference.
“Patients with ESUS have significantly higher fibrosis compared to healthy controls and lacunar stroke patients,” he said. “On the other hand, they have indistinguishable atrial fibrosis burden compared to atrial fibrillation patients, indicating that ESUS is associated with significant fibrosis independent of atrial fibrillation.”
Among those with ESUS, at 30 months, 9.8% had recurrent stroke (median time to stroke, 7 months; mean fibrosis, 15.5%) and 9.8% had new-onset AF (mean time to diagnosis, 18.6 months; mean fibrosis, 19.6%), whereas two patients had both (mean fibrosis, 17.5%), according to the researchers.
Based on data from a previous study indicating that 12% atrial fibrosis may be a good threshold to define a patient with ESUS at high risk, the researchers stratified the ESUS cohort into 20 patients with fibrosis less than 12% and 31 with fibrosis of 12% or more. In the low-risk group, recurrent stroke or new-onset AF occurred in 5% of patients, whereas in the high-risk group, it occurred in 22.6% (likelihood ratio, 3.25; P = .045), Akoum said during the press conference.
Kaplan-Meier curves of the two ESUS groups separated over time but did not reach statistical significance (HR = 4.35; 95% CI, 0.98-12.66), he said. He noted similar analyses for other clinical (eg, CHA2DS2-VASc score) and imaging (eg, atrial volume) parameters also did not reach statistical significance.
“Patients with ESUS have significantly higher atrial fibrosis burden than healthy controls and patients with lacunar strokes, but indistinguishable fibrosis from AF patients,” Akoum said during the press conference. “It argues for the hypothesis that atrial fibrosis is on the causal pathway to AF and stroke independently, and that patients with a high burden of fibrosis are at risk for a recurrent event or new atrial fibrillation, so they may be a target for a selective strategy of oral anticoagulation. As we know with the NAVIGATE-ESUS and RESPECT-ESUS trials, there was no advantage of unselective oral anticoagulation, but this may be a method to identify high-risk patients that may benefit from [oral anticoagulation]. We are trying to recruit patients with ESUS and high fibrosis and randomize them to oral anticoagulation vs. standard of care.”
Measurement of atrial fibrosis by MRI has become more common during the past 10 years, but for centers that want to start assessing it, “the most important thing is to have a champion,” Akoum said during the press conference. “You have to put together a collaborative group in cardiology, radiology, etc. It does not require much infrastructure and investment; it’s about sticking to it and putting the effort in.” – by Erik Swain
Reference:
Akoum N, et al. LBCT03-04. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 6-9, 2020 (virtual meeting).
Disclosures: The authors report no relevant financial disclosures.
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Fred M. Kusumoto, MD, FHRS
Using MRI to quantify atrial fibrosis, patients with ESUS were found to have higher atrial fibrosis levels (14.7%), similar to patients with established AF (16.6%-17.9%) and significantly higher than controls with no AF or prior stroke (8.1%). After an estimated median follow-up of 12 months, eight patients suffered a recurrent stroke, developed AF, or both simultaneously, and these patients were more likely to have higher levels of atrial fibrosis at initial evaluation.
An important message of this study is that patients with ESUS have a high risk (16%) for recurrent stroke or developing AF within the next year and require careful evaluation and follow-up. While this is a preliminary study, it provides evidence that measuring atrial fibrosis in patients with ESUS could be used to identify those patients who are at highest risk.
Looking to the future, it may be that quantifying atrial fibrosis could potentially help guide therapy to improve outcomes. For example, would larger prospective studies find that patients who have not had AF but have high levels of atrial fibrosis benefit from anticoagulation or other interventions targeting AF or its sequelae?
Finally, since atrial fibrosis seems to be an important predictor for the development of AF (as also suggested by PREDICT-AF), this study provides more stimulus for exploring whether one of the many molecules involved in the complex systems that mediate the development of atrial fibrosis could be a potential target for the treatment of AF or perhaps even prevent the development of AF.
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Akoum N, et al. LBCT03-04. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 6-9, 2020 (virtual meeting).
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