Cryptogenic Stroke: Could It Be Undiagnosed Afib?

Mark J. Alberts, MD


September 08, 2014

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Hello, and welcome to this Medscape stroke update. I am Dr. Mark Alberts, Professor and Vice Chair of Neurology at University of Texas Southwestern Medical Center in Dallas, Texas.

Today I would like to share with you the results of two very interesting and important studies published in the New England Journal of Medicine[1,2] in late June of this year. Both studies looked at a population of patients who had cryptogenic strokes, with the hypothesis that in a significant percentage of these patients, atrial fibrillation was the underlying cause of their cryptogenic strokes. Both studies looked at between 441 and 572 patients who had been worked up in a reasonable fashion to determine the cause of their strokes with brain imaging, vascular imaging, cardiac monitoring, and the usual blood tests. They enrolled several hundred patients with cryptogenic stroke.

In the Gladstone study,[1] they used an external event trigger monitor for 30 days, with the primary endpoint being an episode of atrial fibrillation lasting 30 seconds or longer. Sanna and colleagues[2] used an implantable device about the size of a small matchstick, which went under the skin to detect any occurrence of 30 seconds or more of atrial fibrillation over the next six months, then 12 months, and then up to three years. For full disclosure, I was a sub-investigator in the Sanna study, and I enrolled patients in that trial.

What did the studies find? Gladstone and colleagues found that at the end of 30 days of monitoring, the overall rate of atrial fibrillation was 16% vs only 3% in the group who received only a standard workup without a 30-day event monitor. What about the Sanna study? The rate of detection of atrial fibrillation lasting 30 seconds or longer was 9% at six months and 12.5% at one year, compared with 1.5% and 2%, respectively, with a nonimplantable standard monitoring system.

A couple of questions come to mind. Is this significant? The answer is: absolutely. These patients have been well worked up, and finding atrial fibrillation as the underlying etiology of stroke in many cases led to a change of therapy from antiplatelet agents to anticoagulants. Another question is, why was the pickup rate of atrial fibrillation so different in these two studies (16% in the Gladstone study and only about 9%-12% in the Sanna study) at one year?

One possible explanation is the patient population. In the Sanna study, the patients tended to be younger -- 61 years vs 72 years in the Gladstone study -- and increasing age increases the risk for atrial fibrillation. Furthermore, the Gladstone study had more women than men, and perhaps that made a difference in the higher rate of detection of atrial fibrillation. The flipside is that in the Sanna study, there was a subgroup of patients who were followed for up to three years, and atrial fibrillation lasting 30 seconds or longer was found in up to 30% of that subgroup. Clearly, the more you monitor these patients, the higher the pickup rate for atrial fibrillation.

Obviously, the detection paradigms were different -- external event trigger monitor vs an implantable monitor that analyzes the heart rate on a continual basis. But at the end of the day, both studies tell us that the occurrence of atrial fibrillation in patients with cryptogenic stroke is high, that it is important, and in many cases it leads to a change of therapy. What neither study tells us is whether, at the end of treatment, this makes a difference in terms of preventing strokes. This will require larger studies, with more patients treated for longer periods of time.

Thank you very much for joining me for this Medscape stroke update.


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