Cryptogenic Ischemic Stroke Patients May Need Longer Atrial Fibrillation Monitoring, Researchers Report

Neurology Today
20 September 2012; Volume 12(18); pp 1,14–15

Samson, Kurt

Investigators reported finding paroxysmal atrial fibrillation (PAF), in episodes ranging from 5 to 30 seconds, in 10 percent of patients who had cryptogenic ischemic stroke for at least one month after their stroke. They suggest that monitoring for PAF occur for a longer period of time post-stroke.

HOW LONG SHOULD atrial fibrillation be monitored post-stroke? That is the question for a new study.

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Approximately one in nine patients who have an ischemic stroke of undetermined cause may experience undiagnosed sporadic atrial fibrillation, and extended home monitoring may be in order, according to a study published in the Aug. 10 online edition of Stroke.

The significance of the findings, which match those from smaller studies, remains to be seen because it is unclear what role these events might have in causing strokes or what the optimal treatment is in response to these events.

Many cryptogenic ischemic stroke (CIS) patients are outfitted with atrial fibrillation (AF) monitors for a short period of time after being discharged, but researchers at Kaiser Permanente's Northern California Neuroscience Center wanted to determine what happens 30 days post-discharge.

Alexander C. Flint, MD, PhD, director of neuroscience quality, and researchers, at Kaiser's Redwood City department of neuroscience, and the University of California, San Francisco, evaluated data on 239 CIS outpatients who were monitored for 30 days using an external auto-triggered electrocardiographic loop device. They found paroxysmal atrial fibrillation (PAF), in episodes ranging from 5 to 30 seconds, for at least one month after a stroke in more than 10 percent of patients.

Patients were referred as part of Kaiser's Stroke and Monitoring for PAF in Real Time (SMART) Registry, a three-year, prospective multicenter registry. PAF events were automatically recorded by changes in cardiac rhythm or by patients pressing a button when symptoms occurred.

DR. ALEXANDER C. FLINT: “Our results, taken together with similar results in smaller studies, suggest that the yield of 30-day monitoring for PAF in CIS is high enough to merit consideration of routine testing in this patient population.”

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Inclusion criteria included recent diagnosis of ischemic stroke with a negative stroke etiology workup. Exclusions included known AF, carotid stenosis of greater than 70 percent on the symptomatic side, lacunar/small vessel syndrome, and either aortic arch plaque or intracranial atherosclerosis.

Among patients meeting inclusion criteria, 12.1 percent experienced PAF within the first 30 days, with 11 percent of cases confirmed as new events after a chart review. Most events were asymptomatic — just six out of 98 episodes were associated with symptoms. On average, one in nine patients experienced PAF over the study period.

“Our results, taken together with similar results in smaller studies, suggest that the yield of 30-day monitoring for PAF in CIS is high enough to merit consideration of routine testing in this patient population,” according to Dr. Flint.

If all CIS patients were monitored during their first month, the authors reasoned, it might be possible to prevent subsequent strokes, even though the effectiveness of anticoagulant therapy — the frontline treatment for atrial fibrillation in general — has yet to be sufficiently studied in CIS patients with PAF.

Other experts not involved with the study said the conclusions might be premature, however. While the findings are in line with PAF rates in CIS patients that have been reported in smaller studies, there are not enough data yet to recommend one-month monitoring, said Stuart J. Connolly, MD, professor and chair of cardiology, and director of the arrhythmia service at McMaster University Medical Center in Hamilton, Ontario.

“Their recommendation for 30-day monitoring is premature,” he told Neurology Today in a telephone interview. “The current approach is a much shorter monitoring period, and the bottom line is that the more you monitor patients, the more you find. Whether this [study] will change practice is questionable.”

Moreover, rather than the larger external monitoring devices used in the study, technology is moving toward monitors with microchips that are inserted under the skin, he said, adding that large trials of these devices are likely to provide more reliable data.

“The downside is that these implants can cost several thousand dollars, while the ones used in the Kaiser study are around $200.”

The fact that this was a multicenter study, and previous research has been conducted only at single centers, is “a welcome addition” to better understanding PAF in CIS patients, said Ashis H. Tayal, MD, medical director of the Comprehensive Stroke Center at Allegheny General Hospital, and assistant professor of neurology at Drexel University College of Medicine in Pittsburgh, PA.

“I also think that it is nice that they used a non-invasive [monitoring] device that is relatively inexpensive and had two independent cardiologists review the findings and confirm atrial fibrillation,” he told Neurology Today in a telephone interview.

DR. STUART J. CONNOLLY: “The current approach is a much shorter monitoring period, and the bottom line is that the more you monitor patients, the more you find. Whether this [study] will change practice is questionable.”

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However he noted that it remains “more difficult” to determine what role PAF might play in stroke causation, or what the burden of PAF might be or what therapy is most appropriate. “None of this has been established yet,” Dr. Tayal said.

Some answers are expected though from the Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) trial, which has just completed enrollment, he said.

The one-year randomized, prospective study, sponsored by Medtronic, Inc., of Minneapolis, will use an insertable cardiac monitor to evaluate PAF incidence and time to PAF in 400 patients with CIS at 50 sites in Europe, Canada, and the United States. The study will include a continuous monitoring arm with a primary end point of elapsed time to detection within 6 months, with a one-year clinical follow-up. The findings are expected to be available in 2013.

Richard A. Bernstein, MD, PhD, associate professor of neurology at Northwestern University Feinberg School of Medicine, Chicago, who is the principal investigator of the CRYSTAL trial, noted that the Kaiser study included PAF episodes lasting only five seconds.“It is unclear whether this is clinically important,” Dr. Bernstein said. “Even if a patient experiences a 30-second PAF burst, I doubt most practitioners would advise anticoagulant therapy. It is not the same as if it [an episode] lasts for hours or more, which requires anticoagulants for life.”

“Even 30 seconds of Afib is of unknown significance at this time, and when they only included patients in this 30-second category, the end-result was cut in half,” he continued.

Alberto Chiti, MD, a neurologist and researcher at the neurology clinic at the University of Pisa in Italy, has studied the incidence of PAF in CIS patients, as well as cost considerations of longer post CIS monitoring. In an e-mail to Neurology Today, he said both the cost-effectiveness and proportion of positive results could be improved with better patient evaluation after CIS.

“First of all, the diagnostic workup in the acute phase should be as accurate and homogeneous as possible to rule out common causes of stroke.”

Ultrasound examination (including duplex ultrasound scan of cervical arteries, transcranial Doppler or transcranial color-coded sonography, transthoracic and transesophageal echocardiography) is feasible and relatively inexpensive, X-ray-free, and can be performed at the bedside, Dr. Chiti explained, and would enable screening for intracranial stenosis and aortic arch plaque in addition to stenosis of cervical arteries, and some cardiac sources of emboli.

“After that, the selection of patients with CIS and a pre-monitoring of those with a high probability of PAF — or rather, a high probability of a cardiac source of emboli in spite of negative diagnostic workup in the acute phase — would be advisable,” he suggested.

Selection should also include a cardioembolic profile, based on clinical and neuroradiological data, Dr. Chiti said. For example, risk factors for atrial fibrillation, such as advanced age, diabetes, hypertension, obesity, or obstructive sleep apnea, should be evaluated, in addition to neuroimaging for features suggestive of cardioembolism.

• Flint AC, Banki NM, Ren X, et al. Detection of paroxysmal atrial fibrillation by 30-day event monitoring in cryptogenic ischemic stroke. The Stroke and Monitoring for PAF in Real Time (SMART) Registry. 2012; E-pub 2012 Aug 10.

• Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the risk of stroke. 2012;366:120–129; Chiti A, Orlandi G. Comment: Subclinical atrial fibrillation and the risk of stroke.

• Tayal AH, Tian M, Kelly KM, et al. Atrial fibrillation detected by mobile cardiac outpatient telemetry in cryptogenic TIA or stroke. 2008;71:1696–1701.