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ABSTRACT & COMMENTARY
By Edward P. Gerstenfeld, MD
Professor of Medicine, Chief, Cardiac Electrophysiology, University of California, San Francisco
Dr. Gerstenfeld does research for Biosense Webster, Medtronic, and Rhythmia Medical.
SOURCE: Sanna T, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014;370:2478-2486.
The cause of ischemic stroke remains uncertain despite a complete diagnostic evaluation in many cases. Detection of atrial fibrillation (AF) after cryptogenic stroke would have important therapeutic implications. This study was a randomized, controlled study of 441 patients to assess whether long-term monitoring with an implantable cardiac monitor (ICM) was more effective than conventional follow-up for detecting AF in patients with cryptogenic stroke. Patients 40 years of age or older classified as cryptogenic stroke after extensive testing and with no evidence of AF during at least 24 hours of ECG monitoring underwent randomization within 90 days after stroke. The primary endpoint was the time to first detection of AF (lasting > 30 seconds). By 12 months, atrial fibrillation had been detected in 12.4% of patients in the ICM group (29 patients) vs 2.0% of patients in the control group (4 patients) (hazard ratio, 7.3; 95% CI, 2.6-20.8; P < 0.001). The authors concluded that ECG monitoring with an ICM was superior to conventional follow-up for detecting AF after cryptogenic stroke.
Undiagnosed ischemic stroke remains a difficult problem. Despite costly evaluation with carotid Doppler, echocardiography, and Holter monitoring, many patients remain without a clear diagnosis. Most patients are treated empirically with antiplatelet agents. AF is common and it is well known that the initial presentation may be a stroke. Diagnosing AF in stroke patients is important, because treatment with systemic anticoagulation (warfarin, Factor Xa, or direct thrombin inhibitors) can prevent future strokes. Yet, there is significant cost and some risk associated in treating all stroke patients with systemic anticoagulants. Twenty-four or 48-hour Holter monitors are often used to detect asymptomatic AF, but we know these are of limited value. ICMs are now smaller, can be placed in an outpatient setting, and can record ECG data for up to 3 years. Automatic algorithms can detect asymptomatic AF. The main downside is the cost (~$10,000). However, the utility of these devices in detecting asymptomatic AF was impressive in this study, with 12% of cryptogenic stroke patients having AF detected compared to only 2% undergoing standard Holter monitoring. Of course, there remains some debate about the significance of brief AF episodes detected with prolonged monitoring; brief AF may simply be a marker of patients with high stroke risk factors rather than the cause of stroke. Also, we don’t know if AF is causally related to the strokes in these patients. In addition, the effectiveness of anticoagulant therapy in patients with frequent brief episodes of AF is unclear. Current clinical practice suggests that you have to be in AF for > 48 hours before the stroke risk increases significantly. Nevertheless, this study will likely change the paradigm for the workup of cryptogenic stroke. Many neurologists will now refer patients with cryptogenic stroke for ICM implantation. Future studies should examine the clinical benefit of treating these patients with anticoagulants.