Long-term Cardiac Rhythm Monitoring More Likely to Detect A-fib After Cryptogenic Stroke

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Prolonged, continuous heart rhythm monitoring is more effective at detecting silent atrial fibrillation (A-fib) in patients with cryptogenic stroke than routine monitoring, according to 2 multicenter, randomized studies published in the June 26, 2014, issue of the New England Journal of Medicine.

For CRYSTAL AF (Cryptogenic Stroke and Underlying AF), investigators led by Tommaso Sanna, MD, of the Catholic University of the Sacred Heart (Rome, Italy), examined the efficacy of 6 months of continuous monitoring with a subcutaneous insertable cardiac monitor (REVEAL XT; Medtronic; Minneapolis, MN) vs periodic ECG readings for detecting A-fib in 441 cryptogenic stroke patients aged 40 and older with no evidence of A-fib. Patients were enrolled at 55 centers in Europe, Canada, and the United States between June 2009 and April 2012.
In the second study, EMBRACE (30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation after a Cerebral Ischemic Event), David J. Gladstone, MD, PhD, of the University of Toronto (Toronto, Canada), and colleagues randomized 572 patients aged 55 or older with cryptogenic ischemic stroke or TIA and no known A-fib within the previous 6 months to external ambulatory ECG monitoring with either a 30-day event-triggered recorder (ER910AF Cardiac Event Monitor; Braemar; Eagan, MN; n = 287) or standard 24-hour Holter monitoring (n = 285). Patients were enrolled at 16 stroke centers within the Canadian Stroke Consortium from June 2009 through March 2012. 


Continuous Monitoring Increases Diagnostic Yield   

At 6 months, 8.9% of patients in the insertable monitor arm of CRYSTAL AF showed A-fib lasting longer than 30 seconds vs 1.4% in the control group (HR 6.4; 95% CI 1.9-21.7; P < .001). By 12 months, the rates were 12.4% vs 2.0% (HR 7.3; 95% CI 2.6-20.8; P < .001). 

The median time from randomization to detection of A-fib was 84 days in the insertable monitor group and 53 days in the control group. The majority of first episodes (79%) in the insertable monitor group were asymptomatic compared with 50% in the control group. Continuation of monitoring from 6 through 12 months detected an additional 10 first episodes of A-fib in the insertable monitor group vs 1 in the control group despite 34 conventional ECG studies in 33 patients and 12 occurrences of Holter monitoring in 10 patients. 

More than twice as many patients in the insertable monitor group were taking prescription oral anticoagulants at 6 and 12 months than in the control group (table 1). By 12 months, 97% of patients in whom A-fib had been detected were on oral anticoagulants.  

Table 1. Oral Anticoagulant Prescription


Insertable Monitor 

(n = 221) 


(n = 220) 

P Value

6 Months




12 Months





Although the study was not powered to detect differences in rates of ischemic stroke or TIA between groups, events were lower in the insertable monitor group than the control group at both 6 and 12 months in intention-to-treat analysis (5.2% vs 8.6% and 7.1% vs 9.1%, respectively). 

According to the study authors, the number of insertable monitors that would need to be implanted to detect a first episode of A-fib is 14 for 6 months of monitoring, 10 for 12 months, and 4 for 36 months. 

“Further studies are needed to determine which risk factors identify the patients who would derive the most clinical benefit from detection of atrial fibrillation by prolonged monitoring with an [insertable cardiac monitor], as well as the cost effectiveness of this approach,” Dr. Sanna and colleagues conclude.

EMBRACEing Longer Monitoring  

Similarly, in the EMBRACE study, patients who used an external event-triggered monitor for 30 days had improved detection at 90-day follow-up of at least 1 episode of A-fib lasting 30 seconds or longer (the primary outcome) and 2.5 minutes or longer compared with the 24-hour Holter monitor group. The longer-duration monitor group also had higher rates of oral anticoagulant therapy prescription at follow-up (table 2). 

Table 2. A-fib, Anticoagulant Prescription at 90 Days


External 30-Day Monitor

(n = 286)


Holter Monitor

(n = 285)


P Value

A-fib Lasting ≥ 30 sec



< .001

A-fib Lasting ≥ 2.5 min



< .001

Oral Anticoagulants





Additionally, those on long-term monitoring were almost 3 times more likely than those on short-term monitoring to be switched from antiplatelet therapy to anticoagulants (13.6% vs 4.7%; P < .001).

“The finding of even brief atrial fibrillation in this population is considered important, given increasing evidence that brief subclinical atrial fibrillation predicts subsequent episodes of atrial fibrillation and is an independent risk factor for recurrent stroke,” the authors write. “Our primary outcome of atrial fibrillation lasting 30 seconds or longer is consistent with guidelines and, although arbitrary, is a potentially clinically important and actionable finding in this population.” 

They add that the findings “support prolonged monitoring after a recent cryptogenic embolic stroke or TIA in selected patients 55 years of age or older who would be considered appropriate candidates for anticoagulant therapy if atrial fibrillation were found.”

Dr. Gladstone and colleagues say the current practice of 24- or 48-hour monitoring for A-fib after stroke or TIA of undetermined cause is insufficient and should be considered “an initial screen rather than a final test, especially given our finding that the yield of clinical follow-up alone as a means of detecting atrial fibrillation was negligible.” 

Targeting a Modifiable Risk Factor  

In an editorial accompanying both studies, Hooman Kamel, MD, of Weill Cornell Medical College (New York, NY), considers how the results of CRYSTAL AF and EMBRACE should change clinical practice.

“The weight of current evidence suggests that subclinical atrial fibrillation is a modifiable risk factor for stroke recurrence, and its presence should be thoroughly ruled out in this high-risk population. Therefore, most patients with cryptogenic stroke or transient ischemic attack should undergo at least several weeks of rhythm monitoring,” he writes, adding that external loop recorders will probably be cost-effective. “Furthermore, the detection of subclinical atrial fibrillation in these patients should generally prompt a switch from antiplatelet to anticoagulant therapy.”



1. Sanna T, Diener H-C, Passman RS, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014; 370: 2478-2486.

2. Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014; 370:2467-2477.

3. Kamel H. Heart-rhythm monitoring for evaluation of cryptogenic stroke [editorial]. N Engl J Med. 2014; 370:2532-2533.


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  • CRYSTAL AF was funded by Medtronic.
  • Dr. Sanna reports receiving speaker honoraria from Medtronic and serving as a steering committee member for CRYSTAL AF.
  • EMBRACE was supported by peer-reviewed operating grants from the Canadian Stroke Network.
  • Dr. Gladstone reports receiving travel support and fees for participating on advisory boards from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer and consulting and lecture fees from Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and Pfizer.
  • Dr. Kamel reports receiving lecture fees from Genentech.