Atrial Fibrillation in Patients with Cryptogenic StrokeGladstone DJ et al. N Engl J Med 2014; 370:2467-2477

Presented by Kris Huston | July 21, 2014

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EMBRACE trial

30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event

Multicenter, 3-year study funded by the Canadian Stroke Network

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Background

Atrial fibrillation is a major cause of stroke worldwide.

Strokes due to atrial fibrillation are potentially preventable.

Paroxysmal atrial fibrillation often evades detection.

Many strokes have undetermined etiology (cryptogenic).

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Cryptogenic stroke

Brain infarction that is not attributable to a source of definite cardioembolism, large artery atherosclerosis, or small artery disease.

Diagnosis of exclusion based on thorough investigation of other potential etiologies.

Cryptogenic stroke accounts for 30 to 40 percent of ischemic strokes (and half the TIAs).

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Primary objective

To determine the diagnostic yield of a 30-day cardiac event monitor compared to a repeat 24-hour Holter monitor for detecting occult paroxysmal atrial fibrillation in patients with a recent ischemic stroke or TIA of undetermined etiology.

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Study population

• 55 years or older

• Experienced ischemic stroke or TIA within previous 6 months

• No cause identified by post-stroke/TIA diagnostic workup, including ECG, 24-hr Holter, brain imaging, and echo.

• No history of atrial fibrillation or flutter.

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Randomization, ECG Monitoring, and Follow-up

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Baseline Characteristics of the Patients

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Study design

Multicenter, two-arm, unblinded, randomized controlled trial

Sample size: N = 564

Participants were randomized (1:1) to receive either:

(1) a 30-day event-triggered loop recorder (intervention group) or

(2) a repeat 24-hour Holter monitor (control group)

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Study design

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Outcomes

Primary:

Detection of one or more episodes of atrial fibrillation or atrial flutter ≥30 seconds as assessed at the 90 day follow-up

Secondary:

1) Oral anticoagulation use at 90 days

2) Atrial fibrillation lasting 2.5 minutes or longer

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Detection of Atrial Fibrillation in the Two Monitoring Groups

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Incremental Yield of Prolonged ECG Monitoring for the Detection of Atrial Fibrillation in Patients with Cryptogenic Stroke or TIA

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Anticoagulant Therapy in the Two Monitoring Groups

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Protocol Adherence

Intervention group: 233/284 (82%) completed 3 or more weeks of monitoring.

Among patients in whom atrial fibrillation was not detected before 30 days, 204/240 (85%) completed 3 or more weeks, and 148/240 (61.7%) completed 4 weeks.

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Conclusions

• Among patients 55 years or older with a recent cryptogenic stroke or TIA, paroxysmal atrial fibrillation was common.

• Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment, as compared with the standard practice of short-duration ECG monitoring.

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Author-reported Limitations

• Total burden of atrial fibrillation per patient could not be determined due to limited recording capacity of device

• Patients with large, severe strokes were underrepresented

• Monitoring started late (ave 75 days after index event), reducing overall sensitivity of atrial fibrillation detection

• 30-day time limit and noninvasive monitoring diminished diagnostic yield

• No comparison to age-matched controls without stroke or TIA

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Critical Appraisal

Strengths of the study

• Large, multicenter, well-designed RCT

• Good adherence in intervention group

• Device manufacturers had no role in the trial

• Results have potentially important clinical implications

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Critical Appraisal

Weaknesses of the study

• Lack of diversity in study population

• Did not address stroke recurrence and survival benefit

• Detection of atrial fibrillation is not the solution to cryptogenic stroke; need to explore other stroke etiologies

• Benefit of anticoagulant therapy for subclinical AF not proven

• Optimal duration and type of cardiac monitoring still unclear

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CRYSTAL AF trial

In this study, 441 patients with cryptogenic stroke and no evidence of atrial fibrillation during at least 24 hours of ECG monitoring were randomly assigned to prolonged ambulatory cardiac monitoring with a subcutaneous implantable loop recorder or to a control group with conventional follow-up.

At six months, atrial fibrillation detection was significantly higher in the monitored group (8.9 percent, versus 1.4 percent in the control group, hazard ratio 6.4, 95% CI 1.9-21.7).

Sanna T et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014; 370(26):2478

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NEJM editorial June 26, 2014

The results of two studies published in this issue of the Journal indicate that prolonged monitoring of heart rhythm should now become part of the standard care of patients with cryptogenic stroke.