Steven Greenberg, MD, PhD

It is part of a growing trend that many people whom we’ve diagnosed with cryptogenic stroke indeed have bouts of AF. This isn’t the only study to show that, but it is unique in the data I’ve seen in terms of the length of monitoring. Other studies I’ve seen monitor for 1 week or 1 month. As you can see from the curves shown in CRYSTAL AF, a lot of the pickup happens during the first week or the first month, but the curve continues to go up, even past 3 months. It means there is a lot of AF out there.

The missing information is whether all AF is the same and carries the same risk for stroke, and whether it will dictate the same treatment. That is still a question that remains to be answered. The stakes are high to make that decision, because we do have an effective treatment in anticoagulation therapy. If we can fill in a couple of the gaps in knowledge, we may be able to have an enormous impact on stroke prevention. Cryptogenic stroke is a large group, and a large subgroup of cryptogenic stroke is showing up as having AF.

Andrew Epstein, MD, FAHA, FACC, FHRS

Many practitioners have suspected AF to be the cause of many cryptogenic strokes, but AF can be intermittent, asymptomatic, and elude detection by short-term monitoring. Although finding AF after cryptogenic stroke should prompt a change from antiplatelet therapy to oral anticoagulation, the optimal strategy for identifying intermittent AF after cryptogenic stroke has been unknown. Now, the CRYSTAL AF investigators have provided insight: They compared standard cardiac monitoring according to local standards to the use of an insertable cardiac monitor for detecting AF after cryptogenic stroke, and found that the insertable cardiac monitor is superior to standard monitoring to detect AF in both short-term (8.9% at 6 months [HR=6.43]) and longer-term (30% at 36 months [HR=8.78]) follow-up.

In my opinion, the finding of AF in 30% of the patients at 36 months is of huge clinical importance, especially since 92.3% of patients with AF in the insertable cardiac monitor arm had a day with AF lasting 6 minutes or longer; 61.6% of those episodes lasted 6 hours or longer. Furthermore, 74% of the episodes were asymptomatic, and 66% of the patients in CRYSTAL AF had a CHADS2 score ≥3, making the population very clinically relevant. Notably, the complication rate of device implantation was low, and unlike for infections in patients with transvenous cardiac rhythm management devices, removal of insertable cardiac monitors is a simpler procedure by orders of magnitude.

A possible limitation of CRYSTAL AF relates to the accuracy of the insertable cardiac monitor to accurately distinguish AF from other irregular rhythms, such as sinus with premature atrial complexes or premature ventricular contractions. Thus, we do await the final paper to answer these and other questions. For example, the insertable cardiac monitor requires 2 minutes of AF to be present before it is registered, but the trial used AF lasting only 30 seconds to define an episode. Was the occurrence of AF even higher than reported in the insertable cardiac monitor patients? And, did characteristics of AF, the “AF burden” affect outcome? Did multiple short episodes carry the same risk as less frequent longer ones? Regardless, since the consequences of stroke due to AF are devastating and the risk of recurrent stroke substantial, appreciating the frequent occurrence of AF in the cryptogenic stroke population has the potential for hugely impacting management and outcomes in this population; in this study, 97% of patients who had AF detected had their management changed to oral anticoagulation.

Finally, the authors recommend that long-term continuous monitoring be performed in patients with cryptogenic stroke. Questions notwithstanding, the clinical challenge now will be to get the word out, and for the strategy to be adopted.