Results from the CRYSTAL AF trial have shown that atrial fibrillation in patients with cryptogenic stroke is better detected with insertable cardiac monitors than standard monitoring at six, 12 and 36 months.
The study, presented by Richard A Bernstein, member of the CRYSTAL AF steering committee, at a late-breaking clinical trial session of the American Stroke Association’s International Stroke Conference (San Diego, USA, 12–14 February), met its primary endpoint by demonstrating that continuous monitoring with an insertable cardiac monitor detected atrial fibrillation in 6.4 times more patients than standard of care at six months (p=0.0006). CRYSTAL AF also met its secondary endpoints with atrial fibrillation detection in 7.3 times more patients at 12 months (p<0.0001) and 8.8 times more patients at 36 months (p<0.0001) with the insertable cardiac monitor.
Bernstein, who is professor of neurology in the Davee Department of Neurology at Northwestern University and director of the Stroke Program at Northwestern Memorial Hospital in Chicago, USA, told delegates: “We know that atrial fibrillation can be episodic, brief, rare and totally asymptomatic which may be difficult to detect with standard electrocardiographic methods. We have not been able to find the optimal duration and method of modeling after stroke to detect this arrhythmia, to try to answer some of these questions we performed the CRYSTAL AF study.”
CRYSTAL AF (Cryptogenic stroke and underlying atrial fibrillation) was a prospective, randomised, multicentre, post-marketing study aimed to assess whether a long-term cardiac monitoring strategy with an implantable cardiac monitor is superior to standard monitoring for the detection of atrial fibrillation in patients with cryptogenic stroke. Bernstein, told delegates that the study also allowed to determine the proportion of patients with cryptogenic stroke that have underlying atrial fibrillation and to look at the actions by the physicians after a patient was diagnosed with atrial fibrillation.
The study enrolled 441 patients (average age 61 years) at 55 centres in Europe, Canada and USA, from June 2009 to April 2012. Patients included had strokes of undetermined causes (cryptogenic stroke) with infarct seen on MRI or CT within the previous 90 days and no mechanism (including atrial fibrillation) determined after 12-lead ECG, 24-hour ECG monitoring, transesophageal echocardiography, CTA or MRA of head and neck to rule out arterial source and screening for hypercoagulable states in patients older than 55.
They were randomised to receive monitoring with electrocardiograms, Holter monitors and other short-term diagnostic tests (control arm: number of patients 220) or monitoring with the insertable cardiac monitor Reveal XT from Medtronic (n=221). Patients were followed at one, six, twelve and every six months thereafter until study closure.
Bernstein said that at six months the rate of atrial fibrillation detection in the insertable cardiac monitor arm was 8.9% compared to 1.4% in the control arm (Hazard ratio [HR]=6.43). Nineteen patients were found to have atrial fibrillation in the insertable cardiac monitor arm compared to three in the standard of care group. “The atrial fibrillation episodes were largely asymptomatic in the implantable arm (74%) and it is hardly to say anything in the control arm because there were only three patients. It is interesting to see that to find these three patients with atrial fibrillation in the control arm we had 88 ECGs 20 24-hour Holters and one event recorder,” noted Bernstein.
He also commented that the overall superiority of the implantable device for detecting atrial fibrillation was consistent across all pre-specified subgroups.
At 12 months, Bernstein said, the superiority of atrial fibrillation detection was sustained in the insertable cardiac monitor arm compared to the standard monitoring arm (12.4% vs. 2%; HR=7.32). Again, more patients were found to have atrial fibrillation in the insertable cardiac monitor arm (29 vs. four in standard of care).
Bernstein highlighted that “Having and implantable monitor that continuously records ECG gives a lot of information, in particular, it gives the chance to look at atrial fibrillation burden.” In this regard, he said that of the 29 atrial fibrillation patients found at one year with the implantable device, 92.3% had a maximum one-day atrial fibrillation burden of more than six minutes. Moreover, Seventy nine per cent of asymptomatic episodes were detected in the insertable cardiac monitor group compared to 50% in the standard monitoring arm. Bernstein commented that there were five insertable cardiac monitors removed due to insertion site infection or pocket erosion.
At 36 months, the rate of detection in the insertable cardiac monitor group was 30% compared to 3% in the control arm (HR=8.78).
Bernstein commented that 97% of the patients found with atrial fibrillation were put on oral anticoagulants as a long-term treatment strategy, despite the fact that the protocol did not specify any medical therapy. “This is a sign that the investigators and doctors taking care of the patients thought this was clinically important information,” he noted.
Based on this information, Bernstein said, “We suggest that long-term continuous monitoring should be performed in patients with cryptogenic stroke.”
“CRYSTAL AF tells us that we are missing atrial fibrillation in our cryptogenic stroke patients, and therefore not protecting our patients from recurrence as well as we could. If we do not monitor, we do not find, and if we do not find, we cannot treat,” Bernstein told Cardiac Rhythm News. He also said that a cost-effectiveness analysis comparing the insertable cardiac monitor to standard monitoring is under way.