Cardioembolism accounts for 17–35% of all ischemic strokes. In comparison to other stroke etiologies it carries a higher risk of death and recurrent stroke, and a higher risk of severe disability. However, it is estimated that up to 30% of ischemic strokes, labeled cryptogenic ischemic strokes, have an undetermined cause.1–4 Early diagnosis of cardioembolic sources is important in order to initiate anticoagulant therapy, shown to be much more effective than antiplatelet agents for preventing cardioembolic stroke.5 Improved efforts to detect atrial fibrillation (AF) in this subgroup are warranted, as AF is a high-risk source of cardioembolism. Furthermore, detection of AF after cryptogenic ischemic stroke further increased the risk of recurrent stroke, even when compared to patients with known AF.6

Detection of AF in this setting can be challenging given the paroxysmal and asymptomatic nature of arrhythmia episodes.7 Although screening of AF has been traditionally limited to short-duration electrocardiogram (ECG) post-stroke monitoring (mainly 24-h Holter), longer duration significantly improves detection rates, and it is recommended in recent guidelines. However, due to the limitations of existing studies, guidelines have yet to endorse specific strategies for detecting AF in patients with cryptogenic ischemic stroke. The optimum monitoring duration and method of AF detection after stroke remain unknown.8–10

We aim to determine the yield of AF detection in patients with cryptogenic ischemic stroke after a complete diagnostic evaluation, based on the sequential use of diagnostic methods.

The main findings of this study can be summarized as follows: (a) a standardized sequential monitoring strategy is feasible to implement as part of routine stroke care in patients in whom an embolic source is suspected, and detected AF in 35% of patients; (b) in 60% of cases, AF is detected using noninvasive methods, mainly ELR; (c) this approach may allow a reduction in ILR implantation without a significative impairment in diagnostic yield.

Results of previous studies indicate that prolonged monitoring of heart rhythm should become part of the standard care of patients with cryptogenic ischemic stroke. A growing body of evidence indicates that AF likely accounts for a proportion of these events.15–23 Guidelines recommend that the evaluation of patients who present with ischemic stroke should include monitoring for AF, although duration varies across different guidelines.8–10 However, owing to the limitations of existing studies, guidelines have yet to endorse specific strategies for detecting AF, and the optimum monitoring method of AF detection after stroke remains unknown.24 Even more, in a routine basis persists an evidence-practice gap with underutilization of ECG monitoring in these patients.25 Detection of AF has therapeutic implications because documentation of AF is required to initiate anticoagulant therapy after ischemic stroke, while antiplatelet agents are recommended in the absence of AF.

The main available technologies for arrhythmia detection in this setting were validated in the EMBRACE (30-day cardiac Event Monitor Belt for Recording Atrial fibrillation after a Cerebral ischemic Event) trial, using ELR, and the CRYSTAL-AF (CRYptogenic Stroke and underlying Atrial Fibrillation) trial, using an ILR.15,26 As the yield of AF detection continues to increase with increasing duration of the monitoring time, ILRs represent the most sensitive method for detecting sporadic episodes of AF. However, they are costly, (minimally) invasive and not yet widely accessible. Relatively inexpensive ELR, such as Spider Flash reported herein, will probably be cost-effective, although patient compliance may decline rapidly with increased monitoring durations.

We performed 24-h Holter ECG as initial screening in an out-patient setting. Our detection rate of 4% is in consonance with published rates of 2–6%.27–29 When AF has not detected patients underwent additional noninvasive ECG monitoring with Spider-Flash for 2 weeks. This duration of monitoring may be reasonable given the fact that most cases in the EMBRACE trial were detected within the first 2 weeks of monitoring and may be associated with better patient compliance than the 30 days reflected in guidelines without significantly affecting detection rate. In fact, our detection rate of 18% at this point is slightly higher than the one reported in the EMBRACE trial. Time delay after index event may be relevant for diagnostic yield with the ELR, as AF recurrences are clustered. Those patients without AF at this point underwent ILR implantation, with a detection rate of 20%, close to previous noncontrolled trials.

This sequential strategy resulted in a high rate of detection of AF, similar to detection rates reported in studies using directly ILR.23,30 This result should be viewed in the context of the use of a comprehensive systematic baseline diagnostic evaluation to rule out other causes of stroke, including imaging modalities not used in the EMBRACE, in consonance with the diagnostic criteria and assessment recently recommended for the definition of the embolic stroke of unknown etiology.31 Besides, our results may be explained in part because of differences in baseline characteristics, including age, the prevalence of hypertension and severity of stroke (NIHS). The incidence of AF goes up with age and hypertension, and large and severe strokes are likely to be more cardioembolic in origin. All of these factors are increased in our patients compared to patients enrolled in EMBRACE and CRYSTAL trials, for instance, and may explain much of the differences between studies.

Further studies with larger number of patients are needed to determine which risk factors identify the patient who would derive the most clinical benefit for this prolonged monitoring. CHADS2 and CHA2DS2-VASc scores, systematically higher in those patients with AF detected after cryptogenic ischemic stroke have been shown to predict embolic events in patients other than those with established AF.32 Usefulness of these scores as a tool for identifying patients to propose for more prolonged rhythm monitoring merits further exploration. In our series, we found that the number of Holter detected atrial premature beats, runs of nonsustained atrial tachycardia, long PR interval or the presence of interatrial block in the surface ECG were associated with detection of AF. This is in consonance with previous reports,33–35 and suggests that these patients may have a high probability of AF in the context of an atrial myopathy, and could represent ideal candidates for prolonged ECG monitoring. In our patients, we do not find any pattern of acute brain infarction that was significantly associated with AF.36

We propose a sequential approach for detecting AF, starting with noninvasive ELR that may avoid a significant number of ILR. Although a similar approach has been recently suggested by Gladstone et al.,37 to the best of our knowledge it has not been prospectively evaluated. In our series, this monitoring strategy resulted in a high rate of detection of AF, with subsequent oral anticoagulation therapy initiation.

A sequential approach to AF detection in patients with embolic stroke of unknown source after complete diagnostic assessment identifies subclinical AF in 35% of cases. We suggest a 24-h Holter ECG as an initial screen. If AF is not detected additional non-invasive ECG monitoring with ELR for 2 weeks, followed by ILR is performed. This strategy allows the diagnosis with noninvasive methods in more than half of the patients with definitive AF. AF diagnosis provided a firm indication for a switch from antiplatelet therapy to therapeutic anticoagulation. Further studies are needed to determine which risk factors identify patients who would obtain the greatest clinical benefit.

None.