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Atrial fibrillation and cryptogenic stroke. What is the current evidence? Role of electrocardiographic monitoring

Abstract The diagnosis of cryptogenic stroke is made by exclusion. However, current evidence supports the role of atrial fibrillation episodes as a cause of this condition. Prospective data have demonstrated the benefits of long‐term electrocardiographic monitoring to identify atrial fibrillation in association with cryptogenic stroke. This aim of this article was to analyze the contemporary evidence for the possible relationship between atrial fibrillation and cryptogenic stroke and the role of continuous electrocardiographic monitoring to clarify this hypothesis.


| INTRODUCTION
About 15% to 40% of all ischemic strokes have no identifiable etiology. 1 These cases are defined as cryptogenic stroke (CS). The diagnosis of CS is made by exclusion. In clinical practice, the diagnosis of CS is considered in 3 circumstances: (i) when the diagnostic assessment is incomplete, (ii) when a single cause cannot be determined because there are several reasonable causes, or (iii) when despite extensive assessment, there is no identifiable cause. 2 Recent studies suggest that atrial fibrillation (AF) is a possible cause of CS. Most of these studies are based on continuous electrocardiographic (ECG) monitoring. However, there is no consensus on the usefulness of ECG monitoring in this setting and many questions about the association between AF and CS remain. We therefore review the evidence favoring an association between AF and CS with emphasis on future steps that make help reaching definitive conclusions.

MONITORING IN PATIENTS WITH CS?
Following a transient ischemic attack (TIA) or stroke event, paroxysmal AF is detected by a single 12-lead electrocardiogram or 24-hour Holter recording in 2% to 4%. If ECG monitoring extends to 24-72 hours, the incidence of AF increases to 18%. 3  increases the detection rate of AF episodes lasting ≥ 30 seconds after a CS or TIA (2.5% vs 13.8%, P < .00001). The advantage of long-term ECG monitoring over conventional follow-up using serial electrocardiograms or 24-hour Holter was confirmed in the CRYS-TAL-AF 5 study. In this investigation, detection rates of new AF with an implanted long-term monitoring recording device were significantly higher than following conventional monitoring: 8.9% vs 1.4% at 6 months, 12.4% vs 2,0% at 12 months, and 30.0% vs 3.0% at 36 months (P < .001 for all comparisons).
Although there are recommendations to perform at least 24 hours of ECG monitoring to rule out AF following an ischemic stroke, some studies suggest that this recommendation is poorly They found that only 30.6% of patients received a 24-hour Holter monitoring and less than 1% received ECG monitoring longer than 48 hours. Based on these results, the researchers concluded that (i) The mere presence of AF discovered within days, weeks, or months following a CS does not establish the etiology of cardiogenic embolism. In fact, there are no published studies that establish this causality. Furthermore, there is evidence that stroke, including lacunar infarcts, may trigger AF episodes. 7 The ASSERT study 8 included 2580 patients with implanted pacemakers or defibrillators with long-term ECG monitoring capabilities.  13 found that the best predictors of AF were (i) a prolonged PR interval and (ii) advanced age. However, they recognized their moderate predictive ability to discriminate patients with and without AF after CS.
A recent review article summarized the main conditions that predispose to develop low AF burden. 10 1. Increasing age.
2. High CHA2DS2-VASc scores. Another investigation found that the total atrial conduction time measured by Doppler echocardiography using the PA-TDI interval predicts hidden AF in patients with CS with a sensitivity of 93.8% and specificity of 90.5%. After a multivariate analysis, the last parameter was an independent predictor of hidden AF. 14 There are other proposed schemes for prediction of paroxysmal AF following an ischemic stroke. One of the best one studied is the iPAB score, which includes a personal history of arrhythmia or antiarrhythmic drug use, atrial dilatation, and elevation of brain natriuretic peptide. 15 The evidence regarding the monitoring time to be employed in patients with CS for detecting AF is still inconclusive. A recent consensus document recommends "extended ECG monitoring" in patients with CS to detect undiagnosed AF. This expert panel proposes a careful evaluation of each patient prior to device use based on cost-efficacy, patient's acceptance, and compliance. 16