Contemporary ReviewCryptogenic stroke: Is silent atrial fibrillation the culprit?
Introduction
In 1988, J. Mohr wrote, “The day may not be far off when the need for a term such as cryptogenic stroke will have been obviated by mechanism-specific therapies.”1 Unfortunately, that day has yet to arrive. Cryptogenic stroke is defined as a stroke without cause after extensive investigation. Cardioembolism accounts for 17% to 30% of all ischemic strokes, but it is estimated that up to 40% of ischemic strokes have an undetermined cause.2
Patients initially diagnosed with cryptogenic stroke and transient ischemic attack (TIA) of undetermined etiology subsequently can be found to have atrial fibrillation (AF), suggesting that improved efforts to detect AF in this subgroup are warranted. In patients with AF, oral anticoagulation (OAC) with warfarin is clearly superior to aspirin,3 and the novel anticoagulants are at least as effective as, if not superior to, warfarin, with a comparable or lower rate of major bleeding complications.4, 5, 6
AF and paroxysmal AF frequently are asymptomatic, even in patients who previously reported “symptomatic AF,” often making stroke the first manifestation of the disease.7, 8 When newly detected AF is found after cryptogenic stroke, there is an increased risk of recurrent stroke, even when compared to patients with known AF.9
The term “silent AF” has reemerged recently to describe atrial arrhythmias that are detected by cardiac implantable electronic devices (CIEDs) but would go undetected in the clinical setting. Silent AF is perhaps a new classification of an older term for AF, in which AF is discovered only by aggressive monitoring techniques.10 The precise role of “silent AF” in increasing the risk of ischemic and cryptogenic stroke is not fully understood.
There is great debate about the optimal methods to search for possible AF in patients with cryptogenic stroke. This article reviews the methods that have been studied to diagnose occult AF in the cryptogenic stroke population. We review the literature on in-hospital monitoring and on short- and long-term outpatient monitoring, followed by a literature review of insertable cardiac monitors (ICMs). We then present the results of 2 recent large, randomized, prospective trials (CRYSTAL AF11 and EMBRACE12), which compare the incidence of AF in cryptogenic stroke patients found by conventional follow-up vs longer-term monitoring with an ICM11 or 30-day event recorder.12 Finally, we briefly discuss the incidence of silent AF and its attendant stroke risk in the general cardiac population using data that come from patients with CIEDs, the only group to have long-term comprehensive AF monitoring. Because limited results on the treatment impact of silent AF with OAC have been published, recommendations regarding potential treatment of silent AF episodes in the setting of cryptogenic stroke cannot be conclusively stated as part of this review.
Section snippets
In-hospital and brief monitoring for detection of AF in patients with cryptogenic stroke
In the past, in-hospital monitoring and ECGs were the only ways to detect AF after a stroke. Subsequently, Holter monitoring was developed to study arrhythmias in the outpatient realm and provide somewhat longer-term monitoring. It has been estimated that the detection rate of new AF from a standard 12-lead ECG after ischemic stroke/TIA is 2% to 5%13 and from a 24-hour Holter is 2% to 6%.14, 15 However, ECG monitoring with Holter devices, event monitors, and other short-term wearable monitors
Outpatient monitoring for detection of AF in patients with cryptogenic stroke
Mobile cardiac outpatient telemetry (MCOT) was designed to look for arrhythmias in patients outside of the hospital setting. Several studies have looked at the ability to detect AF after cryptogenic stroke using short-term monitoring (Table 1). The incidence of new or silent AF discovered by outpatient monitoring ranges from 0% to 24% over a variable length of follow-up.18, 19, 20, 21, 22, 23, 24 The definition of “an episode of AF” in some of these studies is as short as 5 to 30 seconds in
AF detected by insertable cardiac monitors in patients with cryptogenic stroke
When it was discovered that implanted pacemakers and implantable cardioverter-defibrillators (ICDs) were identifying atrial arrhythmias in patients who had no prior AF history and were entirely asymptomatic, it became clear that there may be a need for an ICM whose sole purpose would be to detect previously undiagnosed arrhythmias such as AF. These monitors usually detect AF by analyzing the irregularity and incoherence of successive R-R intervals. Consequently, ICMs require a minimum amount of
CRYSTAL AF summary
The CRYSTAL AF study was a prospective, multicenter, international, randomized study to determine the incidence of AF among patients randomized to ICM (Reveal XT) vs standard monitoring (Table 2).30 Eligible patients were older than 40 years and had a stroke within the last 90 days defined as cryptogenic after undergoing 12-lead ECG, 24-hour ECG monitoring, transesophageal echocardiography (TEE), computed tomographic angiography or magnetic resonance angiography of the head and neck to rule out
EMBRACE summary
The EMBRACE study randomly assigned 572 patients (age ≥55 years) with cryptogenic stroke to 30-day event-triggered recorder vs conventional 24-hour Holter monitoring.12 Unlike CRYSTAL AF, TEE or intracranial vascular imaging was not required as part of the stroke workup. The primary end-point (detection of AF ≥30 seconds within 90 days) was met in 16.1% and 3.2% of patients in the event recorder and control arms, respectively. The secondary end-point (detection of AF ≥2.5 minutes within 90
Pitfalls in comparison of different studies
Although there is a natural inclination to compare the diagnostic yields between different studies in an effort to better understand the optimal monitoring modality, it is important to recognize that inherent differences in study designs and patient populations make direct comparisons difficult.
AF incidentally detected by implanted CIEDs and stroke risk
In order to put the AF detection rates among cryptogenic stroke patients into context, it is worthwhile to understand the amount of silent AF that is present in the nonstroke cardiac population, based on numbers derived from the CIED population.
Summary and conclusion
The detection rates of AF among cryptogenic stroke patients are a function of the length of monitoring, the definition of AF duration that constitutes an episode, the interval from the index stroke to the start of monitoring, and patient selection. Silent AF in the CIED population is known to increase stroke rates even though AF episodes are not always proximate to the strokes. It is also known that a new AF diagnosis after a stroke event is associated with an increased risk of recurrent stroke.
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Cited by (47)
A cost comparison of atrial fibrillation monitoring strategies after embolic stroke of undetermined source
2022, American Heart Journal Plus: Cardiology Research and PracticeAtrial fibrillation predictors in patients with embolic stroke of undetermined source
2021, Medicina ClinicaComparison of the Effect of Atrial Fibrillation Detection Algorithms in Patients With Cryptogenic Stroke Using Implantable Loop Recorders
2020, American Journal of CardiologyExpert opinion on continuous rhythm monitoring of patients with atrial fibrillation for candidates or patients who have already undergone ablation
2020, International Journal of CardiologyCitation Excerpt :A close relationship was demonstrated between the intensity of rhythm monitoring and the sensitivity of detection of arrhythmia recurrence [3–7]. A longer monitoring duration is associated with a greater likelihood of detecting both symptomatic and asymptomatic AF after the ablation procedure [6,8,9]. Continuous long-term ECG monitoring provided by cardiac implantable electronic devices, such as pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and implantable loop recorders (ILRs) improve the ability to diagnose the presence or absence of AF, compared with intermittent ECG monitoring tools, such as Holter [10–13] or reliance on patient symptoms alone.
Current and Future Use of Insertable Cardiac Monitors
2018, JACC: Clinical ElectrophysiologyCitation Excerpt :There are multiple modalities now available for AECG monitoring, and many have been studied for use in detection of subclinical AF among patients with cryptogenic stroke and in unexplained syncope (11,16–18).
Mr. Ziegler is an employee and shareholder of Medtronic Inc.