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Archives of cardiovascular diseases
Volume 108, n° 3
pages 189-196 (mars 2015)
Doi : 10.1016/j.acvd.2014.11.003
Received : 1 February 2014 ;  accepted : 26 November 2014
Detection of paroxysmal atrial fibrillation by prolonged electrocardiographic recording after ischaemic stroke in patients aged<60years: A study with 21-day recording using the SpiderFlash® monitor
Diagnostic de la fibrillation auriculaire paroxystique au décours d’un accident vasculaire cérébral ischémique chez le sujet jeune<60ans, par un enregistrement électrocardiographique externe de 21jours à l’aide du moniteur SpiderFlash®
 

Komlavi Yayehd a, Didier Irles b, Chrystelle Akret b, Wilfried Vadot c, Gilles Rodier c, Toufek Berremili b, Sophie Perenet b, Marie Chevallier-Grenot b, Loïc Belle b, , Antoine Dompnier b
a Department of Cardiology, Campus University Teaching Hospital, Lomé, Togo 
b Department of Cardiology, Annecy Hospital, Annecy, 74370 Metz-Tessy, France 
c Department of Neurology, Annecy Hospital, Annecy, 74370 Metz-Tessy, France 

Corresponding author. Department of Cardiology, Annecy Hospital, 1, avenue de l’Hôpital, 74370 Metz-Tessy, France.
Summary
Background

Many studies have suggested that longer duration of cardiac monitoring is suitable for the detection of occult paroxysmal atrial fibrillation (AF) after stroke; however, most studies involved patients aged65years – a population with a high stroke rate.

Aims

To assess the incidence of paroxysmal AF in unselected young patients presenting with stroke.

Methods

We included consecutive patients aged<60years with a stroke diagnosis on magnetic resonance imaging. Aetiological screening included clinical history and examination, and biological and cardiac tests. Patients were included if they had no history of AF and if a 24-hour electrocardiogram recording detected no AF or atrial flutter. Patients wore the SpiderFlash® monitor for 21days after discharge from hospital. The primary outcome was detection of paroxysmal AF episodes lasting>30seconds during monitoring. The secondary outcome was detection of paroxysmal AF episodes lasting<30seconds and any arrhythmia during monitoring.

Results

Among the 56 patients included (mean age 48±9years), 39 had cryptogenic stroke (CS) and 17 had stroke of known cause (SKC). Cardiac monitoring was achieved in 54 patients (37 CS, 17 SKC); one CS patient had a paroxysmal AF episode lasting>30seconds and one CS patient had a paroxysmal AF episode lasting<30seconds (versus no patients in the SKC group). Two CS patients and one SKC patient presented numerous premature atrial complexes. Non-sustained ventricular tachycardia was detected in one CS patient.

Conclusion

This prospective observational study showed a low rate of paroxysmal AF among young patients presenting with stroke, on the basis of 21-day cardiac monitoring. This result highlights the need to identify patients who would benefit from such long monitoring.

The full text of this article is available in PDF format.
Résumé
Contexte

De nombreuses études ont suggéré qu’une durée plus étendue d’enregistrement électrocardiographique améliorait le taux de détection de la fibrillation auriculaire (FA) paroxystique occulte après un accident vasculaire cérébral (AVC) ischémique, mais la plupart de ces études ont porté sur les patients65ans d’âge – une population avec un taux élevé d’AVC ischémique.

Objectif

Évaluer l’incidence de la FA paroxystique chez les patients jeunes présentant un AVC ischémique.

Méthodes

Nous avons inclus de manière consécutive des patients âgés de 18 à 60ans avec un diagnostic d’AVC ischémique à l’imagerie par résonance magnétique. Les explorations à visée étiologique ont inclus l’anamnèse, l’examen clinique et des tests biologiques et cardiaques. Les patients ont été inclus s’ils n’avaient pas d’antécédent de FA et si un enregistrement de l’électrocardiogramme des 24heures n’a détecté aucune FA ou flutter auriculaire. Après la sortie de l’hôpital, les patients ont porté le moniteur SpiderFlash® pendant 21jours. Le critère principal de jugement était la détection d’épisodes de FA paroxystique>30secondes pendant la surveillance. Les critères secondaires étaient la détection d’épisodes de FA paroxystique<30 secondes ou de toute autre arythmie.

Résultats

Parmi les 56 patients inclus (âge moyen 48±9ans), 39 avaient un AVC cryptogénique (CS) et 17 un AVC de cause connue (SKC). L’enregistrement de 21jours a été obtenu chez 54 patients (37 CS, 17 SKC) ; un patient dans le groupe des CS a présenté des épisodes de FA paroxystique>30secondes et un patient avec un CS a eu un épisode de FA paroxystique<30secondes (contre aucun patient dans le groupe SKC). Deux patients dans le groupe des CS et un patient avec un SKC ont présenté de nombreuses extrasystoles auriculaires. Un épisode de tachycardie ventriculaire non soutenue a été détecté chez un patient ayant un CS.

Conclusion

Cette étude observationnelle prospective a montré un faible taux de FA paroxystique chez les jeunes patients présentant un AVC ischémique, après un enregistrement de 21jours. Ce résultat met en évidence la nécessité de sélectionner les patients qui pourraient bénéficier de ce suivi électrocardiographique prolongé.

The full text of this article is available in PDF format.

Keywords : Paroxysmal atrial fibrillation, Long external cardiac monitoring, Ischaemic stroke, Young patients

Mots clés : Fibrillation auriculaire paroxystique, Enregistrement électrocardiographique externe de longue durée, Accident vasculaire cérébral ischémique, Patients jeunes

Abbreviations : AF, CI, CS, ECG, MRI, SKC, TIA


Background

Atrial fibrillation (AF) is the cause of 20–25% of all ischaemic strokes, which are more severe and associated with higher mortality rates than strokes resulting from other causes [1]. Oral anticoagulation is recommended in patients diagnosed with AF, leading to an additional 40% reduction in the risk of recurrent stroke compared with that achieved with antiplatelet therapy [2, 3, 4]. The detection of arrhythmias associated with a high cardioembolic risk after stroke/transient ischaemic attack (TIA) is particularly important in the management of such patients.

Despite a thorough aetiological workup, around one third of ischaemic strokes in young patients remain unexplained [5, 6]. Occult paroxysmal AF is a possible cause of cryptogenic stroke and TIA [7, 8] in these patients, as individuals with paroxysmal AF have the same risk of ischaemic stroke as those with sustained AF [9, 10].

Early diagnosis triggers earlier treatment for secondary prevention of stroke [11]. In a systematic review of five studies, in which the duration of electrocardiogram (ECG) recording ranged from 24 to 72hours, the overall rate of newly detected AF or flutter was 4.6% among consecutive patients with ischaemic stroke [12]. Current guidelines from the European Stroke Organization estimate that extending the duration of monitoring (prolonged event-loop recording) may improve the rate of detection of paroxysmal AF [13].

Many devices are now available to manage such patients [14]. However, the feasibility and results of longer monitoring remain conflicting: for example, supplementary paroxysmal AF rates ranging from 5.3% to 20.0% have been detected in patients with cryptogenic stroke/TIA in observational studies [8, 15, 16, 17, 18] versus 0% in one randomized study [19]. Most of these studies involved patients aged65years. The value of longer monitoring in younger patients has been poorly studied, as the rate of paroxysmal AF in patients with stroke increases with age [20, 21].

We aimed to assess the incidence of paroxysmal AF in unselected patients with stroke aged between 18 and 60years, using the SpiderFlash® external loop recorder (ELA Medical, Minneapolis, MN, USA) for 21days.

Methods
Study design and population

This prospective study consecutively included patients aged<60years admitted to the Neurology Department of Annecy Hospital with a diagnosis of stroke confirmed on magnetic resonance imaging (MRI) between February 2011 and July 2012. The diagnosis of stroke required imaging evidence of cerebral or spinal cord infarction consistent with the presenting neurological syndrome, persistent neurological deficits attributable to cerebral ischaemia or confirmed evidence of retinal ischaemia on ophthalmological examination [13].

Data were collected on patient demographics, clinical history, cardiac test results and radiological test results. All patients underwent 24-hour ECG recording, biological tests, transthoracic echocardiography and carotid Doppler assessment. Transoesophageal echocardiography and limb venous Doppler assessment were performed if required.

Patients with a history of AF or any supraventricular tachycardia, those presenting with AF on the resting ECG recording and/or on the 24-hour ECG recording, and those taking antiarrhythmic agents were excluded. Other exclusion criteria were patients with a Rankin score>4, patients in whom baseline screening was not completed, patients not living in the province and those who refused consent. Patients were classified into two stroke groups according to the results of the stroke evaluation: stroke of known cause (SKC) or cryptogenic stroke (CS).

Patients were advised to undergo monitoring for 21 days; they removed and applied the electrodes themselves. Patients were instructed to write in a diary if they had acute cardiac or neurological symptoms.

Device

The SpiderFlash external loop recorder device was used. Patients wear the SpiderFlash device like a necklace. This event recorder monitor, coupled with its analyser EventScope™ (Sorin Group, Milan, Italy), comprises three cardiac leads attached to a small pocket-sized recording device; continuous two-channel ECG data are recorded.

SpiderFlash is programmed to take 12 automatic recordings daily, but it also takes recordings started by the patient in the event of symptom onset. SpiderFlash is based on secure Datacard technology (Datacard Group, Minnetonka, MN, USA), providing markedly expanded memory capacity.

SpiderFlash can record an ECG for up to 6minutes before and 3minutes after arrhythmia detection or patient activation – as often as is needed. Therefore, an event can be recorded even if SpiderFlash is activated after symptom resolution (e.g. after a syncopal episode when the patient has regained consciousness).

The device uses an event detection algorithm well suited to capturing asymptomatic paroxysmal events, including intermittent AF. The event detection algorithm uses RR interval variability and QRS morphology analysis to detect all possible AF events, which are then transmitted to a physician for manual review and confirmation, based on standard diagnostic criteria (absence of P-wave activity and irregular RR interval). In our study, the manual review was done by one of two cardiologists specialized in heart rhythm management who were participating in the study, to confirm the presence or absence of paroxysmal AF episodes.

Outcomes

The primary outcome was the detection of paroxysmal AF episodes lasting>30seconds on the 21-day recording. The secondary outcome was the detection of paroxysmal AF episodes lasting<30seconds and any arrhythmia on the 21-day recording.

Statistical analysis

Continuous variables are expressed as means±standard deviations or medians±interquartile ranges; categorical variables are expressed as percentages. Student's t -test was used for continuous variables and the Chi2 test or Fisher's exact test was used for categorical variables. All tests were two-sided and P values<0.05 were considered statistically significant. Statistical analysis was performed using Epi Info™ version 7 (CDC, Atlanta, GA, USA).

Results

Overall, 56 patients with ischaemic stroke were included; the mean age was 48±9years (range 31–60years). Thirty-nine patients were classified as having CS and 17 as having SKC. Two CS patients were excluded because of premature discontinuation of monitoring (Figure 1). Table 1 shows the patients’ baseline characteristics; there were significant proportions of obese and diabetic patients in the SKC group.



Figure 1


Figure 1. 

Study flow chart: period of inclusion, February 2011 to July 2012. AF: atrial fibrillation; TIA: transient ischaemic attack.

Zoom

An ECG recording, transthoracic echocardiography and cerebral MRI were completed in all patients. Overall, 7% of patients had a dilated left atrium, defined as a left atrium surface>20cm2. None of the patients had mitral stenosis, 61% had cortical stroke and 25% had multiple infarcts in a single territory, without any significant difference between the two groups (Table 2).

Cardiac monitoring results

Outpatient monitoring began a median of 34days (interquartile range 22–57days) after symptom onset, and mean duration of monitoring was 20±3days (Table 2). Monitoring was discontinued prematurely in 2 of 56 (4%) patients.

One patient (1 of 54 [2%], 95% confidence interval [CI] 0.05–10) had a paroxysmal AF episode lasting>30seconds (1 of 37 [3%] CS patients vs 0 of 17 SKC patients); this event occurred in a 37-year-old man presenting with recurrent stroke, who had migraine with aura, no cardiovascular risk factors, no dilatation of the left atrium and preserved left ventricular ejection fraction (Table 3).

One patient (1 of 54 [2%], 95% CI 0.05–10) had a brief paroxysmal AF episode lasting<30seconds (1 of 37 [3%] CS patients vs 0 of 17 SKC patients); this event occurred in a 52-year-old man with recurrent stroke but no cardiovascular risk factors (Table 3).

No patients presented with symptoms and none activated a recording by the SpiderFlash monitor (i.e. there were no patient-triggered recordings). All paroxysmal AF episodes were asymptomatic.

Two CS patients and one SKC patient (3 of 54 [6%], 95% CI 1.2–15.4) presented numerous premature atrial complexes.

Non-sustained ventricular tachycardia was detected in 1 of 37 CS patients (3%) and numerous premature ventricular complexes were detected in 1 of 17 SKC patients (6%).

Discussion

This study showed a lower than expected rate of paroxysmal AF with 21-day cardiac monitoring in young patients presenting with ischaemic stroke, compared with the results reported in several observational studies with long cardiac monitoring [8, 16, 17, 22, 23]. Many reasons may explain this discrepancy.

The low rate of paroxysmal AF in our study could be due to the characteristics of our sample, which comprised young patients with few cardiovascular risk factors, low rates of cardiac diseases and few cases of left atrial dilatation. In comparison, two retrospective studies, reported by Miller et al. [23] and Elijovich et al. [16], which included older patients with more heart failure events, detected rates of paroxysmal AF during long cardiac monitoring of 17% and 20%, respectively, among patients with cryptogenic stroke. Two prospective registries with consecutive inclusion of patients with cryptogenic stroke/TIA found similar results [8, 16, 22]. The relationship between paroxysmal AF and age is strong, as shown in the report by Rabinstein et al. [24]; among 132 patients presenting with stroke, the authors found significantly more paroxysmal AF events in patients aged65years, irrespective of whether they had CS or SKC [24]. Many other studies enrolled only patients aged65years, to check the occurrence of paroxysmal AF events after ischaemic stroke [25, 26]. Kamel et al., however, in a recent randomized study comparing wearing and not wearing a cardiac monitor after stroke, showed that detected rates of AF were lower than expected (0%) among patients with a mean age of 67years. The authors suggested that this might have been due to chance and the study's lack of power to determine clinical outcomes (only 15 patients wore the CardioNet Mobile Cardiac Outpatient Telemetry device; CardioNet, Malvern PA, USA) (Table 4).

In our study, outpatient monitoring started 34days (mean) after the stroke event; this duration might be too long, as the pilot randomized trial by Kamel et al., which began monitoring 22days after the events, also did not register any episodes of paroxysmal AF. The mechanism that links AF and stroke is still not fully understood. AF may lead to mechanical atrial dysfunction and subsequent thrombus formation and dislodgement – a hypothesis supported by the high thromboembolic rate following cardioversion in the absence of anticoagulation [27]. In that setting, the duration and timing of AF determine the risk of stroke, and AF occurs immediately before the thromboembolic event. Thus, monitoring after an embolic event may underdetect AF [24].

The SpiderFlash monitor was worn for 21days in our study, which is a similar duration to that in other studies; the CardioNet Mobile Cardiac Outpatient Telemetry was worn for 21–30days, for example [8, 16, 19, 23]. However, this duration might be too short. By comparison, in the Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) study, which enrolled 2580 hypertensive patients aged65years with an implantable device and no history of AF, subclinical atrial tachyarrhythmias occurred in 36% of patients over a mean follow-up of 2.8 years and were associated with a 2.5-fold increase in the risk of stroke or systemic embolism [26]. Rabinstein et al. suggested that very prolonged monitoring may be necessary to identify patients at risk of stroke from paroxysmal AF [24]. This was also the finding of the Relationship Between Daily Atrial Tachyarrhythmia Burden From Implantable Device Diagnostics and Stroke Risk Study (TRENDS), which showed that 73% of patients with thromboembolic events during the monitoring period had no atrial tachyarrhythmias detected by the implantable device over the 30 days that preceded the event [25].

Further randomized trials will be needed to clarify the best non-invasive cardiac test to detect paroxysmal AF after cryptogenic stroke. In this setting, the current randomized Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial is comparing a repeated standard 24-hour Holter monitor strategy with a 30-day ambulatory cardiac event monitor strategy (using the AccuHeart Electrode Belt, Braemar ER 910AF monitor; Braemar Inc., Eagan, MN, USA) (NCT00846924).

As the ASSERT [26] and TRENDS [25] studies found significant rates of paroxysmal AF using implantable devices, the question of the best method for detecting this arrhythmia remains relevant: non-invasive or invasive cardiac monitoring? No patient presented with symptoms in the present study, which is a common finding; many studies, such as the XPECT [28] and TRENDS [25] studies, found several asymptomatic paroxysmal AF episodes after a stroke event [24, 28, 29]. Brief paroxysmal AF episodes (<30seconds) are also common, but the prognostic value and relevance of treating such brief events are still debated [25, 26] as no randomized study has been conducted to establish whether there is a difference in the prevalence of brief episodes of AF in patients with and without stroke. The ongoing CRYptogenic STroke And underlying Atrial Fibrillation (CRYSTAL-AF) trial, which is comparing the incidence of AF detection using the REVEAL XT cardiac monitor (Medtronic, Minneapolis, MN, USA) with routine monitoring in patients with cryptogenic stroke or TIA [30], and the EMBRACE study, are expected to provide some answers to these questions.

Patients with SKC had a significantly higher body mass index and a higher prevalence of diabetes. However, we recorded no cases of AF in this group, probably because they had a cause of stroke other than AF. We also recorded no ventricular arrhythmia in this group because the SpiderFlash monitors were programmed to prioritize recordings of atrial arrhythmia in their memory. On the other hand, these patients had cardiovascular risk factors, but their left ventricular ejection fractions were normal, and therefore, they were at low risk of ventricular arrhythmias.

Our study was limited by the small number of patients; consequently, these preliminary findings require confirmation in a larger study.

Conclusion

This prospective observational study detected a low rate of paroxysmal AF with 21-day cardiac monitoring among young patients presenting with ischaemic stroke. This result highlights the need to identify patients who would benefit from such long monitoring. Further larger studies are needed to determine the relevance of longer monitoring among young patients.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.


Acknowledgements

This study was conceived by the investigators and was supported by an unrestricted grant from the Sorin Group, France, which provided the monitoring equipment. The Sorin Group also provided a grant for the technician involved in data collection, management and analysis. Sophie Rushton-Smith, PhD, provided editorial assistance and was funded by the authors.

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