Comment
The relevance of atrial fibrillation in stroke prevention
Cerebral infarction is one of the most common causes
of morbidity and mortality worldwide. Although the
identification of the cause of stroke can directly affect
treatment and prognosis, almost a third of ischaemic
stroke cases are of unknown cause or cryptogenic–ie,
the stroke mechanism remains unknown after routine
assessment. Results of EMBRACE1 and CRYSTAL-AF2
showed that undiagnosed atrial fibrillation, which
can be paroxysmal and asymptomatic, might be
the cause of a substantial number of cryptogenic
strokes. In both studies, patients had at least 24 h
of continuous electrocardiography (ECG) without
evidence of atrial fibrillation before enrolment. In
EMBRACE, atrial fibrillation was identified in 3·2% of
277 patients assigned to the control group and in 16·1%
of 280 patients monitored for 30 days.1 In CRYSTAL-AF,
atrial fibrillation at 6 months was detected in 1·4% of
220 patients assigned to the standard care group and
8·9% of 221 patients receiving continuous monitoring.2
Aside from the differences in the yield of cardiac
monitoring, these trials showed that atrial fibrillation
is common in patients with cryptogenic stroke. Atrial
fibrillation is associated with hemispheric stroke, and
increased mortality and recurrence. Additionally, the
risk of stroke in patients with atrial fibrillation can be
reduced by almost 60% with anticoagulation therapy.3
The identification of atrial fibrillation in patients with
cryptogenic stroke might therefore have important
implications for clinical practice.
In The Lancet Neurology, Rolf Wachter and colleagues4
show that prolonged cardiac rhythm monitoring can
identify atrial fibrillation in patients with different
stroke causes. The Find-AFRANDOMISED study included
398 patients with acute ischaemic stroke aged 60 years
or older. Patients were randomly assigned to standard
care (≥24 h ECG) or enhanced cardiac monitoring
(three 10-day Holter monitoring at baseline, 3 months,
and 6 months after randomisation). Atrial fibrillation
lasting 30 seconds or longer at 6 months was detected
in 5% of 198 patients in the control group and 14% of
200 in the study group. About 40% of the patients had
lacunar stroke based on diagnostic cerebral imaging.
In subgroup analyses, no interaction was observed
in the detection of atrial fibrillation based on stroke
subtype. These findings support the hypothesis that
www.thelancet.com/neurology Published online February 7, 2017 http://dx.doi.org/10.1016/S1474-4422(17)30016-9
patients with cryptogenic or non-cryptogenic stroke Lancet Neurol 2017
might benefit from long-term cardiac monitoring. Published Online
February 7, 2017
Importantly, patients with suspected artery-to-artery http://dx.doi.org/10.1016/
embolism were excluded from this study, precluding the S1474-4422(17)30016-9
See Online/Articles
extrapolation of the results to this stroke subtype.
http://dx.doi.org/10.1016/
As the relation between atrial fibrillation and stroke S1474-4422(17)30002-9
unfolds, several questions remain unanswered. The
ASSERT5 trial investigated the occurrence and temporal
relation of asymptomatic atrial tachyarrhythmias
lasting for at least 6 min and thromboembolism in
2580 patients with implantable cardiac devices. The
risk of stroke or systemic embolism was significantly
increased in patients with atrial tachyarrhythmias
(0·7% of 2319 patients without atrial tachyarrhythmias
vs 1·7% of 261 patients with atrial tachyarrhythmias
per year, p=0·007).5 Only a small proportion of the
patients had atrial rhythm abnormalities within
30 days before the stroke and in many cases the stroke
preceded the development of atrial fibrillation.6 Data
from observational studies and animal models show
that cerebral damage, particularly to the insular cortex,
is associated with an increased risk of autonomic
dysfunction and myocardial injury.7 This raises the
question whether the cardiac arrhythmia detected
after cerebral injury is the cause or the consequence of
the stroke. Also, most of the studies that investigated
the rate of atrial fibrillation in cerebral ischaemia,
including EMBRACE, CRYSTAL-AF, and Find-AFRANDOMISED,
did not include a control group of participants with no
history of stroke.1,2 Observational studies show that the
prevalence of atrial fibrillation in the general population
is about 3% and increases steadily with age, which
suggests that atrial fibrillation can be an incidental
bystander.8,9 The relation between atrial arrhythmias
and stroke is further confounded by the coexistence of
anatomical and histological changes in the atrium, and
serological changes that might contribute to enhanced
thrombogenesis.10 Furthermore, evidence links length
and burden of tachyarrhythmias to risk of stroke.5,11
Therefore, the prognostic significance of isolated
and short-lasting atrial arrhythmias needs further
investigation.
Stroke prevention guidelines recommend the use of
anticoagulants for patients with atrial fibrillation and
cerebral ischaemia.12,13 Although stroke is a syndrome
1
 Comment
with different mechanisms, risk stratification paradigms
used for decision making in atrial fibrillation incorporate
stroke as a single entity, irrespective of its pathogenesis.
Lacunar infarction, in particular, is a stroke subtype that
has been associated with microatheroma formation
and lipohyalinosis of small penetrating arteries. The
relative acute angle at which perforating arteries arise
suggests that embolism is unlikely in lacunar stroke.
Also, atherosclerosis is a systemic disease. Therefore,
individuals with cerebrovascular diseases could have an
elevated rate of coexisting heart disease and different
rhythm disorders. In clinical practice, it is reasonable
to offer anticoagulation to patients with radiological
evidence of cerebral embolism and atrial fibrillation,
even if it is found after the stroke. Whether or not
atrial fibrillation is causal or incidental in other stroke
subtypes has not yet been determined.
Fernando D Testai
Department of Neurology and Rehabilitation, University of Illinois
at Chicago Medical Center, Neuropsychiatric Institute, Chicago,
IL 60612-7330, USA
testai@uic.edu
I declare no competing interests.
2 www.thelancet.com/neurology Published online February 7, 2017 http://dx.doi.org/10.1016/S1474-4422(17)30016-9
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3 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to
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4 Wachter R, Gröschel K, Gelbrich G, et al. Holter-electrocardiogram-monitoring
in patients with acute ischaemic stroke (FIND-AFRANDOMISED): an open-label
randomised controlled trial. Lancet Neurol 2017; published online Feb 7.
http://dx.doi.org/10.1016/S1474-4422(17)30002-9.
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fibrillation: Virchow’s triad revisited. Lancet 2009; 373: 155–66.
11 Glotzer TV, Daoud EG, Wyse DG, et al. The relationship between daily atrial
tachyarrhythmia burden from implantable device diagnostics and stroke
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12 Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the
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13 Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of
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