Comment

The relevance of atrial fibrillation in stroke prevention

of morbidity and mortality worldwide. Although the might benefit from long-term cardiac monitoring. Published Online
February 7, 2017
identification of the cause of stroke can directly affect Importantly, patients with suspected artery-to-artery http://dx.doi.org/10.1016/
treatment and prognosis, almost a third of ischaemic embolism were excluded from this study, precluding the S1474-4422(17)30016-9
See Online/Articles
stroke cases are of unknown cause or cryptogenic–ie, extrapolation of the results to this stroke subtype.
http://dx.doi.org/10.1016/
the stroke mechanism remains unknown after routine As the relation between atrial fibrillation and stroke S1474-4422(17)30002-9
assessment. Results of EMBRACE1 and CRYSTAL-AF2 unfolds, several questions remain unanswered. The
showed that undiagnosed atrial fibrillation, which ASSERT5 trial investigated the occurrence and temporal
can be paroxysmal and asymptomatic, might be relation of asymptomatic atrial tachyarrhythmias
the cause of a substantial number of cryptogenic lasting for at least 6 min and thromboembolism in
strokes. In both studies, patients had at least 24 h 2580 patients with implantable cardiac devices. The
of continuous electrocardiography (ECG) without risk of stroke or systemic embolism was significantly
evidence of atrial fibrillation before enrolment. In increased in patients with atrial tachyarrhythmias
EMBRACE, atrial fibrillation was identified in 3·2% of (0·7% of 2319 patients without atrial tachyarrhythmias
277 patients assigned to the control group and in 16·1% vs 1·7% of 261 patients with atrial tachyarrhythmias
of 280 patients monitored for 30 days.1 In CRYSTAL-AF, per year, p=0·007).5 Only a small proportion of the
atrial fibrillation at 6 months was detected in 1·4% of patients had atrial rhythm abnormalities within
220 patients assigned to the standard care group and 30 days before the stroke and in many cases the stroke
8·9% of 221 patients receiving continuous monitoring.2 preceded the development of atrial fibrillation.6 Data
Aside from the differences in the yield of cardiac from observational studies and animal models show
monitoring, these trials showed that atrial fibrillation that cerebral damage, particularly to the insular cortex,
is common in patients with cryptogenic stroke. Atrial is associated with an increased risk of autonomic
fibrillation is associated with hemispheric stroke, and dysfunction and myocardial injury.7 This raises the
increased mortality and recurrence. Additionally, the question whether the cardiac arrhythmia detected
risk of stroke in patients with atrial fibrillation can be after cerebral injury is the cause or the consequence of
reduced by almost 60% with anticoagulation therapy.3 the stroke. Also, most of the studies that investigated
The identification of atrial fibrillation in patients with the rate of atrial fibrillation in cerebral ischaemia,
cryptogenic stroke might therefore have important including EMBRACE, CRYSTAL-AF, and Find-AFRANDOMISED,
implications for clinical practice. did not include a control group of participants with no
In The Lancet Neurology, Rolf Wachter and colleagues4 history of stroke.1,2 Observational studies show that the
show that prolonged cardiac rhythm monitoring can prevalence of atrial fibrillation in the general population
identify atrial fibrillation in patients with different is about 3% and increases steadily with age, which
stroke causes. The Find-AFRANDOMISED study included suggests that atrial fibrillation can be an incidental
398 patients with acute ischaemic stroke aged 60 years bystander.8,9 The relation between atrial arrhythmias
or older. Patients were randomly assigned to standard and stroke is further confounded by the coexistence of
care (≥24 h ECG) or enhanced cardiac monitoring anatomical and histological changes in the atrium, and
(three 10-day Holter monitoring at baseline, 3 months, serological changes that might contribute to enhanced
and 6 months after randomisation). Atrial fibrillation thrombogenesis.10 Furthermore, evidence links length
lasting 30 seconds or longer at 6 months was detected and burden of tachyarrhythmias to risk of stroke.5,11
in 5% of 198 patients in the control group and 14% of Therefore, the prognostic significance of isolated
200 in the study group. About 40% of the patients had and short-lasting atrial arrhythmias needs further
lacunar stroke based on diagnostic cerebral imaging. investigation.
In subgroup analyses, no interaction was observed Stroke prevention guidelines recommend the use of
in the detection of atrial fibrillation based on stroke anticoagulants for patients with atrial fibrillation and
subtype. These findings support the hypothesis that cerebral ischaemia.12,13 Although stroke is a syndrome

www.thelancet.com/neurology Published online February 7, 2017 http://dx.doi.org/10.1016/S1474-4422(17)30016-9 1

with different mechanisms, risk stratification paradigms 1 Gladstone DJ, Spring M, Dorian P, et al. Atrial fibrillation in patients with
cryptogenic stroke. N Engl J Med 2014; 370: 2467–77.
used for decision making in atrial fibrillation incorporate 2 Sanna T, Diener HC, Passman RS, et al. Cryptogenic stroke and underlying
stroke as a single entity, irrespective of its pathogenesis. atrial fibrillation. N Engl J Med 2014; 370: 2478–86.
3 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to
Lacunar infarction, in particular, is a stroke subtype that prevent stroke in patients who have nonvalvular atrial fibrillation.
has been associated with microatheroma formation Ann Intern Med 2007; 146: 857–67.
4 Wachter R, Gröschel K, Gelbrich G, et al. Holter-electrocardiogram-monitoring
and lipohyalinosis of small penetrating arteries. The in patients with acute ischaemic stroke (FIND-AFRANDOMISED): an open-label
relative acute angle at which perforating arteries arise randomised controlled trial. Lancet Neurol 2017; published online Feb 7.
http://dx.doi.org/10.1016/S1474-4422(17)30002-9.
suggests that embolism is unlikely in lacunar stroke. 5 Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial fibrillation and the
risk of stroke. N Engl J Med 2012; 366: 120–29.
Also, atherosclerosis is a systemic disease. Therefore, 6 Brambatti M, Connolly SJ, Gold MR, et al. Temporal relationship between
individuals with cerebrovascular diseases could have an subclinical atrial fibrillation and embolic events. Circulation 2014;
129: 2094–99.
elevated rate of coexisting heart disease and different 7 Al-Qudah ZA, Yacoub HA, Souayah N. Disorders of the autonomic nervous
rhythm disorders. In clinical practice, it is reasonable system after hemispheric cerebrovascular disorders: an update.
J Vasc Interv Neurol 2015; 8: 4–52.
to offer anticoagulation to patients with radiological 8 Norberg J, Backstrom S, Jansson JH, Johansson L. Estimating the prevalence
evidence of cerebral embolism and atrial fibrillation, of atrial fibrillation in a general population using validated electronic
health data. Clin Epidemiol 2013; 5: 475–81.
even if it is found after the stroke. Whether or not 9 Zoni-Berisso M, Lercari F, Carazza T, Domenicucci S. Epidemiology of atrial
fibrillation: European perspective. Clin Epidemiol 2014; 6: 213–20.
atrial fibrillation is causal or incidental in other stroke
10 Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial
subtypes has not yet been determined. 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
Fernando D Testai risk: the TRENDS study. Circ Arrhythm Electrophysiol 2009; 2: 474–80.
Department of Neurology and Rehabilitation, University of Illinois 12 Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the
management of atrial fibrillation developed in collaboration with EACTS.
at Chicago Medical Center, Neuropsychiatric Institute, Chicago, Eur Heart J 2016; 37: 2893–962.
IL 60612-7330, USA 13 Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of
[email protected] stroke in patients with stroke and transient ischemic attack: a guideline for
healthcare professionals from the American Heart Association/American
I declare no competing interests. Stroke Association. Stroke 2014; 45: 2160–236.

2 www.thelancet.com/neurology Published online February 7, 2017 http://dx.doi.org/10.1016/S1474-4422(17)30016-9