Detection of Atrial Fibrillation in Cryptogenic Stroke
Purpose of Review
To summarize the literature on the detection of atrial fibrillation (AF) in patients with “cryptogenic” stroke, a cohort including about 25% of all ischemic stroke patients and patients with embolic stroke of undetermined source (ESUS).
A first episode of AF is detected in up to one third of cryptogenic stroke and in up to one fourth of ESUS patients during long-term monitoring. AF prevalence correlates to patient selection, duration, and quality of ECG monitoring. Higher rates of AF were reported in stroke patients with left atrial pathology, specific ECG alterations, or increased natriuretic peptides. While AF detection impacts on medical stroke prevention in the vast majority of patients, patient selection for prolonged monitoring is largely left at the physician’s discretion.
AF detection after cryptogenic stroke or ESUS is a frequent, potentially causal condition. Whether subsequent oral anticoagulation may improve outcome remains open.
KeywordsIschemic stroke Atrial fibrillation ECG monitoring Stroke unit Cryptogenic stroke Embolic stroke of undetermined source
Compliance with Ethical Standards
Conflict of Interest
Karl Georg Haeusler has received grants and personal fees from Bayer and Sanofi, personal fees from Boehringer Ingelheim, Daiichi-Sankyo, Pfizer, BMS, Medtronic, EIP Pharma, Edwards Lifesciences, and non-financial support from Getemed.
Serdar Tütüncü has received lecture fees from DTN-Kompakt (meeting/conference).
Renate B. Schnabel has received a grant from the European Research Council, and personal fees from BMS/Pfizer and the German Cardiac Society.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.• Kirchhof P, Benussi S, Kotecha D, Ahlsson A, Atar D, Casadei B, et al. ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–962. https://doi.org/10.1093/eurheartj/ehw210. Present guidelines of the ESC/EACTS. CrossRefGoogle Scholar
- 2.Brachmann J, Morillo CA, Sanna T, Di Lazzaro V, Diener H, Bernstein RA, et al. Uncovering atrial fibrillation beyond short-term monitoring in cryptogenic stroke patients: three-year results from the cryptogenic stroke and underlying atrial fibrillation trial. Circ Arrhythm Electrophysiol. 2016;9:e003333. https://doi.org/10.1161/CIRCEP.115.003333.CrossRefPubMedGoogle Scholar
- 3.Poli S, Diedler J, Härtig F, Götz N, Bauer A, Sachse T, et al. Insertable cardiac monitors after cryptogenic stroke--a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation. Eur J Neurol. 2016;23:375–81. https://doi.org/10.1111/ene.12843.CrossRefPubMedGoogle Scholar
- 7.Grond M, Jauss M, Hamann G, Stark E, Veltkamp R, Nabavi D, et al. Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study. Stroke. 2013;44:3357–64. https://doi.org/10.1161/STROKEAHA.113.001884.CrossRefPubMedGoogle Scholar
- 8.Stahrenberg R, Weber-Krüger M, Seegers J, Edelmann F, Lahno R, Haase B, et al. Enhanced detection of paroxysmal atrial fibrillation by early and prolonged continuous holter monitoring in patients with cerebral ischemia presenting in sinus rhythm. Stroke. 2010;41:2884–8. https://doi.org/10.1161/STROKEAHA.110.591958.CrossRefPubMedGoogle Scholar
- 10.Marini C, de Santis F, Sacco S, Russo T, Olivieri L, Totaro R, et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke. 2005;36:1115–9. https://doi.org/10.1161/01.STR.0000166053.83476.4a.CrossRefPubMedGoogle Scholar
- 12.• Hart RG, Diener H, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, et al. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol. 2014;13:429–38. https://doi.org/10.1016/S1474-4422(13)70310-7. Position paper defining the term embolic stroke of undetermined source, further providing an excellent review of present knowledge. CrossRefGoogle Scholar
- 14.•• Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD, et al. Rivaroxaban for stroke prevention after embolic stroke of undetermined source. N Engl J Med. 2018;378:2191–201. https://doi.org/10.1056/NEJMoa1802686. Randomized double-blind study reporting the results of the NAVIGATE ESUS trial, comparing rivaroxaban to acetylsalicylic acid in ESUS patients. CrossRefPubMedGoogle Scholar
- 17.Ganesan AN, Chew DP, Hartshorne T, Selvanayagam JB, Aylward PE, Sanders P, et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding: a systematic review and meta-analysis. Eur Heart J. 2016;37:1591–602. https://doi.org/10.1093/eurheartj/ehw007.CrossRefPubMedGoogle Scholar
- 18.• Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45:2160–236. https://doi.org/10.1161/STR.0000000000000024. Present guidelines of the AHA/ASA. CrossRefGoogle Scholar
- 19.Higgins P, Dawson J, MacFarlane PW, McArthur K, Langhorne P, Lees KR. Predictive value of newly detected atrial fibrillation paroxysms in patients with acute ischemic stroke, for atrial fibrillation after 90 days. Stroke. 2014;45:2134–6. https://doi.org/10.1161/STROKEAHA.114.005405.CrossRefPubMedGoogle Scholar
- 27.•• Sanna T, Diener H, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med. 2014;370:2478–86. https://doi.org/10.1056/NEJMoa1313600. Randomized study reporting the prevalence of AF detection in patients with cryptogenic stroke. CrossRefPubMedGoogle Scholar
- 29.Haeusler KG, Gröschel K, Köhrmann M, Anker SD, Brachmann J, Böhm M, et al. Expert opinion paper on atrial fibrillation detection after ischemic stroke. Clin Res Cardiol. 2018; https://doi.org/10.1007/s00392-018-1256-9.
- 31.Wallmann D, Tüller D, Wustmann K, Meier P, Isenegger J, Arnold M, et al. Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy. Stroke. 2007;38:2292–4. https://doi.org/10.1161/STROKEAHA.107.485110.CrossRefPubMedGoogle Scholar
- 32.Wachter R, Gröschel K, Gelbrich G, Hamann GF, Kermer P, Liman J, et al. Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial. Lancet Neurol. 2017;16:282–90. https://doi.org/10.1016/S1474-4422(17)30002-9.CrossRefPubMedGoogle Scholar
- 33.Israel C, Kitsiou A, Kalyani M, Deelawar S, Ejangue LE, Rogalewski A, et al. Detection of atrial fibrillation in patients with embolic stroke of undetermined source by prolonged monitoring with implantable loop recorders. Thromb Haemost. 2017;117:1962–9. https://doi.org/10.1160/TH17-02-0072.CrossRefPubMedGoogle Scholar
- 36.The European Stroke Organization (ESO) Executive Committee and the ESO Writing Committee. Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis. 2008;25:457–507. https://doi.org/10.1159/000131083.
- 39.Rizos T, Güntner J, Jenetzky E, Marquardt L, Reichardt C, Becker R, et al. Continuous stroke unit electrocardiographic monitoring versus 24-hour Holter electrocardiography for detection of paroxysmal atrial fibrillation after stroke. Stroke. 2012;43:2689–94. https://doi.org/10.1161/STROKEAHA.112.654954.CrossRefPubMedGoogle Scholar
- 41.Uphaus T, Grings A, Gröschel S, Müller A, Weber-Krüger M, Wachter R, et al. Automatic detection of paroxysmal atrial fibrillation in patients with ischaemic stroke: better than routine diagnostic workup? Eur J Neurol. 2017;24:990–4. https://doi.org/10.1111/ene.13326.CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Dussault C, Toeg H, Nathan M, Wang ZJ, Roux J, Secemsky E. Electrocardiographic monitoring for detecting atrial fibrillation after ischemic stroke or transient ischemic attack: systematic review and meta-analysis. Circ Arrhythm Electrophysiol. 2015;8:263–9. https://doi.org/10.1161/CIRCEP.114.002521.CrossRefPubMedGoogle Scholar
- 45.• Gladstone DJ, Dorian P, Spring M, Panzov V, Mamdani M, Healey JS, et al. Atrial premature beats predict atrial fibrillation in cryptogenic stroke: results from the EMBRACE trial. Stroke. 2015;46:936–41. https://doi.org/10.1161/STROKEAHA.115.008714. Substudy of a randomized study reporting the importance of atrial premature beats to detect AF in patients with cryptogenic stroke. CrossRefPubMedGoogle Scholar
- 46.Broughton ST, O’Neal WT, Salahuddin T, Soliman EZ. The influence of left atrial enlargement on the relationship between atrial fibrillation and stroke. J Stroke Cerebrovasc Dis. 2016;25:1396–402. https://doi.org/10.1016/j.jstrokecerebrovasdis.2016.02.004.CrossRefPubMedGoogle Scholar
- 47.Waldenhjort D, Sobocinski Doliwa P, Alam M, Frykman-Kull V, Engdahl J, Rosenqvist M, et al. Echocardiographic measures of atrial function may predict atrial fibrillation in stroke patients. Scand Cardiovasc J. 2016;50:236–42. https://doi.org/10.1080/14017431.2016.1175657.CrossRefPubMedGoogle Scholar
- 49.Haeusler KG, Kirchhof P, Heuschmann PU, Laufs U, Busse O, Kunze C, et al. Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): rationale and design of a prospective randomized multicenter study. Am Heart J. 2016;172:19–25. https://doi.org/10.1016/j.ahj.2015.10.010.CrossRefPubMedGoogle Scholar
- 50.• Sposato LA, Cerasuolo JO, Cipriano LE, Fang J, Fridman S, Paquet M, et al. Atrial fibrillation detected after stroke is related to a low risk of ischemic stroke recurrence. Neurology. 2018;90:e924–31. https://doi.org/10.1212/WNL.0000000000005126. Retrospective analysis of a large registry reporting the recurrent stroke rate in stroke patients with sinus rhythm, a first episode of AF after stroke, or known AF before stroke. CrossRefPubMedGoogle Scholar