Thromb Haemost 2021; 121(06): 826-833
DOI: 10.1055/a-1346-2899
Stroke, Systemic or Venous Thromboembolism

Atrial Fibrillation in Patients with Embolic Stroke of Undetermined Source during 3 Years of Prolonged Monitoring with an Implantable Loop Recorder

1   Department of Neurology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Andreas Rogalewski*
1   Department of Neurology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Malik Kalyani
2   Department of Cardiology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Sameera Deelawar
2   Department of Cardiology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Sona Tribunyan
2   Department of Cardiology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Isabell Greeve
1   Department of Neurology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Jens Minnerup
3   Department of Neurology, University Hospital Münster, Münster, Germany
,
Carsten Israel
2   Department of Cardiology, Evangelical Hospital Bethel, Bielefeld, Germany
,
Wolf-Rüdiger Schäbitz
1   Department of Neurology, Evangelical Hospital Bethel, Bielefeld, Germany
› Author Affiliations

Abstract

Background Undocumented atrial fibrillation (AF) is suspected as a main stroke cause in patients with embolic stroke of undetermined source (ESUS), but its prevalence is largely unknown. This prospective study therefore aimed at delineating the prevalence of AF in patients with ESUS using continuous cardiac monitoring by implantable loop recorder (ILR) with daily remote interrogation over a period of 3 years and its clinical consequences, including recurrent stroke.

Methods In consecutive patients with an ESUS diagnosis after complete work-up, an ILR was implanted and followed by daily remote monitoring until AF was detected or a follow-up of at least 3 years was completed. Additionally, the ILR was interrogated in-hospital in 6-month intervals.

Results A total of 123 patients (74 male, mean age 65 ± 9 years) were enrolled and completed the 3 years study period. AF was detected in 51 patients (41.4%). In 43 of the 51 AF positive patients (84%) oral anticoagulation was established. Recurrent strokes occurred in 18 patients (14.6%) of this ESUS population, 9 of these patients being AF positive (17.6% of the AF-positive patients) and 9 being AF negative (12.5% of AF-negative patients). Patients with AF were slightly older than patients without AF (63.1 ± 8.8 vs. 67.5 ± 9.6 years, p = 0.12). Other parameters such as CHA2DS2-VASc score, infarct localization, micro- and macroangiopathy, carotid or aortic plaques, or stroke recurrence were not significantly different between groups.

Conclusion In ESUS patients, early implantation of an ILR with cardiac monitoring and remote transmission over a 3-year period detected AF in 41.4% and resulted in oral anticoagulation in 84% of these patients.

* Both authors contributed equally to this manuscript.




Publication History

Received: 15 April 2020

Accepted: 02 January 2021

Accepted Manuscript online:
05 January 2021

Article published online:
16 February 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Marini C, De Santis F, Sacco S. et al. Contribution of atrial fibrillation to incidence and outcome of ischemic stroke: results from a population-based study. Stroke 2005; 36 (06) 1115-1119
  • 2 Hart RG, Diener HC, Coutts SB. et al; Cryptogenic Stroke/ESUS International Working Group. Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol 2014; 13 (04) 429-438
  • 3 Wachter R, Freedman B. The role of atrial fibrillation in patients with an embolic stroke of unknown source (ESUS). Thromb Haemost 2017; 117 (10) 1833-1835
  • 4 Ntaios G, Papavasileiou V, Milionis H. et al. Embolic strokes of undetermined source in the Athens stroke registry: a descriptive analysis. Stroke 2015; 46 (01) 176-181
  • 5 Yushan B, Tan BYQ, Ngiam NJ. et al. Association of bilateral infarct pattern and detection of occult atrial fibrillation in ESUS patients with insertable cardiac monitor. J Stroke Cerebrovasc Dis 2019; 28: 2448-2452
  • 6 Jordan K, Yaghi S, Poppas A. et al. Left atrial volume index is associated with cardioembolic stroke and atrial fibrillation detection after ESUS. Stroke 2019; 50: 1997-2001
  • 7 Israel C, Kitsiou A, Kalyani M. 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 (10) 1962-1969
  • 8 Víctor CU, Carolina PE, Jorge TR. et al. Incidence and predictive factors of hidden atrial fibrillation detected by implantable loop recorder after an embolic stroke of undetermined source. J Atr Fibril 2018; 11 (03) 2078
  • 9 Sanna T, Diener HC, Passman RS. et al; CRYSTAL AF Investigators. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014; 370 (26) 2478-2486
  • 10 Hindricks G, Pokushalov E, Urban L. et al; XPECT Trial Investigators. Performance of a new leadless implantable cardiac monitor in detecting and quantifying atrial fibrillation: results of the XPECT trial. Circ Arrhythm Electrophysiol 2010; 3 (02) 141-147
  • 11 Nasir JM, Pomeroy W, Marler A. et al. Predicting Determinants of Atrial Fibrillation or Flutter for Therapy Elucidation in Patients at Risk for Thromboembolic Events (PREDATE AF) study. Heart Rhythm 2017; 14 (07) 955-961
  • 12 Reiffel JA, Verma A, Kowey PR. et al; REVEAL AF Investigators. Incidence of previously undiagnosed atrial fibrillation using insertable cardiac monitors in a high-risk population: the REVEAL AF study. JAMA Cardiol 2017; 2 (10) 1120-1127
  • 13 Healey JS, Alings M, Ha A. et al; ASSERT-II Investigators. Subclinical atrial fibrillation in older patients. Circulation 2017; 136 (14) 1276-1283
  • 14 Ntaios G, Perlepe K, Lambrou D. et al. Prevalence and overlap of potential embolic sources in patients with ESUS. J Am Heart Assoc 2019; 8: e012858
  • 15 Schäbitz WR, Köhrmann M, Schellinger PD, Minnerup J, Fisher M. Embolic stroke of undetermined source: gateway to a new stroke entity?. Am J Med 2020; 133 (07) 795-801
  • 16 Ntaios G, Pearce LA, Meseguer E. et al; NAVIGATE ESUS Investigators. Aortic arch atherosclerosis in patients with embolic stroke of undetermined source: an exploratory analysis of the NAVIGATE ESUS trial. Stroke 2019; 50 (11) 3184-3190
  • 17 Ntaios G, Perlepe K, Sirimarco G. et al. Carotid plaques and detection of atrial fibrillation in embolic stroke of undetermined source. Neurology 2019; 92 (23) e2644-e2652
  • 18 Tandon K, Tirschwell D, Longstreth Jr WT, Smith B, Akoum N. Embolic stroke of undetermined source correlates to atrial fibrosis without atrial fibrillation. Neurology 2019; 93 (04) e381-e387
  • 19 Kasner SE, Swaminathan B, Lavados P. et al; NAVIGATE ESUS Investigators. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol 2018; 17 (12) 1053-1060
  • 20 Kernan WN, Ovbiagele B, Black HR. et al; American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. 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. [published correction appears in Stroke. 2015 Feb;46(2):e54] Stroke 2014; 45 (07) 2160-2236
  • 21 Hindricks G, Potpara T, Dagres N. et al; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020; ehaa612
  • 22 Healey JS, Connolly SJ, Gold MR. et al; ASSERT Investigators. Subclinical atrial fibrillation and the risk of stroke. N Engl J Med 2012; 366 (02) 120-129 Erratum in: N Engl J Med 2016 Mar 10;374(10):998. PMID: 22236222
  • 23 Van Gelder IC, Healey JS, Crijns HJGM. et al. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT. Eur Heart J 2017; 38 (17) 1339-1344
  • 24 Camm AJ, Kirchhof P, Lip GY. et al; European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery. Guidelines for the management of atrial fibrillation. Eur Heart J 2010; 31 (19) 2369-2429
  • 25 Calkins H, Kuck KH, Cappato R. et al. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and re- search trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Heart Rhythm 2012; 9: 632-696
  • 26 Lopes RD, Alings M, Connolly SJ. et al. Rationale and design of the Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESiA) trial. Am Heart J 2017; 189: 137-145
  • 27 Kirchhof P, Blank BF, Calvert M. et al. Probing oral anticoagulation in patients with atrial high rate episodes: Rationale and design of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6) trial. Am Heart J 2017; 190: 12-18