Atrial Fibrillation After Ischemic Stroke Detected by Chest Strap-Style 7-Day Holter Monitoring and the Risk Predictors: EDUCATE-ESUS

Yuichi Miyazaki, Kazunori Toyoda, Yasuyuki Iguchi, Teruyuki Hirano, Norifumi Metoki, Masanori Tomoda, Masayuki Shiozawa, Junpei Koge, Yasushi Okada, Yuka Terasawa, Muneaki Kikuno, Haruko Okano, Joji Hagii, Masanori Nakajima, Teppei Komatsu, Masahiro Yasaka, Yuichi Miyazaki, Kazunori Toyoda, Yasuyuki Iguchi, Teruyuki Hirano, Norifumi Metoki, Masanori Tomoda, Masayuki Shiozawa, Junpei Koge, Yasushi Okada, Yuka Terasawa, Muneaki Kikuno, Haruko Okano, Joji Hagii, Masanori Nakajima, Teppei Komatsu, Masahiro Yasaka

Abstract

Aim: This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708).

Methods: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors.

Results: The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively).

Conclusions: In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.

Keywords: Acute stroke; Atrial premature contraction; Brain natriuretic peptide; Cardioembolism; Insertable cardiac monitors.

Figures

Fig. 1. The chest strap-style monitor for…
Fig. 1. The chest strap-style monitor for 7-day Holter ECG monitoring
[EV-201 (Parama-Tech, Fukuoka, Japan)]
Fig. 2.
Fig. 2.
Findings of atrial fibrillation detected by 7-day Holter monitoring
Fig. 3. Distribution of data from the…
Fig. 3. Distribution of data from the pre-entry screening examinations
Horizontal lines show cutoff levels for predicting detection of atrial fibrillation by ROC curve analysis. Box and whisker plots show 10th, 25th, 50th, 75th, and 90th percentile values. AF: atrial fibrillation
Fig. 4. Distribution of bivariate data from…
Fig. 4. Distribution of bivariate data from the pre-entry screening examinations
Lines show cutoff levels for predicting detection of atrial fibrillation by ROC curve analysis.

References

    1. Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O’Donnell MJ, Sacco RL, Connolly SJ; Cryptogenic Stroke/ESUS International Working Group: Embolic strokes of undetermined source: the case for a new clinical construct. Lancet Neurol, 2014; 13(4): 429-438
    1. Toyoda K, Okumura K, Hashimoto Y, Ikeda T, Komatsu T, Hirano T, Fukuda H, Matsumoto K, Yasaka M: Identification of covert atrial fibrillation in cryptogenic ischemic stroke: current clinical practice in Japan. J Stroke Cerebrovasc Dis, 2016; 25(8): 1829-1837
    1. Hart RG, Catanese L, Perera KS, Ntaios G, Connolly SJ: Embolic stroke of undetermined source: a systematic review and clinical update. Stroke, 2017; 48(4): 867-872
    1. Kamel H, Okin PM, Elkind MS, Iadecola C: Atrial fibrillation and mechanisms of stroke: time for a new model. Stroke, 2016; 47(3): 895-900
    1. Hart RG, Pearce LA, Aguilar MI: Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med, 2007; 146(12): 857-867
    1. Ntaios G, Papavasileiou V, Diener HC, Makaritsis K, Michel P: Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials. Int J Stroke, 2017; 12(6): 589-596
    1. Diener HC, Bernstein R, Hart R: Secondary stroke prevention in cryptogenic stroke and embolic stroke of undetermined source (ESUS). Curr Neurol Neurosci Rep, 2017; 17(9): 64
    1. Hart RG, Sharma M, Mundl H, Kasner SE, Bangdiwala SI, Berkowitz SD, Swaminathan B, Lavados P, Wang Y, Wang Y, Davalos A, Shamalov N, Mikulik R, Cunha L, Lindgren A, Arauz A, Lang W, Czlonkowska A, Eckstein J, Gagliardi RJ, Amarenco P, Ameriso SF, Tatlisumak T, Veltkamp R, Hankey GJ, Toni D, Bereczki D, Uchiyama S, Ntaios G, Yoon BW, Brouns R, Endres M, Muir KW, Bornstein N, Ozturk S, O’Donnell MJ, De Vries Basson MM, Pare G, Pater C, Kirsch B, Sheridan P, Peters G, Weitz JI, Peacock WF, Shoamanesh A, Benavente OR, Joyner C, Themeles E, Connolly SJ; NAVIGATE ESUS Investigators: Rivaroxaban for Stroke Prevention after Embolic Stroke of Undetermined Source. N Engl J Med, 2018; 378(23): 2191-2201
    1. Diener H-C, Sacco RL, Easton JD, Granger CB, Bernstein RA, Uchiyama S, Kreuzer J, Cronin L, Cotton D, Grauer C, Brueckmann M, Chernyatina M, Donnan G, Ferro JM, Grond M, Kallmünzer B, Krupinski J, Lee BC, Lemmens R, Masjuan J, Odinak M, Saver JL, Schellinger PD, Toni D, Toyoda K; RE-SPECT ESUS Steering Committee and Investigators: Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. N Engl J Med, 2019; 380(20): 1906-1917
    1. European Stroke Organisation (ESO) Executive Committee, ESO Writing Committee: Guidelines for management of ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis, 2008; 25(5): 457-507
    1. Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL: Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke, 2019; 50(12): e344-e418
    1. Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, Vaid H, O’Donnell M, Laupacis A, Côté R, Sharma M, Blakely JA, Shuaib A, Hachinski V, Coutts SB, Sahlas DJ, Teal P, Yip S, Spence JD, Buck B, Verreault S, Casaubon LK, Penn A, Selchen D, Jin A, Howse D, Mehdiratta M, Boyle K, Aviv R, Kapral MK, Mamdani M; EMBRACE Investigators and Coordinators: Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med, 2014; 370(26): 2467-2477
    1. Sanna T, Diener H-C, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA, Rymer MM, Thijs V, Rogers T, Beckers F, Lindborg K, Brachmann J; CRYSTAL AF Investigators: Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med, 2014; 370(26): 2478-2486
    1. Wachter R, Gröschel K, Gelbrich G, Hamann GF, Kermer P, Liman J, Seegers J, Wasser K, Schulte A, Jürries F, Messerschmid A, Behnke N, Gröschel S, Uphaus T, Grings A, Ibis T, Klimpe S, Wagner-Heck M, Arnold M, Protsenko E, Heuschmann PU, Conen D, Weber-Krüger M; Find-AF(randomised) Investigators and Coordinators: Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AFRANDOMISED): an open-label randomised controlled trial. Lancet Neurol, 2017; 16(4): 282-290
    1. Mairesse GH, Moran P, Van Gelder IC, Elsner C, Rosenqvist M, Mant J, Banerjee A, Gorenek B, Brachmann J, Varma N, Glotz de Lima G, Kalman J, Claes N, Lobban T, Lane D, Lip GYH, Boriani G; ESC Scientific Document Group: Screening for atrial fibrillation: a European Heart Rhythm Association (EHRA) consensus document endorsed by the Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLAECE). Europace, 2017; 19(10): 1589-1623
    1. European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery: Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J, 2010; 31(19): 2369-2429
    1. Kishore A, Vail A, Majid A, Dawson J, Lees KR, Tyrrell PJ, Smith CJ: Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis. Stroke, 2014; 45(2): 520-526
    1. Sposato LA, Cipriano LE, Saposnik G, Ruíz Vargas E, Riccio PM, Hachinski V: Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol, 2015; 14(4): 377-387
    1. Dussault C, Toeg H, Nathan M, Wang ZJ, Roux J-F, 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(2): 263-269
    1. Wachter R, Gröschel K, Gelbrich G, Hamann GF, Kermer P, Liman J, Seegers J, Wasser K, Schulte A, Jürries F, Messerschmid A, Behnke N, Gröschel S, Uphaus T, Grings A, Ibis T, Klimpe S, Wagner-Heck M, Arnold M, Protsenko E, Heuschmann PU, Conen D, Weber-Krüger M; Find-AF(randomised) Investigators and Coordinators: Holter-electrocardiogram-monitoring in patients with acute ischaemic stroke (Find-AF(RANDOMISED)): an open-label randomised controlled trial. Lancet Neurol, 2017; 16(4): 282-290
    1. Iwata T, Todo K, Yamagami H, Morimoto M, Hashimoto T, Doijiri R, Furuya H: High detection rate of atrial fibrillation with insertable cardiac monitor implantation in patients with cryptogenic stroke diagnosed by Magnetic Resonance Imaging. J Stroke Cerebrovasc Dis, 2019; 28(9): 2569-2573
    1. Giancaterino S, Lupercio F, Nishimura M, Hsu JC: Current and future use of insertable cardiac monitors. JACC Clin Electrophysiol, 2018; 4(11): 1383-1396
    1. Sposato LA, Cipriano LE, Riccio PM, Hachinski V, Saposnik G: Very short paroxysms account for more than half of the cases of atrial fibrillation detected after stroke and TIA: a systematic review and meta-analysis. Int J Stroke, 2015; 10(6): 801-807
    1. Wallmann D, Tüller D, Wustmann K, Meier P, Isenegger J, Arnold M, Mattle HP, Delacrétaz E: Frequent atrial premature beats predict paroxysmal atrial fibrillation in stroke patients: an opportunity for a new diagnostic strategy. Stroke, 2007; 38(8): 2292-2294
    1. Poli S, Diedler J, Härtig F, Götz N, Bauer A, Sachse T, Müller K, Müller I, Stimpfle F, Duckheim M, Steeg M, Eick C, Schreieck J, Gawaz M, Ziemann U, Zuern CS: 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(2): 375-381
    1. Wasser K, Weber-Krüger M, Gröschel S, Uphaus T, Liman J, Hamann GF, Kermer P, Seegers J, Binder L, Gelbrich G, Gröschel K, Wachter R: Brain natriuretic peptide and discovery of atrial fibrillation after stroke: a subanalysis of the Find-AF(RANDOMISED) Trial. Stroke, 2020; 51(2): 395-401
    1. Todo K, Iwata T, Doijiri R, Yamagami H, Morimoto M, Hashimoto T, Sonoda K, Yamazaki H, Junpei K, Okazaki S, Sasaki T, Mochizuki H: Frequent premature atrial contractions in cryptogenic stroke predict atrial fibrillation detection with insertable cardiac monitoring. Cerebrovasc Dis, 2020; 49(2): 144-150
    1. Schnabel RB, Larson MG, Yamamoto JF, Sullivan LM, Pencina MJ, Meigs JB, Tofler GH, Selhub J, Jacques PF, Wolf PA, Magnani JW, Ellinor PT, Wang TJ, Levy D, Vasan RS, Benjamin EJ: Relations of biomarkers of distinct pathophysiological pathways and atrial fibrillation incidence in the community. Circulation, 2010; 121(2): 200-207
    1. Smith JG, Newton-Cheh C, Almgren P, Struck J, Morgenthaler NG, Bergmann A, Platonov PG, Hedblad B, Engström G, Wang TJ, Melander O: Assessment of conventional cardiovascular risk factors and multiple biomarkers for the prediction of incident heart failure and atrial fibrillation. J Am Coll Cardiol, 2010; 56(21): 1712-1719
    1. Sinner MF, Stepas KA, Moser CB, Krijthe BP, Aspelund T, Sotoodehnia N, Fontes JD, Janssens AC, Kronmal RA, Magnani JW, Witteman JC, Chamberlain AM, Lubitz SA, Schnabel RB, Vasan RS, Wang TJ, Agarwal SK, McManus DD, Franco OH, Yin X, Larson MG, Burke GL, Launer LJ, Hofman A, Levy D, Gottdiener JS, Kääb S, Couper D, Harris TB, Astor BC, Ballantyne CM, Hoogeveen RC, Arai AE, Soliman EZ, Ellinor PT, Stricker BH, Gudnason V, Heckbert SR, Pencina MJ, Benjamin EJ, Alonso A: B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies. Europace, 2014; 16(10): 1426-1433
    1. Ho JE, Yin X, Levy D, Vasan RS, Magnani JW, Ellinor PT, McManus DD, Lubitz SA, Larson MG, Benjamin EJ: Galectin 3 and incident atrial fibrillation in the community. Am Heart J, 2014; 167(5): 729-734
    1. Chua W, Purmah Y, Cardoso VR, Gkoutos GV, Tull SP, Neculau G, Thomas MR, Kotecha D, Lip GYH, Kirchhof P, Fabritz L: Data-driven discovery and validation of circulating blood-based biomarkers associated with prevalent atrial fibrillation. Eur Heart J, 2019; 40(16): 1268-1276
    1. Kamel H, Longstreth WT Jr, Tirschwell DL, Kronmal RA, Broderick JP, Palesch YY, Meinzer C, Dillon C, Ewing I, Spilker JA, Di Tullio MR, Hod EA, Soliman EZ, Chaturvedi S, Moy CS, Janis S, Elkind MS: The AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke randomized trial: Rationale and methods. Int J Stroke, 2019; 14(2): 207-214
    1. Binici Z, Intzilakis T, Nielsen OW, Køber L, Sajadieh A: Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke. Circulation, 2010; 121(17): 1904-1911
    1. Weber-Krüger M, Lutz C, Zapf A, Stahrenberg R, Seegers J, Witzenhausen J, Wasser K, Hasenfuß G, Gröschel K, Wachter R: Relevance of supraventricular runs detected after cerebral ischemia. Neurology, 2017; 89(15): 1545-1552

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner