Heart Arrhythmias in Young Patients with Cryptogenic Ischemic Stroke

Czech version

Authors: D. Šaňák ¹; M. Hutyra ²; M. Král ¹; History Study Group ^*
Authors‘ workplace: Komplexní cerebrovaskulární centrum, Neurologická klinika LF UP a FN Olomouc ¹; 1. interní klinika – kardiologická LF UP a FN Olomouc ²
Published in: Cesk Slov Neurol N 2015; 78/111(6): 669-674
Category: Original Paper
doi: https://doi.org/10.14735/amcsnn2015669

*HISTORY study group: T. Veverka, A. Bártková, A. Kunčarová, T. Dorňák, D. Franc, P. Kaňovský (Neurologická klinika LF UP a FN Olomouc), M. Fedorco, J. Galuzska, D. Vindiš, T. Skála, M. Táborský (1. interní klinika – kardiologická LF UP a Olomouc), E. Čecháková, Z. Tüdös, M. Černá, M. Köcher, (Radiologická klinika LF UP a FN Olomouc), J. Úlehlová, L. Slavík (Hemato-onkologická klinika LF UP a FN Olomouc), J. Zapletalová, K. Langová (Ústav lékařské biofyziky, biometrie a statistiky, LF UP v Olomouci), R. Herzig (Neurologická klinika LF UK a FN Hradec Králové), D. Školoudík (Ústav ošetřovatelství, Fakulta zdravotních věd, UP v Olomouci).

Overview

Background and aim:
The cause of ischemic stroke (IS) in young patients remains often cryptogenic. In elderly population, undetected heart arrhythmias with a risk of embolization are considered the cause of cryptogenic IS (CIS). The aim of this prospective study was to assess the presence of heart arrhythmias in young CIS patients using a long-term ECG-Holter monitoring and implantable subcutaneous heart monitor.

Patients and methods:
Study set consisted of acute IS patients < 50 years enrolled in the HISTORY (Heart and Ischemic STrOke Relationship studY) study. CIS was defined according to the TOAST criteria. In all patients, brain ischemia was confirmed on CT/MRI. Admission ECG, serum levels of cardio-markers, markers of thrombophilia including genetic screening, neurosonology, transoesophageal echocardiography, 24-hour and 3-week ECG-Holter monitoring were performed in all patients. In selected patients with negative 3-week Holter, subcutaneous heart monitor was implanted.

Results:
Out of 838 patients enrolled in the HISTORY study, 123 patients were < 50 years and 102 (83%) of them were identified as cryptogenic (56 males, mean age 39 ± 8.5 years). Cardiac arrhythmia was detected in 12 (12%) patients (nine males, mean age 43 ± 4.2 years). In nine (75%) patients, atrial fibrillation was presented. In three patients, the arrhythmia was detected during 24-h ECG-Holter and during 3-week monitoring in the remaining nine patients. The subcutaneous monitor was implanted in 12 patients, but no arrhythmia was detected during study period (median 122 days). Conclusion: Heart arrhythmia was detected in 12% of young CIS patients. Prolongation of ECG-Holter monitoring increased the detection rate significantly. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01541163.

Key words:
cryptogenic ischemic stroke – cardiac arrhythmias – atrial fibrillation – ECG-Holter monitoring

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Sources

1. Grau AJ, Weimar C, Buggle F, Al‑ Khalaf A, Werle E, Valois N et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German stroke data bank. Stroke 2001; 32(11): 2559– 2566.

2. Kolominsky‑ Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long‑term survival in ischemic stroke subtypes: a population‑based study. Stroke 2001; 32(12): 2735– 2740.

3. Wohlfahrt J, Stahrenberg R, Weber‑ Krüger M, Gröschel S, Wasser K, Edelmann F et al. Clinical predictors to identify paroxysmal atrial fibrillation after ischaemic stroke. Eur J Neurol 2014; 21(1): 21– 27. doi: 10.1111/ ene.12198.

4. Go AS, Mozzaffarian D, Roger VL, Benjamin EJ, Berry JD, Dai S et al. Heart disease and stroke statistics – 2014 update: a report from the American Heart Association. Circulation 2014; 129(3): e28– e292. doi: 10.1161/ 01.cir.0000441139.02102.80.

5. 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(12): 2884– 2888. doi: 10.1161/ STROKEAHA.110.591958.

6. Wachter R, Weber‑ Krüger M, Seegers J, Edelmann F, Wohlfahrt J, Wasser K et al. Age‑ dependent yield of screening for undetected atrial fibrillation in stroke patients: the Find‑ AF study. J Neurol 2013; 260(8): 2042– 2045. doi: 10.1007/ s00415‑ 013‑ 6935‑ x.

7. Hart RG, Diener HC, Connolly SJ. Embolic strokes of undetermined source: support for a new clinical construct – authors‘ reply. Lancet Neurol 2014; 13(10): 967. doi: 10.1016/ S1474‑ 4422(14)70196‑ 6.

8. Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Math M et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med 2014; 370(26): 2467– 2477. doi: 10.1056/ NEJMoa1311376.

9. Cerrato P, Grasso M, Imperiale D, Priano L, Baima C, Giraudo M et al. Stroke in young patients: etiopathogenesis and risk factors in different age classes. Cerebrovasc Dis 2004; 18(2): 154– 159.

10. Putaala J, Metso AJ, Metso TM, Konkola N, Kraemer Y. Analysis of 1,008 consecutive patients aged 15 to 49 with first‑ ever ischemic stroke: the Helsinki young stroke registry. Stroke 2009; 40(4): 1195– 1203. doi: 10.1161/ STROKEAHA.108.529883.

11. Putaala J, Haapaniemi E, Metso AJ, Metso TM, Artto V, Kaste M et al. Recurrent ischemic events in young adults after first‑ ever ischemic stroke. Ann Neurol 2010; 68(5): 661– 671. doi: 10.1002/ ana.22091.

12. Ferro JM, Massaro AR, Mas JL. Aetiological diagnosis of ischaemic stroke in young adults. Lancet Neurol 2010; 9(11): 1085– 1096. doi: 10.1016/ S1474‑ 4422(10)70251‑ 9.

13. Varona JF, Guerra JM, Bermejo F, Molina JA, Gomez de la Camara A. Causes of ischemic stroke in young adults, and evolution of the etiological diagnosis over the long term. Eur Neurol 2007; 57(4): 212– 218.

14. Seet RC, Friedman PA, Rabinstein AA. Prolonged rhythm monitoring for the detection of occult paroxysmal atrial fibrillation in ischemic stroke of unknown cause. Circulation 2011; 124(4): 477– 486. doi: 10.1161/ CIRCULATIONAHA.111.029801.

15. Wolf PA. Awareness of the role of atrial fibrillation as a cause of ischemic stroke. Stroke 2014; 45(2): e19– e21. doi: 10.1161/ STROKEAHA.113.003282.

16. Gattellari M, Goumas C, Aitken R, Worthington JM. Outcomes for patients with ischaemic stroke and atrial fibrillation: the PRISM study (a Program of Research Informing Stroke Management). Cerebrovasc Dis 2011; 32(4): 370– 382. doi: 10.1159/ 000330637.

17. Potpara TS, Lip GY. Ischemic stroke and atrial fibrillation – a deadly serious combination. Cerebrovasc Dis 2011; 32(5): 461– 462. doi: 10.1159/ 000332030.

18. Hart RG, Pearce LA, Rothbart RM, McAnulty JH, Asinger RW, Halperin JL. Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. Stroke Prevention in Atrial Fibrillation Investigators. J Am Coll Cardiol 2000; 35(1): 183– 187.

19. Chatzikonstantinou A, Wolf ME, Hennerici MG. Ischemic stroke in young adults: classification and risk factors. J Neurol 2012; 259(4): 653– 659. doi: 10.1007/ s00415‑ 011‑ 6234‑ 3.

20. Prefasi D, Martinez‑ Sanchez P, Rodrıguez‑ Sanz A, Fuentes B, Filgueiras‑ Rama D, Ruiz‑ Ares G et al. Atrial fibrillation in young stroke patients: do we underestimate its prevalence? Eur J Neurol 2013; 20(10): 1367– 1374. doi: 10.1111/ ene.12187.

21. Fonseca AC, Ferro JM. Cryptogenic stroke. Eur J Neurol 2015; 22(4): 618– 623. doi: 10.1111/ ene.12673.

22. Winkler S, Axmann C, Schannor B, Kim S, Leuthold T, Scherf M et al. Diagnostic accuracy of a new detection algorithm for atrial fibrillation in cardiac telemonitoring with portable electrocardiogram devices. J Electrocardiol 2011; 44(4): 460– 464. doi: 10.1016/ j.jelectrocard.2011.01.011.

23. Sanna T, Diener HC, Passman RS, Di Lazzaro V, Bernstein RA, Morillo CA et al. Cryptogenic stroke and underlying atrial fibrillation. N Engl J Med 2014; 370(26): 2478– 2486. doi: 10.1056/ NEJMoa1313600.

24. Ziegler PD, Rogers JD, Ferreira SW, Nichols AJ, Sarkar S, Koehler JL et al. Real‑ world experience with insertable cardiac monitors to find atrial fibrillation in cryptogenic stroke. Cerebrovasc Dis 2015; 40(3– 4): 175– 181. doi: 10.1159/ 000439063.

25. Favilla CG, Ingala E, Jara J, Fessler E, Cucchiara B, Messé SR et al. Predictors of finding occult atrial fibrillation after cryptogenic stroke. Stroke 2015; 46(5): 1210– 1215. doi: 10.1161/ STROKEAHA.114.007763.

26. Kral M, Skoloudik D, Sanak D, Veverka T, Bartkova A, Dornak T et al. Assessment of relationship between acute ischemic stroke and heart disease – protocol of a prospective observational trial. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012; 156(3): 284– 289. doi: 10.5507/ bp.2012.094.

27. Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA et al. ACC/ AHA/ ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114(7): e257– e354.

28. Kirchhof P, Auricchio A, Bax J, Crijns H, Camm J, Diener HC et al. Outcome parameters for trials in atrial fibrillation: recommendations from a consensus conference organized by the German Atrial Fibrillation Competence Network and the European Heart Rhythm Association. Europace 2007; 9(11): 1006– 1023.

29. Stoddard MF, Dawkins PR, Prince CR, Ammash NM. Left atrial appendage thrombus is not uncommon in patients with acute atrial fibrillation and a recent embolic event: a transesophageal echocardiographic study. J Am Coll Cardiol 1995; 25(2): 452– 459.

30. Manning WJ, Silverman DI, Waksmonski CA, Oettgen P, Douglas PS. Prevalence of residual left atrial thrombi among patients with acute thromboembolism and newly recognized atrial fibrillation. Arch Intern Med 1995; 155(20): 2193– 2198.

31. Kerr CR, Humphries KH, Talajic M, Klein GJ, Connolly SJ, Green M et al. Progression to chronic atrial fibrillation after the initial diagnosis of paroxysmal atrial fibrillation: result from the Canadian Registry of Atrial Fibrillation. Am Heart J 2005; 149(3): 489– 496.

32. 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(10): 2689– 2694.

33. 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(12): 3357– 3364. doi: 10.1161/ STROKEAHA.113.001884.

34. 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(7): 2160– 2236. doi: 10.1161/ STR.0000000000000024.

35. Ritter MA, Kochhäuser S, Duning T, Reinke F, Pott C, Dechering DG et al. Occlut atrial fibrillation in cryptogenic stroke: detection by 7- day electrocardiogram versus implantable cardiac monitors. Stroke 2013; 44(5): 1449– 1452. doi: 10.1161/ STROKEAHA.111.676189.

36. Cotter PE, Martin PJ, Ring L, Warburton EA, Belham M, Pugh PJ. Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke. Neurology 2013; 80(17): 1546– 1550. doi: 10.1212/ WNL.0b013e31828f1828.

37. Anegawa T, Kai H, Adachi H, Hirai Y, Enomoto M, Fukami A et al. High‑sensitive troponin T is associated with atrial fibrillation in a general population. Int J Cardiol 2012; 156(1): 98– 100. doi: 10.1016/ j.ijcard.2011.12.117.

38. Patton KK, Heckbert SR, Alonso A, Bahrami H, Lima JA, Burke G et al. N‑terminal pro‑B‑type natriuretic peptide as a predictor of incident atrial fibrillation in the Multi‑Ethnic Study of Atherosclerosis: the effects of age, sex and ethnicity. Heart 2013; 99(24): 1832– 1836. doi: 10.1136/heartjnl‑ 2013‑ 304724.