HEart and BRain interfaces in Acute ischemic Stroke (HEBRAS)--rationale and design of a prospective oberservational cohort study

Karl Georg Haeusler, Ulrike Grittner, Jochen B Fiebach, Matthias Endres, Thomas Krause, Christian H Nolte, Karl Georg Haeusler, Ulrike Grittner, Jochen B Fiebach, Matthias Endres, Thomas Krause, Christian H Nolte

Abstract

Background: An effective diagnostic work-up in hospitalized patients with acute ischemic stroke is vital to optimize secondary stroke prevention. The HEart and BRain interfaces in Acute ischemic Stroke (HEBRAS) study aims to assess whether an enhanced MRI set-up and a prolonged Holter-ECG monitoring yields a higher rate of pathologic findings as compared to diagnostic procedures recommended by guidelines (including stroke unit monitoring for at least 24 h, echocardiography and ultrasound of brain-supplying arteries).

Methods/design: Prospective observational single-center study in 475 patients with acute ischemic stroke and without known atrial fibrillation. Patients will receive routine diagnostic care in hospital as wells as brain MRI, cardiac MRI, MR angiography of the brain-supplying arteries and Holter-monitoring for up to 10 days. Study patients will be followed up for cardiovascular outcomes at 3 and 12 months after enrollment.

Discussion: By comparing the results of routine diagnostic care to the study-specific MRI/ECG approach, the primary outcome of HEBRAS is the proportion of stroke patients with pathologic diagnostic findings. Predefined secondary outcomes are the association of stroke localization, autonomic dysbalance and cardiac dysfunction as well as the effect of impaired heart-rate-variability on long-term clinical outcome. The investigator-initiated HEBRAS study will assess whether an enhanced MRI approach and a prolonged ECG monitoring yield a higher rate of pathological findings than current standard diagnostic care to determine stroke etiology. These findings might influence current diagnostic recommendations after acute ischemic stroke. Moreover, HEBRAS will determine the extent and clinical impact of stroke-induced cardiac damage.

Trial registration: Clinicaltrials.gov NCT02142413.

References

    1. Heidrich J, Heuschmann PU, Kolominsky-Rabas P, Rudd AG, Wolfe CD, European BIISoSCG Variations in the use of diagnostic procedures after acute stroke in Europe: results from the BIOMED II study of stroke care. Eur J Neurol. 2007;14(3):255–61. doi: 10.1111/j.1468-1331.2006.01573.x.
    1. Herm J, Konieczny M, Jungehulsing GJ, Endres M, Villringer A, Malzahn U, et al. Should transesophageal echocardiography be performed in acute stroke patients with atrial fibrillation? J Clin Neurosci. 2013;20(4):554–9. doi: 10.1016/j.jocn.2012.03.049.
    1. Rizos T, Rasch C, Jenetzky E, Hametner C, Kathoefer S, Reinhardt R, et al. Detection of paroxysmal atrial fibrillation in acute stroke patients. Cerebrovasc Dis. 2010;30(4):410–7. doi: 10.1159/000316885.
    1. Hart RG, Diener HC, 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(4):429–38. doi: 10.1016/S1474-4422(13)70310-7.
    1. Barkhausen J, Hunold P, Eggebrecht H, Schuler WO, Sabin GV, Erbel R, et al. Detection and characterization of intracardiac thrombi on MR imaging. AJR Am J Roentgenol. 2002;179(6):1539–44. doi: 10.2214/ajr.179.6.1791539.
    1. Pagan RJ, Parikh PP, Mergo PJ, Gerber TC, Mankad R, Freeman WD, et al. Emerging role of cardiovascular CT and MRI in the evaluation of stroke. AJR Am J Roentgenol. 2015;204(2):269–80. doi: 10.2214/AJR.14.13051.
    1. Harloff A, Dudler P, Frydrychowicz A, Strecker C, Stroh AL, Geibel A, et al. Reliability of aortic MRI at 3 Tesla in patients with acute cryptogenic stroke. J Neurol Neurosurg Psychiatry. 2008;79(5):540–6. doi: 10.1136/jnnp.2007.125211.
    1. Nederkoorn PJ, van der Graaf Y, Hunink MG. Duplex ultrasound and magnetic resonance angiography compared with digital subtraction angiography in carotid artery stenosis: a systematic review. Stroke. 2003;34(5):1324–32. doi: 10.1161/01.STR.0000068367.08991.A2.
    1. Gladstone DJ, Spring M, Dorian P, Panzov V, Thorpe KE, Hall J, et al. Atrial fibrillation in patients with cryptogenic stroke. N Engl J Med. 2014;370(26):2467–77. doi: 10.1056/NEJMoa1311376.
    1. 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):2478–86. doi: 10.1056/NEJMoa1313600.
    1. Glotzer TVZP. Silent atrial fibrillation as a stroke risk factor and anticoagulation indication. Can J Cardiol. 2013;7(29):S14–23. doi: 10.1016/j.cjca.2013.03.023.
    1. Rizos T, Quilitzsch A, Busse O, Haeusler KG, Endres M, Heuschmann P, et al. Diagnostic work-up for detection of paroxysmal atrial fibrillation after acute ischemic stroke: cross-sectional survey on german stroke units. Stroke. 2015;46(6):1693–5. doi: 10.1161/STROKEAHA.115.009374.
    1. Jauch EC, Saver JL, Adams HP, Jr, Bruno A, Connors JJ, Demaerschalk BM, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2013;44(3):870–947. doi: 10.1161/STR.0b013e318284056a.
    1. January CT, Wann LS, Alpert JS, Calkins H, Cigarroa JE, Cleveland JC, Jr, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society. Circulation. 2014;130(23):2071–104. doi: 10.1161/CIR.0000000000000040.
    1. Dittrich R, Schmidt WP, Heidrich J, Bucker-Nott HJ, Ringelstein EB, Heuschmann PU, et al. Differences in the extent of diagnostic procedures after acute stroke in patients treated in departments of neurology, internal medicine and geriatric medicine. Fortschr Neurol Psychiatr. 2005;73(2):68–73. doi: 10.1055/s-2004-830103.
    1. Scheitz JF, Erdur H, Haeusler KG, Audebert HJ, Roser M, Laufs U, et al. Insular cortex lesions, cardiac troponin, and detection of previously unknown atrial fibrillation in acute ischemic stroke: insights from the troponin elevation in acute ischemic stroke study. Stroke. 2015;46(5):1196–201. doi: 10.1161/STROKEAHA.115.008681.
    1. Scheitz JF, Mochmann HC, Erdur H, Tutuncu S, Haeusler KG, Grittner U, et al. Prognostic relevance of cardiac troponin T levels and their dynamic changes measured with a high-sensitivity assay in acute ischaemic stroke: analyses from the TRELAS cohort. Int J Cardiol. 2014;177(3):886–93. doi: 10.1016/j.ijcard.2014.10.036.
    1. Adams HP, Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993;24(1):35–41. doi: 10.1161/01.STR.24.1.35.
    1. von Reutern GM, Goertler MW, Bornstein NM, Del Sette M, Evans DH, Hetzel A, et al. Grading carotid stenosis using ultrasonic methods. Stroke. 2012;43(3):916–21. doi: 10.1161/STROKEAHA.111.636084.
    1. Bates E, Wilson SM, Saygin AP, Dick F, Sereno MI, Knight RT, et al. Voxel-based lesion-symptom mapping. Nat Neurosci. 2003;6(5):448–50.
    1. Rorden C, Karnath HO, Bonilha L. Improving lesion-symptom mapping. J Cogn Neurosci. 2007;19(7):1081–8. doi: 10.1162/jocn.2007.19.7.1081.
    1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J. 2012;33(21):2719–47. doi: 10.1093/eurheartj/ehs253.
    1. Wallmann D, Tuller 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(8):2292–4. doi: 10.1161/STROKEAHA.107.485110.
    1. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task force of the european society of cardiology and the North American society of pacing and electrophysiology. Circulation. 1996, 93(5):1043–65.
    1. Brott T, Adams HP, Jr, Olinger CP, Marler JR, Barsan WG, Biller J, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989;20(7):864–70. doi: 10.1161/01.STR.20.7.864.
    1. van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604–7. doi: 10.1161/01.STR.19.5.604.
    1. Weber-Kruger M, Gelbrich G, Stahrenberg R, Liman J, Kermer P, Hamann GF, et al. Finding atrial fibrillation in stroke patients: Randomized evaluation of enhanced and prolonged Holter monitoring--Find-AF(RANDOMISED) --rationale and design. Am Heart J. 2014;168(4):438–45. doi: 10.1016/j.ahj.2014.06.018.
    1. 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):3357–64. doi: 10.1161/STROKEAHA.113.001884.
    1. Rizos T, Guntner 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):2689–94. doi: 10.1161/STROKEAHA.112.654954.
    1. Faiz KW, Thommessen B, Einvik G, Brekke PH, Omland T, Ronning OM. Determinants of high sensitivity cardiac troponin T elevation in acute ischemic stroke. BMC Neurol. 2014;14:96. doi: 10.1186/1471-2377-14-96.
    1. Scheitz JF, Endres M, Mochmann HC, Audebert HJ, Nolte CH. Frequency, determinants and outcome of elevated troponin in acute ischemic stroke patients. Int J Cardiol. 2012;157(2):239–42. doi: 10.1016/j.ijcard.2012.01.055.
    1. Feher G, Tibold A, Koltai K, Szapary L. The clinical importance of troponin elevation in ischaemic cerebrovascular events: a clinical review. J Cardiol Ther. 2014;7(1):141–9.
    1. Scheitz JF, Nolte CH, Laufs U, Endres M. Application and interpretation of high-sensitivity cardiac troponin assays in patients with acute ischemic stroke. Stroke. 2015;46(4):1132–40. doi: 10.1161/STROKEAHA.114.007858.
    1. Shibazaki K, Kimura K, Fujii S, Sakai K, Iguchi Y. Brain natriuretic peptide levels as a predictor for new atrial fibrillation during hospitalization in patients with acute ischemic stroke. Am J Cardiol. 2012;109(9):1303–7. doi: 10.1016/j.amjcard.2011.12.022.
    1. Suissa L, Bresch S, Lachaud S, Mahagne MH. Brain natriuretic peptide: a relevant marker to rule out delayed atrial fibrillation in stroke patient. J Stroke Cerebrovasc Dis. 2013;22(7):e103–10. doi: 10.1016/j.jstrokecerebrovasdis.2012.08.010.
    1. Wachter R, Lahno R, Haase B, Weber-Kruger M, Seegers J, Edelmann F, et al. Natriuretic peptides for the detection of paroxysmal atrial fibrillation in patients with cerebral ischemia--the Find-AF study. PLoS One. 2012;7(4):e34351. doi: 10.1371/journal.pone.0034351.
    1. Association TCCotNYH . Functional capacity and objective assessment. In: Dolgin M, editor. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9. Boston, MA: Little, Brown and Company; 1994. pp. 253–5.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera