Multicenter Study

. 2025 Jul;56(7):1704-1713.

doi: 10.1161/STROKEAHA.124.049249. Epub 2025 Apr 21.

Role of NT-proBNP for Atrial Fibrillation Detection After Ischemic Stroke: A Time-Dependent Relationship

Isra Hatab^#¹, Markus Kneihsl^#^{1

2}, Markus Arnold³, Thomas Pokorny³, Laura P Westphal⁴, Giulio Bicciato⁴, Corinne Inauen⁴, Egbert Bisping⁵, Simon Fandler-Höfler¹, Marcel Arnold⁶, Gian Marco De Marchis^{7

8}, Timo Kahles⁹, Carlo W Cereda¹⁰, Georg Kägi^{7

6

8}, Alejandro Bustamante¹¹, Joan Montaner^{12

13

14}, George Ntaios¹⁵, Christian Foerch¹⁶, Katharina Spanaus¹⁷, Arnold von Eckardstein¹⁷, Alan Cameron¹⁸, Christian Enzinger¹, Thomas Gattringer¹, Urs Fischer^{4

6}, Mira Katan³

Affiliations

¹ Department of Neurology (I.H., M. Kneihsl, S.F.-H., C.E., T.G.), Medical University of Graz, Austria.
² Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology (M. Kneihsl), Medical University of Graz, Austria.
³ Department of Neurology, University Hospital Basel (Markus Arnold, T.P., M. Katan), University of Basel, Switzerland.
⁴ Department of Neurology (L.P.W., G.B., C.I., U.F.), University Hospital of Zurich, University of Zurich, Switzerland.
⁵ Division of Cardiology, Department of Internal Medicine, Medical University Graz, Austria (E.B.).
⁶ Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Switzerland (Marcel Arnold, G.K., U.F.).
⁷ Department of Clinical Research (G.M.D.M., G.K.), University of Basel, Switzerland.
⁸ Department of Neurology and Stroke Center, Cantonal Hospital St. Gallen, Switzerland (G.M.D.M., G.K.).
⁹ Department of Neurology, Cantonal Hospital Aarau, Switzerland (T.K.).
¹⁰ Stroke Center, Deperatment of Neurology, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Regional Hospital of Lugano, Switzerland (C.W.C.).
¹¹ Stroke Unit, Department of Neurology, Hospital Universitari Germans Trias i Pujol, Germans Trias i Pujol Research Institute (IGTP) Barcelona, Spain (A.B.).
¹² Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Barcelona, Spain (J.M.).
¹³ Stroke Research Program, Institute of Biomedicine of Seville, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, University of Seville, Spain (J.M.).
¹⁴ Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain (J.M.).
¹⁵ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece (G.N.).
¹⁶ Department of Neurology, Goethe University Frankfurt, Germany (C.F.).
¹⁷ Institute of Clinical Chemistry (K.S., A.v.E.), University Hospital of Zurich, University of Zurich, Switzerland.
¹⁸ School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom (A.C.).

^# Contributed equally.

PMID: 40255172
DOI: 10.1161/STROKEAHA.124.049249

Free article

Multicenter Study

Role of NT-proBNP for Atrial Fibrillation Detection After Ischemic Stroke: A Time-Dependent Relationship

Isra Hatab et al. Stroke. 2025 Jul.

Free article

. 2025 Jul;56(7):1704-1713.

doi: 10.1161/STROKEAHA.124.049249. Epub 2025 Apr 21.

Authors

Affiliations

¹ Department of Neurology (I.H., M. Kneihsl, S.F.-H., C.E., T.G.), Medical University of Graz, Austria.
² Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology (M. Kneihsl), Medical University of Graz, Austria.
³ Department of Neurology, University Hospital Basel (Markus Arnold, T.P., M. Katan), University of Basel, Switzerland.
⁴ Department of Neurology (L.P.W., G.B., C.I., U.F.), University Hospital of Zurich, University of Zurich, Switzerland.
⁵ Division of Cardiology, Department of Internal Medicine, Medical University Graz, Austria (E.B.).
⁶ Department of Neurology, Inselspital, University Hospital Bern, University of Bern, Switzerland (Marcel Arnold, G.K., U.F.).
⁷ Department of Clinical Research (G.M.D.M., G.K.), University of Basel, Switzerland.
⁸ Department of Neurology and Stroke Center, Cantonal Hospital St. Gallen, Switzerland (G.M.D.M., G.K.).
⁹ Department of Neurology, Cantonal Hospital Aarau, Switzerland (T.K.).
¹⁰ Stroke Center, Deperatment of Neurology, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale, Regional Hospital of Lugano, Switzerland (C.W.C.).
¹¹ Stroke Unit, Department of Neurology, Hospital Universitari Germans Trias i Pujol, Germans Trias i Pujol Research Institute (IGTP) Barcelona, Spain (A.B.).
¹² Neurovascular Research Laboratory, Vall d'Hebron Institute of Research, Barcelona, Spain (J.M.).
¹³ Stroke Research Program, Institute of Biomedicine of Seville, Hospital Universitario Virgen del Rocío, Consejo Superior de Investigaciones Científicas, University of Seville, Spain (J.M.).
¹⁴ Department of Neurology, Hospital Universitario Virgen Macarena, Seville, Spain (J.M.).
¹⁵ Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece (G.N.).
¹⁶ Department of Neurology, Goethe University Frankfurt, Germany (C.F.).
¹⁷ Institute of Clinical Chemistry (K.S., A.v.E.), University Hospital of Zurich, University of Zurich, Switzerland.
¹⁸ School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom (A.C.).

^# Contributed equally.

PMID: 40255172
DOI: 10.1161/STROKEAHA.124.049249

Abstract

Background: Atrial fibrillation detected after stroke (AFDAS) affects secondary stroke prevention, yet identification can be challenging. Easily accessible cardiac blood biomarkers such as NT-proBNP (N-terminal pro-B-type natriuretic peptide) could guide diagnostic workup, but optimal cutoff values and the time-dependent relationship between NT-proBNP and AFDAS are unclear. We aimed (1) to externally validate earlier presented NT-proBNP cutoffs for atrial fibrillation prediction and (2) to assess the time-dependent relationship of NT-proBNP and early in-hospital AFDAS versus AFDAS after discharge.

Methods: We conducted a pooled data analysis of patients with ischemic stroke from the prospective international multicenter BIOSIGNAL (Biomarker Signature of Stroke Aetiology) cohort study (European Stroke Centers from October 2014 to October 2017) and the prospective single-center Graz stroke pathway study (Austria from May 2018 to August 2020). AFDAS was defined as ≥30-s atrial fibrillation/flutter diagnosed within 1 year post-admission and categorized in in-hospital versus after discharge. NT-proBNP was assessed ≤24 hours of symptom onset. The association between NT-proBNP and AFDAS was evaluated by a multivariable logistic regression analysis.

Results: AFDAS was diagnosed in 374 (16%) of 2292 patients with ischemic stroke (median age, 74 years; 42% female), 268 (72%) during hospitalization, and 106 (28%) after discharge (median duration of hospitalization, 15 days). NT-proBNP levels at admission had a good predictive capacity for in-hospital AFDAS (area under the receiver operating characteristic curve, 0.83 [95% CI, 0.81-0.86]). For patients diagnosed with AFDAS after discharge, the predictive capacity of NT-proBNP was poor (area under the receiver operating characteristic curve, 0.65 [95% CI, 0.60-0.70]), and 20% had normal NT-proBNP values <125 pg/mL at admission. The NT-proBNP cutoff of 505 pg/mL exhibited high sensitivity (82%) and specificity (71%) for in-hospital AFDAS, with a negative predictive value of 96%.

Conclusions: In patients with ischemic stroke, the admission NT-proBNP cutoff of 505 pg/mL seems to be a reliable predictor for in-hospital AFDAS, while the predictive capacity of NT-proBNP for AFDAS after discharge is limited. Our results might influence the designs of future secondary stroke prevention trials.

Keywords: anticoagulants; atrial fibrillation; embolic stroke; ischemic stroke; patient discharge.

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Conflict of interest statement

Dr Kneihsl received a grant from the European Academy of Neurology, not related to the submitted work, and has served on advisory boards of Novartis and Bristol Myers Squibb (BMS) Pfizer. Dr Marcel Arnold reports compensation from Boehringer Ingelheim, Amgen, Covidien, Medtronic, and Novo Nordisk for consultant services and compensation from AstraZeneca, Bayer, BMS, Covidien, Daiichi Sankyo, Novartis, Sanofi, and Pfizer for consultant services, outside the submitted work. Dr Fandler-Höfler received speakers’ honoraria from AstraZeneca, outside the submitted work. Dr De Marchis received an unrestricted grant from B.R.A.H.M.S. for the CoRISK study (Copeptin for Risk Stratification in Acute Stroke Patients) in 2012, not related to the submitted work. Dr Cereda has served on the advisory boards of iSchemaView, Inc, Bayer, AstraZeneca, and Medtronic, outside the submitted work. Dr Kägi received grants from the Swiss Hear Foundation, the Swiss National Foundation, the Swiss Parkinson Foundation, the Bangerter-Rhyner Stiftung, and the Deutschschweizer Logopädinnen und Logopädenverband and has served on the advisory boards of Bayer, Bial, Medtronic, and Alexion, outside the submitted work. Dr Ntaios received speaker fees or honoraria from Abbott, Amgen, AstraZeneca, Bayer, BMS/Pfizer, Boehringer Ingelheim, Elpen, Ferrer, Javelin, Novartis, and Sanofi. Dr Foerch reports compensation from Prediction Bioscience, Alexion Pharmaceuticals, and Boehringer Ingelheim for consultant services; compensation from BMS and AstraZeneca for other services; grants from the Keep Fighting Foundation and AstraZeneca; and a patent issued for GFAP (glial fibrillary acidic protein) for identification of intracerebral hemorrhage licensed to Banyan Biomarkers. Dr von Eckardstein received personal fees from Amgen and Sanofi, outside the submitted work. Dr Cameron received research grants from Pfizer and honoraria from BMS, Pfizer, AstraZeneca, and Boehringer Ingelheim. Dr Gattringer received a research grant from the Austrian Science Fund and the Austrian Neurological Society; received speakers’ honoraria and travel support from BMS Pfizer, Bayer, Amgen, Astra Zeneca, and Boehringer Ingelheim; and has served on advisory boards of Novartis and Boehringer Ingelheim. Dr Fischer received research support from the Swiss National Science Foundation and the Swiss Heart Foundation; research grants from Medtronic (BEYOND SWIFT and SWIFT DIRECT [Solitaire™ With the Intention For Thrombectomy Plus Intravenous t-PA Versus DIRECT Solitaire™ Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke]), Stryker, Rapid Medical, Penumbra, and Phenox (DISTAL, EnDovascular Therapy Plus Best Medical Treatment [BMT] Versus BMT Alone for MedIum VeSsel Occlusion sTroke); consultancies for Medtronic, Stryker, and CSL Behring (fees paid to institution); has participated on an advisory board for Alexion/Portola, Boehringer Ingelheim, Biogen, and Acthera (fees paid to institution); is a PI of the ELAN (Early versus Late initiation of direct oral Anticoagulants in postischaemic stroke patients with atrial fibrillatioN) trial; is a Co-Principal Investigator of the DISTAL, TECNO (Safety and Efficacy of Intra-arterial Tenecteplase for Noncomplete Reperfusion of Intracranial Occlusions), SWIFT DIRECT and SWITCH (Swiss Trial of Decompressive Craniectomy Versus Best Medical Treatment of Spontaneous Supratentorial Intracerebral Hemorrhage) trials; is a member of a clinical event committee of the COATING (Coating to Optimize Aneurysm Treatment In The New Flow Diverter Generation) study (Phenox) and the data and safety monitoring committee of the TITAN (Thrombectomy In TANdem Occlusion), LATE_MT (Large Artery Occlusion Treated in Extended Time with Mechanical Thrombectomy), and IN EXTREMIS trials; and is the president of the Swiss Neurological Society. Dr Katan reports grants from the Swiss National Science Foundation, Thermo Fisher Scientific, Roche Diagnostics GmbH, and the USZ Foundation for other services and employment by the Universitätsspital Basel. The other authors report no conflicts.

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Role of NT-proBNP for Atrial Fibrillation Detection After Ischemic Stroke: A Time-Dependent Relationship

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Role of NT-proBNP for Atrial Fibrillation Detection After Ischemic Stroke: A Time-Dependent Relationship

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