Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source

Thies Ingwersen; Manuel C. Olma; Eckhard Schlemm; Carola Mayer; Bastian Cheng; Serdar Tütüncü; Paulus Kirchhof; Roland Veltkamp; Joachim Röther; Ulrich Laufs; Darius G. Nabavi; George Ntaios; Matthias Endres; Karl Georg Haeusler; Götz Thomalla

doi:10.1186/s42466-023-00279-z

Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source

Thies Ingwersen^*, Manuel C. Olma, Eckhard Schlemm, Carola Mayer, Bastian Cheng, Serdar Tütüncü, Paulus Kirchhof, Roland Veltkamp, Joachim Röther, Ulrich Laufs, Darius G. Nabavi, George Ntaios, Matthias Endres, Karl Georg Haeusler, Götz Thomalla

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial.

Methods: The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods.

Results: Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ² = 4.2, p = 0.1).

Conclusions: This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.

Original language	English
Article number	51
Number of pages	10
Journal	Neurological Research and Practice
Volume	5
Issue number	1
DOIs	https://doi.org/10.1186/s42466-023-00279-z
Publication status	Published - 5 Oct 2023

Bibliographical note

Funding:
Open Access funding enabled and organized by Projekt DEAL. The MonDAFIS study is an investigator‑initiated, prospective, randomised, multicentre study sponsored by the Charité ‑ Universitätsmedizin Berlin, Germany and supported by an unrestricted research grant from Bayer Vital GmbH, Germany to the Charité ‑ Universitätsmedizin Berlin, Germany.

Keywords

ESUS
Stroke recurrence
Ischemic stroke
Stroke recurrence score
Embolic stroke of undetermined source
External validation

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IngwersenT2023IndependentFinal published version, 1.07 MBLicence: Creative Commons: Attribution (CC BY)

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Ingwersen, T., Olma, M. C., Schlemm, E., Mayer, C., Cheng, B., Tütüncü, S., Kirchhof, P., Veltkamp, R., Röther, J., Laufs, U., Nabavi, D. G., Ntaios, G., Endres, M., Haeusler, K. G., & Thomalla, G. (2023). Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source. Neurological Research and Practice, 5(1), Article 51. https://doi.org/10.1186/s42466-023-00279-z

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title = "Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source",

abstract = "Background: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. Methods: The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. Results: Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). Conclusions: This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model{\textquoteright}s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.",

keywords = "ESUS, Stroke recurrence, Ischemic stroke, Stroke recurrence score, Embolic stroke of undetermined source, External validation",

author = "Thies Ingwersen and Olma, {Manuel C.} and Eckhard Schlemm and Carola Mayer and Bastian Cheng and Serdar T{\"u}t{\"u}nc{\"u} and Paulus Kirchhof and Roland Veltkamp and Joachim R{\"o}ther and Ulrich Laufs and Nabavi, {Darius G.} and George Ntaios and Matthias Endres and Haeusler, {Karl Georg} and G{\"o}tz Thomalla",

note = "Funding: Open Access funding enabled and organized by Projekt DEAL. The MonDAFIS study is an investigator‑initiated, prospective, randomised, multicentre study sponsored by the Charit{\'e} ‑ Universit{\"a}tsmedizin Berlin, Germany and supported by an unrestricted research grant from Bayer Vital GmbH, Germany to the Charit{\'e} ‑ Universit{\"a}tsmedizin Berlin, Germany.",

year = "2023",

month = oct,

day = "5",

doi = "10.1186/s42466-023-00279-z",

language = "English",

volume = "5",

journal = "Neurological Research and Practice",

issn = "2524-3489",

publisher = "BioMed Central",

number = "1",

}

Ingwersen, T, Olma, MC, Schlemm, E, Mayer, C, Cheng, B, Tütüncü, S, Kirchhof, P, Veltkamp, R, Röther, J, Laufs, U, Nabavi, DG, Ntaios, G, Endres, M, Haeusler, KG & Thomalla, G 2023, 'Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source', Neurological Research and Practice, vol. 5, no. 1, 51. https://doi.org/10.1186/s42466-023-00279-z

TY - JOUR

T1 - Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source

AU - Ingwersen, Thies

AU - Olma, Manuel C.

AU - Schlemm, Eckhard

AU - Mayer, Carola

AU - Cheng, Bastian

AU - Tütüncü, Serdar

AU - Kirchhof, Paulus

AU - Veltkamp, Roland

AU - Röther, Joachim

AU - Laufs, Ulrich

AU - Nabavi, Darius G.

AU - Ntaios, George

AU - Endres, Matthias

AU - Haeusler, Karl Georg

AU - Thomalla, Götz

N1 - Funding: Open Access funding enabled and organized by Projekt DEAL. The MonDAFIS study is an investigator‑initiated, prospective, randomised, multicentre study sponsored by the Charité ‑ Universitätsmedizin Berlin, Germany and supported by an unrestricted research grant from Bayer Vital GmbH, Germany to the Charité ‑ Universitätsmedizin Berlin, Germany.

PY - 2023/10/5

Y1 - 2023/10/5

N2 - Background: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. Methods: The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. Results: Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). Conclusions: This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.

AB - Background: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. Methods: The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. Results: Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3–11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02–5.93) times higher risk of stroke recurrence than patients with a score of 0–4. The cumulative probability of stroke recurrence in the low-(0–4), intermediate-(5–6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). Conclusions: This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model’s performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. Trial registration: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267.

KW - ESUS

KW - Stroke recurrence

KW - Ischemic stroke

KW - Stroke recurrence score

KW - Embolic stroke of undetermined source

KW - External validation

U2 - 10.1186/s42466-023-00279-z

DO - 10.1186/s42466-023-00279-z

M3 - Article

SN - 2524-3489

VL - 5

JO - Neurological Research and Practice

JF - Neurological Research and Practice

IS - 1

M1 - 51

ER -

Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source

Abstract

Bibliographical note

Keywords

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