Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit

Noor Samuels; Kars C J Compagne; Nadinda A M van der Ende; Vicky Chalos; Praneeta R Konduri; Pieter Jan van Doormaal; Wim H van Zwam; Charles B L M Majoie; Henk A Marquering; Bob Roozenbeek; Hester F Lingsma; Diederik W J Dippel; Aad van der Lugt; MR CLEAN Investigators

doi:10.1016/j.jstrokecerebrovasdis.2022.106906

Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit

Noor Samuels^*, Kars C J Compagne, Nadinda A M van der Ende, Vicky Chalos, Praneeta R Konduri, Pieter Jan van Doormaal, Wim H van Zwam, Charles B L M Majoie, Henk A Marquering, Bob Roozenbeek, Hester F Lingsma, Diederik W J Dippel, Aad van der Lugt, MR CLEAN Investigators

^*Corresponding author for this work

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

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Abstract

OBJECTIVES: The beneficial effect of endovascular thrombectomy (EVT) on clinical outcome is assumed to be caused by reduced follow-up infarct volume (FIV), which could serve as an early imaging endpoint. However, the effect of EVT on the modified Rankin Scale (mRS) was poorly explained by FIV. NIHSS at 5-7 days could be a more specific measure of the effect of reperfusion therapy, as opposed to the mRS at 3 months. Therefore, we aimed to assess to what extent the effect of EVT on NIHSS is explained by FIV.

MATERIALS AND METHODS: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n = 500) trial to evaluate the mediating role of FIV within 1 week in the relationship between EVT and baseline adjusted NIHSS at 5-7 days.

RESULTS: Larger FIVs were associated with higher NIHSS after treatment (adjusted beta-coefficient (aβ) 0.47;95%CI 0.39-0.55). EVT was associated with smaller FIVs (β -0.35;95%CI-0.64 to -0.06) and lower NIHSS (β -0.63;95%CI-0.90 to -0.35). After adjustment for FIV, the effect of EVT on NIHSS decreased (aβ -0.47;95%CI-0.72 to -0.23), indicating that effect of EVT on neurologic deficit is partially mediated by FIV. Reduction of FIV explained 34% (95%CI;5%-93%) of the effect of EVT on the NIHSS at 5-7 days.

CONCLUSIONS: Larger FIV was significantly associated with larger neurological deficits after treatment. Reduced infarct volume after EVT explains one third of treatment benefit in terms of neurological deficit. This suggests that FIV is of interest as an imaging biomarker of stroke treatment effect.

Original language	English
Article number	106906
Number of pages	7
Journal	Journal of Stroke & Cerebrovascular Diseases
Volume	32
Issue number	2
Early online date	3 Dec 2022
DOIs	https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106906
Publication status	Published - Feb 2023

Keywords

Endovascular treatment
Infarct volume
Stroke
Treatment effect

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10.1016/j.jstrokecerebrovasdis.2022.106906

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Samuels, N., Compagne, K. C. J., van der Ende, N. A. M., Chalos, V., Konduri, P. R., van Doormaal, P. J., van Zwam, W. H., Majoie, C. B. L. M., Marquering, H. A., Roozenbeek, B., Lingsma, H. F., Dippel, D. W. J., van der Lugt, A., & MR CLEAN Investigators (2023). Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit. Journal of Stroke & Cerebrovascular Diseases, 32(2), Article 106906. https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106906

@article{efd4f3fe3f56460b8eddc50f2245444c,

title = "Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit",

abstract = "OBJECTIVES: The beneficial effect of endovascular thrombectomy (EVT) on clinical outcome is assumed to be caused by reduced follow-up infarct volume (FIV), which could serve as an early imaging endpoint. However, the effect of EVT on the modified Rankin Scale (mRS) was poorly explained by FIV. NIHSS at 5-7 days could be a more specific measure of the effect of reperfusion therapy, as opposed to the mRS at 3 months. Therefore, we aimed to assess to what extent the effect of EVT on NIHSS is explained by FIV.MATERIALS AND METHODS: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n = 500) trial to evaluate the mediating role of FIV within 1 week in the relationship between EVT and baseline adjusted NIHSS at 5-7 days.RESULTS: Larger FIVs were associated with higher NIHSS after treatment (adjusted beta-coefficient (aβ) 0.47;95%CI 0.39-0.55). EVT was associated with smaller FIVs (β -0.35;95%CI-0.64 to -0.06) and lower NIHSS (β -0.63;95%CI-0.90 to -0.35). After adjustment for FIV, the effect of EVT on NIHSS decreased (aβ -0.47;95%CI-0.72 to -0.23), indicating that effect of EVT on neurologic deficit is partially mediated by FIV. Reduction of FIV explained 34% (95%CI;5%-93%) of the effect of EVT on the NIHSS at 5-7 days.CONCLUSIONS: Larger FIV was significantly associated with larger neurological deficits after treatment. Reduced infarct volume after EVT explains one third of treatment benefit in terms of neurological deficit. This suggests that FIV is of interest as an imaging biomarker of stroke treatment effect.",

keywords = "Endovascular treatment, Infarct volume, Stroke, Treatment effect",

author = "Noor Samuels and Compagne, {Kars C J} and {van der Ende}, {Nadinda A M} and Vicky Chalos and Konduri, {Praneeta R} and {van Doormaal}, {Pieter Jan} and {van Zwam}, {Wim H} and Majoie, {Charles B L M} and Marquering, {Henk A} and Bob Roozenbeek and Lingsma, {Hester F} and Dippel, {Diederik W J} and {van der Lugt}, Aad and {MR CLEAN Investigators}",

note = "Funding Information: Dr van Doormaal, reports consulting fees from Stryker. Dr van Zwam chairs DSMBs of WETRUST, Solonda and InExtremis studies, and received speaker fees from Stryker, Cerenovus and NicoLab, all paid to institution. Dr Majoie reports grants from CVON/Dutch Heart Foundation, TWIN Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker (paid to institution); and is (minority interest) shareholder of NicoLab. Dr Marquering is co-founder and shareholder of Nicolab. Dr Roozenbeek reports funding from the Dutch Heart Foundation and the Netherlands Organization of Health Research and Development, paid to institution. Dr Dippel and Dr van der Lugt report unrestricted grants from Stryker, Penumbra, Medtronic, Cerenovus, Thrombolytic Science, LLC, Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and Thrombolytic Science, LLC for research, paid to institution. The other authors report no conflicts. Funding Information: The authors received no funding for this study. The MR CLEAN trial was partly funded by the Dutch Heart Foundation and by unrestricted grants from AngioCare BV, Medtronic/Covidien/EV3{\textregistered}, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Stryker{\textregistered}, and Top Medical/Concentric. The MR CLEAN is registered under number NTR1804 in the Dutch trial register and under ISRCTN10888758 in the ISRCTN register. The study was additionally funded by the European Union's Horizon 2020 research and innovation program under grant agreement No 777072 (IN-SIlico trials for treatment of acute Ischemic STroke; INSIST). The funding sources had no role in study design, patient enrolment, data collection, analysis, writing of the manuscript, approval of the manuscript, and decision to submit the manuscript for publication. Funding Information: We thank the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) investigators. Noor. Samuels, Kars C.J. Compagne, Aad van der Lugt performed the study concept, statistical analysis, interpretation of the results and drafting of the article. Wim H. van Zwam, Charles B.L.M. Majoie, Diederik W.J. Dippel performed data aquisition and critical revision of the manuscript. Nadinda A.M. van der Ende, Vicky Chalos, Praneeta R. Konduri, Pieter Jan van Doormaal, Henk A. Marquering, Bob Roozenbeek, Hester F. Lingsma, performed the critical revision of the manuscript. Publisher Copyright: {\textcopyright} 2022",

year = "2023",

month = feb,

doi = "10.1016/j.jstrokecerebrovasdis.2022.106906",

language = "English",

volume = "32",

journal = "Journal of Stroke & Cerebrovascular Diseases",

issn = "1052-3057",

publisher = "Elsevier",

number = "2",

}

Samuels, N, Compagne, KCJ, van der Ende, NAM, Chalos, V, Konduri, PR, van Doormaal, PJ, van Zwam, WH, Majoie, CBLM, Marquering, HA, Roozenbeek, B, Lingsma, HF, Dippel, DWJ, van der Lugt, A & MR CLEAN Investigators 2023, 'Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit', Journal of Stroke & Cerebrovascular Diseases, vol. 32, no. 2, 106906. https://doi.org/10.1016/j.jstrokecerebrovasdis.2022.106906

Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit. / Samuels, Noor; Compagne, Kars C J; van der Ende, Nadinda A M et al.
In: Journal of Stroke & Cerebrovascular Diseases, Vol. 32, No. 2, 106906, 02.2023.

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

TY - JOUR

T1 - Infarct volume after ischemic stroke as a mediator of the effect of endovascular thrombectomy on early postprocedural neurologic deficit

AU - Samuels, Noor

AU - Compagne, Kars C J

AU - van der Ende, Nadinda A M

AU - Chalos, Vicky

AU - Konduri, Praneeta R

AU - van Doormaal, Pieter Jan

AU - van Zwam, Wim H

AU - Majoie, Charles B L M

AU - Marquering, Henk A

AU - Roozenbeek, Bob

AU - Lingsma, Hester F

AU - Dippel, Diederik W J

AU - van der Lugt, Aad

AU - MR CLEAN Investigators

N1 - Funding Information: Dr van Doormaal, reports consulting fees from Stryker. Dr van Zwam chairs DSMBs of WETRUST, Solonda and InExtremis studies, and received speaker fees from Stryker, Cerenovus and NicoLab, all paid to institution. Dr Majoie reports grants from CVON/Dutch Heart Foundation, TWIN Foundation, European Commission, Healthcare Evaluation Netherlands, and Stryker (paid to institution); and is (minority interest) shareholder of NicoLab. Dr Marquering is co-founder and shareholder of Nicolab. Dr Roozenbeek reports funding from the Dutch Heart Foundation and the Netherlands Organization of Health Research and Development, paid to institution. Dr Dippel and Dr van der Lugt report unrestricted grants from Stryker, Penumbra, Medtronic, Cerenovus, Thrombolytic Science, LLC, Dutch Heart Foundation, Brain Foundation Netherlands, The Netherlands Organization for Health Research and Development, Health Holland Top Sector Life Sciences & Health, and Thrombolytic Science, LLC for research, paid to institution. The other authors report no conflicts. Funding Information: The authors received no funding for this study. The MR CLEAN trial was partly funded by the Dutch Heart Foundation and by unrestricted grants from AngioCare BV, Medtronic/Covidien/EV3®, MEDAC Gmbh/LAMEPRO, Penumbra Inc., Stryker®, and Top Medical/Concentric. The MR CLEAN is registered under number NTR1804 in the Dutch trial register and under ISRCTN10888758 in the ISRCTN register. The study was additionally funded by the European Union's Horizon 2020 research and innovation program under grant agreement No 777072 (IN-SIlico trials for treatment of acute Ischemic STroke; INSIST). The funding sources had no role in study design, patient enrolment, data collection, analysis, writing of the manuscript, approval of the manuscript, and decision to submit the manuscript for publication. Funding Information: We thank the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) investigators. Noor. Samuels, Kars C.J. Compagne, Aad van der Lugt performed the study concept, statistical analysis, interpretation of the results and drafting of the article. Wim H. van Zwam, Charles B.L.M. Majoie, Diederik W.J. Dippel performed data aquisition and critical revision of the manuscript. Nadinda A.M. van der Ende, Vicky Chalos, Praneeta R. Konduri, Pieter Jan van Doormaal, Henk A. Marquering, Bob Roozenbeek, Hester F. Lingsma, performed the critical revision of the manuscript. Publisher Copyright: © 2022

PY - 2023/2

Y1 - 2023/2

N2 - OBJECTIVES: The beneficial effect of endovascular thrombectomy (EVT) on clinical outcome is assumed to be caused by reduced follow-up infarct volume (FIV), which could serve as an early imaging endpoint. However, the effect of EVT on the modified Rankin Scale (mRS) was poorly explained by FIV. NIHSS at 5-7 days could be a more specific measure of the effect of reperfusion therapy, as opposed to the mRS at 3 months. Therefore, we aimed to assess to what extent the effect of EVT on NIHSS is explained by FIV.MATERIALS AND METHODS: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n = 500) trial to evaluate the mediating role of FIV within 1 week in the relationship between EVT and baseline adjusted NIHSS at 5-7 days.RESULTS: Larger FIVs were associated with higher NIHSS after treatment (adjusted beta-coefficient (aβ) 0.47;95%CI 0.39-0.55). EVT was associated with smaller FIVs (β -0.35;95%CI-0.64 to -0.06) and lower NIHSS (β -0.63;95%CI-0.90 to -0.35). After adjustment for FIV, the effect of EVT on NIHSS decreased (aβ -0.47;95%CI-0.72 to -0.23), indicating that effect of EVT on neurologic deficit is partially mediated by FIV. Reduction of FIV explained 34% (95%CI;5%-93%) of the effect of EVT on the NIHSS at 5-7 days.CONCLUSIONS: Larger FIV was significantly associated with larger neurological deficits after treatment. Reduced infarct volume after EVT explains one third of treatment benefit in terms of neurological deficit. This suggests that FIV is of interest as an imaging biomarker of stroke treatment effect.

AB - OBJECTIVES: The beneficial effect of endovascular thrombectomy (EVT) on clinical outcome is assumed to be caused by reduced follow-up infarct volume (FIV), which could serve as an early imaging endpoint. However, the effect of EVT on the modified Rankin Scale (mRS) was poorly explained by FIV. NIHSS at 5-7 days could be a more specific measure of the effect of reperfusion therapy, as opposed to the mRS at 3 months. Therefore, we aimed to assess to what extent the effect of EVT on NIHSS is explained by FIV.MATERIALS AND METHODS: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; n = 500) trial to evaluate the mediating role of FIV within 1 week in the relationship between EVT and baseline adjusted NIHSS at 5-7 days.RESULTS: Larger FIVs were associated with higher NIHSS after treatment (adjusted beta-coefficient (aβ) 0.47;95%CI 0.39-0.55). EVT was associated with smaller FIVs (β -0.35;95%CI-0.64 to -0.06) and lower NIHSS (β -0.63;95%CI-0.90 to -0.35). After adjustment for FIV, the effect of EVT on NIHSS decreased (aβ -0.47;95%CI-0.72 to -0.23), indicating that effect of EVT on neurologic deficit is partially mediated by FIV. Reduction of FIV explained 34% (95%CI;5%-93%) of the effect of EVT on the NIHSS at 5-7 days.CONCLUSIONS: Larger FIV was significantly associated with larger neurological deficits after treatment. Reduced infarct volume after EVT explains one third of treatment benefit in terms of neurological deficit. This suggests that FIV is of interest as an imaging biomarker of stroke treatment effect.

KW - Endovascular treatment

KW - Infarct volume

KW - Stroke

KW - Treatment effect

U2 - 10.1016/j.jstrokecerebrovasdis.2022.106906

DO - 10.1016/j.jstrokecerebrovasdis.2022.106906

M3 - Article

C2 - 36473395

SN - 1052-3057

VL - 32

JO - Journal of Stroke & Cerebrovascular Diseases

JF - Journal of Stroke & Cerebrovascular Diseases

IS - 2

M1 - 106906

ER -