Journal article
Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient‐level Analysis of EXTEND‐IA Trials and SELECT Prospective Cohort
Annals of neurology, Vol.93(4), pp.793-804
04/2023
DOI: 10.1002/ana.26587
PMID: 36571388
Abstract
Objective: Reperfusion therapy is highly beneficial for ischemic stroke. Reduction in both infarct growth and edema are plausible mediators of clinical benefit with reperfusion. We aimed to quantify these mediators and their interrelationship. Methods: In a pooled, patient-level analysis of the EXTEND-IA trials and SELECT study, we used a mediation analysis framework to quantify infarct growth and cerebral edema (midline shift) mediation effect on successful reperfusion (modified Treatment in Cerebral Ischemia ≥ 2b) association with functional outcome (modified Rankin Scale distribution). Furthermore, we evaluated an additional pathway to the original hypothesis, where infarct growth mediated successful reperfusion effect on midline shift. Results: A total 542 of 665 (81.5%) eligible patients achieved successful reperfusion. Baseline clinical and imaging characteristics were largely similar between those achieving successful versus unsuccessful reperfusion. Median infarct growth was 12.3ml (interquartile range [IQR] = 1.8–48.4), and median midline shift was 0mm (IQR = 0–2.2). Of 249 (37%) demonstrating a midline shift of ≥1mm, median shift was 2.75mm (IQR = 1.89–4.21). Successful reperfusion was associated with reductions in both predefined mediators, infarct growth (β = −1.19, 95% confidence interval [CI] = −1.51 to −0.88, p < 0.001) and midline shift (adjusted odds ratio = 0.36, 95% CI = 0.23–0.57, p < 0.001). Successful reperfusion association with improved functional outcome (adjusted common odds ratio [acOR] = 2.68, 95% CI = 1.86–3.88, p < 0.001) became insignificant (acOR = 1.39, 95% CI = 0.95–2.04, p = 0.094) when infarct growth and midline shift were added to the regression model. Infarct growth and midline shift explained 45% and 34% of successful reperfusion effect, respectively. Analysis considering an alternative hypothesis demonstrated consistent results. Interpretation: In this mediation analysis from a pooled, patient-level cohort, a significant proportion (~80%) of successful reperfusion effect on functional outcome was mediated through reduction in infarct growth and cerebral edema. Further studies are required to confirm our findings, detect additional mediators to explain successful reperfusion residual effect, and identify novel therapeutic targets to further enhance reperfusion benefits. ANN NEUROL 2023.
Details
- Title: Subtitle
- Mediation of Successful Reperfusion Effect through Infarct Growth and Cerebral Edema: A Pooled, Patient‐level Analysis of EXTEND‐IA Trials and SELECT Prospective Cohort
- Creators
- Amrou Sarraj - Case Western Reserve UniversityDeep K Pujara - University Hospitals of ClevelandLeonid Churilov - The University of MelbourneClark Sitton - UTHealth McGovern Medical School Diagnostic and Interventional Radiology Houston TX USAFelix Ng - The University of MelbourneAmeer E Hassan - The University of Texas Rio Grande ValleyMichael G Abraham - University of Kansas Medical CenterSpiros L Blackburn - UTHealth McGovern Medical School Neurosurgery Houston TX USAGagan Sharma - The University of MelbourneNawaf Yassi - The University of MelbourneTimothy Kleinig - Royal Adelaide HospitalDarshan Shah - Gold Coast University Hospital Neurology Southport Queensland AustraliaTeddy Y Wu - Christchurch Hospital Neurology Christchurch Canterbury New ZealandWondwossen G Tekle - The University of Texas Rio Grande ValleyRonald F. Budzik - Riverside Methodist HospitalWilliam J Hicks - Riverside Methodist HospitalNirav Vora - Riverside Methodist HospitalRandall C Edgell - Sain Louis University Neurology St. Louis MO USADiogo Haussen - Emory UniversitySantiago Ortega‐Gutierrez - University of Iowa Neurology Iowa City IA USAGabor Toth - Cleveland ClinicLaith Maali - University of Kansas Medical CenterMohammad Ammar Abdulrazzak - Cleveland ClinicFaisal Al‐Shaibi - Case Western Reserve UniversityTareq AlMaghrabi - University of TabukVignan Yogendrakumar - The University of MelbourneFaris Shaker - UTHealth McGovern Medical School Neurosurgery Houston TX USAOsman Mir - Baylor Scott & White HealthAshish Arora - Cone HealthKelsey Duncan - University Hospitals of ClevelandSophia Sundararajan - Case Western Reserve UniversityAmanda Opaskar - University Hospitals of ClevelandYin Hu - University Hospitals of ClevelandAbhishek Ray - University Hospitals of ClevelandJeffrey Sunshine - University Hospitals of ClevelandNicholas Bambakidis - University Hospitals of ClevelandSheryl Martin‐Schild - Touro Infirmary and New Orleans East Hospital Neurology New Orleans LA USAM. Shazam Hussain - Cleveland ClinicRaul Nogueira - University of Pittsburgh Medical CenterAnthony Furlan - Case Western Reserve UniversityCathy A. Sila - Case Western Reserve UniversityJames C Grotta - Memorial HermannMark Parsons - University of Newcastle Neurology Newcastle NSW AustraliaPeter J Mitchell - The University of MelbourneGeoffrey A Donnan - The University of MelbourneStephen M Davis - The University of MelbourneGregory W Albers - Stanford UniversityBruce CV Campbell - The University of MelbourneSELECT, EXTEND‐IA, EXTEND‐IA TNK and EXTEND‐IA TNK Part‐II Investigators
- Resource Type
- Journal article
- Publication Details
- Annals of neurology, Vol.93(4), pp.793-804
- DOI
- 10.1002/ana.26587
- PMID
- 36571388
- NLM abbreviation
- Ann Neurol
- ISSN
- 0364-5134
- eISSN
- 1531-8249
- Language
- English
- Electronic publication date
- 12/26/2022
- Date published
- 04/2023
- Academic Unit
- Neurology; Radiology; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984354393002771
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