How Much of the Outcome Improvement after Successful Recanalization is Explained by Follow-up Infarct Volume Reduction?

Background Follow-up infarct volume (FIV) is used as surrogate for treatment efficiency in Mechanical Thrombectomy (MT). In contrast to these assumptions, previous works suggest that MT-related infarct volume reduction has only limited association with outcome comparing MT vs. medical care. It remains unclear to what extent the causal relationship between successful recanalization vs. persistent occlusion and functional outcome is explained by treatment-related reduction in FIV. Results might allow quantification of pathophysiological effects and could improve the understanding of the value of FIV as imaging endpoint in clinical trials. Methods All patients from our institution enrolled in the German Stroke Registry from 05/2015-12/2019 with anterior circulation stroke, availability of the relevant clinical data and follow-up CT were analyzed. A mediation analysis was conducted to investigate the effect of successful recanalization (Tici≥2b) on good functional outcome (90d mRS≤2) with mediation through final infarct volume. Results 429 patients were included. 309(72 %) patients had a successful recanalization and 127(39%) achieved good functional outcome. Probability of good outcome was significantly associated with age (OR=0.89,p<0.001), pre-stroke mRS (OR=0.38,p<0.001), FIV (OR=0.98,p<0.001), hypertension (OR=2.08,p<0.05) and successful recanalization (OR=3.57,p<0.01). Using linear regression in the mediator pathway, FIV was significantly associated with ASPECTS (Coefficient(Co)=-26.13,p<0.001), NIHSS admission (Co=3.69,p<0.001), age (Co=-1.18,p<0.05) and successful recanalization (Co=-85.22,p<0.001). Mediation analysis suggest a 23 percentage points (pp) increase of probability of good functional outcome (95%CI:16pp-29pp) in patients with successful recanalization. 56% (95%CI:38%-78%) of the improvement in good outcome was explained FIV reduction. Conclusions 56% of the improvement of functional outcome after successful recanalization is explained by FIV reduction. Results corroborate established pathophysiological assumptions and confirm the value of infarct volume as imaging endpoint in clinical trials. 44% of the improvement in outcome is not explained by FIV reduction and reflects the remaining mismatch between radiological and clinical outcome measures. Trial Registration ([NCT03356392][1]) ### Competing Interest Statement Helge Kniep and Fabian Flottmann are consultants for Eppdata GmbH. Helge Kniep is shareholder of Eppdata GmbH. Milani Deb-Chatterji has received research grants from the Werner Otto Stiftung and serves in the advisory board of the PRECIOUS Trial. Tobias Faizy has received research grants from the Deutsche Forschungsgemeinschaft / German Research Foundation. Götz Thomalla received fees as consultant from Acandis, Boehringer Ingelheim, Bayer, and Portola, and fees as lecturer from Acandis, Alexion, Amarin, Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichii Sankyo and Portola. He serves in the board of the TEA Stroke Study and of ESO. Jens Fiehler is consultant for Cerenovus, Medtronic, Microvention, Penumbra, Phenox, Roche and Tonbridge. He serves in the advisory board of Stryker and Phenox. He is stock holder of Tegus Medical, Eppdata and Vastrax. ### Clinical Trial ### Funding Statement This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the ethics committee of the chamber of physicians at Ludwig-Maximillians University LMU, Munich (689-15) as the leading ethics committee, in accordance with the Declaration of Helsinki. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Not Applicable The data that support the findings of this study are available from the GSR-ET registry and the corresponding author, restrictions may apply to the availability of these data. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03356392&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F08%2F2023.02.05.23285506.atom