BACKGROUND: A third of endovascularly treated patients with stroke experience incomplete reperfusion (expanded Thrombolysis in Cerebral Infarction [eTICI] <3), and the natural evolution of this incomplete reperfusion remains unknown. We systematically reviewed the literature and performed a meta-analysis on the natural evolution of incomplete reperfusion after endovascular therapy. METHODS: A systematic review of MEDLINE, Embase, and PubMed up until March 1, 2024, using a predefined strategy. Only full-text English-written articles reporting rates of either favorable (ie, delayed reperfusion (DR) or no new infarct) or unfavorable progression (ie, persistent perfusion deficit or new infarct) of incompletely reperfused tissue were included. The primary outcome was the rate of DR and its association with functional independence (modified Rankin Scale score, 0-2) at 90 days postintervention. Pooled odds ratios with 95% CIs were calculated using a random-effects model. RESULTS: Six studies involving 950 patients (50.7% female; median age, 71 years; interquartile range, 60-79) were included. Four studies assessed the evolution of incomplete reperfusion on magnetic resonance imaging perfusion imaging, while 2 studies used diffusion-weighted imaging and noncontrast computed tomography imaging, where new infarct was used to denote unfavorable progression. Five studies defined incomplete reperfusion as eTICI 2b50 or 2c. DR occurred in 41% (interquartile range, 33%-51%) of cases 24 hours postintervention. Achieving DR was associated with a higher likelihood of functional independence at 90 days (odds ratio, 2.5 [95% CI, 1.9-3.4]). CONCLUSIONS: Nearly half of eTICI <3 patients achieve DR, leading to favorable clinical outcomes. This subgroup may derive limited or potentially harmful effects from pursuing additional reperfusion strategies (eg, intra-arterial lytics or secondary thrombectomy). Accurately predicting the evolution of incomplete reperfusion could optimize patient selection for adjunctive reperfusion strategies at the end of an intervention. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT05499832.

Department of Clinical Neurosciences Department of Community Health Sciences Department of Medicine Department of Radiology Hotchkiss Brain Institute University of Calgary Cumming School of Medicine Calgary Alberta Canada

Department of Diagnostic and Interventional Neuroradiology University Hospital Bern Inselspital

Department of Medical Imaging St Anne's University Hospital Brno and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Neurology University Hospital Bern Inselspital University of Bern Switzerland

Department of Neuroradiology University Hospital Freiburg Germany

Department of Radiology Department of Clinical Neurosciences Hotchkiss Brain Institute University of Calgary Cumming School of Medicine Calgary Alberta Canada

Diagnostic and Interventional Neuroradiology CIC IT 1415 CHRU de Tours France

Graduate School for Health Sciences University of Bern Switzerland

Le Studium Loire Valley Institute for Advanced Studies Orléans France

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Majoie CB, Cavalcante F, Gralla J, Yang P, Kaesmacher J, Treurniet KM, Kappelhof M, Yan B, Suzuki K, Zhang Y, et al. ; IRIS Collaborators. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. Lancet. 2023;402:965–974. doi: 10.1016/S0140-6736(23)01142-X PubMed

Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Buck BH, Field TS, Dowlatshahi D, et al. ; ESCAPE-NA1 Investigators. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet. 2020;395:878–887. doi: 10.1016/S0140-6736(20)30258-0 PubMed

Kurmann CC, Mujanovic A, Piechowiak EI, Dobrocky T, Zibold F, Beyeler M, Vynckier J, Seiffge D, Meinel TR, Mordasini P, et al. . Heterogeneity of the relative benefits of TICI 2c/3 over TICI 2b50/2b67: are there patients who are less likely to benefit? Clin Neuroradiol. 2022;32:817–827. doi: 10.1007/s00062-021-01131-0 PubMed PMC

Maïer B, Finitsis S, Mazighi M, Lapergue B, Marnat G, Sibon I, Richard S, Viguier A, Cognard C, Gory B, et al. ; the ETIS Registry Investigators. The benefit of a complete over a successful reperfusion decreases with time. Ann Neurol. 2023;93:934–941. doi: 10.1002/ana.26599 PubMed

LeCouffe NE, Kappelhof M, Treurniet KM, Lingsma HF, Zhang G, van den Wijngaard IR, van Es ACGM, Emmer BJ, Majoie CBLM, Roos YBWEM, et al. . 2B, 2C, or 3: what should be the angiographic target for endovascular treatment in ischemic stroke? Stroke. 2020;51:1790–1796. doi: 10.1161/STROKEAHA.119.028891 PubMed

Kaesmacher J, Ospel JM, Meinel TR, Boulouis G, Goyal M, Campbell BCV, Fiehler J, Gralla J, Fischer U. Thrombolysis in Cerebral Infarction 2b reperfusions: to treat or to stop? Stroke. 2020;11:3461–3471. doi: 10.1161/STROKEAHA.120.030157 PubMed

Mujanovic A, Jungi N, Kurmann CC, Dobrocky T, Meinel TR, Almiri W, Grunder L, Beyeler M, Lang MF, Jung S, et al. . Importance of delayed reperfusions in patients with incomplete thrombectomy. Stroke. 2022;53:3350–3358. doi: 10.1161/STROKEAHA.122.040063 PubMed PMC

Mujanovic A, Kurmann CC, Serrallach BL, Dobrocky T, Meinel TR, Windecker D, Grunder L, Beyeler M, Seiffge DJ, Pilgram-Pastor S, et al. . Intra-arterial thrombolysis is associated with delayed reperfusion of remaining vessel occlusions following incomplete thrombectomy. AJNR Am J Neuroradiol. 2023;44:1050–1056. doi: 10.3174/ajnr.A7943 PubMed PMC

Rubiera M, Garcia-Tornel A, Olivé-Gadea M, Campos D, Requena M, Vert C, Pagola J, Rodriguez-Luna D, Muchada M, Boned S, et al. . Computed tomography perfusion after thrombectomy: an immediate surrogate marker of outcome after recanalization in acute stroke. Stroke. 2020;51:1736–1742. doi: 10.1161/STROKEAHA.120.029212 PubMed

Tan Z, Parsons M, Bivard A, Sharma G, Mitchell P, Dowling R, Bush S, Xu A, Yan B. Optimal tissue reperfusion estimation by computed tomography perfusion post-thrombectomy in acute ischemic stroke. Stroke. 2021;52:e760–e763. doi: 10.1161/STROKEAHA.121.034581 PubMed

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, et al. . The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71 PubMed PMC

Riley RD, Higgins JPT, Deeks JJ. Interpretation of random effects meta-analyses. BMJ. 2011;342:d549. doi: 10.1136/bmj.d549 PubMed

Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, et al. . ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355: i4919. doi: 10.1136/bmj.i4919 PubMed PMC

Cimflova P, Singh N, Kappelhof M, Ospel JM, Sehgal A, Kashani N, Almekhlafi MA, Demchuk AM, Berrouschot J, Dorn F, et al. . Effect of incomplete reperfusion patterns on clinical outcome: insights from the ESCAPE-NA1 trial. J Neurointerv Surg. 2023;16:809–814. doi: 10.1136/jnis-2023-020553 PubMed

Fuller E, Vivanco-Suarez J, Fain NH, Zevallos CB, Lu Y, Ortega-Gutierrez S, Derdeyn C. Predictors of tissue infarction from distal emboli after mechanical thrombectomy. J Neurointerv Surg. 2023;16:959–965. doi: 10.1136/jnis-2023-020782 PubMed

Laredo C, Rodríguez A, Oleaga L, Hernández-Pérez M, Renú A, Puig J, Román LS, Planas AM, Urra X, Chamorro A. Adjunct thrombolysis enhances brain reperfusion following successful thrombectomy. Ann Neurol. 2022;92:860–870. doi: 10.1002/ana.26474 PubMed PMC

Luby M, Merino JG, Davis R, Ansari S, Fisher M, Hsia AW, Kim Y, Latour LL, McCreedy ES, Sukhdeo Singh R, et al. . Association of multiple passes during mechanical thrombectomy with incomplete reperfusion and lesion growth. Cerebrovasc Dis. 2022;51:394–402. doi: 10.1159/000519796 PubMed PMC

Luijten SPR, Bos D, van Doormaal PJ, Goyal M, Dijkhuizen RM, Dippel DWJ, Roozenbeek B, van der Lugt A, Warnert EAH. Cerebral blood flow quantification with multi-delay arterial spin labeling in ischemic stroke and the association with early neurological outcome. Neuroimage Clin. 2023;37:103340. doi: 10.1016/j.nicl.2023.103340 PubMed PMC

Mujanovic A, Brigger R, Kurmann CC, Ng F, Branca M, Dobrocky T, Meinel TR, Windecker D, Almiri W, Grunder L, et al. . Prediction of delayed reperfusion in patients with incomplete reperfusion following thrombectomy. Eur Stroke J. 2023;8:456–466. doi: 10.1177/23969873231164274 PubMed PMC

Mujanovic A, Ng FC, Branca M, Deutschmann HA, Meinel TR, Churilov L, Nistl O, Mitchell PJ, Yassi N, Parsons MW, et al. . External validation of a model for persistent perfusion deficit in patients with incomplete reperfusion after thrombectomy: EXTEND-PROCEED. Neurology. 2024;103:e209401. doi: 10.1212/WNL.0000000000209401 PubMed PMC

Burian E, Sepp D, Lehm M, Bernkopf K, Wunderlich S, Riederer I, Maegerlein C, Alegiani A, Zimmer C, Boeckh-Behrens T. Start, stop, continue? The benefit of overlapping intravenous thrombolysis and mechanical thrombectomy: a matched case-control analysis from the German stroke registry. Clin Neuroradiol. 2023;33:187–197. doi: 10.1007/s00062-022-01200-y PubMed PMC

Weller JM, Dorn F, Petzold GC, Bode FJ; GSR-ET Investigators. Intravenous thrombolysis upon flow restoration improves outcome in endovascular thrombectomy. J Neurointerv Surg. 2023;15:e229–e231. doi: 10.1136/jnis-2022-019522 PubMed PMC

Mujanovic A, Kammer C, Kurmann CC, Grunder L, Beyeler M, Lang MF, Piechowiak EI, Meinel TR, Jung S, Almiri W, et al. . Association of intravenous thrombolysis with delayed reperfusion after incomplete mechanical thrombectomy. Clin Neuroradiol. 2023;33:87–98. doi: 10.1007/s00062-022-01186-7 PubMed PMC

Goyal M, Ospel JM, Menon B, Almekhlafi M, Jayaraman M, Fiehler J, Psychogios M, Chapot R, Van Der Lugt A, Liu J, et al. . Challenging the ischemic core concept in acute ischemic stroke imaging. Stroke. 2020;3147:3147–3155. doi: 10.1161/STROKEAHA.120.030620 PubMed

Ballout AA, Liebeskind DS, Jovin TG, Najjar S. The imaging-neuropathological gap in acute large vessel occlusive stroke. Stroke. 2024;55:2909–2920. doi: 10.1161/strokeaha.124.047384 PubMed

Kaesmacher J, Mordasini P, Arnold M, López-Cancio E, Cerdá N, Boeckh-Behrens T, Kleine JF, Goyal M, Hill MD, Pereira VM, et al. . Direct mechanical thrombectomy in tPA-ineligible and-eligible patients versus the bridging approach: a meta-analysis. J Neurointerv Surg. 2019;11:20–27. doi: 10.1136/neurintsurg-2018-013834 PubMed PMC

Mujanovic A, Imhof A, Zheng S, Piechowiak EI, Serrallach BL, Meinel TR, Dobrocky T, Aziz YN, Seiffge DJ, Goeldlin M, et al. . Perfusion abnormalities on 24-hour perfusion imaging in patients with complete endovascular reperfusion. Stroke. 2024;55:2315–2324. doi: 10.1161/STROKEAHA.124.047441 PubMed PMC

Mujanovic A, Kurmann CC, Manhart M, Piechowiak EI, Pilgram-Pastor SM, Serrallach BL, Boulouis G, Meinel TR, Seiffge DJ, Jung S, et al. . Value of immediate flat panel perfusion imaging after endovascular therapy (AFTERMATH): a proof of concept study. AJNR Am J Neuroradiol. 2024;45:163–170. doi: 10.3174/ajnr.A8103 PubMed PMC

Renu A, Millan M, San Roman L, Blasco J, Marti-Fàbregas J, Terceño M, Amaro S, Serena J, Urra X, Laredo C, et al. ; CHOICE Investigators. Effect of intra-arterial alteplase vs placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: the CHOICE randomized clinical trial. JAMA. 2022;327:826–835. doi: 10.1001/jama.2022.1645 PubMed PMC

Kaesmacher J, Meinel TR, Kurmann C, Zaidat OO, Castonguay AC, Zaidi SF, Mueller-Kronast N, Kappelhof M, Dippel DWJ, Soudant M, et al. . Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data. J Neurointerv Surg. 2020;13:1073–1080. doi: 10.1136/neurintsurg-2020-016680 PubMed PMC

Yogendrakumar V, Vandelanotte S, Mistry EA, Hill MD, Coutts SB, Nogueira RG, Nguyen TN, Medcalf RL, Broderick JP, De Meyer SF, et al. . Emerging adjuvant thrombolytic therapies for acute ischemic stroke reperfusion. Stroke. 2024;55:2536–2546. doi: 10.1161/STROKEAHA.124.045755 PubMed

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NCT05499832