Recanalization Outcomes and Procedural Complications in Patients With Acute Ischemic Stroke and COVID-19 Receiving Endovascular Treatment
Article information
, Davide Strambo2,*, George Ntaios3, Thanh N Nguyen4, Pawel Wrona5, Simon Escalard6, Simona Marcheselli7, Ossama Yassin Mansour8, Blanca Fuentes9, Malgorzata Dorobek10, Marta Nowakowska-Kotas11, Elena Oana Terecoasa12, Jonathan M. Coutinho13, Mariana Carvalho-Dias14, Patricia Calleja15, João Sargento-Freitas16, Ana Paiva-Nunes17, Martin Šrámek18, Priyank Khandelwal19, Torcato Meira20, Mohamad Abdalkader4, Pascal Jabbour21, Martin Kovář22, Oscar Ayo-Martin23, Patrik Michel2, Roman Herzig24, Anna Członkowksa25, Jelle Demeestere26, Raul G. Nogueira27, Alexander Salerno2, Susanne Wegener28, Philipp Baumgartner28, Carlo W. Cereda29, Giovanni Bianco29, Morin Beyeler30, Marcel Arnold30, Emmanuel Carrera31, Paolo Machi32, Valerian Altersberger33, Leo Bonati33, Henrik Gensicke33, Manuel Bolognese34, Nils Peters35, Stephan Wetzel35, Marta Magriço1, João Nuno Ramos36, Rita Machado16, Carolina Maia16, Egídio Machado37, Patrícia Ferreira17, Teresa Pinho-e-Melo14, André Paula38, Manuel Alberto Correia38, Pedro Castro39, Elsa Azevedo39, Luís Albuquerque40, José Nuno-Alves41, Joana Ferreira-Pinto41, Liliana Pereira42, Miguel Rodrigues42, André Araújo43, Marta Rodrigues43, Mariana Rocha44, Ângelo Pereira-Fonseca45, Luís Ribeiro45, Ricardo Varela46, Sofia Malheiro46, Manuel Cappellari47, Cecilia Zivelonghi47, Giulia Sajeva47, Andrea Zini48, Mauro Gentile48, Stefano Forlivesi48, Ludovica Migliaccio48, Maria Sessa49, Sara La Gioia49, Alessandro Pezzini50, Davide Sangalli51, Marialuisa Zedde52, Rosario Pascarella53, Carlo Ferrarese54, Simone Beretta54, Susanna Diamanti54, Ghil Schwarz55,56, Giovanni Frisullo57, Pierre Seners58, Candice Sabben58, Michel Piotin6, Benjamin Maier6, Guillaume Charbonnier59, Fabrice Vuillier59, Loic Legris60, Pauline Cuisenier60, Francesca R. Vodret60, Gaultier Marnat61, Jean-Sebastien Liegey61, Igor Sibon61, Fabian Flottmann62, Gabriel Broocks62, Nils-Ole Gloyer62, Ferdinand O. Bohmann63, Jan Hendrik Schaefer63, Christian H. Nolte64, Heinrich Audebert64, Eberhard Siebert65, Marek Sykora66, Wilfried Lang66, Julia Ferrari66, Lukas Mayer-Suess67, Michael Knoflach67, Elke-Ruth Gizewski68, Jeffrey Stolp13, Lotte J. Stolze13, Paul J. Nederkoorn13, Ido van-den-Wijngaard69, Joke de Meris69, Robin Lemmen26, Sylvie De Raedt70, Fenne Vandervorst70, Matthieu Pierre Rutgers71, Antoine Guilmot71, Anne Dusart72, Flavio Bellante72, Fernando Ostos15, Guillermo Gonzalez-Ortega15, Paloma Martín-Jiménez15, Sebastian García-Madrona73, Antonio Cruz-Culebras73, Rocio Vera73, Maria-Consuelo Matute73, María Alonso-de-Leciñana9, Ricardo Rigual9, Exuperio Díez-Tejedor9, Soledad Pérez-Sánchez74, Joan Montaner74, Fernando Díaz-Otero75, Natalia Perez-de-la-Ossa76, Belén Flores-Pina76, Lucia Muñoz-Narbona76, Angel Chamorro77, Alejandro Rodríguez-Vázquez77, Arturo Renú77, Francisco Hernandez-Fernandez23, Tomas Segura23, Herbert Tejada-Meza78, Daniel Sagarra-Mur78, Marta Serrano-Ponz78, Thant Hlaing79, Isaiah See80, Robert Simister80, David J. Werring81, Espen Saxhaug Kristoffersen82, Annika Nordanstig83, Katarina Jood83, Alexandros Rentzos84, Libor Šimu˚ne24, Dagmar Krajíčková24, Antonín Krajina85, Robert Mikulík86, Martina Cviková86, Jan Vinklárek86, David Školoudík87, Martin Roubec87, Eva Hurtikova87, Rostislav Hrubý88, Svatopluk Ostry88, Ondrej Skoda89, Marek Pernicka89, Lubomír Kočí90, Zuzana Eichlová90, Martin Jíra90, Michal Panský22, Pavel Mencl22, Hana Paloušková91, Aleš Tomek92, Petr Janský92, Anna Olšerová92, Roman Havlíček18, Petr Malý18, Lukáš Trakal18, Jan Fiksa93, Matěj Slovák93, Michał Karlińsk25, Maciej Nowak25, Halina Sienkiewicz-Jarosz94, Anna Bochynska94, Tomasz Homa5, Katarzyna Sawczynska5, Agnieszka Slowik5, Ewa Wlodarczyk5, Marcin Wiącek95, Izabella Tomaszewska-Lampart95, Bartosz Sieczkowski95, Halina Bartosik-Psujek95, Marta Bilik96, Anna Bandzarewicz96, Justyna Zielińska-Turek10, Krystian Obara11, Paweł Urbanowski11, Sławomir Budrewicz11, Maciej Guziński97, Milena Świtońska97, Iwona Rutkowska98, Paulina Sobieszak-Skura98, Beata Łabuz-Roszak99, Aleksander Dębiec100, Jacek Staszewski100, Adam Stępień100, Jacek Zwiernik101, Grzegorz Wasilewski102, Cristina Tiu12, Razvan-Alexandru Radu12, Anca Negrila12, Bogdan Dorobat103, Cristina Panea104, Vlad Tiu104, Simona Petrescu105, Atilla Özcan-Özdemir106, Mostafa Mahmoud107, Hussam El-Samahy107, Hazem Abdelkhalek108, Jasem Al-Hashel109, Ismail Ibrahim Ismail109, Athari Salmeen110, Abdoreza Ghoreishi111, Sergiu Sabetay112, Hana Gross4, Piers Klein4, Kareem El Naamani19, Stavropoula Tjoumakaris19, Rawad Abbas19, Ghada-A Mohamed113, Alex Chebl114, Jiangyong Min115, Majesta Hovingh115, Jenney-P Tsai115, Muhib-A Khan115, Krishna Nalleballe116, Sanjeeva Onteddu116, Hesham-E Masoud117, Mina Michael117, Navreet Kaur117, Laith Maali118, Michael Abraham118, Ivo Bach19, Melody Ong19, Denis Babici19, Ayaz-M. Khawaja119, Maryam Hakemi119, Kumar Rajamani119, Vanessa Cano-Nigenda120, Antonio Arauz120, Pablo Amaya121, Natalia Llanos122, Akemi Arango122, Miguel A. Vences123, José-Domingo Barrientos124, Rayllene Caetano125, Rodrigo Targa125, Sergio Scollo126, Patrick Yalung127, Shashank Nagendra128, Abhijit Gaikwad128, Kwon-Duk Seo129, on Behalf of the Global COVID-19 Stroke Registry†
Dear Sir:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of cerebrovascular and other thrombotic events [1]. Previous studies have shown that patients with acute ischemic stroke (AIS) and coronavirus disease 2019 (COVID-19) have a worse functional outcome than those without concomitant SARS-CoV-2 infection [2,3]. In patients receiving acute revascularization treatments, our large retrospective analysis of the Global COVID-19 Stroke Registry revealed higher rates of intracranial bleeding and worse clinical outcomes in patients with AIS and COVID-19 compared to contemporary AIS controls without COVID-19 [4]. Subsequent sub-analyses emphasized the impact of SARS-CoV-2 infection in this subgroup of patients showing differences in outcome between patients with asymptomatic COVID-19 and controls without COVID-19 [5].
Several factors can contribute to poorer outcomes in patients with AIS and COVID-19 undergoing acute revascularization treatments [2,3,6], including lower recanalization rates and higher rates of procedural complications after endovascular treatment (EVT) [7,8].
We aimed to assess recanalization outcomes and procedural complication rates in patients with AIS and COVID-19 undergoing EVT in an international cohort by comparing them with a contemporary control group of non–COVID-19 patients from the same centers.
We conducted a secondary analysis on the Global COVID-19 Stroke Registry [4]. Inclusion and exclusion criteria for the Global COVID-19 Stroke Registry were previously described [4]. For this study, only patients receiving EVT for intracranial occlusions were included (Supplementary Figure 1). All study procedures, study variables, and ethical standards were previously described [4].
The primary outcome of this study was recanalization after EVT assessed by the modified Thrombolysis in Cerebral Infarction (mTICI) score. Secondary procedural outcomes were: (1) successful recanalization after EVT (mTICI ≥2b); (2) first pass effect; (3) number of passes during EVT; and (4) procedure duration. Secondary safety outcomes were: (1) arterial perforation observed during EVT; (2) reocclusion during EVT; and (3) embolization into new non-ischemic territory during EVT. To assess the association of COVID-19 with the primary outcome and secondary procedural outcomes, we used multivariable regression models entering as independent variables the COVID-19 status together with prespecified baseline clinical and radiological variables identified from previous literature as variables known to be associated with the outcomes of interest. Depending on whether the outcome was ordinal, binary, or continuous, we used ordered logit regression, logistic regression, and quantile regression models, respectively. Data regarding EVT complications were available for all COVID-19 patients but only in a subset of controls. As such, to evaluate the association between COVID-19 and EVT complications, we performed a 1:3 propensity-score matching procedure between COVID-19 patients and the subset of controls with EVT complication data available. The association between COVID-19 and EVT complications was assessed using univariable binary logistic regression on the matched population. A detailed description on the statistical analysis methodology is available in Supplementary Methods.
Of the 15,128 patients included in the Global COVID-19 Stroke Registry, 8,292 fulfilled the inclusion criteria for the present analysis (Supplementary Figure 1). Of these, 497 (6.0%) patients were diagnosed with COVID-19. Comparisons between groups are shown in Table 1.
Baseline, stroke characteristics, imaging and treatment data
In the adjusted analysis, COVID-19 was associated with worse final mTICI score, lower successful recanalization, and a trend toward a lower first pass effect (Table 2).
Recanalization outcomes after endovascular treatment
EVT procedural complications were assessed in 493 (99.0%) patients with COVID-19 and in 2,275 (29.0%) controls. Control patients with and without data on procedural complications had similar baseline characteristics (Supplementary Table 1). Among patients with information on procedural complications after EVT, 491 with COVID-19 and 2,246 in the control group had complete data on the covariates selected for matching and were included in the analysis. After propensity-score matching of these patients, COVID-19 patients and their matched controls had a well-balanced distribution of baseline characteristics (Supplementary Figure 2). Patients with COVID-19 had higher rates of arterial perforation and reocclusion during EVT, and a trend toward higher rates of embolization into a new non-ischemic territory (Table 3).
Procedural complications during endovascular treatment
In this secondary analysis on the Global COVID-19 Stroke Registry, we found that patients with COVID-19 had worse recanalization outcomes and higher rates of procedural complications such as arterial perforation and reocclusion in comparison with contemporaneous patients with AIS without COVID-19. To our knowledge, this was the first study to show such associations in a large sample of consecutive patients with and without COVID-19 that used adjustment for potential confounders. The presented results add to our previous finding, showing higher rates of intracranial bleeding and worse clinical outcomes in patients with AIS and COVID-19 compared to contemporary AIS controls without COVID-19 [9].
Several pathophysiological mechanisms associated with COVID-19 may explain these findings. Endothelial inflammation and dysfunction, induced platelet aggregation, coagulation cascade activation, and formation of antiphospholipid antibody complexes associated with COVID-19 likely lead to higher clot burden and clot adherence [9,10]. This complex interplay probably results in lower recanalization and increased rates of reocclusion. These same mechanisms, combined with SARS-CoV-2-induced hyperfibrinolysis and direct viral-mediated damage to the neurovascular unit [9,10] may contribute to lower integrity of vessel walls and to subsequent elevated rates of arterial perforation. Alternatively, emboli in patients with COVID-19 may be more difficult to recanalize and retrieve due to the activation of the coagulation cascade activation, requiring more aggressive and longer EVT procedures with increased perforation risk.
Our analysis has several strengths, including the large sample size from 30 countries across five continents, increasing the validity and generalizability of our results.
Limitations of our study include the retrospective design, non-blinded assessment, and absence of centralized imaging review, which may have influenced our results. The use of different thrombectomy equipment and techniques by stroke interventionists may have affected our results but were tentatively addressed by adjustment with a center cluster level variable. A significant number of centers did not report safety outcomes in control patients, which could have biased our results.
In conclusion, in this cohort study, patients with AIS and COVID-19 receiving EVT had lower rates of recanalization and a higher risk of arterial perforation and reocclusion, in comparison with contemporary AIS controls without COVID-19. These findings may contribute to the poorer outcome found in patients with AIS and COVID-19.
Supplementary materials
Supplementary materials related to this article can be found online at https://doi.org/10.5853/jos.2024.04077.
Comparison between control patients included and excluded in procedural complications analysis
Inclusion flowchart.
Standardized mean differences before (red points) and after (blue points) propensity-score matching (PSM) between the patients with COVID-19 and controls, for the variables used for matching. NIHSS, National Institutes of Health Stroke Scale; LVO, large vessel occlusion; ic-ICA, intracranial internal carotid artery; M1, middle cerebral artery (M1 segment); BA, basilar artery; IVT, intravenous thrombolysis.
Notes
Funding statement
None
Conflicts of interest
Roman Herzig reports receiving research grants from the Ministry of Health of the Czech Republic (grant number DRO – UHHK 00179906) and Charles University, Czech Republic (grant number PROGRES Q40). Christian Nolte reports receiving research grants from the German Ministry of Research and Education, the German Center for Neurodegenerative Diseases, and the German Center for Cardiovascular Research. He has also received speaker and/or advisory fees from Abbott, Alexion, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, and Pfizer Pharma. Stavropoula Tjoumakaris reports receiving advisory fees from Medtronic and MicroVention. Jiangyong Min reports receiving advisory fees from Medtronic and Abbott. Muhib-A Khan reports receiving research grants from the National Institute of Health, Spectrum Health-Michigan State University Research Alliance, and Genentech. Patrik Michel reports receiving research grants from the Swiss National Science Foundation and the Swiss Heart Foundation. All other authors report no conflicts of interest.
Author contribution
Conceptualization: JPM, DS, GN, PM. Study design: JPM, DS, GN, PM. Data collection: all authors. Statistical analysis: DS. Writing—original draft: JPM, DS; GN, PM. Writing—review & editing: all authors. Approval of final manuscript: all authors.