Mediation of Age and Thrombectomy Outcome by Neuroimaging Markers of Frailty in Patients With Stroke
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Published:2024-01-02
Issue:1
Volume:7
Page:e2349628
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ISSN:2574-3805
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Container-title:JAMA Network Open
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language:en
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Short-container-title:JAMA Netw Open
Author:
Benali Faysal12345, Singh Nishita1236, Fladt Joachim12347, Jaroenngarmsamer Tanaporn1, Bala Fouzi12348, Ospel Johanna M.12349, Buck Brian H.10, Dowlatshahi Dar11, Field Thalia S.12, Hanel Ricardo A.13, Peeling Lissa14, Tymianski Michael15, Hill Michael D.123416, Goyal Mayank123, Ganesh Aravind1231617, Barber Philip A.18, Smith Eric E.18, Bal Simerpreet18, Subramanian Suresh18, Peters Steven18, Couillard Philippe18, Klein Gary18, Stys Peter18, Coutts Shelagh B.18, Wong John18, Mitha Alim18, Eesa Muneer18, Morrish William18, Alqatani Saad18, Kashani Nima18, Venkatesan Prasanna18, Teleg Ericka18, Sitaram Amith18, Graham Brett18, Gaal Stephen van18, Moussaddy Aimen18, Chakraborty Debabrata18, Maraj Nicholar18, Lockey Andrew18, Chen Shuo18, Singh Ravinder18, Alsultan Abdulaziz Sulaiman18, Asunsian Ria18, Tse Dominic18, Doshi Darshan18, Volny Ondrej18, Ojha Piyush18, Wadhwa Ankur18, Marko Martha18, Singh Nishita18, Wasyliw Sanchea18, Ryckborst Karla J.18, Kenney Carol18, Save Supriya18, Jambula Anitha18, Newcommon Nancy18, Hull Gavin18, Blackstock Darcy18, Kiszczak Sharon18, Zimmel Leslie18, Wright Michelle18, Jahraus Cari18, Andersen Linda18, Bohn Shelly18, Paul Joseph18, Buck Brian H.18, Butcher Kenneth S.18, Shuaib Ashfaq18, Jeerakathil Tom18, Jickling Glen18, Emery Derek J.18, Rempel Jeremy18, Ower Richard J.18, Ashforth Robert18, Yeo Tom18, Kotylak Trevor B.18, O;Kelly Cian18, Chow Michael18, Siddiqui Mizaffar18, Saqqur Maher18, D'Souza Atlantic18, Lloret Mar18, Butt Asif18, Nomani Ali18, Kalashyan Hayrapet18, Thirunavukkarasu Sibi18, Jabs Juline18, Fairall Paige18, Piquette Lori18, Phillips Stephen J.18, Green A. Laine18, Gubitz Gordon J.18, Heidenreich Jens O.18, Huynh Thien18, Shankar Jai J. S.18, Maloney William J.18, Vandorpe Robert18, Schmidt Matthias H.18, Pickett Gwynedd E.18, Weeks Adrienne18, Jarrett Juditch18, MacDonald Debbie18, Arsenault Joanna18, Kinnear Ruth18, Mandzia Jennifer L.18, Mayich Michael18, Boulton Melfort18, Bullrich Maria Bres18, Fridman Sebastian18, Kiwan Ruba18, Lee Donald18, Lownie Stephen18, Khaw Alexander V.18, Pandey Sachin K.18, Sharma Manas18, Sposato Luciano A.18, Wade Kevin18, Beauchamp Beth18, Lambourn Lindsay18, Amato-Marziali Belinda18, Roy Daniel18, Deneault Nicole18, Deschaintre Yan18, Gioia Laura C.18, Jacquin Grégory18, Odier Céline18, Stapf Christian18, Iancu Daniela18, Raymond Jean18, Weill Alain18, Lapierre Marlène18, Jadil Nadia18, Jolteus Judlène18, Teitelbaum Jeanne18, Angle Mark18, Hannouche Mathew18, Badawy Mohamed18, Letourneau Justin18, Cortes Maria18, Linnell Grant18, Tampieri Donatella18, Vieira Lucy18, Legault Catherine18, Durcan Liam18, Moore Angela18, Cole Erin18, Magnussen Claire18, Salmon Kristiana18, Khalil Salma18, Desloges Isabelle18, Waxman Lindsay18, Abdon Wynne18, Lai Sonia18, Dowlatshahi Dar18, Shamy Michel18, Stotts Grant18, Blacquiere Dylan18, Lesiuk Howard18, Quateen Aiman18, Drake Brian18, Dewar Brian18, Daham Zeinab18, Kelly Michael E.18, Hunter Gary18, Peeling Lissa M.18, Graham Brett R.18, Whelan Ruth18, Garner Aaron J.18, Urroz Lilian18, Maley Sharleen18, Silver Frank L.18, Casaubon Leanne18, Pikula Aleksanda18, Campo Martin del18, Schaafsma Joanna18, Jaigobin Cheryl18, Krings Timo18, Pereira Vitor18, Agid Ronit18, Farb Richard18, Kalman Libby18, Cayley Anne18, Williams Janice18, Stewart Tim18, Misquitta Karen18, Bharatha Aditya18, Selchen Daniel H.18, Marotta Thomas R.18, Sarma Dipanka18, Montanera Walter J.18, Spears Julian18, Saposnik Gustavo18, Kostyrko Pawel18, Li Yangmei18, Parra-Farinas Carmen18, Diestro Jose Danilo Bengzon18, Camden Marie-Christine18, Verreault Steve18, Mackey Ariane18, Audet Marie-Eve18, Milot Geneviève18, Lavoie Pascale18, Gariépy Jean-Luc18, Collard Karine18, Haché Annette18, Sahlas Demetrios J.18, Alshanbari Ahmed M.18, Baldwin Josephine18, Catanese Luciana18, Chen Bing Y.18, Sa Boasquevisque Danielle de18, Deshmukh Aviraj S.18, Knapman Josrdan M.18, Lamers Shana18, Larrazabal Ramiro A.18, MacMillan Susan V.18, Mai Lauren M.18, Mattai Alicia M.18, Nayar Sumiti18, Ng Kuan H.18, Oczkowski Wieslaw J.18, Perera Kanjana S.18, Shawawrah Mays A. K.18, Shoamanesh Ashkan18, Sobhi Gita18, Syed Nabeel M.18, Yaher Noran Y.18, Vandervelde Cheyanne18, Wang Di18, Field Thalia S.18, Van Gaal Stephen C.18, Teal Philip A.18, Benavente Oscar R.18, Wilson Laura K.18, Mann Sharanpal K.18, Yip Samuel18, Murphy Colleen B.18, Heran Manraj K.S.18, Rohr Axel18, Settecase Fabio18, Redekop Gary J.18, Haw Charles S.18, Maclean Genoveva18, Murray Karina18, Chiu Rosalin18, Flexman Alana M.18, Strecha Eilidh18, Gayton Yolanda18, Yip Judy18, Swartz Richard H.18, Boulos Mark I.18, Gladstone David J.18, Yu Amy Y.18, Hopyan Julia J.18, Khosravani Houman18, Manosalva Alzate Herbert A.18, Southwell Alisia18, Kamra Maneesha18, Lopes Kaitlyn N.18, Kapoor Arunima18, da Costa Leodante18, Yang Victor X. D.18, Dyer Erin E.18, Shah Ruchir A.18, Knowles Brenda M.18, Nichols Jennifer18, Patterson Jennifer L.18, Cope Krista A.18, Dickerson Lee18, Barton Katrina K.18, Gray Kimberly D.18, Massengale Ticey N.18, Miller Melanie G.18, Simpson Cindy18, Walker Sabrina18, Tennyson-Yemm Chlin R.18, Frei Donald F.18, Bellon Richard J,18, Atchie Benjamin N.18, Kaminsky Ian A.18, Wilson Duandelyn C.18, Schraeder Nicolle L.18, Arias Eric J.18, Kodis Lisa M.18, Talley Mark E.18, Edinger Alex A.18, Talley Tiffany C.18, Dempsey Ita P.18, Williams Laurie A.18, Williams Scott A.18, Kupniewski Sonny18, Fasbinder Brad K.18, Snead Joanna M.18, Choe Hana18, Mackenzie Larami18, Weisman David C.18, Kozak Osman S.18, Shah Qaisar A.18, Gzesh Dan18, Kulandaivel Kandan18, Khoury John S.18, Klein Brad18, Bussinger Patricia A.18, Griffin Lisa R.18, DePalmo Ashley L.18, Oliva Cynthia18, Jadhav Ashutosh18, Jovin Tudor18, Kenmuir Cynthia18, Jankowitz Brian18, Gross Bradley18, Rocha Marcelo18, Starr Matthew18, Brown Merritt18, Hawkes Chrstine18, Shah Kavit18, Tememe Danoushka18, Walker Gregory18, Patel Pratit18, Klein Bradley18, Ziayee Habibullah18, Limaye Kaustubh18, Baxendell Lisa18, Glichrist Vicki18, Feineigle Patricia18, Toseki Haibach Kelsea18, Van Every Cathy18, Desai Shasvat18, Zulfiqar Maryam18, Gibson Linda18, Barrett Sean18, Turkel-Parrella David18, Arcot Karthikeyan18, DiCrescento Steven18, Farkas Jeffrey18, Filipowski Gregory18, Frontera Jennifer18, Joset Danielle18, Liff Jeremy18, Scher Erica18, McDougall Cameron G.18, Kelly Cheryl E.18, Patel Akshal S.18, Monteith Stephen J.18, Starkman Sidney18, Atchaneeyasakul Kunakorn C.18, Burgos Adrian M.18, Anne Y. Chua Janice18, Gaines Nathan D.18, Grunberg Ileana D.18, Guzy Judy18, Liu Zuolu18, Maluste Neil D.18, Ramirez Lucas18, Sharma Latisha K.18, Heck Donald18, Brown Morry18, McDonald Colin18, Calderon Mateo18, Hargis Mitch18, Roels Christina18, Emmady Prabhu18, Alvi Talat18, Jayaraman Mahesh V.18, Cutting Shawna M.18, Smith Wendy J.18, Foley Susan M.18, Paolucci Gino A.18, Haas Richard A.18, Quinn Katie A.18, Fuller Lindsey R.18, Brierley Rebecca E.18, Watkins Christina C.18, Demir Nicole C.18, Lopez George A.18, Vargas Alejandro18, Osteraas Nicholas18, Holtz Becky18, Sauvageau Eric18, Aghaebrahim Amin18, Chmayssani Mohamad18, Naval Neeraj S.18, Day Jason S.18, Dellorso Scott M.18, Ludwig Benjamin J.18, Schemmel Derek J.18, Ebreo Nancy18, Bell Karen18, Lewis Lanai18, Delucia Marjorie18, Haussen Diogo18, Frankel Michael18, Bhatt Nirav18, Bianchi Nicolas18, Anderson Aaron18, Belagaje Samir18, Liberato Bernardo18, Rangaraju Srikant18, Al-Bayati Alhamza R.18, Grossber Jonathan18, Craft Leah P.18, Schindler Kiva18, Schaad Erin18, Schultz Meagan18, Sutherly Lorretta J.18, Doppelheuer Shannon18, Charlton Jacquelyn18, Faggard Jason18, Barbret Zuzana18, DukSoo Han Ethan18, Walters Robin18, Dolia Jaydevsinh18, El-Jamal Sleiman18, Eby Brendan18, Saleem Yasir18, Pearl Harrison18, Patel Kishan18, Rahman Haseeb18, Butt Reema18, English Stephen18, Puri Ajit S.18, Howk Mary18, Singh Jasmeet18, Massari Francesco18, DeMacedo Rodrigues Katyucia18, Kuhn Anna L.18, English Joey D.18, Barazangi Nobl18, Telischak Nick18, Kim Warren18, Ross Josh18, DeVole Nata18, Redford Jessica18, Ferreira Melina18, Ponting Katie18, Shen Helen18, Bedenk Ann18, Patel Susila18, Fernandess Julia18, Ke Michael18, Spokoyny Illanit18, Gao Billy18, Tong David18, Chen Charlene18, Wong Christine18, Choe Jessica18, Martin Coleman O18, Summers Debbie V.18, Boutwell Christine M.18, Olds Karin E.18, Crandall Suzanne C.18, Eatman John D.18, Akhtar Naveed18, Holloway William18, Halpin Jared S.18, Donegan Brett18, Schindler Joseph L.18, Hwang Daiv Y.18, Gilmore Emily J.18, Petersen Nils18, Sheth Kevin N.18, Brown Stacy Y.18, Beekman Rachel B.18, George Benjamin P.18, Kaddouh Firas18, Falcone Guido J.18, Wira Charles R.18, Matouk Charles C.18, Loomis Caitlin18, Amin Hardik18, Stretz Hans Christoph18, Narula Reshma18, Jasne Adam S.18, Sansing Lauren H.18, Agarwal Tijil18, Jasak Sara D.18, Fontaine Briana D.18, King Zachary18, Kouhn Lindsey R.18, Orgass Hailey18, Leary Megan A.18, Nye Joan L.18, Halbert Kelsey18, Nystrom Karin V.18, Neuschatz Kaile B.18, Petrucci Dawn M.18, Coppola Anna M.18, Joyce Treasure A.18, Hou Sam Y.18, Umekubo Mark S.18, Nakamura Catrice M.18, Ovando Renee M.18, Zuniga Diana18, Nien Yih Lin18, Basto Fernando Mayor18, Arch Allison E.18, Jong Laura T.18, Conrad William A.18, Abbott Tara C.18, Yao Jay Z.18, Caganap Scott D.18, Jordan John E.18, Teitelbaum George P.18, Darflinger Robert J.18, Kelly Daniel F.18, Gupta Rishi18, Budzik Ronald F.18, Czerniak Jennifer H.18, Groezinger Katherine M.18, Hicks William J.18, Kaskar Omran B.18, Katz Brian S.18, Loochtan Aaron I.18, Pema Peter J.18, Rai Vivek18, Vora Nirav A.18, Brown Amanda18, Goodman Diane18, Danenbergs Barb18, Gossett Monica18, Bang Oh Young18, Chung Jong-Won18, Jeon Pyoung18, Kim Keon Ha18, Lim Yun Jeong18, Hoe Heo Ji18, Nam Hyo Suk18, Kim Young Dae18, Park HyungJong18, Hwang In Gun18, Ha Wooseok18, Choi Jin Kyo18, Jeong Kyungsun18, Rha Joung-Ho18, Park Hee-Kwon18, Yoon Cindy W.18, Kim Bo-Kyung18, Sohn Sung-Il18, Kim Chang-Hyun18, Yoo Joonsang18, Hong Jeong-Ho18, Park Hyungjong18, Kim Sohyeon18, Choi Moonkyung18, Bae Hyoeun18, Lee Jun Seok18, Lee Jae-Joon18, Jun Go-Eun18, Jeon Sujeong18, Campbell Bruce C. V.18, Mitchell Peter J.18, Yassi Nawaf18, Davis Stephen M.18, Donnan Geoffrey A.18, Parsons Mark W.18, Yan Bernard18, Dowling Richard J.18, Bush Steven J.18, Wu Teddy Y.18, Shan Darshan G.18, Zhao Henry18, Salvaris Patrick18, Alemseged Fana18, Ng Felix C.18, Williams Cameron18, Balabanski Anna18, dos Santos Angela18, Ng Jo-Lyn18, McDonald Amy18, Jackson David18, Tsoleridis Jessica18, Pesavento Lauren18, Kleinig Timothy John18, Drew Roy18, Cranefield Jennifer18, Scroop Rebecca18, Cagi Lavenia18, Harvey Jackson18, Waters Michael J.18, Thornton John18, Brennan Robert P.18, O'Hare Alan18, Power Sarah18, Williams David JP18, Boyle Karl18, Moynihan Barry J.18, Liddy Ann-Marie18, Large Margaret18, Cullen Ailbhe18, Walsh Roisin18, Martin Emma18, Lynch Julie18, McElroy Sinéad18, Murphy Seán18, Coveney Sarah A.18, Deegan Caroline18, Horgan Gillian18, Kelly Peter18, Laffan Aoife18, Llamas-Osorio Yudy18, Lynch Catherine T.18, Mac Mahon Peter J.18, Marnane Michael18, McCabe John J.18, Burns Paul A.18, Tauro Suzanne18, Cuddy Sarah18, Rennie Ian18, Smyth Graham18, Flynn Peter18, Wiggam Ivan18, Kerr Enda18, Gordon Patricia18, Fearon Patricia18, Roberts Geralt18, Patterson Cathy18, Adams Karen18, Wells Brian18, McFarland Margaret18, Moreira Tiago18, Sjöstrand Christina18, Mazya Michael18, Almqvist Håkan18, Wahlgren Nils18, Steinberg Anna18, Cooray Charith18, Eriksson Einar18, Thorén Magnus18, Keselman Boris18, Ahmed Niaz18, Holmberg Åke18, Axelsson Maria C.18, Berglund Annika18, Golsari Amir18, Hoppe Julia18, Deb-Chatterji Milani18, Cheng Bastian18, Barow Ewgenia18, Schlemm Eckhard18, Lettow Iris18, Jensen Märit18, Otto Dagmar18, Jaramillo Kirsten18, Appelbohm Hannes18, Fiehler Jens18, Bester Maxim18, Schönfeld Michael18, Brekenfeld Caspar18, Holst Brigette18, Wortmann Ginette18, Koch Friederike18, Gerber Johannes C.18, Abramyuk Andrij18, Kaiser Daniel18, Winzer Simon18, Prakapenia Alexandra18, Pallesen Lars-Peder18, Siepmann Timo18, Barlinn Kristian18, Haase Kathrin18, Sauer Angela18, Psychogios Marios-Nikos18, Liman Jan18, Brehm Alex18, Maus Volker18, Hollstein Nicole18, Reinke Annika18, Neitz Gustav18, Schnieder Marlena18, Schwarz Margret18, Ibrahim Allam18, Müller Julia18, Meister Stefanie18, Bäumle Berit18, Chapot René18, Pilgram-Pastor Sara18, Wallocha Marta18, Stauder Michael18, Celik Ekin18, Stracke Paul18, Müller Nicole18, Weber Ralph18, Veltkamp R.18, Nagel Simon18, Ringleb Peter Arthur18, Heyse Miriam18, Amiri Hemasse18, Mundiyanapurath Sibu18, Chen Min18, Beyrle Elisabeth18, Beck Perdita18, Möhlenbruch Markus Alfred18,
Affiliation:
1. Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 2. Hotchkiss Brain Institute, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 3. Mathison Centre for Mental Health Research and Education, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 4. Department of Radiology, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 5. Department of Radiology and Nuclear Medicine, Maastricht UMC+, Maastricht, the Netherlands 6. Neurology Division, Department of Internal Medicine, University of Manitoba, Max Rady College of Medicine, Winnipeg, Manitoba, Canada 7. Department of Neurology, University Hospital Basel, University of Basel, Basel, Switzerland 8. Diagnostic and Interventional Neuroradiology Department, University Hospital of Tours, Tours, France 9. Department of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland 10. Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada 11. Department of Medicine (Neurology), Neuroradiology Section, The Ottawa Hospital, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada 12. Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada 13. Lyerly Neurosurgery, Baptist Neurological Institute, Baptist Health, Jacksonville, Florida 14. Saskatoon Stroke Program, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada 15. NoNO Inc, Toronto, Ontario, Canada 16. Department of Community Health Sciences, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 17. O’Brien Institute for Public Health, University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada 18. for the ESCAPE-NA1 Investigators
Abstract
ImportanceAge is a leading predictor of poor outcomes after brain injuries like stroke. The extent to which age is associated with preexisting burdens of brain changes, visible on neuroimaging but rarely considered in acute decision-making or trials, is unknown.ObjectivesTo explore the mediation of age on functional outcome by neuroimaging markers of frailty (hereinafter neuroimaging frailty) in patients with acute ischemic stroke receiving endovascular thrombectomy (EVT).Design, Setting, and ParticipantsThis cohort study was a post hoc analysis of the Safety and Efficacy of Nerinetide (NA-1) in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) randomized clinical trial, which investigated intravenous (IV) nerinetide in patients who underwent EVT within a 12-hour treatment window. Patients from 48 acute care hospitals in 8 countries (Canada, US, Germany, Korea, Australia, Ireland, UK, and Sweden) were enrolled between March 1, 2017, and August 12, 2019. Markers of brain frailty (brain atrophy [subcortical or cortical], white matter disease [periventricular or deep], and the number of lacunes and chronic infarctions) were retrospectively assessed while reviewers were blinded to other imaging (eg, computed tomography angiography, computed tomography perfusion) or outcome variables. All analyses were done between December 1, 2022, and January 31, 2023.ExposuresAll patients received EVT and were randomized to IV nerinetide (2.6 mg/kg of body weight) and alteplase (if indicated) treatment vs best medical management.Main Outcome and MeasuresThe primary outcome was the proportion of the total effect of age on 90-day outcome, mediated by neuroimaging frailty. A combined mediation was also examined by clinical features associated with frailty and neuroimaging markers (total frailty). Structural equation modeling was used to create latent variables as potential mediators, adjusting for baseline, early ischemic changes; stroke severity; onset-to-puncture time; nerinetide treatment; and alteplase treatment.ResultsAmong a total of 1105 patients enrolled in the study, 1102 (median age, 71 years [IQR, 61-80 years]; 554 [50.3%] male) had interpretable imaging at baseline. Of these participants, 549 (49.8%) were treated with IV nerinetide. The indirect effect of age on 90-day outcome, mediated by neuroimaging frailty, was associated with 85.1% of the total effect (β coefficient, 0.04 per year [95% CI, 0.02-0.06 per year]; P < .001). When including both frailty constructs, the indirect pathway was associated with essentially 100% of the total effect (β coefficient, 0.07 per year [95% CI, 0.03-0.10 per year]; P = .001).Conclusions and RelevanceIn this cohort study, a secondary analysis of the ESCAPE-NA1 trial, most of the association between age and 90-day outcome was mediated by neuroimaging frailty, underscoring the importance of features like brain atrophy and small vessel disease, as opposed to chronological age alone, in predicting poststroke outcomes. Future trials could include such frailty features to stratify randomization or improve adjustment in outcome analyses.
Publisher
American Medical Association (AMA)
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