ORIGINALRESEARCHWhatIsMeantbyTICIJEFugateAMKlunderandDFKall - PDF document

1 ORIGINALRESEARCHWhatIsMeantbyTICIŽ?J.E.
ORIGINALRESEARCHWhatIsMeantbyTICIŽ?J.E.Fugate,A.M.Klunder,andD.F.KallmesIn2003,HigashidaetalproposedtheThrombolysisInCerebralInfarctionscaletoevaluateangiographicintracranial”ow.Ouraimistoreviewhowsubsequentlypublishedstudiesde“neTICI.MATERIALSANDMETHODS:WeusedtheISIWebofKnowledgeandSciVerseScopusdatabasestosearchforTICIŽandthrombolysis ThrombolysisinCerebralInfarction;TIMIThrombolysisinMyocardialInfarction heThrombolysisinMyocardialInfarctionscaleisawidelyapplied,gradedresponsescaleforassessmentoftreatmentoutcomeinthecoronaryarteries.In2003,HigashidaetalposedaseeminglysimplemodificationoftheTIMIscaletoeval-uateintracranialperfusionassessedincerebralangiography.This ReceivedSeptember3,2012;acceptedafterrevisionDecember13. bralperfusion,whetherornotthesepapersreferencedorutilizedtheoriginalTICIpaper.IntheinitialdescriptionoftheTICIscalein2003,grade0indicatesnoperfusionasevidencedbynoantegradeflowbeyondthepointofarterialocclusion.Grade1isdefinedaspenetrationwithminimalperfusion”andapplieswhenthe“contrastmaterialpassesbeyondtheareaofobstructionbutfailstoopacifytheentirecerebralbeddistaltotheobstruction.”Grade2isbroadlydefinedaspartialperfusion,whichoccurswhenthecontrastmaterialpassesbeyondtheobstruction,opacifiesthedistalarterialbed,buttherateofentryofcontrastand/oritsrateofclearancefromthevascularbedareslowerthancomparableareasnotperfusedbythepreviouslyoccludedvessel.Theoppositecerebralarteryorthearterialbedproximaltotheocclusioncanbeusedforcom-parisonrates.Grade2issubdividedinto2aand2b.Agradeof2aindicatespartialfilling(lessthantwo-thirds)oftheentirevascularterritoryand2bindicatescompletefillingoftheexpectedvascularterritory,butwithaperceptiblyslowerfillingratethannormal.Finally,grade3isdefinedascompleteperfusionandapplieswhen“antegradeflowintothebeddistaltotheobstructionoccursaspromptlyasintotheobstructionandclearanceofthecontrastmaterialfromtheinvolvedbedisasrapidasfromanuninvolvedotherbedofthesamevesselortheoppositecerebralartery.”Withourliteraturesearch,weidentifiedatotalof236articles.WeexcludedarticlesthatdidnotrelatetotheTICIscale(115articles)andarticlesthatwereinlanguagesotherthanEnglishorthatwerenotaccessibleinfulllength(49articles).Wequalita-tivelyassessedwhetherthedefinitionofTICIineacharticlead-heredtotheoriginaldefinitionoftheTICIscaleandevaluatedthearticlesthatwerecitedwhenTICIwasdescribed.Wethenaccord-inglycategorizedthearticlesinto4groups:1)articlesthatexplic-itlystatedthescaleandfollowedtheoriginalTICIscalecom-pletely,2)articlesthatdidnotexplicitlydefinethescalebutcitedtheoriginalTICIpaper,3)articlesthatdefinedamodifiedscale,and4)articlesthatusedTICIbutdidnotdefinethescaleanddidnotcitetheoriginalTICIpaper.Wealsocataloguedthetypeandnumberofdefinitionsofsubcategory2aandnotedifasubcate-goryofTICIwasusedasathresholdfor“successfulrevasculariza-tion.”ThisstudywasexemptfrominstitutionalreviewboardOf74totalincludedarticles,8(11%)followedtheoriginalTICIscalecompletelyandexplicitlystatedthecategories.Onearticleclaimedtohavefollowedthescalecompletelybutdidnotstatethecategories.Thirty-seven(50%)articlesdidnotexplicitlydefinethescalebutstillcitedtheoriginalpaperbyHigashidaetModificationsoftheTICIscalewereusedin15(20%)Ofthese,8citedonlytheoriginalTICIpaper,4citedtheoriginalTICIpaperandotherpapers,and3citedonlyotherpapers.Thirteen(18%)articlesusedTICIbutdidnotdefinethescaleanddidnotcitetheoriginalTICIpaper.TheseresultsaredepictedinFig1.Eighteen(24%)ofarticlesmentionedtherateofcontrastfill-ingintheiruseofTICI.MostmodificationsofTICIeliminatedthesubcategoriesof2aand2b.Only18(24%)articlesspecifieda2asubcategory.Ofthese,9defined2aasfillingof67%oftheaffectedvascularterritory(compatiblewiththeoriginalTICI)and6defined2aasfillingof50%oftheaffectedvascularterri-tory.A2csubcategorywasaddedin2articles,andacategory4wasaddedin1article.ExamplesofthevariabilityindefinitionsofTICIcategoriesaredetailedinTable2.Mostarticles(52,70%)definedathresholdwithintheTICIscalethatindicated“successfulrevascularization”asoneofthestudyendpoints.Ofthese,34(65%)usedTICI2,17(33

2 %)usedTICI2b(althoughonly1ofthesestudies
%)usedTICI2b(althoughonly1ofthesestudiesdefinedaprecise FIG1.Distributionofde“nitionandcitationoftheTICIscaleintheliterature.ArticlesintheEnglishliteraturethatusetheTICI(Throm-bolysisinCerebralInfarction)gradingscale,distributedaccordingtode“nitionandcitationofTICI.Table1:TheoriginalThrombolysisinCerebralInfarctionperfusionscale CategoryTitleDescriptionGrade0NoPerfusionNoantegrade”owbeyondthepointofocclusion.Grade1PenetrationwithMinimalThecontrastmaterialpassesbeyondtheareaofobstructionbutfailstoopacifytheentirecerebralbeddistaltotheobstruction.Grade2PartialPerfusionThecontrastmaterialpassesbeyondtheobstructionandopaci“esthearterialbeddistaltotheobstruction.However,therateofentryofcontrastintothevesseldistaltotheobstructionand/oritsrateofclearancefromthedistalbedareperceptiblyslowerthanitsentryintoand/orclearancefromcomparableareasnotperfusedbythepreviouslyoccludedvessel.Grade2aOnlypartial“lling(lessthantwo-thirds)oftheentirevascularterritoryisvisualized.Grade2bComplete“llingofalloftheexpectedvascularterritoryisvisualizedbutthe“llingisslowerthannormal.Grade3CompletePerfusionAntegrade”owintothebeddistaltotheobstructionoccursaspromptlyasintotheobstructionandclearanceofcontrastmaterialfromtheinvolvedbedisasrapidasfromanuninvolvedotherbedofthesamevesselortheoppositecerebralartery.AJNRAmJNeuroradiol34:1792…97Sep2013www.ajnr.org cutofffor2b;67%fillingofthevascularterritory),and1used3.Thesethresholdsforsuccessfulangiographicrevascu-larizationwereprespecifiedinthemethodsin40(77%)oftheseTheterm“TICI”connotesastandardandwidelyacceptedmetricofrevascularization,analogoustotheubiquitousTIMIoutcomeforcoronaryrevascularization.Inthecurrentstudy,wefoundsubstan-tialvariabilityinhowtheterm“TICI”scaleisbothdefinedandusedintherecentEnglishliterature.Farfrombeingaconsistentanduni-versalscale,wenotedthatonlyasmallminorityofstudies,byuseoftheterm“TICI”whenreportingoutcomesafterrevascularization,actuallyusedtheoriginalTICIscale.Furthermore,manystudiesfailedtoprovidesufficientdetailtoallowthereadertounderstandexactlywhatcategorieswereused.Finally,thedefinitionofsuccessfulrevascularizationvariedwidelyamongstudies.Thesecurrentfind-ingsarerelevantforseveralreasons.First,ourunderstandingofthecurrentliteraturehasthepo-tentialtobegreatlyaffectedbythesefindings.ThemodificationthatchangedthecutoffpointbetweenTICIsubcategories2aand2bhasparticularrelevancebecauseagradeontheTICIscalewasusedasanendpointtodefinesuccessfulreperfusioninone-thirdofthearticlesthatspecifiedthisendpointinourstudy.Second,thedefinitionofTICIwillaffectstudydesignforfuturetrialsofendovasculartherapyforacuteischemicstroke.TheTICIgradingscaleisincreasinglyusedtodefineendpointsofrevascularizationsuccessinstudies.IfwedefinesuccessasachievingacertaingradeofTICI(eg,TICI2b)butwedonothaveconsistentgradingsystems,wecannotcompareorcombineresultsofclin-icalstudies.Toachieveenoughpatientsforstudiestobepoweredadequately,itisnec-essaryforinvestigatorsfromdifferentcen-terstocollaboratetogether.Withoutastan-dardizedgradingscale,thiswillnotbepossible.Itisessentialthatwecommuni-cateclearlywithconsistentterminology.Toourknowledge,ourstudyisthefirsttospecificallydescribethevaryingdefini-tionsoftheTICIscaleasitisreportedintheliterature.Others,however,haveprevi-ouslycalledattentiontotheconfusionsur-roundingtheTICIscale.In2007,Tomacknowledgedconfusionaboutthedifferentrevascularizationscales.Henotedtheinconsistentdescriptionsandapplica-tionsintheliterature;somefocusonrecan-alization,somefocusonreperfusion,andothersconfusingly(anderroneously)usethetermsinterchangeably.LettersdenotingacronymsfordifferentscalesarelitteredthroughouttheliteratureandincludetheTICI,TIMI,TIBI(ThrombolysisinBrainIschemia),andAOL(ArterialOcclusiveLe-sion)scales.InapreviousreviewoftheTICIscale,theinherentinconsistencieswithintheoriginalTICIscaleitselfwereidentified.Forexample,thereisnoapplicableTICIgradeforacaseinwhichgreaterthantwo-thirdsbutlessthan“complete”fillingofthevascularterritoryisvisualized.Inaddition,thereisnoapplicableTICIgradeforapartiallyrevascu-

3 larizedterritorywithnormalrateofdistalop
larizedterritorywithnormalrateofdistalopacification,asce-narionotuncommonlyencountered.TheTIMIscale—unliketheTICIscale—hasnotbeenthesub-jectoffrequentmodifications.ThedefinitionoftheTIMIscalethroughouttheabundantcardiologyliteraturehasnotbeensys-temicallyevaluated,butthereisgeneralconsensusthatwhenusedfortheevaluationofmyocardialperfusionbeforeandaftercoro-naryreperfusiontherapies,itisusedconsistently.Inthemid1990s,aquantitativeassessmentofcoronaryflowcalledthecorrectedTIMIFrameCount(CTFC)wasreportedinanattempttostandardizethescale,buttheoriginalsemiqualitativeTIMIscalehascontinuedtobethestandardusedbyinterventionalcardiologists.However,theTIMIscalecannotbeeasilyappliedtothemorecomplexcerebralarteries.Onereviewfoundthat7dif-ferentoperationalizedversionsoftheTIMIscalehavebeenusedinmajorstroketrials,emphasizingagaintheneedforasingle,uniform,consistentscaleforgradingofperfusionincerebralThisstudyhasseverallimitations.Somearticlesfromourlit-eraturesearchwerenotreviewedbecauseofalackofaccessibilityoffull-lengtharticlesorbecausetheywerewritteninlanguagesTable2:Varyingde“nitionsofTICIgradesintheliterature CategoryDe“nitionGrade0No”owNocanalizationCompleteocclusionNorecanalization/reperfusionGrade1Minimalrecanalization(Minimal”ow(veryslow)withoutsigni“cant”owdistaltotheocclusionsiteLimitedornoreperfusionDistalmovementofthrombuswithoutreperfusionPerfusionpastinitialocclusion,butlimiteddistalbranchGrade2Partialrecanalization„recanalizationofsomebutnotalloftheoccludedIncompleterecanalization/reperfusionNear-normal”ow,with”owdistaltotheocclusionbutnot“llingthedistalbranchesnormallyGrade2aPerfusionof50%oftheMCAdistributionPartial“llingoftheentirevascularterritoryPartialperfusionwithincompletedistal“llingof50%ofexpectedterritoryPartial“llingoftheentirevascularterritoryGrade2bPartialperfusionwithincompletedistalbranch“llingof50…99%oftheexpectedterritoryComplete“lling,butthe“llingisslowerthannormalPerfusionofhalforgreaterofthevasculardistributionoftheoccludedarteryGrade2cNear-completeperfusionwithoutclearlyvisiblethrombusbutwithdelayincontrastrun-offGrade3Fullperfusionwith“llingofalldistalbranches,includingM3,M4Normal”owPartialrecanalizationwith50%reperfusionFullperfusionwithnormal“llingofdistalbranchesinanormalhemodynamicGrade4Completerecanalization/reperfusionFugateSep2013www.ajnr.org otherthanEnglish,creatingaselectionbias.However,increasingthenumberofstudieswereviewedmayhaveincreasedtheob-servedvariabilityinTICIdefinitions.Also,thecategoriesintowhicharticlesweredividedweresubjectivelychosenandwereevaluatedbyonly2investigators.Furtheropportunitiestorefineourgradingscalesandfurtherourunderstandingofbrainreperfusionabound.Weaknessesincurrentgradingscalesforcerebralperfusionarenotlimitedtoconfusingterminology.Vesselrecanalizationinthetreatmentofacuteischemicstrokehasbeenshowntobeassociatedwithfavor-ableclinicalfunctionaloutcomes,butwhenreperfusionisonlypartial,theclinicalrelevanceoftheuseofdifferentTICIgrade2subdivisionsisnotknown.Furthermore,therearefewdatare-gardingtheintra-observerandinterobservervariabilitywhenap-plyingtheTICIscaletoangiographyresults.Italsoremainsun-clearwhetheritisappropriatetoapplyTICItotheposteriorcirculationandwhetherthedegreeofcollateralflow—particu-larlyincaseswithdistalM3–4occlusions—modifiestheeffectofrevascularization(asmeasuredbyTICI)onclinicaloutcomes.Scalesaredesignedtoaidintheobjectivedescriptionofangio-graphicresults,standardizedataforresearchstudies,andassistinoutcomeprediction.Wehopethatbyclarifyingwhatwemeanby“TICI,”wewillbebetterabletoevaluatetheefficacyofrevas-cularizationtherapiesforacuteischemicstrokeinthefuture.ThereissubstantialvariabilityinhowtheTICIscaleisdefinedandappliedinthecerebrovascularliterature.Fewstudiesprovidesuf-ficientdetailforreaderstounderstandwhatismeantbyeachTICIgrade.BecauseTICIscoreisincreasinglyusedasanoutcomemea-sureinstudiesofrevascularizationtherapiesinacuteischemicstroke,thisvariabilityhasthepotentialtoconsiderablyimpactresultsandourunderstandingofthesetherapies.Disclosures:DavidKallmes„UNREL

4 ATED:Consultancy:Grants/GrantsPend-Micro
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