Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3751_Библиотеки_им_академика_М_И_Перельмана
.pdf
Mesentericarterystenosiscancausesymptomsofchronicmesentericischemia;stenosesmustusuallybe
presentinat least two ofthe three major splanchnicarteries, the celiac trunk,the superior mesenteric
artery, andthe inferior mesenteric artery. In mostcases, ostial or proximal atherosclerotic lesionsare
responsible for the ischemia, and these lesions are amenable to endovascular intervention. Rarely,
fibromusculardiseasemaycausemoredistalstenoses,whichcannotbeintervenedupon.
7.AbdominalAorticAneurysms
Endovascular aneurysm repair (EVAR) may be performed to reduce the risk of rupture or
thromboembolism.Indicationsfor EVARincludesymptoms (typicallyabdominalor backpain,embolic
phenomena)atanydiameter,ananeurysmdiameterof≥5.5cmregardlessofsymptoms,orexpansionby
>5mmover6months.42AnatomiccriteriaforEVARincludenormalaorticnecklengthofatleast1cm
withoutsevereangulation,healthycommonorexternaliliacarterylandingzonesofatleast15mm,and
commonfemoralarterydiameteradequatetoaccommodatea14Frenchsheath.ThoracicEVAR(TEVAR)
isindicatedforpatientswithdescendingthoracicaorticaneurysms≥2timesthediameteroftheadjacent
aortawithatleast2cmofnormallandingzonebothproximallyanddistally.43Reportedoff-labelusesof
TEVAR include traumatic aortic rupture, focal penetrating ulcer, and descending thoracic aortic
dissection. Patients with connective tissue disorders are poor TEVAR candidates because of the high
likelihoodoffurtheraorticdegeneration.
8.DeepVenousThrombosis
Catheter-directed thrombolysis (CDT) is indicated in patients with ileofemoral thrombus, symptom
duration<14days,goodfunctionalstatus,lifeexpectancy≥1year,andlowbleedingrisk.Forpulmonary
embolism, there is some evidence to support low-dose CDT over full-dose systemic thrombolytic
therapy. In patients with shock, high bleeding risk, or failed systemic thrombolysis, catheter-assisted
thrombusremovalisrecommended.
44
B.InformedConsent
Beforeanyendovascularprocedure,ahealthcareprovidermustinformacompetentpatientorsurrogate
aboutthedetailsoftheplannedprocedure,expectedbenefits,potentialrisks,andreasonablealternatives.
The provider should answer relevant questions, assess the individual’s understanding, and ultimately
allow the individualtoacceptor declinetoprocedure.For medicolegal clarity, this informedconsent
process is documentedwith the patient’sor surrogate’s signature on a documentindicating his or her
understandingandacceptanceoftheinformationpresentedbytheprovider.Forachild,consentmustbe
givenbytheparents,butthechildshouldalsoassentifcapableofcomprehendingsomeinformationabout
the intendedprocedure.The informed consentrequirement may onlybe waived incases of emergency
whendelaytoobtainconsentmayjeopardizethepatient’shealth.
45
SuggestedReadings
1.NickoloffEL.AAPM/RSNAphysicstutorialforresidents:physicsofflat-panelfluoroscopysystems:Surveyofmodernfluoroscopy
imaging:flat-paneldetectorsversusimageintensifiersandmore.Radiographics.2011;31(2):591-602.
46
2.LimacherMC,DouglasPS,GermanoG,etal.ACCexpertconsensusdocument.Radiationsafetyinthepracticeofcardiology.American
CollegeofCardiology.JAmCollCardiol.1998;31(4):892-913.
24
3.WennbergPW.Approachtothepatientwithperipheralarterialdisease.Circulation.2013;128(20):2241-2250.
47
4.ThukkaniAK,KinlayS.Endovascularinterventionforperipheralarterydisease.CircRes.2015;116(9):1599-1613.
48
https://t.me/med1917
References
5.RöntgenWC.Onanewkindofrays.Science.1896;3(59):227-231.
6.TselosGD.NewJersey’sThomasEdisonandthefluoroscope.NJMed.1995;92(11):731-733.
7.HaschekE,LindenthalO.AcontributiontothepracticaluseofthephotographyaccordingtoRoentgen.WienKlin.1896;9:63-64.
8.OsborneED,SutherlandCG,SchollAJ,RowntreeLG.Roentgenographyoftheurinarytractduringexcretionofsodiumiodide.JAMA.
1923;80:368-373.
9.HeuserC.Pieloradiografíaconioduropotásicoylasinyeccionesintravenosasdeioduropotásicoenradiografia.Radiología.1919.
(SessionsattheArgentineMedicalAssociation,April24,1919).
10.BrooksB.Intraarterialinjectionofsodiumiodide.JAMA.1924;82:1016.
11.MonizE.L’encephalographiearterielle,sonimportancedanslalocalizationdestemeurscerebrales.RevNeurol.1927;2:72-89.
12.BinzA,RathC.UberbiochemischeeigenschafternvonDerivatendesPyridinsundChinolins.BiochemZtschr.1928;(203):218.
13.SwickM.Excretionurographywithparticularreferencetoanewlydevelopedcompund:sodiumortho-iodohippurate.JAMA.
1933;101(24):1853-1857.
14.NymanU,EkbergO,AspelinP.TorstenAlmén(1931–2016):thefatherofnon-ioniciodinecontrastmedia.ActaRadiol.
2016;57(9):1072-1078.
15.SetteP,DorizziRM,AzziniAM.Vascularaccess:anhistoricalperspectivefromSirWilliamHarveytothe1956NobelprizetoAndréF.
Cournand,WernerForssmann,andDickinsonW.Richards.JVascAccess.2012;13(2):137-144.
16.SeldingerSI.Catheterreplacementoftheneedleinpercutaneousarteriography;anewtechnique.ActaRadiol.1953;39(5):368-376.
17.SonesFM,ShireyEK.Cinecoronaryarteriography.ModConceptsCardiovascDis.1962;31:735-738.
18.DotterCT,JudkinsMP.Transluminaltreatmentofarterioscleroticobstruction.Descriptionofanewtechnicandapreliminaryreportof
itsapplication.Circulation.1964;30:654-670.
19.FogartyTJ,CranleyJJ.Cathetertechnicforarterialembolectomy.AnnSurg.1965;161:325-330.
20.GrüntzigA.Percutaneousrecanalisationofchronicarterialocclusions(Dotterprinciple)withanewdoublelumendilatationcatheter
(author’stransl).Rofo.1976;124(1):80-86.
21.GruntzigA.Transluminaldilatationofcoronary-arterystenosis.Lancet.1978;1(8058):263.
22.PuelJ,JoffreF,RousseauH,etal.Self-expandingcoronaryendoprosthesisinthepreventionofrestenosisfollowingtransluminal
angioplasty.Preliminaryclinicalstudy.ArchMalCoeurVaiss.1987;80(8):1311-1312.
23.SigwartU,PuelJ,MirkovitchV,JoffreF,KappenbergerL.Intravascularstentstopreventocclusionandrestenosisaftertransluminal
angioplasty.NEnglJMed.1987;316(12):701-706.
24.RoguinA.Stent:themanandwordbehindthecoronarymetalprosthesis.CircCardiovascInterv.2011;4(2):206-209.
25.WhiteNW,YockPG.Intravascularultrasound:catheter-basedDopplerandtwo-dimensionalimaging.CardiolClin.1989;7(3):525-536.
26.FourrierJL,BertrandME,AuthDC,LablancheJM,GommeauxA,BrunetaudJM.Percutaneouscoronaryrotationalangioplastyin
humans:preliminaryreport.JAmCollCardiol.1989;14(5):1278-1282.
27.AinsburyEA,BoufflerSD,DörrW,etal.Radiationcataractogenesis:areviewofrecentstudies.RadiatRes.2009;172(1):1-9.
28.LimacherMC,DouglasPS,GermanoG,etal.ACCexpertconsensusdocument.Radiationsafetyinthepracticeofcardiology.
AmericanCollegeofCardiology.JAmCollCardiol.1998;31(4):892-913.
29.SlocumNK,GrossmanPM,MoscucciM,etal.Thechangingdefinitionofcontrast-inducednephropathyanditsclinicalimplications:
insightsfromtheBlueCrossBlueShieldofMichiganCardiovascularConsortium(BMC2).AmHeartJ.2012;163(5):829-834.
30.TsaiTT,PatelUD,ChangTI,etal.Validatedcontemporaryriskmodelofacutekidneyinjuryinpatientsundergoingpercutaneous
coronaryinterventions:insightsfromtheNationalCardiovascularDataRegistryCath-PCIRegistry.JAmHeartAssoc.2014;3(6):e001380.
31.GurmHS,SethM,KooimanJ,ShareD.Anoveltoolforreliableandaccuratepredictionofrenalcomplicationsinpatientsundergoing
percutaneouscoronaryintervention.JAmCollCardiol.2013;61(22):2242-2248.
32.SolomonR.Contrast-inducedacutekidneyinjury(CIAKI).RadiolClinNorthAm.2009;47(5):783-788.
33.GurmHS,DixonSR,SmithDE,etal.Renalfunction-basedcontrastdosingtodefinesafelimitsofradiographiccontrastmediain
patientsundergoingpercutaneouscoronaryinterventions.JAmCollCardiol.2011;58(9):907-914.
34.BrarSS,AharonianV,MansukhaniP,etal.Haemodynamic-guidedfluidadministrationforthepreventionofcontrast-inducedacute
kidneyinjury:thePOSEIDONrandomisedcontrolledtrial.Lancet.2014;383(9931):1814-1823.
35.ChoKJ.Carbondioxideangiography:scientificprinciplesandpractice.VascSpecialistInt.2015;31(3):67-80.
36.CronenwettJL,JohnstonKW.Rutherford’sVascularSurgery.7thed.Saunders;2010.
37.FergusonGG,EliasziwM,BarrHW,etal.TheNorthAmericansymptomaticcarotidendarterectomytrial:surgicalresultsin1415
patients.Stroke.1999;30(9):1751-1758.
38.Randomisedtrialofendarterectomyforrecentlysymptomaticcarotidstenosis:finalresultsoftheMRCEuropeanCarotidSurgeryTrial
(ECST).Lancet.1998;351(9113):1379-1387.
39.HallidayA,HarrisonM,HayterE,etal.10-yearstrokepreventionaftersuccessfulcarotidendarterectomyforasymptomaticstenosis
(ACST-1):amulticentrerandomisedtrial.Lancet.2010;376(9746):1074-1084.
https://t.me/med1917
40.Endarterectomyforasymptomaticcarotidarterystenosis.ExecutiveCommitteefortheAsymptomaticCarotidAtherosclerosisStudy.
JAMA.1995;273(18):1421-1428.
41.BrottTG,HowardG,RoubinGS,etal.Long-termresultsofstentingversusendarterectomyforcarotid-arterystenosis.NEnglJMed.
2016;374(11):1021-1031.
42.GurmHS,YadavJS,FayadP,etal.Long-termresultsofcarotidstentingversusendarterectomyinhigh-riskpatients.NEnglJMed.
2008;358(15):1572-1579.
43.BrottTG,HalperinJL,AbbaraS,etal.2011ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS
guidelineonthemanagementofpatientswithextracranialcarotidandvertebralarterydisease:areportoftheAmericanCollegeof
CardiologyFoundation/AmericanHeartAssociationTaskForceonPracticeGuidelines,andtheAmericanStrokeAssociation,American
AssociationofNeuroscienceNurses,AmericanAssociationofNeurologicalSurgeons,AmericanCollegeofRadiology,AmericanSociety
ofNeuroradiology,CongressofNeurologicalSurgeons,SocietyofAtherosclerosisImagingandPrevention,SocietyforCardiovascular
AngiographyandInterventions,SocietyofInterventionalRadiology,SocietyofNeuroInterventionalSurgery,SocietyforVascularMedicine,
andSocietyforVascularSurgery.JAmCollCardiol.2011;57(8):e16-94.
44.PowersWJ,DerdeynCP,BillerJ,etal.2015AmericanHeartAssociation/AmericanStrokeAssociationfocusedupdateofthe2013
guidelinesfortheearlymanagementofpatientswithacuteischemicstrokeregardingendovasculartreatment:aguidelineforhealthcare
professionalsfromtheAmericanHeartAssociation/AmericanStrokeAssociation.Stroke.2015;46:3020-3035.
doi:10.1161/STR.0000000000000074.
45.HirschAT,HaskalZJ,HertzerNR,etal.ACC/AHA2005PracticeGuidelinesforthemanagementofpatientswithperipheralarterial
disease(lowerextremity,renal,mesenteric,andabdominalaortic):acollaborativereportfromtheAmericanAssociationforVascular
Surgery/SocietyforVascularSurgery,SocietyforCardiovascularAngiographyandInterventions,SocietyforVascularMedicineand
Biology,SocietyofInterventionalRadiology,andtheACC/AHATaskForceonPracticeGuidelines(WritingCommitteetoDevelop
GuidelinesfortheManagementofPatientsWithPeripheralArterialDisease):endorsedbytheAmericanAssociationofCardiovascular
andPulmonaryRehabilitation;NationalHeart,Lung,andBloodInstitute;SocietyforVascularNursing;TransAtlanticInter-Society
Consensus;andVascularDiseaseFoundation.Circulation.2006;113(11):e463-e654.
46.ChaikofEL,BrewsterDC,DalmanRL,etal.SVSpracticeguidelinesforthecareofpatientswithanabdominalaorticaneurysm:
executivesummary.JVascSurg.2009;50(4):880-896.
47.BavariaJE,AppooJJ,MakarounMS,etal.Endovascularstentgraftingversusopensurgicalrepairofdescendingthoracicaortic
aneurysmsinlow-riskpatients:amulticentercomparativetrial.JThoracCardiovascSurg.2007;133(2):369-377.
48.KearonC,AklEA,OrnelasJ,etal.AntithrombotictherapyforVTEdisease:CHESTguidelineandexpertpanelreport.Chest.
2016;149(2):315-352.
49.AppelbaumPS.Clinicalpractice.Assessmentofpatients’competencetoconsenttotreatment.NEnglJMed.2007;357(18):1834-1840.
50.NickoloffEL.AAPM/RSNAphysicstutorialforresidents:physicsofflat-panelfluoroscopysystems:Surveyofmodernfluoroscopy
imaging:flat-paneldetectorsversusimageintensifiersandmore.Radiographics.2011;31(2):591-602.
51.WennbergPW.Approachtothepatientwithperipheralarterialdisease.Circulation.2013;128(20):2241-2250.
52.ThukkaniAK,KinlayS.Endovascularinterventionforperipheralarterydisease.CircRes.2015;116(9):1599-1613.
https://t.me/med1917
C H A P T E R 2
AcuteStrokeIntervention
RyanM.HebertMD,FouadChouairiBS,BrandenCordMDPhD,SamuelSommarugaMD,MichaelMercierBA,AnnaLynnBS,
AndrewKooBS,StacyChuMD,andCharlesMatoukMDFRCS(C)
I.Introduction
II.AcuteStroke101
A.StrokeEpidemiology
B.StrokePathophysiology
III.IntravenousTissuePlasminogenActivator—Long-TimeStandardofCareandImportantLimitations
A.NINDSandECASS
B.IntravenousTissuePlasminogenActivatorforIschemicStrokeLimitations
IV.Intra-arterialThrombolytics,First-GenerationMechanicalThrombectomyDevices,andFailedClinicalTrials
A.PROACTI,PROACTII,IMSTrials
B.MERCITrial
C.SYNTHESIS,IMS-III,andMRRESCUE:2013Trials
V.MRCLEANandtheEmergenceofaNewStandardofCare
A.MRCLEANTrial
B.ESCAPETrial
C.EXTEND-IATrial
D.SWIFTPRIMEandREVASCATTrials
VI.TheNumberofPatientsEligibleforMechanicalThrombectomyContinuestoIncrease
A.PosteriorCirculationStrokes/AcuteBasilarOcclusion
B.ExtendingtheTherapeuticWindowforMechanicalThrombectomy
A.MechanicalThrombectomyforAnteriorCirculation
C.ChasingMoreDistalClots
D.ExampleCasesFromYaleNewHavenHospital(YNHH)
KeyPoints
■An occlusion inmajor blood vessels atthe base of theskull supplyingthe brain(paired
internal and vertebral arteries) as well as their proximal intracranial branches (anterior
cerebral artery, middle cerebralartery, and basilar artery)is referred to asanLVO (large
https://t.me/med1917
vesselocclusion).
■ItisestimatedthatLVOsaccountforatleast10%-15%ofallacuteischemicstrokes.
■MechanicalthrombectomyforanteriorcirculationLVOsisnowstandardofcareforpatients
presentingwithin6hoursofstrokeonsetbutinselectcasescanbeofvalueupto24hours
sincetheevent.
I.Introduction
In2015,fiveclinicaltrialswerepublishedthatestablishedmechanicalthrombectomyasanewstandard
ofcareinthemanagementoflargevesselocclusions(LVOs)ofthebrain.
1-5
Thesestudiesandthosethat
followed forever changed the paradigm ofacutestokemanagement from solely focused on the timely
administrationofintravenous(IV)thrombolyticstoemergentinterventionalrevascularization.
6-9
Thisisa
watershedmomentinacutestrokecare.Thestrokecommunityiscurrentlyreorganizingtriageprotocols
sothatasmanypeopleaspossiblecanbenefitfromthislifesavingintervention.
Thischapterwillprovideabriefreviewofstrokeepidemiologyandpathophysiology,clinicaltrialsdata,
andmechanical revascularization strategies for the nonexpertinterventionist.The focus will be onthe
subsetofacuteischemicstrokespotentiallyamenabletomechanicalrevascularization,ie,LVOs.
II.AcuteStroke101
A.StrokeEpidemiology
1. Thedefinition of stroke is anacute-onset loss of neurological function (typicallyfocal) that results
fromavascularetiology.Therearetwomaintypesofstrokes:(1)ischemic(resultingfromanobstruction
withinabrainbloodvessel)and(2)hemorrhagic(resultingfromvesselrupture).Ischemicstrokeisfar
morecommon(accountingfor87%ofallstrokecases)andisthetopicofthisreview.
10
2.Strokeisacommondisease.EveryyearintheUnitedStates,approximately800,000peoplewillhave
astroke.Morethanthree-fourthofthesecaseswillbefirstpresentations,andnearly20%willsuffera
secondstrokewithin4years.
11,12
3. Strokeis a leading cause of death and disability. Itis the 5th leading causeof death behind heart
disease, cancer, chronic lower respiratory disease, and accidents (unintentional injuries). Every
4minutes,someoneintheUnitedStatesdiesofastroke,accountingfor130,000deathsperyear(or1in
20deaths overall). Becausestrokeoftentakes peopleout ofthe workforce,it representsa tremendous
societalcostestimatedat34billiondollarsperyear.
13
4.Often,thelargeststrokesyndromeswiththeworstclinicaloutcomesresultfromamajorbloodvessel
inthebrainbeingoccluded.Thesemajorbloodvesselsarethevesselsatthebaseoftheskullsupplying
thebrain(pairedinternalandvertebralarteries)aswellastheirproximalintracranialbranches(anterior
cerebralartery,middlecerebralartery,andbasilarartery).Ablockageinanyofthesevesselsisreferred
toasanLVO.ItisestimatedthatLVOsaccountfor10%-15%ofallacuteischemicstrokes.
14,15
Itisthese
ischemicstrokepatientswhoarepotentiallycandidatesformechanicalrevascularization.
B.StrokePathophysiology
1. In acute ischemic stroke,if a territoryof thebrainis solely supplied by a single-endvessel, then
occlusionofthevesselwillresultinbraininfarctionwithinaveryshortperiodoftime.Thismost-at-risk
https://t.me/med1917
brainterritoryisreferredtoastheischemiccore.Justoutsideofthiscoreareaisanareaofthebrainthat
experiences decreased, but somewhat maintained, cerebral blood flow (CBF) because of arterial
collaterals. This area is referred to as the penumbra. Average CBF in a healthy adult is around
50mL/100g/min.CellularfunctionisperturbedinareaswhereCBFdropsto15-20mL/100g/min.Cells
in this penumbral region may survive for several hours before irreversible cell death, ie, cerebral
infarction, ensues. CBF <10 mL/100 g/min produces failure of cellular ionic gradients. If flow is not
improved,celldeathoccursinlessthan60minutes.16Animportantclinicalcorrelateofthisbasicstroke
pathophysiology is that a clinician at the bedside cannot determine whether a patient with an acute
ischemic stroke, eg, acute-onset hemiplegia, has a penumbral (reversible) or core (irreversible)
neurologicaldeficit.
2.Althoughtimeplaysasignificantroleinstrokepathophysiology,itisnottheonlyfactor.Thebrainis
suppliedbyarobustnetworkofarterialcollaterals,primarilyarisingfromthecircleofWillis(COW).
TheCOWissuppliedanteriorlybytheinternalcarotidarteries(anteriorcirculation)andposteriorlyby
thevertebrobasilarsystem(posteriorcirculation).AcompleteCOWisfoundinlessthan50%ofpeople.
AnincompleteCOWhasbeenassociatedwithincreasedstrokerisk.17COW facilitatesleptomeningeal
collateralization between the middle cerebral artery (MCA), anterior cerebral artery (ACA) and
posterior cerebral artery(PCA) territories. Some patients have good collateral circulations,others do
not.Itisthestrengthofthesecollateralsthathelpsdefine,inlargepart,thesizeoftheischemiccoreand
penumbra.Asecondimportantclinicalcorrelateisthatthepenumbralareaisdynamicinspaceandtime.
For example, blood pressure augmentation may better support brain tissue supplied by a collateral
networkforalongerperiodoftime,effectivelyincreasingthesizeofthepenumbra.Collateralstatuscan
beassessednoninvasivelyandhasbeencorrelatedtostrokeoutcome.
18,19
3.NoninvasiveImagingof“At-RiskBrain”—ClinicalAssessmentofIschemicCore,Penumbra,and
CollateralCirculation
a. Patientsbeingevaluatedforstrokeuniversallyundergononcontrastcomputed tomography(NCCT)
ofthebrain.Thisisprimarilyusedtoidentifyhemorrhagicstrokeforintravenoustissueplasminogen
activator (IV tPA) exclusion. NCCT is also useful in identifying early ischemic parenchymal
changes.TheAlberta StrokeProgramEarlyCT(ASPECT) Scoreis apopular methodtoquantify
anterior circulation early ischemic change (EIC) on computed tomography (CT) to predict the
outcomeafterIVthrombolysis.Inthisscoringsystem,7pointsareassignedtotheMCAterritoryand
3tosubcorticalstructures.Thescoringsystemstartsat10.EachregionshowingEICaccountsfora
1-pointdeduction.LowerASPECTScoreswereassociatedwithpooroutcomesafterIVtPA.
20
b. CTangiography(CTA)isanextremelyusefuldiagnostictoolandestablishesthediagnosisofLVO.
Inaddition,itprovidestheinterventionistwithvaluabletechnicalinformationabouttheaorticarch,
vessel tortuosity, and carotid bifurcation disease. CTA of the head also provides important
informationaboutcollateralbloodflowtotheterritoryatrisk.Severalstudieshaveshownthatgood
collateralsonCTAarepredictorsofgoodoutcomeaftermechanicalthrombectomy.
18,21
c. CTperfusionis performedbyintravenously administering abolusofcontrastandusingserialCT
scans to follow the contrast bolus through the intracranial circulation. This imaging technique
provides estimates of CBF, mean transit time (MTT), time-to-peak (TTP), and cerebral blood
volume (CBV). Decreased CBF and CBV reflect the ischemic core, ie, irreversibly injured
(nonsalvageable)brain.ThepenumbraisdemonstratedasaregionofbrainwithpreservedCBVand
increasedMTT(orTTP).
22-27
d. MRI(magneticresonanceimaging)ismoresensitive than CTfordetecting cerebral ischemiaand
infarction. Diffusion-weightedimaging (DWI)candetectischemic changeswithin5-10minutesof
symptom onset. T2-weighted sequences identify subacute infarction 6-24 hours after ictus.
https://t.me/med1917
HyperintensityonDWIisthebestimagingcorrelateoftheischemiccore.
28,29
e. ThereisvigorousdebateregardingutilizationofCTperfusionandMRIintheevaluationandtriage
ofacuteischemicstroke.Bothhavebeenshowntoincreasetimetopunctureandarenotassociated
with improved outcomes. However,incertainscenarios, both provideinvaluable datathataidin
complexclinicaldecision-making.
30
III.IntravenousTissuePlasminogenActivator—Long-Time
StandardofCareandImportantLimitations
A.NINDSandECASS
In 1995, the NationalInstituteofNeurologicalDisordersandStroke(NINDS)publisheda paperinthe
New England Journal of Medicine supporting the efficacy of IV recombinant tissue plasminogen
activator (tPA) in the settingof acute stroke.31 Their results failed toshow a statistically significant,
clinical improvement orresolutionofstrokesymptomsat24 hours.However,at3 months,there was a
statistical,clinicalimprovementintheIVtPAgroupcomparedwithplacebo.Thisclinicalimprovement
was realized despite an increase in the rate of symptomatic intracerebral hemorrhage (6% vs 0.6%).
These results were confirmed by the European Cooperative Acute Stroke Study (ECASS) that also
extendedthetimewindowinwhichIVtPAcouldbeadministered(4.5hoursafterstrokeonset).32These
studiesestablishedthefirsteffective treatmentforacuteischemicstrokeanddefinedanewstandardof
care.
B.IntravenousTissuePlasminogenActivatorforIschemicStroke
Limitations
1. A narrow therapeuticwindow. Thenarrowwindowfrom stroke onsetto administrationofIV tPA
meansthatmostpatientsarriveinhospitaltoolatetoreceivethemedication.Approximatelyone-fourthof
patients have so-called “wake up” strokes of uncertain time of onset and are therefore ineligible to
receiveIVtPA.Onaverage,only7%ofpatientspresentingwithacuteischemicstrokereceiveIVtPA.
33-
37
2. Limited efficacy for LVOs and large stroke syndromes. In 2006, Smith et al. reported on a
consecutive series of patients with large stroke syndromes and LVOs.38 They divided their study
population into two groups: one group in which IV tPA achieved recanalization and another with
persistentvesselocclusion.Thegroupinwhichrecanalizationwasachieved,albeitmuchsmallerthanthe
groupwith persistentocclusion,realizedmuchbetterclinicaloutcomes. Thesedataare consistentwith
other reports demonstrating poor recanalization rates for internal carotid artery (ICA) terminus and
basilararteryocclusions.
39
3.Increasedrateofsystemichemorrhage.Theadministrationofasystemicthrombolyticexcludesan
importantsegmentofpatientsonoralanticoagulantsordirectorfactorXainhibitors;recentneurosurgery,
stroke,headtrauma,orothermajorsurgery;andhistoryofintracranialhemorrhage.
37
IV.Intra-arterialThrombolytics,First-GenerationMechanical
ThrombectomyDevices,andFailedClinicalTrials
https://t.me/med1917
A.PROACTI,PROACTII,IMSTrials
GiventhelimitedefficacyofIVtPA,especiallyforpatientswithlargestrokesyndromesandLVOs,intraarterial (IA) administration of thrombolytics was studied. In 1998, the Prolyse in Acute Cerebral
Thromboembolism(PROACT)trialcomparedrecombinantpro-urokinasewithplacebo(IVheparin)for
MCA occlusion.40 Recanalization and hemorrhage were more common in patients receiving pro-
urokinase,withonlyrecanalizationreachingstatisticalsignificance.PROACTIIaimedtoproveclinical
efficacy by comparing modified Rankin scores at 90 days of patients receiving pro-urokinase versus
placebo.41 Recanalization in the treatment arm was 66% compared with 18% in the placebo group.
ModifiedRankinScore(mRS)lessthanorequalto2,ie,favorableoutcome,at90dayswas40%inthe
treatmentarmcomparedwith25%intheplaceboarm.Symptomaticintracranialhemorrhage(ICH)was
10%inthetreatmentarmcomparedwith2%intheplaceboarm.Itisimportanttonotethatnoneofthe
patientsinPROACTIorIIreceivedIVtPA.TheInterventionalManagementofStroke(IMS)trialwasa
single-armed, safety,andfeasibilitystudyofIVtPAplus IAtPA.42In addition to0.6mg/kgofIV tPA,
patientsreceiveda2mgIAbolusoftPAintoandbeyondtheclot.Atotalof22mgoftPAwasgivenover
2hours.Treatmentwas stoppedifTIMI3recanalizationwasachievedbefore2 hours. Comparedwith
historicalNINDSplacebo–treatedpatients,IA-treatedpatientsinIMShadsignificantlybetteroutcomesat
3months.IMSIIconfirmedthesefindings.
43
B.MERCITrial
In2005,theMERCItrialwasconductedtoevaluatethesafetyandefficacyoftheMerciretrieverdevice
formechanical thrombectomyin patients ineligible for IV tPA.44 The Merci retriever is a preshaped,
tapered,helicaldeviceconsistingof5loops.The described procedureconsistedofplacinga9-French
balloonguidecatheter(BGC)intothecarotidartery.Amicrocatheterwasnavigatedthroughthethrombus.
The Mercidevicewas deployedacross thethrombus.The BGCwasinflated,suctionapplied, andthe
Mercidevicerotatedfivetimes.Thedeviceandmicrocatheterwerethenretrievedinunison.45Resultsof
theMERCItrial were promising. TheMERCIdevicealoneled toarecanalizationrateof54%,while
recanalizationratesforMERCIplusIVtPAwas69%.
46,47
Complicationrateswere10%forsymptomatic
ICH(4%higherthanIVtPAalone)and10%forvesselperforation.
47,48
C.SYNTHESIS,IMS-III,andMRRESCUE:2013Trials
1.In2013,threetrialswerepublishedintheNewEnglandJournalofMedicinecomparingIVtPAwith
endovasculartherapyforacuteischemicstroke.
49-51
SYNTHESISrandomizedpatientstoIValteplaseor
endovascular therapy. Noncontrast CT was the only imagingmodality used for screening. Intervention
occurred within 6 hours of stroke onset. If no occlusion was present on angiography, alteplase was
administeredtothepresumedvascularterritory.Ifocclusionwasseenonangiography,theendovascular
device used for clot retrieval was at the discretion of the interventionist. Of the 109 patients in the
interventionalgroup,only56weretreatedwithadevice.TherewasnodifferenceinmRSat3months
betweentheinterventionalgroupandtheIValteplasegroup.Inaddition,interventionaltreatmentdelayed
therapybyonehour.
49
2.IMS-IIIwasthelargestofthe2013trialsenrolling656participants.
50
Patientswererequiredtohave
abaselineNIHSSof10orgreater,ie,largestrokesyndromes.AllpatientsreceivedIVtPAwithin3hours
of stroke onset. Patients randomized to the interventional arm received treatment within 5 hours of
symptomonset.Treatmenthadtobecompletedbefore7hoursofstrokeonset.AlthoughCTAwasusedin
the latter part of the study, most patients were randomized to intervention without proving a LVO.
https://t.me/med1917
Interventionwasprimarilymicrocatheter-basedadministrationofIAtPA.TheMercidevicewasusedin
28.4%oftheinterventionalgroup.TheSolitairestentretrieverwasavailabletowardtheendofthestudy
andonlyusedin1.5%ofstudypatients.52Therewasnotasignificantdifferenceinindependentoutcomes
betweentheinterventionalgroupandtheIVtPAgroup.AmajordeficiencyoftheIMS-IIIstudywasthat
CTAwasnotutilizedtorandomizepatientsbetweentreatmentgroups.AsubgroupanalysisoftheIMS-III
subjectswithaprovenlargevesselocclusionrevealedastatisticallysignificantdifferenceintherateof
24-hourrecanalization.Therewasalsoatrendtowardimprovedfunctionalindependence.
53
3. Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE)
randomized patientstomechanical thrombectomyversus medical therapy based ona documentedLVO
afterIVtPAand“favorablepenumbralpattern.”51A“favorablepenumbralpattern”wasdefinedasacore
infarctvolumelessthan90mLandapredictedinfarctof70%orlessoftheterritoryatrisk.Mechanical
thrombectomy was initiated within 8 hours of onset. There was no significant difference in mRS at
90daysbetweenthegroups.Interestingly,revascularizationmeasuredonday7byMRAorCTAwasnot
differentbetweenthe2groups.Interestingly,thepatientswhohadafavorablepenumbralpattern3hours
afteronsethadbetteroutcomes,regardlessoftreatmentarm.Thissupportsthehypothesisthatcollateral
status is an important predictor of stroke outcome. The 2013 trials were marred by a number of
suboptimalconditions. Patientselection was poor. Indeed,most ofthe studies didnot confirmanLVO
beforerandomization!Studyconclusionswereinappropriatelygeneralizedtomechanicalthrombectomy
as a concept even though IA administration of thrombolytics was the dominant form of endovascular
therapy.Finally,earlygenerationdeviceswereinefficientand,simplyput,hadpoorrecanalizationrates.
V.MRCLEANandtheEmergenceofaNewStandardofCare
In 2015, five clinical trials were published which studied mechanical thrombectomy in the era or
improvedpatientselectionandsecond-generationmechanicalthrombectomydevices,ie,stentretrievers.
1-5
A.MRCLEANTrial
TheMulticenterRandomizedClinicalTrialofEndovascularTreatmentforAcuteIschemicStrokeinthe
Netherlands(MRCLEAN)wasthefirstofthesetrialstobereported.1500patientswithCTA-confirmed
LVOs ofthe distal ICAor proximal MCA were randomized to IVtPA plusmechanical thrombectomy
within6 hours ofstrokeonsetor IV tPA alone.Mechanical thrombectomywas performed witha stent
retriever in 97.4% of the interventions. A favorable outcome, defined as mRS 0-2 at 90 days, was
achievedin33%oftheinterventionalgroup,comparedwith19%oftheIVtPA–alonegroup.Therewas
nosignificantdifferenceinICHor90-daymortality.
B.ESCAPETrial
TheEndovasculartreatmentforSmallCoreandAnteriorcirculationProximalocclusionwithEmphasis
onminimizingCTtorecanalizationtimes(ESCAPE)trialsoughttoenroll500patientsbutstoppedat316
owingtoefficacy.3PatientshadanASPECTSgreaterthanorequalto6.CTAconfirmedanLVOofthe
anteriorcirculation.Interventionhadtobestartedwithin12hoursofstrokeonset.Intheinterventionarm,
53%ofpatientsachievedagoodoutcome,measuredbyanmRS0-2at90days,comparedwithonly29%
of the medical arm. A stent retriever was used in 86% of cases. There was no difference in ICH.
Mortalitywasreducedintheinterventionalarm.
https://t.me/med1917
C.EXTEND-IATrial
The Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial
(EXTEND-IA) trial randomized patients with ICA or MCA occlusions to IV tPA plus mechanical
thrombectomy,usingtheSolitairerevascularizationdevice(astentretriever,MedtronicNeurovascular),
versusIVtPAalone.2PerfusionimagingusingRAPIDsoftwarewasusedinallsubjects.CTperfusion
inclusioncriteriaconsistedofmismatchratio>1.2,absolutemismatchvolume>10mL,andischemiccore
volume <70 mL. There were two primary outcomes: reperfusionof the vascular territory at24 hours
(measuredbypercentagereductionin the perfusionlesion volume) and8-point improvementinNIHSS
(orNIHSS0-1)atday3.Thetrialwasstoppedearly(afterenrollmentof70patients)owingtotheresults
ofMRCLEAN.Medianreperfusionat24hourswas100%.Neurologicimprovementoccurredin80%of
themechanicalthrombectomygroupcomparedwith37%oftheIVtPAgroup.
D.SWIFTPRIMEandREVASCATTrials
The Solitaire with the Intention for Thrombec-tomy as Primary Endovascular Treatment for Acute
Ischemic Stroke(SWIFT PRIME) compared IV tPA alonewith IV tPAwith stentretriever mechanical
thrombectomyinpatientswithLVOpresentingwithin6hoursofsymptomonset.5Perfusionimagingwas
usedin158of196patients(83oftheinterventionalgroup)toscreenpatients.Thetrialwasstoppedearly
owingtoefficacy.ThechanceofhavinganmRS0-2was60%inthestentretrievergroupcomparedwith
35%treatedwithIVtPAalone.Thenumberneededtotreatwas2.6.AtthesametimeSWIFTPRIMEwas
published, the Randomized Trial of Revascularization with Solitaire FR Device versus BestMedical
TherapyintheTreatmentofAcuteStrokeDuetoAnteriorCirculationLargeVesselOcclusionPresenting
within8hours ofSymptomOnset(REVASCAT)trial reporteditsoutcomes afterclosingthe trialearly
due to the positive results of MR CLEAN.4 Again, patients with known LVO assigned to the
interventionalgroupweremorelikelytobeindependentat90dayscomparedtothepatientsreceivingIV
tPA alone. Infarct volume at 24 hours was smaller in the interventional group (16.3 mL) versus the
medicalgroup(38.6mL).
Takentogether,the2015stentretrievertrialsdefineda newstandardofcare foracuteischemic stroke
secondary toanterior circulationLVOs. MRCLEANandESCAPEshowed a benefit from mechanical
thrombectomyeveninpatientsolderthan80years.Patientswithlargestrokesyndromesasmeasuredby
NIHSS(SWIFTPRIME>17,ESCAPE>20,MRCLEAN>20)alsoshowedbenefit.
VI.TheNumberofPatientsEligibleforMechanical
ThrombectomyContinuestoIncrease
A.PosteriorCirculationStrokes/AcuteBasilarOcclusion
continuestoincreaseincludingposteriorcirculationstrokes/acutebasilarocclusion.Withtheexceptionof
a handful of patients in IMS III and SYNTHESIS, the 2015 mechanical thrombectomy trials studied
anterior circulation LVOs. In part,this reflectsthe exceptionallyhighmorbidity and mortality of acute
basilar artery occlusion (80%-90%) without intervention. Most interventionists are reluctant to offer
aggressivetreatmentgiventhe grave naturalhistory. Amajority ofreportsintheliterature support this
philosophy.Itisunlikelythatarandomizedclinicaltrialwilleverbeperformedtoanswerthisquestion
conclusively.
54,55
https://t.me/med1917
Соседние файлы в папке Библиотека им академика М.И. Перельмана