第三版心肌梗死定義英文版

AllanS.Jaffe,IntroductionTheThirdUniversalDefinitionofMyocardialInfarction(MI)wasrecentlypublishedconjointlybythemajorcardiologyorganizationsthroughouttheworldandinthejournalsoftheWorldHealthOrganization(WHO).Thisdefinitionbuildsontwoprevioustwoiterationswhichweredevelopedtomakethediagnosisofmyocardialinfarction(MI)moreconsistent.Theeffortsstartedoriginallyin1999intheconferenceinNicestimulatedbytheinnovationofDr.KristianThygesenandDr.JosephAlbertwhohadrecognizedthisproblemandwhodevelopedataskforcejointlysponsoredbytheACC(AmericanCollegeofCardiology)andtheESC(EuropeanSocietyofCardiology)toattempttostandardizethedefinitionofMI[1].ThismajorstepledtothefirstdocumentwhichmovedthefieldfromtheepidemiologicallyorienteddefinitionofMIwhichhadbeendevelopedbytheWHOtotracktheincidenceofcoronarydiseaseandthereforewasorientedtowardsspecificitytoamoreclinicallyorienteddefinitionwhichreliedonbiomarkersasakeyfeatureofthediagnosis.Thisresultedinaparadigmshiftwherethediagnosisrequireddocumentationofmyocardialnecrosiswithbiomarkersandespeciallycardiactroponin(cTn)whichwasemergingatthetimeintheproperclinicalsituation.Aseconditerationin2007[2]updatedtheguidelinesandthe2023definitionrefinesthedefinitionstillfurtherparticularlyasitrelatestobiomarkers[3]whichhaveinthepastdecadebecomeprogressivelymoreandmoresensitive.Intrinsically,increasesinsensitivityofthissorttendtoresultinadiminutionofspecificitysinceincreasinglysensitivemeasurementsoftenunmasknewetiologiesforinthisinstance,elevationsofthesesensitivecTnbiomarkers.Areasofthe2023definitionthatremainsimportantbutunchangedTable

1.Criteriaforacutemyocardialinfarction(ThirdUniversalDefinitionofMyocardialInfarction).

?Detectionofariseand/orafallofcardiacbiomarkervalues(preferablycardiactroponin(cTn))withatleastonevalueabovethe99thpercentileupperreferencelimit(URL)andatleastoneofthefollowing:?Ischemicsymptoms?ECGchangesofnewischemia(newST–TchangesornewLBBB)?DevelopmentofpathologicQwavesintheECG?Imagingevidenceofnewlossofviablemyocardiumornewregionalwallmotionabnormality?IdentificationofanintracoronarythrombusbyangiographyorautopsyFull-sizetableTableoptionsThemetricsfortheuseofthesebiomarkersremainthesame.Oneneedsavalueabovethe99thpercentileoftheupperreferencelimitwitharisingand/orafallingpatternofvalues.However,ascTnassaysensitivityhasimproved,theabilitytoconsistentlyoperationalizethesecriteriahasbecomemoreproblematicaswillbeIssuesrelatedtobiomarkersAsinthepast,cTnisthemarkerofchoiceandariseand/orafallinvaluesisnecessarytodefineanacuteeventsuchasMI.Itisrecognizedthatthereissometensionabouthowonedefinesthe99thpercentile.Itisassaydependentandisoftendefinedbasedonconveniencesamples.Therefore,thereisconcernthatperhapstheyarenotasreliableasifthesamplepopulationsweremoreintensivelystudied[4].Thevaluesfortheseassaysshouldbeexpressedinng/Lsothattheyarewholenumbersbecauseasassaysbecomemorecomplicatedandmoresensitive,thenumberofzeroscouldleadtoclinicaldysfunction.TheassaysshouldbepreciseandthedocumentprefersassaysthathaveexcellentprecisionwithaCVof10%orlessofthe99thpercentiletoallowdetectionofchangingvalues.However,thedocumentallowsforassayswithCVsupto20%tobeused[5].Italsoisnotedthatanalyticandpre-analyticproblemscanbeproblematicandleadtofalse-positiveandfalse-negativevaluesespeciallywithmoresensitiveassays.Itisalsorecommendedthatsexdependentvaluesmaybeusedwithhighsensitivityassays.Samplingshouldbedoneat0,3,and6

handlaterifadditionalepisodesoccurorifthetimingoftheinitialsymptomsisunclear.Thediagnosisrequiresarisingandafallingpatternwhichisessentialtodifferentiateelevationsthatareacutefromthosethatarechronicandassociatedwithstructuralheartdiseasesuchaspatientswithrenalfailure,heartfailure,leftventricularhypertrophy,andthelike.Itisrecognizedthatoneneedstobecarefulbecauseattimesonecouldpresentsufficientlylateastomissanelevatedvalueorcouldbenearthetimeofpeakvaluesatwhichpointintimeonecouldbelievethatachangehadnotoccurredwhensimplythevaluesweresimilaronbothsidesofthepeak.ItisrecognizedandallowedthattheremaybecircumstancesinwhichcardiacinjurycouldbepresentbutnotmeetthediagnosisofMIbecauseitisnotintheTable

2.Elevationsofcardiactroponinvaluesbecauseofmyocardialinjury(ThirdUniversalDefinitionofMyocardialInfarction).

?Injuryrelatedtoprimarymyocardialischemia(MItype1;i.e.,plaguerupture,intraluminalcoronaryarterythrombusformation)?Injuryrelatedtosupply/demandimbalanceofmyocardialischemia(MItype2;i.e.,tachy-/brady-arrhythmias,aorticdissection,orsevereaorticvalvedisease,hypertrophiccardiomyopathy,cardiogenicorsepticshock,severerespiratoryfailure,severeanemia,hypertensionwithorwithoutLVH,coronaryspasm,coronaryembolismorvasculitis,coronaryendothelialdysfunctionwithoutsignificantCAD)?Injurynotrelatedtomyocardialischemia(i.e.,cardiaccontusion,surgery,ablation,pacing,defibrillatorshocks,rhabdomyolysiswithcardiacinvolvement,myocarditis,cardiotoxicagents)?Multifactorialorindeterminatemyocardialinjury(i.e.,heartfailure,stress(takotsubo)cardiomyopathy,severepulmonaryembolismorpulmonaryhypertension,sepsisandcriticallyillpatients,renalfailure,severeacuteneurological(e.g.,stroke)infiltrativediseases(e.g.,amyloidosis),strenuousexercise)OperationalizingchangeincTnvaluesiscomplexandassaydependent.Itshouldbeclearthatgivenpreviouswaysofdiagnosinginfarctionhaveoftennotrequiredchangesovertimethatasonestartstoimplementthesechanges,onewillhavedifferencesinbothsensitivityandspecificity[6].Infact,mostofthedatainthisareasuggeststhattheuseofdeltachangecriteriaimprovesspecificitybutatthecostofsensitivity.Therearemultiplereasonswhythiscouldbethecase.Thefirstisthatitmaybethattherearepatientsbeingdiagnosedwithacuteinfarctionwhodonothavearisingandafallingpatternbasedonclinicaljudgmentsinceonecanhaveinadequate.Therealsoareissuesrelatedtothespontaneouschangethatcanoccur.Thishasbeentermedbiologicalvariationandclearlyismuchmoresubstantialthanjustthevariabilityassociatedwiththeimprecisionoftheassays[8].Nonetheless,itisclearthereissomeoverlapbetweenthevaluesthatonebelievesareassociatedwithpatientswithMIandthevaluesthatareconsideredpartofthespontaneousbiologicalvariation[9].Inaddition,theoptimalvaluestousewitheachassayarenotclear.OnecouldcalculateanROCcurvewhichmanylaboratoriansareenamoredofdoingandpickthevaluethatclassifiesthemostpatientscorrectly.However,thismaynotbewhatcliniciansneed.Cardiologistswantrelativelyhighspecificitytoavoidunnecessaryproceduresinpatientswhoarenotatrisk,whereasemergencydepartmentphysiciansoftenwantmoresensitivecriteriasothattheydonotinadvertentlydischargepatientswhoareatrisk[10].Thebalancebetweenthesetwoneedstobefoundateachinstitutionallevel.Thus,thecomplexityofthisissue,withhigh-sensitivityassays,needstobediscussedateachlocalsiteandadjudicatedonacasebycasebyassaybasis.ClassificationofMIsTherearemultiplereasonswhycTncouldbeelevatedthatneedtobedistinguishedfromMI.OnecouldhavearisingandafallingpatternofcTnduetosepsisorpulmonaryembolism,oracuteheartfailurewithmyocardialstretch;noneofwhichwouldbeassociated,norshouldbeconsideredthesameasMI.Inaddition,therearetypesofMIsaswellanditmaywellbeofsomeimportancetodistinguishthetypesasthecareoftheseindividualsmaybedifferent.ThetaskforcerecognizedmultipletypesofacuteMI[3].Theydefinetype1whichmanyhavecalledthesocalled“wild”typeasanepisodeassociatedwithplaqueruptureandspontaneousinnature.Thus,thesepatientsmostoftenpresentafteranepisodeofchestdiscomfortoftenwithECGchanges,elevatedbiomarkers,andinthestudiesofsuchpatientsitisclearthathavinganelevatedcTnindicatesabeneficialresponsetoanaggressivestrategywithanticoagulationandtheuseofIIb/IIIaagentsandearlyinvasivestrategy[11].Soextremetachycardia,hyper-orhypotension.Thesescenarioscanbecomecomplex.Onecouldsuggestthatthereisacontinuumbetweenmyocardialinjurywhichmightbediagnosed,forexample,inayoungpersonwithtachycardiawhohadanelevatedcTnthanwhowastotallyasymptomatic,toasimilarpatientwhomighthavemoretypicalchestpainwhomightbecalledatype1MI,toanindividualwhomighthavevaguesymptomsthataredifficulttoclassifyinwhomadiagnosisoftype2MImightbemade.ThisisanareawhereclinicaljudgmentwillbeimportantforcliniciansbutitshouldbeclearthatsolitaryelevationofcTnevenwitharisingandafallingpatterndoesnotmandateadiagnosisofMI.Thesedistinctionsaremademoredifficultbythefactthatincertaincircumstancessuchastheelderly,thediabetic,andpatientswhoarepostoperativeclassicfindingsmaynotbeobserved.Type3MIsubsumesthatcircumstancewherethereisapatientwithaclassicMIdocumentedeitherbyelectrocardiographyorangiographywherethebiomarkershavenotbeenobtainedorhavenothadsufficienttimetobeelevated.Thisisrarelyaproblemexceptinthosepatientswhosuccumbataveryearlytimeduringtheprocess.TherealsoaremyocardialinfarctionsassociatedwithrevascularizationproceduressuchasPCIorCABG.Thesearecomplexandwillbecoveredbelow.ElectrocardiographicchangesTheelectrocardiographicchangesthatshouldbeobservedfordidnotchangemarkedlybutlookingforevidenceofcircumflexcoronaryarteryischemiaisemphasized.Posteriorleads(V7–V9)shouldberecordedinpatientswhomayhavecircumflexinvolvement.ThismaybesuspectedifthereisSTsegmentdepressioninV1–V3.TheECGcriteriaforacuteMIandcommonECGpitfallsindiagnosinginfarctionaredetailedintheThirdUniversalDefinitionofMyocardialInfarction[3].Thisisanareaofintensecontroversy.Itisclearthatmyocardialinjurycanoccurafterpercutaneousprocedures.Thiscanbeduetoemboli,whethertheyareaclotofatherosclerotic,occlusionofasidebranch,orsimplyprolongedischemia.Whathasbeenproblematichasbeentheabilitytoknowforsurethattheseeventsareassociatedwithanadverseprognosis[12].Thecriteriaprovideddonotattempttomakethatdistinctionsincesuchadistinctionrequiresoutcomedata.Thethoughtwiththatisthatformanysuchelevations,elevationspriortotheprocedurearepresentbuthavebeenignored[12].Indeedinrecentmeta-analysis,notonestudythatclaimedtohaveanormalbaselinehadsuchabaseline.Therefore,theproponentsofthisparticularpointofviewwouldarguethatthereisrarelyprognosticsignificance.Ifso,thequestionarisesastowhetherornotdiagnosingthesepatientswithacuteMIisofvalue.Theopposingviewisthatpriorstudies,particularlydonewithlesssensitivemarkerswhereonecouldignorethebaselinechangesbecausemarkerslikeCK-MBwereinsensitiveanddidnotdetectverymanysuchelevationssuggestedthattherewasprognosticsignificancetotheseevents.GiventhetaskforcehasmovedstronglytowardacTnorientedstructureanddidnothaveto,nordid,dwellontheissueofprognosticsignificance,thequestionthenwasviewedashowtodefineadistinctionbetweenthecardiacinjurythatmighthaveledtotheprocedureandsomesortofadditionalinsultcausedbytheprocedureitself.ThetaskforcethendecidedtomandatetheneedforanormalcTnvalueordocumentationofastableorafallingpatternatbaselineandthentorelyona5foldelevationofcTnwhentherewasaclearcutabnormalityinducedbytheprocedureitselformarkedsymptomsoccurred.Thecriteriausespreviouslyofathreefoldwasincreasedtofivefoldalongwiththeseancillarycriteriagiventheincreaseinassaysensitivitythathasoccurredsince2007butitshouldbeclearthatgiventheheterogeneityofpresentdaycardiactroponinassaysthatthiswillbeamovingtargetdependingupontheassaythatoneutilizesinanygivensituation.AsimilarstatementcanbemadeforCABG.Unfortunately,giventheheterogeneityofassays,thereisnosinglecutoffvaluethatcanbeutilized.However,itisclearthatindividualswhostartwithanelevatedcTnpreoperativelyelaboratemorecTn[3].Thus,anormalbaselinevalueisimportantforcomparativeinformation.ItisalsoclearthatthemorecTnthatiselaborated,themoreadversetheprognosis;thus,makingmanymorecomfortablewiththisdiagnosisthanwiththepost-PCIdiagnosis[13].However,therealsoisanobligatoryamountofinjurythatisindigenoustotheNovelcircumstancesSeveralothercircumstancesarerecognizedintheguidelinesthatareofrelevance.Forexample,anyproceduredoneontheheartislikelytocauseelevationsofcTn.Therefore,transcatheteraorticvalveimplantations,thesocalledTAVIormitralclipproceduresarelikelytocausesuchcardiacinjury.ThetaskforcesuggestedthatthecriteriaforCABGbeappliedinthatcircumstance.Innon-cardiacsurgicalprocedures,thereoftenarecTnelevations.Manyoftheseknowntobeassociatedtosuchelevations.However,thepathologicliteraturewouldsuggest,andthisiswhyoneneedstobecautiousinthisarea,thatthoseeventsthatleadtomortalityoftenareassociatedwithplaqueruptureandmaybemoretype1events[15].Thus,thereisstillambiguityaboutexactlywhattypesofinfarctionsmightexistandthereforethecriteriaarehighlynuancedinthatregard.Similarstatementscanbemadeaboutpatientswhoarecriticallyillwhomayhaveelevationsforavarietyofreasons,someofwhichhavenothingtodowiththesupplydemandimbalanceandsomeofwhichdo.SomeoftheelevationsincTncouldberelatedtothetoxiceffectsofthedisease(sepsisandheatshockproteinsand/orTNF)orofmedicationsthatarebeingusedtherapeutically[16].Whatissuggestedbythetaskforceisthattheclinicianneedstodevelophisorherownsenseofwhentheseelevationsareduetoischemiaandanimbalancebetweenmyocardialoxygensupplyanddemandandthenonecandiagnosethatepisodeasatype2MI.Intheabsenceofsuchadiagnosis,onewouldsuggestthepresenceofcardiacinjuryduetowhateverpathophysiologyisthoughttobepresent.Heartfailureperhapsisoneofthosemorecommonsituationswherethisissuemayarise.ManypatientshaveheartfailuredueClinicaltrialsandsocietalissuesItwasacknowledgedintheguidelinesthattheimplementationofthecriteriasuggestedforthediagnosisofMIcouldcausesubstantialdifficultiesbothforpatientsandforthosewhoaredoingclinicaltrials.ThediagnosisofMIcarrieswithitsubstantialnegativeconsequencesandcliniciansshouldbeawareandsensitivetothatissuewhentheyaremakingthisdiagnosis.Inaddition,clinicaltrialgroupsmayhavedifficultyattimescollectingtheidealinformationtoemploythecriteriaproposed.Theirabilitytocomeascloseaspossiblehowevertomoreclearlymimictherealworldofclinicalcardiologywillbeimportantifthosetrialsaretohaverealapplicabilitytotheeverydaypatient.Nonetheless,itisclearthattheremaybetimeswhenresourcelimitationsand/orcircumstancemaketotaladherenceimpossible.ConclusionThe2023guidelinesexpandonthecriteriapreviouslyestablishedandamplifyonthecriteria.However,itisclearthatasadditionaldataaredeveloped,theseguidelinesareapttochangestillfurther.DisclosuresDr.Jaffehasorpresentlyconsultsformostofthemajordiagnosticcompanies.References[1]TheJointEuropeanSocietyofCardiology/AmericanCollegeofCardiologyCommitteeJAmCollCardiol,36(2000),pp.959–969[2]K.Thygesen,J.S.Alpert,H.D.WhiteJointESC/ACCF/AHA/WHFtaskforcefortheredefinitionofmyocardialinfarction.UniversaldefinitionofmyocardialinfarctionCirculation,116(2007),pp.2634–2653ViewRecordinScopus|FullTextviaCrossRef

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Citingarticles(1445)[3]K.Thygesen,J.S.Alpert,A.S.Jaffe,M.L.Simoons,B.R.Chaitman,H.D.White,etal.ThirdUniversalDefinitionofMyocardialInfarctionEurHeartJ,33(2023),pp.2551–2567ViewRecordinScopus|FullTextviaCrossRef

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Citingarticles(77)[5]A.S.Jaffe,F.S.Apple,D.A.Morrow,B.Lindahl,H.A.KatusBeingrationalabout(im)precision:astatementfromtheBiochemistrySubcommitteeoftheJointEuropeanSocietyofCardiology/AmericanCollegeofCardiologyFoundation/AmericanHeartAssociation/WorldHeartFederationtaskforceforthedefinitionofmyocardialinfarctionClinChem,56(2023),pp.941–943ViewRecordinScopus|FullTextviaCrossRef[6]S.F.Aldous,C.M.Florkowski,I.G.Crozier,J.Elliott,P.George,J.G.Lainchbury,etal.ComparisonofhighsensitivityandcontemporarytroponinassaysfortheearlydetectionofacutemyocardialinfarctionintheemergencydepartmentAnnClinBiochem,48(2023),pp.241–248FullTextviaCrossRef[7]G.Korosoglou,S.Lehrke,D.Mueller,W.Hosch,H.U.Kauczor,P.M.Humpert,etal.Determinantsoftroponinreleaseinpatientswithstablecoronaryarterydisease:insightsfromCTangiographycharacteristicsofatheroscleroticplaqueHeart,97(2023),pp.823–831ViewRecordinScopus|FullTextviaCrossRef

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Citingarticles(75)[8]F.S.Apple,P.O.CollinsonIFCCtaskforceonclinicalapplicationsofcardiacbiomarkers.Analyticalcharacteristicsofhigh-sensitivitycardiactroponinassaysClinChem,58(2023),pp.54–61ViewRecordinScopus|FullTextviaCrossRef[9]ViewRecordinS