6/14/2016 RiskstratificationafternonSTelevationacutecoronarysyndrome

OfficialreprintfromUpToDate
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RiskstratificationafternonSTelevationacutecoronarysyndrome

Authors SectionEditors DeputyEditor

JeffreyABreall,MD,PhD ChristopherPCannon,MD GordonMSaperia,MD,FACC
MichaelSimons,MD JuanCarlosKaski,DSc,MD,DM
JosephSAlpert,MD (Hons),FRCP,FESC,FACC,FAHA
PamelaSDouglas,MD AllanSJaffe,MD
PeterWFWilson,MD BernardJGersh,MB,ChB,DPhil,
FRCP,MACC
PatriciaAPellikka,MD,FACC,FAHA,
FASE

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:May2016.|Thistopiclastupdated:Jan05,2016.
INTRODUCTIONAllpatientswithnonSTelevationacutecoronarysyndromes(NSTEACS),whichincludesunstable
angina(UA)andnonSTelevationmyocardialinfarction(NSTEMI),shouldundergoearlyandlateriskstratification.This
processimpactsdecisionmakingregardingtreatmentandprovidesthepatientwithsomesenseofwhatthefutureholds.

ThegeneralapproachtoriskstratificationforpatientswithUA/NSTEMIwillbereviewedhere.Riskstratificationis
accomplishedwiththeuseofvalidatedriskpredictionmodelsthatincludethemostimportantpredictorsofoutcome.
Theseindividualpredictorsarediscussedseparately.(See"RiskfactorsforadverseoutcomesafternonSTelevation
acutecoronarysyndromes".)

RiskstratificationforpatientswithanacuteSTelevationMI(STEMI)andforthoseatriskforlifethreateningarrhythmias
isdiscussedseparately.(See"RiskstratificationafteracuteSTelevationmyocardialinfarction"and"Incidenceofandrisk
stratificationforsuddencardiacdeathafteracutemyocardialinfarction".)

VERYHIGHRISKPATIENTSIndividualswithanyoneofthefollowingclinicalcharacteristicsaredeemedtobeat
suchhighriskthatformalearlyriskstratificationisnotnecessary.Thesepatientstypicallyneedtoproceedtourgent
coronaryangiography:

Cardiogenicshock
Overtheartfailure(HF)orsevereleftventriculardysfunction
Recurrentorpersistentrestanginadespiteintensivemedicaltherapy
Hemodynamicinstabilityduetomechanicalcomplications(eg,acutemitralregurgitation,ventricularseptaldefect)
Unstableventriculararrhythmias

Thisissueisdiscussedseparately.(See"CoronaryangiographyandrevascularizationforunstableanginaornonST
elevationacutemyocardialinfarction".)

EARLYRISKSTRATIFICATIONTOOLSPatientswithunstableangina(UA)/nonSTelevationmyocardialinfarction
(NSTEMI)wholackfeaturesindicatingtheneedforimmediateintervention(see'Veryhighriskpatients'above)should
undergoearlyriskstratification,assoonaspossibleafterthediagnosisissecured,toidentifyindividualswhoshouldbe
treatedwithanearlyinvasivestrategy.Werecommendriskstratification,usingvalidatedriskpredictiontools,ofall
patientswithnonSTelevationacutecoronarysyndromes(NSTEACS),particularlythosewithSTdepressiononthe
electrocardiogramorelevatedcardiacbiomarkers.WeandothersprefertheGRACEorTIMItools,astheyarederived
fromlargepopulationsandhavebeenwellvalidatedinthissetting[1].

However,mostoftheseindividualsundergoearlyangiographyintheabsenceofacontraindicationinourhospitals.(See
"CoronaryangiographyandrevascularizationforunstableanginaornonSTelevationacutemyocardialinfarction".)

Theresultsofearlyriskstratificationarealsousedtopredict30dayandlongtermoutcomes.Forexample,forlowerrisk
patientswithchestpain,butnoSTsegmentdeviationonthefirstelectrocardiogram,andnormaltroponinlevels,theriskof
deathormyocardialinfarctionmaybeaslowas6.7percentatoneyear[2].

Thefollowingarevalidatedriskpredictionmodelsortoolsthatcanbeusedearlyintothecareofpatientshospitalizedwith
NSTEACS.Thesetoolsdiffersomewhatintheirpopulations,outcomes,andtimeframes.

TIMIriskscoreAnalysisofdatafromtheTIMI11BandESSENCEtrialsfoundsevenvariablestobeindependently
predictiveofoutcomeinpatientswithUAoranNSTEMI.ThesecriteriaweredefinedastheTIMIriskscore.Tocalculate
thescore,avalueof1isassignedwheneachvariablewaspresentand0whenitwasabsent[3]:

Age65years
Presenceofatleastthreeriskfactorsforcoronaryheartdisease(CHD)
Priorcoronarystenosisof50percent
PresenceofSTsegmentdeviationonadmissionECG
Atleasttwoanginalepisodesinprior24hours
Elevatedserumcardiacbiomarkers
Useofaspirininpriorsevendays

AhigherTIMIriskscorecorrelatedsignificantlywithincreasednumbersofevents(allcausemortality,neworrecurrentMI,
orsevererecurrentischemiarequiringrevascularization)at14days(calculator1):

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Scoreof0/14.7percent
Scoreof28.3percent
Scoreof313.2percent
Scoreof419.9percent
Scoreof526.2percent
Scoreof6/740.9percent

TheTIMIriskscorehasbeenvalidatedinmultiplecohorts[4,5].

Asimilarpredictivevaluehasbeennotedforpostdischargeeventsatsixweeks[6]andformajorcardiaceventsat30
daysinpatientswhohaveundergonepercutaneouscoronaryintervention(PCI).(See"Coronaryangiographyand
revascularizationforunstableanginaornonSTelevationacutemyocardialinfarction".)

Notsurprisingly,higherTIMIriskscoreshavebeencorrelatedwithmoresevereangiographicdisease.Inananalysisfrom
PRISMPLUS,increasingTIMIriskscoresfrom0to2(lowrisk)to5to7(highrisk)wereassociatedwithprogressive
increasesinthefrequencyofhighriskangiographicfindingssuchassevere(>70percent)culpritstenosis(from58to81
percent),multivesseldisease(43to80percent),visiblethrombus(30to41percent),andleftmaindisease[7].

TheTIMIriskscorecanalsoidentifypatientsmostlikelytobenefitfromparticulartherapies:

InTACTICSTIMI18,onlypatientsatmoderatetohighrisk(score3)benefitedfromanearlyinvasivestrategy[8].
ThepresenceofbiomarkerelevationandSTsegmentdeviationaretwooftheTIMIriskscorevariables.However,a
lateranalysisfromTACTICSTIMI18showedthatthedegreeoftroponinelevationandmagnitudeofSTsegment
deviationwereindependentpredictorsofanadverseoutcomeandofbenefitfromanearlyinvasivestrategy[9].

InPRISMPLUS,onlypatientswithascore4benefitedfromtheadditionoftirofibantoheparin[4].

InTIMI11BandESSENCE,enoxaparinwasassociatedwithbetter14dayandsixweekpostdischargeoutcomes
comparedtounfractionatedheparinthesebenefitswereprimarilyseeninhighriskpatientswithriskscores4and
5,respectively[3,6].

TIMIriskindexTheTIMIriskindex(TRI)isasimplermodelderivedfromtheInTIMEIItrialoffibrinolytictherapy
forSTelevationMI.ItcanbeusedsimultaneouslywiththeTIMIriskscore.(See"RiskstratificationafteracuteST
elevationmyocardialinfarction",sectionon'TIMIriskindex'.)

TheTRIiscalculatedfromthefollowingequation,usingdataobtainedatpresentation(table1)[10]:

TRI=(Heartratex[age/10]squared)systolicpressure

Whenappliedtoover337,000patientswithnonSTelevationMIintheNationalRegistryofMyocardialInfarction(NRMI)
intheUnitedStates,therewasagradedrelationshiptoinhospitalmortality,rangingfrom1.0to34.4percentfromthe
lowest(0to<10)tothehighestscores(80)[11].PatientswithaTRI<30wereatlowrisk.Patientswithhigherrisk
indicesweremoreoftenKillipclass>1andhadmorefrequentcomorbiditiessuchasheartfailure,renalfailure,andchronic
obstructivepulmonarydisease.

GRACEriskmodelTheTIMIriskscore,whileextensivelyvalidatedasdescribedabove,isderivedfromtwoclinical
trialdatabases.TheGRACEregistry,aglobalregistryofACSpatientsfrom94hospitalsin14countries,developedtwo
modelstoestimatetheriskofinhospitalandsixmonthmortalityamongallpatientswithanACS.Thisendpointis
differentfromthecompositeendpointintheTIMIriskscoreofallcausemortality,neworrecurrentMI,orsevererecurrent
ischemiarequiringrevascularization.

TheinhospitalGRACEmodel(table2)wasbasedupondatafrom11,389patientswitheitheranSTEMIoranNSTEACS
[12].Thismodelwasthenvalidatedbasedupondatafromanadditional3972patientsfromGRACEand12,142patients
fromtheGUSTOIIbtrial.Eightindependentriskfactorswerefoundtoaccountforalmost90percentoftheprognostic
information:

Age
Killipclass(see"RiskfactorsforadverseoutcomesafternonSTelevationacutecoronarysyndromes",sectionon
'Killipclass')
Systolicbloodpressure
PresenceofSTsegmentdeviation
Cardiacarrestduringpresentation
Serumcreatinineconcentration
Presenceofelevatedserumcardiacbiomarkers
Heartrate

Pointscoreswereassignedforeachpredictivefactorandareaddedtogethertoarriveatanestimateoftheriskofin
hospitalmortality.AnomogramwaspublishedwiththeGRACEriskmodeltoallowcalculationoftheriskscore.Software
isavailableathttp://www.outcomesumassmed.org/grace/acs_risk/acs_risk_content.htmltoenablecalculationofthe
GRACEriskscore.

Althoughdesignedtoassesstheriskofinhospitalmortality,thisGRACEriskmodelalsopredictsmortalityorrecurrentMI
atsixmonthsandatoneyear.ItspredictivevalueatoneyearisslightlygreaterthanthatfortheTIMIriskscore(figure1)
[13,14].

Thesixmonthmodelwasbasedupondatafrom15,007patientsandvalidatedinacohortof7638patients,allinthe

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GRACEregistry[15].Thevariablesincorporatedintothismodelincludeage,priorhistoryofheartfailure,priorhistoryof
myocardialinfarction,restingheartrate,systolicbloodpressure,STsegmentdepression,initialserumcreatinine
concentration,elevatedserumcardiacbiomarkers,andperformanceofinhospitalPCI.Thesixmonthmortalityriskbased
uponthismodelcanbecalculatedusingthewebsitewww.outcomesumassmed.org/grace/.

Toimprovetheusabilityofthescore,theGRACEinvestigatorsdevelopedtheGRACEriskscore2.0andelectronictools
toassistwiththecalculation(http://www.gracescore.org/WebSite/default.aspx?ReturnUrl=%2f)[16].Thescoreprovides
prognosisatsixmonths,oneyear,andthreeyearsandwasdevelopedinover30,000patientswithACSandvalidated
externallyinaregistryofnearly3000patients.Significantnonlinearassociationswerefoundforage,systolicblood
pressure,pulse,andcreatinine.Overall,cliniciansshouldfinditeasiertousetheGraceScore2.0andrecommenditsuse
comparedtoprioriterations.

CRUSADElongtermmortalityriskscoreUsingtheCRUSADEregistry,over43,000patients65yearswereused
todevelopalongtermmortalityriskscore[17].Themodelincludes13variablesandshowsgooddiscriminationinthe
derivationandvalidationsamples.

CHADS2scoreWhiletheGRACEpredictionmodeliswellvalidatedanditsuseisrecommendedbymultipleguideline
organizations,itscomplexitymakesitsomewhatdifficulttouseinsomeclinicalsettings.ThevalueoftheCHADS2score
(table3),whichisawellvalidatedtoolforpredictingtheriskofstrokeinpatientswithatrialfibrillation,wasevaluatedina
studyofmorethan2300patientswithACS(73percentwithUA/NSTEMI19percentwithatrialfibrillation[AF])caredfor
between1995and2001[18].Allcausemortalityat10yearswasstronglyassociatedwiththeCHADS2scoreinpatients
withandwithoutAF.Asexpected,themorecomplexGRACEscoreprovidedabetterpredictionforshortandlongterm
mortality.(See"Atrialfibrillation:Riskofembolization",sectionon'Epidemiology'.)

USINGTHERESULTSOFEARLYRISKSTRATIFICATIONPatientsathighriskasdeterminebytheuseoftherisk
scoresdiscussedaboveareusuallyreferredforangiography,ifithasnotalreadybeenperformed.Forintermediateand
lowriskpatientswhodonotundergoearlyangiography,noninvasivetestingpriortodischargemayprovideinformationthat
leadstoadecisiontoperformangiography.

LATERISKSTRATIFICATIONLateriskstratification,performedthreetosevendaysaftertheevent,helpsin
determininglongtermmanagementandprognosis.Theimportanceofriskstratificationpriortodischargeisillustratedby
theobservationthat,amongallmajorcardiaceventsthatoccurinthefirstsixweeks,approximatelyonefourthoccurafter
discharge[6].

Themaincomponentsaremeasurementoftheleftventricularejectionfractionand,primarilyinmedicallymanaged
patients,stresstestingtodetectpossibleresidualischemia.ThepotentialuseofcontinuousSTsegmentmonitoringis
alsodiscussed.

AbsenceofsignificantcoronarydiseaseIndifferentclinicaltrials,aswellasintheCRUSADEregistry,9to14
percentofpatientswithanonSTelevationacutecoronarysyndrome(NSTEACS)whoundergoearlyangiographyhaveno
significantcoronarystenosis[8,1922].Approximatelyonehalfofthesepatientshavenocoronarystenosisandonehalf
haveanoncritical(lessthan50to60percent)coronarystenosis[1921].(See"Classificationofunstableanginaandnon
STelevationmyocardialinfarction",sectionon'Absenceofsignificantcoronarydisease'.)

Suchpatientshaveamuchbettershorttermprognosisthanthosewithacriticalculpritlesion.Inareportfromthe
PURSUITtrial,forexample,thepatientswithnoormildcoronarydiseasehadamuchlowerrateofdeathornonfatal
myocardialinfarction(MI)at30daysthanthosewithsignificantdisease(2and6versus17percent)[20].Similarfindings
werenotedinareportfromtheCRUSADEregistry[22].AmongpatientswithanonSTelevationmyocardialinfarction
(NSTEMI),theinhospitaldeathratewassignificantlylowerinthepatientswithoutsignificantcoronarydisease(0.65
versus2.36percentforthosewithcoronarydisease).

Outcomesatoneyearinpatientswithnormalormilddiseasewereprovidedinananalysisof7656patientspooledfrom
threeTIMItrials,whichlookedatacompositeprimaryendpointofdeath,MI,unstableanginarequiringhospitalization,
revascularization,orstroke[19].Amongthe710(9percent)patientswithnonobstructivecoronaryarterydisease,a
primaryendpointoccurredin12percent,includinganeventrateof2percentfordeathandMI.

LeftventricularfunctionAssessmentofrestingleftventricularfunctionisanimportantpartofriskstratificationin
patientswithanNSTEACSandisrecommendedinallpatients[1,23].Patientswithleftventricularsystolicdysfunction
haveincreasedmortalityatlongtermfollowupandmorethana50percentprobabilityofhavingmultivesselcoronary
disease[24].

Intheabsenceofaspecificindication(eg,heartfailureorsuspectedmechanicalcomplication),theleftventricularejection
fraction(LVEF)isusuallymeasuredbeforedischarge.However,earlymeasurementsmaybemisleading,since
improvementinLVEF,beginningwithinthreedaysandlargelycompleteby14days,iscommoninpatientswhoeither
reperfusespontaneouslyorundergopercutaneouscoronaryintervention(PCI),apresumedreflection,atleastinpart,of
recoveryfrommyocardialstunning[25].(See"Clinicalsyndromesofstunnedorhibernatingmyocardium",sectionon
'Acutemyocardialinfarction'.)

Multipleimagingtechniquesforassessingleftventricularfunctionareavailableandeachhasequivalentprognosticvalue
inthepostMIpatient.Ingeneral,echocardiographyshouldbeusedforroutineassessmentofLVEFafteranNSTEACS.
AmongpatientswhohavehadanonSTelevationmyocardialinfarction(NSTEMI),ithastheaddedadvantageof
detectingotherfactorsthatcanbeassociatedwithaworseprognosissuchasdiastolicdysfunction,concurrentright
ventriculardysfunction,increasedleftatrialvolume,mitralregurgitation,andahighwallmotionscoreindex,whichreflects
amoresevereimpairmentinoverallleftventricularsystolicfunction[2631].(See"Roleofechocardiographyinacute
myocardialinfarction",sectionon'Leftventricularsystolicfunction'and"Roleofechocardiographyinacutemyocardial

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infarction",sectionon'Leftventriculardiastolicfunction'and"Managementandprognosisofchronicsecondarymitral
regurgitation".)

StresstestingStresstesting,usuallywithexercise,canbeusedtodetectresidualischemiaandtoassessthe
exercisecapacityneededforthecardiacrehabilitationexerciseprescription.(See"ExerciseECGtesting:Performingthe
testandinterpretingtheECGresults".)

PredischargestresstestingisgenerallynotperformedinpatientswhohaveundergonePCIorcoronaryarterybypassgraft
surgery(CABG)andhavebeenfullyrevascularized(eg,singlevesseldiseaseandsuccessfulPCI).Suchpatientsoften
undergoexercisetestingafewweeksormoreafterdischargeaspartofacardiacrehabilitationprogramorforactivity
counseling.

Incontrast,patientswhohaveundergonepartialrevascularizationornorevascularizationarecandidatesforpredischarge
testing,butshouldbeproperlyscreened.Exercisetestingappearstobesafeif:

Thepatienthasundergoneinhospitalcardiacrehabilitation
Therehavenotbeensymptomsofheartfailureorrecurrentanginafor12to24hours
Theelectrocardiogramhasbeenstablefor12to24hours

Astresstestshouldbeobtainedbeforeorsoonafterdischarge.Whilethehighriskpatientwilloftenundergoaninvasive
study,lowerriskpatientsmayundergostresstestingafterbeingsymptomfreeandstablefor12to24hours.

StressprotocolTheappropriatestressprotocolinpatientswhohavenotbeencompletelyrevascularizedvaries
withphysicianpreferences,patientcharacteristics,andlocallaboratoryexpertise.ExerciseECGtesting,whichismost
oftenperformed,reliesonbothsymptomsandobjectivechangesontheECG.

Inselectedlowriskpatients(ie,withoutheartfailure,arrhythmias,orangina),anearlyfullBruce(symptomlimited)
protocolhasbeensafelycompletedasearlyas24hoursorbeforedischarge[3234].Itprovidesagreaterexercisestress
andismorelikelythanasubmaximaltesttodetectresidualischemia[33,34].

AccuratestressECGinterpretationcannotbeachievedinpatientswithbaselineECGabnormalitiessuchasleftbundle
branchblock,leftventricularhypertrophywithSTTwavechanges,ventricularpreexcitation,orventricularpacing.Insuch
patients,eitherexerciseradionuclidemyocardialperfusionimaging(rMPI)orexerciseechocardiographycanbeperformed.
Pharmacologicstressisrequiredinpatientswhocannotexercise,althoughsuchmodalitiesprovidelessinformationthan
exercisetestingbecausetheyarenotabletoassessfunctionalcapacity(algorithm1)[23,35].(See"Selectingtheoptimal
cardiacstresstest"and"Radionuclidemyocardialperfusionimaginginpredischargeriskstratificationofmedicallytreated
patientswithnonSTelevationacutecoronarysyndrome".)

ExerciseECGtestingisassociatedwithahigherfalsepositiverateinwomenthanmen,dueatleastinparttoalower
pretestprobability[36,37].However,amongpatientswithanNSTEACS,exerciseECGriskscoresappeartobeashelpful
forpredictingprognosisinwomenasinmen[38]andrecommendationsforstresstestinginwomeninthissettingare
generallysimilartothoseinmen.(See"Stresstestingforthediagnosisofobstructivecoronaryheartdisease".)

ThemanagementofsilentischemiadiscoveredonstresstestingafteranNSTEACSisdiscussedseparately.(See"Silent
myocardialischemia:Prognosisandtherapy",sectionon'Treatmentwithrevascularization'.)

ContinuouselectrocardiographySilentischemiadetectedoncontinuouselectrocardiography(continuousST
segmentmonitoring)isassociatedwithanincreasedshorttermriskofcardiovascularevents.(See"Riskfactorsfor
adverseoutcomesafternonSTelevationacutecoronarysyndromes",sectionon'Silentischemia'.)

Similarfindingshavebeennotedatlongertermfollowup[39,40].IntheMERLINTIMI36trial,whichcomparedranolazine
toplaceboinpatientswithNSTEMI,6355patientsunderwentanaverageofsixdaysofuninterrupted2lead(Holter)
monitoring[40].(See"Newtherapiesforanginapectoris",sectionon'Acutecoronarysyndrome'.)

Oneormoretransientischemicepisodeswerenotedin20percentofpatients.Afteramedianfollowupofalmostone
year,thepatientswithtransientischemicepisodeshadsignificantincreasesintheriskofcardiovasculardeath(7.7versus
2.7percent),MI(9.4versus5.0percent),andrecurrentischemia(17.5versus12.3percent).Theassociationbetween
transientischemicepisodesandsymptomaticischemiawasnotassessed.

SUMMARYANDRECOMMENDATIONS

AllpatientswithnonSTelevationacutecoronarysyndromeshouldundergoearlyriskstratificationassoonas
possibleafterthediagnosisissecured.Theresultsofriskstratificationareusedtohelpchoosebetweenimmediate
coronaryangiography,anearlyinvasivestrategy,oraconservativeapproach.(See'Earlyriskstratificationtools'
above.)

Forearlyriskstratification,weprefereithertheGRACEriskmodelortheTIMIriskscore.(See'TIMIriskscore'
aboveand'GRACEriskmodel'above.)

Priortodischarge,patientswhohavebeenmedicallytreatedandthosewhohavereceivedincomplete
revascularizationshouldundergononinvasiveassessmentforresidualinducibleischemia.(See'Stresstesting'
above.)

Intheabsenceofaspecificindication(eg,heartfailureorsuspectedmechanicalcomplication),theleftventricular
ejectionfractionisusuallymeasuredbeforedischargeandechocardiographyisoftenthepreferredmethod.If
revascularizationhasbeenperformed,someexpertsarecomfortablewaitinguntilafterdischargetoobtainan
assessmentofleftventricularfunction.(See'Leftventricularfunction'above.)

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27.MllerJE,SndergaardE,PoulsenSH,EgstrupK.Pseudonormalandrestrictivefillingpatternspredictleft
ventriculardilationandcardiacdeathafterafirstmyocardialinfarction:aserialcolorMmodeDoppler
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6/14/2016 RiskstratificationafternonSTelevationacutecoronarysyndrome
echocardiographicstudy.JAmCollCardiol200036:1841.
28.ZornoffLA,SkaliH,PfefferMA,etal.Rightventriculardysfunctionandriskofheartfailureandmortalityafter
myocardialinfarction.JAmCollCardiol200239:1450.
29.MollerJE,HillisGS,OhJK,etal.Leftatrialvolume:apowerfulpredictorofsurvivalafteracutemyocardial
infarction.Circulation2003107:2207.
30.GrigioniF,EnriquezSaranoM,ZehrKJ,etal.Ischemicmitralregurgitation:longtermoutcomeandprognostic
implicationswithquantitativeDopplerassessment.Circulation2001103:1759.
31.MllerJE,HillisGS,OhJK,etal.Wallmotionscoreindexandejectionfractionforriskstratificationafteracute
myocardialinfarction.AmHeartJ2006151:419.
32.SenaratneMP,SmithG,GulamhuseinSS.FeasibilityandsafetyofearlyexercisetestingusingtheBruceprotocol
afteracutemyocardialinfarction.JAmCollCardiol200035:1212.
33.JuneauM,CollesP,ThrouxP,etal.Symptomlimitedversuslowlevelexercisetestingbeforehospitaldischarge
aftermyocardialinfarction.JAmCollCardiol199220:927.
34.JainA,MyersGH,SapinPM,O'RourkeRA.Comparisonofsymptomlimitedandlowlevelexercisetolerancetests
earlyaftermyocardialinfarction.JAmCollCardiol199322:1816.
35.GibbonsRJ,BaladyGJ,BrickerJT,etal.ACC/AHA2002guidelineupdateforexercisetesting:summaryarticle:a
reportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines
(CommitteetoUpdatethe1997ExerciseTestingGuidelines).Circulation2002106:1883.
36.KwokY,KimC,GradyD,etal.Metaanalysisofexercisetestingtodetectcoronaryarterydiseaseinwomen.AmJ
Cardiol199983:660.
37.AlexanderKP,ShawLJ,ShawLK,etal.Valueofexercisetreadmilltestinginwomen.JAmCollCardiol1998
32:1657.
38.SfstrmK,LindahlB,SwahnE.RiskstratificationinunstablecoronaryarterydiseaseexercisetestandtroponinT
fromagenderperspective.FRISCStudyGroup.FragminduringInStabilityinCoronaryarterydisease.JAmColl
Cardiol200035:1791.
39.GoodmanSG,BarrA,SobtchoukA,etal.Lowmolecularweightheparindecreasesreboundischemiainunstable
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STElevationAcuteCoronarySyndromeThrombolysisInMyocardialInfarction36)trial.JAmCollCardiol2009
53:1411.

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GRAPHICS

TIMIriskindextopredictshorttermmortalityafteracutemyocardial
infarction

Riskofdeath Riskofdeath
Riskindex Riskgroup
24h Inhospital 30days

12.5 1 0.2 0.6 0.8

>12.5to17.5 2 0.4 1.5 1.9

>17.5to22.5 3 1.0 3.1 3.3

>22.5to30 4 2.4 6.5 7.3

>30 5 6.9 15.8 17.4

TIMIriskindexisderivedfromthefollowingformula:Heartrateinbeats/minx([age/10]squared)/
systolicbloodpressure.

ReproducedwithpermissionfromMorrowDA,AntmanEM,GiuglianoRP,etal.Lancet2001358:1571.
Copyright2001TheLancet,Ltd.

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GRACEriskscore

Riskcategory Inhospitaldeath
GRACEriskscore
(tertile) (percent)
Low 108 <1

Intermediate 109140 13

High >140 >3

Postdischargetosix
Riskcategory
GRACEriskscore monthdeath
(tertile)
(percent)
Low 88 <3

Intermediate 89118 38

High >118 >8

From:HammCW,BassandJP,AgewallS,etal.ESCGuidelinesforthemanagementofacutecoronary
syndromesinpatientspresentingwithoutpersistentSTsegmentelevation:TheTaskForceforthemanagement
ofacutecoronarysyndromes(ACS)inpatientspresentingwithoutpersistentSTsegmentelevationofthe
EuropeanSocietyofCardiology(ESC).EurHeartJ201132:2999.BypermissionoftheEuropeanSocietyof
Cardiology.Copyright2013OxfordUniversityPress.

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TIMIriskscorefornonSTelevationACS

Ratesofallcausemortality,myocardialinfarction,andsevere
recurrentischemiapromptingurgentrevascularizationat14daysafter
randomizationaccordingtothenumberofriskfactorsamongpatients
withanonSTelevationacutecoronarysyndrome(ACS)inTIMI11B
andESSENCE.Theriskfactorswereage65yearspresenceofat
leastthreeriskfactorsforcoronarydiseasepriorcoronarystenosisof
50percentpresenceofSTsegmentdeviationonadmissionECGat
leasttwoanginalepisodesinprior24hoursuseofaspirininprior
sevendaysandelevatedserumcardiacbiomarkers.Eventrates
increasedsignificantlyastheTIMIriskscorerose.Patientsare
consideredtobeatlowriskwithascoreof0to2intermediaterisk
withascoreof3to4andhighriskwithascoreof5to7.

Adaptedfrom:AntmanEM,CohenM,BerninkPJ,etal.JAMA2000284:835.

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CHADS2score,thromboembolicrisk,andeffectofwarfarin
anticoagulation

Clinicalparameter Points
Congestiveheartfailure(anyhistory) 1

Hypertension(priorhistory) 1

Age75years 1

Diabetesmellitus 1

Secondarypreventioninpatientswithapriorischemicstrokeoratransient 2
ischemicattackmostexpertsalsoincludepatientswithasystemicembolic
event

Eventsper100personyears*
CHADS2score NNT
Warfarin Nowarfarin

0 0.25 0.49 417

1 0.72 1.52 125

2 1.27 2.50 81

3 2.20 5.27 33

4 2.35 6.02 27

5or6 4.60 6.88 44

NNT:numberneededtotreattopreventonestrokeperyearwithwarfarin.
*TheCHADS2scoreestimatestheriskofstroke,whichisdefinedasfocalneurologicsignsorsymptomsthat
persistformorethan24hoursandthatcannotbeexplainedbyhemorrhage,trauma,orotherfactors,or
peripheralembolization,whichismuchlesscommon.Transientischemicattacksarenotincluded.Alldifferences
betweenwarfarinandnowarfaringroupsarestatisticallysignificant,exceptforatrendwithaCHADS2scoreof
0.Patientsareconsideredtobeatlowriskwithascoreof0,atintermediateriskwithascoreof1or2,andat
highriskwithascore3.Oneexceptionisthatmostexpertswouldconsiderpatientswithapriorischemic
stroke,transientischemicattack,orsystemicemboliceventtobeathighrisk,eveniftheyhadnootherrisk
factorsand,therefore,ascoreof2.However,thegreatmajorityofthesepatientshavesomeotherriskfactor
andascoreofatleast3.

Datafrom:GoAS,HylekEM,ChangY,etal.Anticoagulationtherapyforstrokepreventioninatrialfibrillation:
howwelldorandomizedtrialstranslateintoclinicalpractice?JAMA2003290:2685andCHADS2scorefrom
GageBF,WatermanAD,ShannonW,etal.Validationofclinicalclassificationschemesforpredictingstroke:
resultsfromtheNationalRegistryofAtrialFibrillation.JAMA2001285:2864.

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Choiceofexercisetestingmodalityindifferent
clinicalsettings

"MarkedbaselineECGabnormalities"includepreexcitation(Wolff
ParkinsonWhite)syndrome,morethan1mmofSTdepressionat
rest,andpatientstakingdigoxinorwithECGcriteriaforleft
ventricularhypertrophy,eveniftheyhavelessthan1mmofbaseline
STdepression.Evaluationofpatientswithleftbundlebranchblockor
pacedventricularrhythmisnotincludedinthisalgorithm.

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ContributorDisclosures
JeffreyABreall,MD,PhDConsultant/AdvisoryBoards:Siemens[InterventionalCardiology(cathlabequipment)].
Employment:Fujifilm[CPACssystems(SynapseCVimageandreportarchiving)]Norelevantconflictontopic.
MichaelSimons,MDNothingtodisclose.JosephSAlpert,MDNothingtodisclose.PamelaSDouglas,MD
Grant/Research/ClinicalTrialSupport:NationalInstitutesofHealth(NIH)NHLBI,NCI,NIAIDUniversityofSouth
Florida[Cancer]ColumbiaUniversity[Diagnostictesting]MassachusettsGeneralHospital[Diagnostictesting(FFRCT)]
BristolMeyersSquibb[HepatitisC]EdwardsLifesciences[Valvularheartdisease(Sapienvalves)]GEHealthCare
[Diagnostictesting(Optison)]Gilead[HepatitisC(Sofosbuvir)]HeartFlow[CADdiagnosis(FFRCT)]Ikaria/Bellerophon
[Heartfailure(IK5001)]ResMed[HeartFailure(ASVventilation)]Roche[Heartfailure]Stealthpeptides[Heartfailure
(Bendavia)].Consultant/AdvisoryBoards:PatientAdvocateFoundationGeneralElectricHealthcareDSMB[Heartfailure
(AdreScan)]Alere,IncGenomeMagazineOmiciaTGENHealthVenturesThirdPointLLCUSDiagnosticStandards
CardioDxInterleukinGeneticsPappasVenturesQCROC/PMPC/PreTheraTheHeart.orgMedscape/WebMD
Medscape,LLC,GenomicMedicineInstituteUSDefenseAdvancedResearchProjectsAgencyNationalInstitutesof
HealthNHGRI,NIAID,NHLBI,NIGMSGatesFoundationUnitedStatesAirForceHenryJacksonFoundation
NovartisMerck.EquityOwnership/StockOptions:CardioDXOmicia.PeterWFWilson,MDNothingtodisclose.
ChristopherPCannon,MDGrant/ResearchSupport:Amgen(Lipids[evolocumab],heartfailure[ivabradine])Arisaph
(Lipids)AstraZeneca(ACS,lipids,andGI[Ticagrelor,Rosuvastatin,PPI])BoehringerIngelheim(AF[Dabigatran])
Essentialis(Lipids)GlaxoSmithKline(LipidsandDM)Janssen(AFandDM[RivaroxabanandCangliflozen)Merck
(Lipids[Ezetimibe])Regeneron(Lipids)Sanofi(LipidsandACS[clopidogrel])Takeda(DM[Pioglitazone]).
Consultant/AdvisoryBoards:Amgen(Lipids[evolocumab],heartfailure[ivabradine])BristolMyersSquibb(AF
[Apixaban])Lipimedix(Lipids)Pfizer(AF,DM,andLipids[Apixaban,Etrugliflozin,Atorvastatin])Kowa(lipids).Juan
CarlosKaski,DSc,MD,DM(Hons),FRCP,FESC,FACC,FAHASpeakersBureau:Menarini[Anginapectoris
(Ranolazine)]ServierUKSanofi[Anginapectoris(Ivabradine)].AllanSJaffe,MDConsultant/AdvisoryBoards:
BeckmanAlereAbbottETHealthcareRocheSiemensRadiometertheheart.orgDiadexusLpathNovartis
[Biomarkers(Diagnostictests)].BernardJGersh,MB,ChB,DPhil,FRCP,MACCConsultant/AdvisoryBoards:Mount
SinaiSt.Luke's[Coronaryintervention(Ticagrelor)]BostonScientific[REPRISEstudy]TevaPharmaceutical
[Congestiveheartfailure]JanssenScientificAffairs[ORBITAFstudy]St.JudeMedical[FAMEIItrial]Janssen
Research&Development[Acutecoronarysyndrome(Rivaroxaban)]BaxterHealthcareCorporation[Stemcells]
CardiovascularResearchFoundation[AcuteSTelevationandheartfailure]Medtronic[REVEALstudy]Xenon
Pharmaceuticals[Humandisease]CiplaLimited[Generalconsulting]ThrombosisResearchInstitute[GARFIELDstudy]
Armetheon[Anticoagulation,atrialfibrillation].PatriciaAPellikka,MD,FACC,FAHA,FASENothingtodisclose.
GordonMSaperia,MD,FACCNothingtodisclose.

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