Definition of Myocardial Infarction the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF ...

58 Pages·2012·5.05 MB·English

Third Universal Definition of Myocardial Infarction
Kristian Thygesen, Joseph S. Alpert, Allan S. Jaffe, Maarten L. Simoons, Bernard R. Chaitman
and Harvey D. White
the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal
Definition of Myocardial Infarction
Circulation. 2012;126:2020-2035; originally published online August 24, 2012;
doi: 10.1161/CIR.0b013e31826e1058
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ESC/ACCF/AHA/WHF Expert Consensus Document
Third Universal Definition of Myocardial Infarction
Kristian Thygesen, Joseph S. Alpert, Allan S. Jaffe, Maarten L. Simoons, Bernard R. Chaitman, and
Harvey D. White: the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the
Universal Definition of Myocardial Infarction
AUTHORS/TASK FORCE MEMBERS CHAIRPERSONS
KristianThygesen(Denmark),*JosephS.Alpert(USA),*HarveyD.White(NewZealand),*BiomarkerSubcommittee:
AllanS.Jaffe(USA),HugoA.Katus(Germany),FredS.Apple(USA),BertilLindahl(Sweden),DavidA.Morrow(USA),
ECGSubcommittee:BernardR.Chaitman(USA),PeterM.Clemmensen(Denmark),PerJohanson(Sweden),
HanochHod(Israel),ImagingSubcommittee:RichardUnderwood(UK),JeroenJ.Bax(TheNetherlands),
RobertO.Bonow(USA),FaustoPinto(Portugal),RaymondJ.Gibbons(USA),ClassificationSubcommittee:
KeithA.Fox(UK),DanAtar(Norway),L.KristinNewby(USA),MarcelloGalvani(Italy),
ChristianW.Hamm(Germany),InterventionSubcommittee:BarryF.Uretsky(USA),Ph.GabrielSteg(France),
WilliamWijns(Belgium),Jean-PierreBassand(France),PhillippeMenasché(France),JanRavkilde(Denmark),
Trials&RegistriesSubcommittee:E.MagnusOhman(USA),ElliottM.Antman(USA),LarsC.Wallentin(Sweden),
PaulW.Armstrong(Canada),MaartenL.Simoons(TheNetherlands),HeartFailureSubcommittee:
JamesL.Januzzi(USA),MarkkuS.Nieminen(Finland),MihaiGheorghiade(USA),GerasimosFilippatos(Greece),
EpidemiologySubcommittee:RussellV.Luepker(USA),StephenP.Fortmann(USA),WayneD.Rosamond(USA),
DanLevy(USA),DavidWood(UK),GlobalPerspectiveSubcommittee:SidneyC.Smith(USA),DayiHu(China),
José-LuisLopez-Sendon(Spain),RoseMarieRobertson(USA),DouglasWeaver(USA),MichalTendera(Poland),
AlfredA.Bove(USA),AlexanderN.Parkhomenko(Ukraine),ElenaJ.Vasilieva(Russia),ShantiMendis(Switzerland)
ESCCOMMITTEEFORPRACTICEGUIDELINES(CPG)
JeroenJ.Bax(CPGChairperson)(Netherlands),HelmutBaumgartner(Germany),ClaudioCeconi(Italy),
VeronicaDean(France),ChristiDeaton(UK),RobertFagard(Belgium),ChristianFunck-Brentano(France),
DavidHasdai(Israel),ArnoHoes(Netherlands),PaulusKirchhof(Germany/UK),JuhaniKnuuti(Finland),
PhilippeKolh(Belgium),TheresaMcDonagh(UK),CyrilMoulin(France),BogdanA.Popescu(Romania),
ŽeljkoReiner(Croatia),UdoSechtem(Germany),Per Anton Sirnes (Norway), Michal Tendera (Poland),
Adam Torbicki (Poland), Alec Vahanian (France), Stephan Windecker (Switzerland)
*Correspondingauthors/co-chairpersons:ProfessorKristianThygesen,DepartmentofCardiology,AarhusUniversityHospital,Tage-HansensGade2,
DK-8000AarhusC,Denmark.Tel:(cid:1)457846-7614;fax:(cid:1)457846-7619:E-mail:[email protected],DepartmentofMedicine,
Univ.ofArizonaCollegeofMedicine,1501N.CampbellAve.,P.O.Box245037,TucsonAZ85724,USA,Tel:(cid:1)15206262763,Fax:(cid:1)1520626
0967,E-mail:[email protected],GreenLaneCardiovascularService,AucklandCityHospital,PrivateBag92024,
1030Auckland,NewZealand.Tel:(cid:1)6496309992,Fax:(cid:1)6496309915,E-mail:[email protected].
TheEuropeanSocietyofCardiology,AmericanCollegeofCardiologyFoundation,AmericanHeartAssociation,andtheWorldHeartFederationmake
everyefforttoavoidanyactualorpotentialconflictsofinterestthatmayariseasaresultofanoutsiderelationshiporapersonal,professional,orbusiness
interestofamemberofthewritingpanel.Specifically,allmembersofthewritinggrouparerequiredtocompleteandsubmitaDisclosureQuestionnaire
showingallsuchrelationshipsthatmightbeperceivedasrealorpotentialconflictsofinterest.
ThisdocumentwasapprovedbytheEuropeanSocietyofCardiology,AmericanCollegeofCardiologyFoundation,AmericanHeartAssociation,and
WorldHeartFederationinJuly2012.
TheAmericanHeartAssociationrequeststhatthisdocumentbecitedasfollows:ThygesenK,AlpertJS,JaffeAS,SimoonsML,ChaitmanBR,White
HD;theWritingGrouponbehalfoftheJointESC/ACCF/AHA/WHFTaskForcefortheUniversalDefinitionofMyocardialInfarction.Thirduniversal
definitionofmyocardialinfarction.Circulation.2012;126:2020–2035.
ThisarticlehasbeencopublishedintheEuropeanHeartJournal,JournaloftheAmericanCollegeofCardiology,andGlobalHeart.
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Thygesen et al ESC/ACCF/AHA/WHF Third Universal Definition of MI 2021
DOCUMENT REVIEWERS
JoaoMorais(CPGReviewCo-ordinator)(Portugal),CarlosAguiar(Portugal),
WaelAlmahmeed(UnitedArabEmirates),DavidO.Arnar(Iceland),FabioBarili(Italy),KennethD.Bloch(USA),
AnnF.Bolger(USA),HansErikBøtker(Denmark),BiykemBozkurt(USA),RaffaeleBugiardini(Italy),
ChristopherCannon(USA),JamesdeLemos(USA),FranzR.Eberli(Switzerland),EdgardoEscobar(Chile),
MarkHlatky(USA),StefanJames(Sweden),KarlB.Kern(USA),DavidJ.Moliterno(USA),
ChristianMueller(Switzerland),AleksandarN.Neskovic(Serbia),BurkertMathiasPieske(Austria),
StevenP.Schulman(USA),RobertF.Storey(UK),KathrynA.Taubert(Switzerland),PascalVranckx(Belgium),
DanielR.Wagner(Luxembourg)
Table of Contents
Abbreviations and Acronyms ....................2021
AbbreviationsandAcronyms
Definition of Myocardial Infarction ...............2022
Criteria for Acute Myocardial Infarction............2022 ACCF AmericanCollegeofCardiologyFoundation
Criteria for Prior Myocardial Infarction ............2022
ACS acutecoronarysyndrome
Introduction..................................2022
AHA AmericanHeartAssociation
Pathological Characteristics of Myocardial Ischaemia
and Infarction ................................2023 CAD coronaryarterydisease
BiomarkerDetectionofMyocardialInjuryWithNecrosis...2023 CABG coronaryarterybypassgrafting
ClinicalFeaturesofMyocardialIschaemiaandInfarction...2024
CKMB creatinekinaseMBisoform
Clinical Classification of Myocardial Infarction ......2024
cTn cardiactroponin
Spontaneous Myocardial Infarction (MI Type 1)....2024
MyocardialInfarctionSecondarytoanIschaemic CT computedtomography
Imbalance(MIType2)........................2024 CV coefficientofvariation
CardiacDeathDuetoMyocardialInfarction(MIType3)..2025
ECG electrocardiogram
MyocardialInfarctionAssociatedWithRevascularization
ESC EuropeanSocietyofCardiology
Procedures(MITypes4and5)...................2026
ElectrocardiographicDetectionofMyocardialInfarction..2026 FDG fluorodeoxyglucose
Prior Myocardial Infarction......................2027 h hour(s)
Silent Myocardial Infarction.....................2027 HF heartfailure
Conditions that Confound the ECG Diagnosis of
LBBB leftbundlebranchblock
Myocardial Infarction ..........................2027
LV leftventricle
Imaging Techniques ...........................2027
Echocardiography ...........................2028 LVH leftventricularhypertrophy
Radionuclide Imaging........................2028 MI myocardialinfarction
Magnetic Resonance Imaging ..................2028
mlBG meta-iodo-benzylguanidine
Computed Tomography.......................2028
Applying Imaging in Acute Myocardial Infarction ..2028 min minute(s)
Applying Imaging in Late Presentation of MONICA MultinationalMONItoringoftrendsanddeterminantsin
Myocardial Infarction .......................2029 CArdiovasculardisease
Diagnostic Criteria for Myocardial Infarction With MPS myocardialperfusionscintigraphy
PCI (MI Type 4)..............................2029 MRI magneticresonanceimaging
Diagnostic Criteria for Myocardial Infarction With
mV millivolt(s)
CABG (MI Type 5) ...........................2029
ng/L nanogram(s)perlitre
Assessment of MI in Patients Undergoing Other
Cardiac Procedures............................2030 Non-QMl non-Qwavemyocardialinfarction
Myocardial Infarction Associated With NSTEMI non-ST-elevationmyocardialinfarction
Non-Cardiac Procedures ........................2030 PET positronemissiontomography
Myocardial Infarction in the Intensive Care Unit .....2030
pg/mL pictogram(s)permillilitre
Recurrent Myocardial Infarction..................2030
Reinfarction..................................2030 PCI percutaneouscoronaryintervention
MyocardialInjuryorInfarctionAssociatedWithHeart QwaveMl Qwavemyocardialinfarction
Failure ......................................2031 RBBB rightbundlebranchblock
Application of MI in Clinical Trials and Quality
sec second(s)
Assurance Programmes.........................2031
SPECT singlephotonemissioncomputedtomography
Public Policy Implications of the Adjustment of
STEMI STelevationmyocardialinfarction
the MI Definition.............................2031
GlobalPerspectivesoftheDefinitionofMyocardial ST-T ST-segment-Twave
Infarction ....................................2032 URL upperreferencelimit
Conflicts of Interest............................2032
WHF WorldHeartFederation
Acknowledgments.............................2033
WHO WorldHealthOrganization
References...................................2033
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2022 Circulation October 16, 2012
Introduction amounts of myocardial injury or necrosis. Additionally, the
Myocardial infarction (MI) can be recognised by clinical managementofpatientswithMIhassignificantlyimproved,
features,includingelectrocardiographic(ECG)findings,ele- resultinginlessmyocardialinjuryandnecrosis,inspiteofa
vated values of biochemical markers (biomarkers) of myo- similar clinical presentation. Moreover, it appears necessary
cardial necrosis, and by imaging, or may be defined by to distinguish the various conditions which may cause MI,
pathology. It is a major cause of death and disability world- such as ‘spontaneous’ and ‘procedure-related’ MI. Accord-
wide. MI may be the first manifestation of coronary artery ingly, physicians, other healthcare providers and patients
disease (CAD) or it may occur, repeatedly, in patients with require an up-to-date definition of MI.
established disease. Information on MI rates can provide In 2000, the First Global MI Task Force presented a new
useful information regarding the burden of CAD within and definition of MI, which implied that any necrosis in the
across populations, especially if standardized data are col- setting of myocardial ischaemia should be labelled as MI.1
lected in a manner that distinguishes between incident and These principles were further refined by the Second Global
recurrentevents.Fromtheepidemiologicalpointofview,the MI Task Force, leading to the Universal Definition of
incidenceofMIinapopulationcanbeusedasaproxyforthe Myocardial Infarction Consensus Document in 2007, which
prevalenceofCADinthatpopulation.Theterm‘myocardial emphasized the different conditions which might lead to an
infarction’mayhavemajorpsychologicalandlegalimplica- MI.2 This document, endorsed by the European Society of
tionsfortheindividualandsociety.Itisanindicatorofoneof Cardiology (ESC), the American College of Cardiology
theleadinghealthproblemsintheworldanditisanoutcome Foundation(ACCF),theAmericanHeartAssociation(AHA),
measure in clinical trials, observational studies and quality and the World Heart Federation (WHF), has been well
assurance programmes. These studies and programmes re- accepted by the medical community and adopted by the
quire a precise and consistent definition of MI. WHO.3 However, the development of even more sensitive
In the past, a general consensus existed for the clinical assays for markers of myocardial necrosis mandates further
syndromedesignatedasMI.Instudiesofdiseaseprevalence, revision,particularlywhensuchnecrosisoccursinthesetting
the World Health Organization (WHO) defined MI from ofthecriticallyill,afterpercutaneouscoronaryproceduresor
symptoms, ECG abnormalities and cardiac enzymes. How- after cardiac surgery. The Third Global MI Task Force has
ever,thedevelopmentofevermoresensitiveandmyocardial continued the Joint ESC/ACCF/AHA/WHF efforts by inte-
tissue-specific cardiac biomarkers and more sensitive imag- gratingtheseinsightsandnewdataintothecurrentdocument,
ing techniques now allows for detection of very small whichnowrecognizesthatverysmallamountsofmyocardial
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Thygesen et al ESC/ACCF/AHA/WHF Third Universal Definition of MI 2023
injury or necrosis can be detected by biochemical markers
and/or imaging.
Pathological Characteristics of Myocardial
Ischaemia and Infarction
MI is defined in pathology as myocardial cell death due to
prolonged ischaemia. After the onset of myocardial isch-
aemia, histological cell death is not immediate, but takes a
finiteperiodoftimetodevelop—aslittleas20min,orlessin
some animal models.4 It takes several hours before myocar-
dialnecrosiscanbeidentifiedbymacroscopicormicroscopic
post-mortem examination. Complete necrosis of myocardial
cells at risk requires at least 2–4 h, or longer, depending on
the presence of collateral circulation to the ischaemic zone,
persistent or intermittent coronary arterial occlusion, the
sensitivity of the myocytes to ischaemia, pre-conditioning,
andindividualdemandforoxygenandnutrients.2Theentire
process leading to a healed infarction usually takes at least Figure1.Thisillustrationshowsvariousclinicalentities:for
example,renalfailure,heartfailure,tachy-orbradyarrhythmia,
5–6 weeks. Reperfusion may alter the macroscopic and
cardiacornon-cardiacproceduresthatcanbeassociatedwith
microscopic appearance.
myocardialinjurywithcelldeathmarkedbycardiactroponin
elevation.However,theseentitiescanalsobeassociatedwith
Biomarker Detection of Myocardial Injury myocardialinfarctionincaseofclinicalevidenceofacutemyo-
cardialischaemiawithriseand/orfallofcardiactroponin.
With Necrosis
Myocardial injury is detected when blood levels of sensitive
tissuespecificityaswellashighclinicalsensitivity.Detection
and specific biomarkers such as cTn or the MB fraction of
of a rise and/or fall of the measurements is essential to the
creatine kinase (CKMB) are increased.2 Cardiac troponin I
diagnosis of acute MI.7 An increased cTn concentration is
and T are components of the contractile apparatus of myo-
definedasavalueexceedingthe99thpercentileofanormal
cardialcellsandareexpressedalmostexclusivelyintheheart.
reference population [upper reference limit (URL)]. This
Although elevations of these biomarkers in the blood reflect
discriminatory 99th percentile is designated as the decision
injury leading to necrosis of myocardial cells, they do not
levelforthediagnosisofMIandmustbedeterminedforeach
indicate the underlying mechanism.5 Various possibilities
specific assay with appropriate quality control in each labo-
have been suggested for release of structural proteins from
ratory.8,9 The values for the 99th percentile URL defined
the myocardium, including normal turnover of myocardial
by manufacturers, including those for many of the high-
cells, apoptosis, cellular release of troponin degradation
sensitivity assays in development, can be found in the
products,increasedcellularwallpermeability,formationand
release of membranous blebs, and myocyte necrosis.6 Re- packageinsertsfortheassaysorinrecentpublications.10,11,12
Values should be presented as nanograms per litre (ng/L)
gardless of the pathobiology, myocardial necrosis due to
orpicogramspermillilitre(pg/mL)tomakewholenumbers.
myocardial ischaemia is designated as MI.
CriteriafortheriseofcTnvaluesareassay-dependentbutcan
Also, histological evidence of myocardial injury with
necrosis may be detectable in clinical conditions associated bedefinedfromtheprecisionprofileofeachindividualassay,
with predominantly non-ischaemic myocardial injury. Small including high-sensitivity assays.10,11 Optimal precision, as
amountsofmyocardialinjurywithnecrosismaybedetected, describedbycoefficientofvariation(CV)atthe99thpercen-
which are associated with heart failure (HF), renal failure, tileURLforeachassay,shouldbedefinedas(cid:1)10%.Better
myocarditis, arrhythmias, pulmonary embolism or otherwise precision (CV (cid:1)10%) allows for more sensitive assays and
uneventful percutaneous or surgical coronary procedures. facilitates the detection of changing values.13 The use of
These should not be labelled as MI or a complication of the assays that do not have optimal precision (CV (cid:2)10% at the
procedures, but rather as myocardial injury, as illustrated in 99th percentile URL) makes determination of a significant
Figure 1. It is recognized that the complexity of clinical changemoredifficultbutdoesnotcausefalsepositiveresults.
circumstancesmaysometimesrenderitdifficulttodetermine AssayswithCV(cid:2)20%atthe99thpercentileURLshouldnot
where individual cases may lie within the ovals of Figure 1. be used.13 It is acknowledged that pre-analytic and analytic
In this setting, it is important to distinguish acute causes of problemscaninduceelevatedandreducedvaluesofcTn.10,11
cTnelevation,whichrequireariseand/orfallofcTnvalues, Blood samples for the measurement of cTn should be
fromchronicelevationsthattendnottochangeacutely.Alist drawn on first assessment and repeated 3–6 h later. Later
ofsuchclinicalcircumstancesassociatedwithelevatedvalues samples are required if further ischaemic episodes occur, or
of cTn is presented in Table 1. The multifactorial contribu- when the timing of the initial symptoms is unclear.14 To
tionsresultinginthemyocardialinjuryshouldbedescribedin establishthediagnosisofMI,ariseand/orfallinvalueswith
the patient record. at least one value above the decision level is required,
The preferred biomarker—overall and for each specific coupledwithastrongpre-testlikelihood.Thedemonstration
category of MI—is cTn (I or T), which has high myocardial of a rising and/or falling pattern is needed to distinguish
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2024 Circulation October 16, 2012
Table1. ElevationsofCardiacTroponinValuesBecauseof increased CKMB value is defined as a measurement above
MyocardialInjury the99thpercentileURL,whichisdesignatedasthedecision
levelforthediagnosisofMI.22Sex-specificvaluesshouldbe
employed.22
Clinical Features of Myocardial Ischaemia
and Infarction
Onset of myocardial ischaemia is the initial step in the
development of MI and results from an imbalance between
oxygen supply and demand. Myocardial ischaemia in a
clinical setting can usually be identified from the patient’s
history and from the ECG. Possible ischaemic symptoms
include various combinations of chest, upper extremity,
mandibularorepigastricdiscomfort(withexertionoratrest)
oranischaemicequivalentsuchasdyspnoeaorfatigue.The
discomfort associated with acute MI usually lasts (cid:2)20 min.
Often, the discomfort is diffuse—not localized, nor posi-
tional, nor affected by movement of the region—and it may
beaccompaniedbydiaphoresis,nauseaorsyncope.However,
these symptoms are not specific for myocardial ischaemia.
Accordingly, they may be misdiagnosed and attributed to
gastrointestinal, neurological, pulmonary or musculoskeletal
disorders. MI may occur with atypical symptoms—such as
palpitationsorcardiacarrest—orevenwithoutsymptoms;for
example in women, the elderly, diabetics, or post-operative
andcriticallyillpatients.2Carefulevaluationofthesepatients
is advised, especially when there is a rising and/or falling
pattern of cardiac biomarkers.
Clinical Classification of
Myocardial Infarction
For the sake of immediate treatment strategies, such as
reperfusion therapy, it is usual practice to designate MI in
patientswithchestdiscomfort,orotherischaemicsymptoms
thatdevelopSTelevationintwocontiguousleads(seeECG
section), as an ‘ST elevation MI’ (STEMI). In contrast,
acute-from chronic elevations in cTn concentrations that are patients without ST elevation at presentation are usually
associatedwithstructuralheartdisease.10,11,15–19Forexample, designated as having a ‘non-ST elevation MI’ (NSTEMI).
patientswithrenalfailureorHFcanhavesignificantchronic Many patients with MI develop Q waves (Q wave MI), but
elevationsincTn.Theseelevationscanbemarked,asseenin others do not (non-Q MI). Patients without elevated bio-
manypatientswithMI,butdonotchangeacutely.7However, markervaluescanbediagnosedashavingunstableangina.In
arisingorfallingpatternisnotabsolutelynecessarytomake addition to these categories, MI is classified into various
thediagnosisofMIifapatientwithahighpre-testriskofMI types, based on pathological, clinical and prognostic differ-
presentslateaftersymptomonset;forexample,nearthepeak ences, along with different treatment strategies (Table 2).
ofthecTntime-concentrationcurveorontheslow-declining
portionofthatcurve,whendetectingachangingpatterncan Spontaneous Myocardial Infarction (MI Type 1)
be problematic. Values may remain elevated for 2 weeks or This is an event related to atherosclerotic plaque rupture,
more following the onset of myocyte necrosis.10 ulceration, fissuring, erosion, or dissection with resulting
Sex-dependent values may be recommended for high- intraluminalthrombusinoneormoreofthecoronaryarteries,
sensitivity troponin assays.20,21 An elevated cTn value leadingtodecreasedmyocardialbloodflowordistalplatelet
((cid:2)99thpercentileURL),withorwithoutadynamicpatternof emboliwithensuingmyocytenecrosis.Thepatientmayhave
values or in the absence of clinical evidence of ischaemia, underlying severe CAD but, on occasion (5 to 20%), non-
should prompt a search for other diagnoses associated with obstructiveornoCADmaybefoundatangiography,partic-
myocardial injury, such as myocarditis, aortic dissection, ularly in women.23–25
pulmonary embolism, or HF. Renal failure and other more
non-ischaemic chronic disease states, that can be associated Myocardial Infarction Secondary to an Ischaemic
with elevated cTn levels, are listed in Table 1.10,11 Imbalance (MI Type 2)
If a cTn assay is not available, the best alternative is In instances of myocardial injury with necrosis, where a
CKMB (measured by mass assay). As with troponin, an condition other than CAD contributes to an imbalance be-
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Thygesen et al ESC/ACCF/AHA/WHF Third Universal Definition of MI 2025
Table2. UniversalClassificationofMyocardialInfarction
tween myocardial oxygen supply and/or demand, the term Cardiac Death Due to Myocardial Infarction (MI
‘MI type 2’ is employed (Figure 2). In critically ill patients, Type 3)
or in patients undergoing major (non-cardiac) surgery, ele- Patientswhosuffercardiacdeath,withsymptomssuggestive
vatedvaluesofcardiacbiomarkersmayappear,duetothedirect of myocardial ischaemia accompanied by presumed new
toxic effects of endogenous or exogenous high circulating ischaemic ECG changes or new LBBB—but without avail-
catecholaminelevels.Alsocoronaryvasospasmand/orendothe- able biomarker values—represent a challenging diagnostic
lialdysfunctionhavethepotentialtocauseMI.26–28 group. These individuals may die before blood samples for
Figure2.Differentiationbetweenmyo-
cardialinfarction(MI)types1and2
accordingtotheconditionofthecoro-
naryarteries.
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2026 Circulation October 16, 2012
biomarkers can be obtained, or before elevated cardiac Table3. ECGManifestationsofAcuteMyocardialIschaemia
biomarkers can be identified. If patients present with clinical
features of myocardial ischaemia, or with presumed newisch-
aemicECGchanges,theyshouldbeclassifiedashavinghada
fatalMI,evenifcardiacbiomarkerevidenceofMIislacking.
Myocardial Infarction Associated With
Revascularization Procedures (MI Types 4 and 5)
Periprocedural myocardial injury or infarction may occur at
somestagesintheinstrumentationoftheheartthatisrequired
during mechanical revascularization procedures, either by
PCIorbycoronaryarterybypassgrafting(CABG).Elevated
cTnvaluesmaybedetectedfollowingtheseprocedures,since
various insults may occur that can lead to myocardial injury
withnecrosis.29–32Itislikelythatlimitationofsuchinjuryis
ST-segment depression, usually reflects acute coronary occlu-
beneficialtothepatient:however,athresholdforaworsening
sion and results in myocardial injury with necrosis. As in
prognosis, related to an asymptomatic increase of cardiac
cardiomyopathy, Q waves may also occur due to myocardial
biomarkervaluesintheabsenceofproceduralcomplications,
isnotwelldefined.33–35SubcategoriesofPCI-relatedMIare fibrosisintheabsenceofCAD.
connectedtostentthrombosisandrestenosisthatmayhappen ECG abnormalities of myocardial ischaemia or infarction
after the primary procedure. may be inscribed in the PR segment, the QRS complex, the
ST-segment or the T wave. The earliest manifestations of
Electrocardiographic Detection of myocardial ischaemia are typically T wave and ST-segment
Myocardial Infarction changes. Increased hyperacute T wave amplitude, with promi-
TheECGisanintegralpartofthediagnosticwork-upofpatients nentsymmetricalTwavesinatleasttwocontiguousleads,isan
with suspected MI and should be acquired and interpreted early sign that may precede the elevation of the ST-segment.
promptly(i.e.targetwithin10min)afterclinicalpresentation.2 TransientQwavesmaybeobservedduringanepisodeofacute
DynamicchangesintheECGwaveformsduringacutemyocar- ischaemia or (rarely) during acute MI with successful reperfu-
dial ischaemic episodes often require acquisition of multiple sion.Table3listsST-Twavecriteriaforthediagnosisofacute
ECGs, particularly if the ECG at initial presentation is non-di- myocardial ischaemia that may or may not lead to MI. The J
agnostic. Serial recordings in symptomatic patients with an point is used to determine the magnitude of the ST-segment
initial non-diagnostic ECG should be performed at 15–30 min shift. New, or presumed new, J point elevation (cid:2)0.1 mV is
intervals or, if available, continuous computer-assisted 12-lead requiredinallleadsotherthanV2andV3.Inhealthymenunder
ECGrecording.Recurrenceofsymptomsafteranasymptomatic age40,J-pointelevationcanbeasmuchas0.25mVinleadsV2
intervalareanindicationforarepeattracingand,inpatientswith or V3, but it decreases with increasing age. Sex differences
evolving ECG abnormalities, a pre-discharge ECG should be requiredifferentcut-pointsforwomen,sinceJpointelevationin
acquiredasabaselineforfuturecomparison.Acuteorevolving healthy women in leads V2 and V3 is less than in men.38
changes in the ST-T waveforms and Q waves, when present, ‘Contiguous leads’ refers to lead groups such as anterior leads
potentiallyallowthecliniciantotimetheevent,toidentifythe (V –V ), inferior leads (II, III, aVF) or lateral/apical leads (I,
1 6
infarct-relatedartery,toestimatetheamountofmyocardiumat aVL).SupplementalleadssuchasV RandV Rreflectthefree
3 4
riskaswellasprognosis,andtodeterminetherapeuticstrategy. walloftherightventricleandV –V theinfero-basalwall.
7 9
MoreprofoundST-segmentshiftorTwaveinversioninvolving ThecriteriainTable3requirethattheSTshiftbepresentin
multiple leads/territories is associated with a greater degree of two or more contiguous leads. For example, (cid:2)0.2 mV of ST
myocardialischaemiaandaworseprognosis.OtherECGsigns elevationinleadV ,and(cid:2)0.1mVinleadV ,wouldmeetthe
2 1
associated with acute myocardial ischaemia include cardiac criteriaoftwoabnormalcontiguousleadsinaman(cid:2)40years
arrhythmias,intraventricularandatrioventricularconductionde- old. However, (cid:2)0.1 mV and (cid:3)0.2 mV of ST elevation, seen
lays,andlossofpre-cordialRwaveamplitude.Coronaryartery only in leads V –V in men (or (cid:3)0.15 mV in women), may
2 3
size and distribution of arterial segments, collateral vessels, representanormalfinding.Itshouldbenotedthat,occasionally,
location, extent and severity of coronary stenosis, and prior acute myocardial ischaemia may create sufficient ST-segment
myocardial necrosis can all impact ECG manifestations of shifttomeetthecriteriainoneleadbuthaveslightlylessthanthe
myocardial ischae-mia.36 Therefore the ECG at presentation required ST shift in a contiguous lead. Lesser degrees of ST
should always be compared to prior ECG tracings, when displacementorTwaveinversiondonotexcludeacutemyocar-
available. The ECG by itself is often insufficient to diagnose dial ischaemia or evolving MI, since a single static recording
acute myocardial ischaemia or infarction, since ST deviation may miss the more dynamic ECG changes that might be
maybeobservedinotherconditions,suchasacutepericarditis, detected with serial recordings. ST elevation or diagnostic Q
left ventricular hypertrophy (LVH), left bundle branch block waves in contiguous lead groups are more specific than ST
(LBBB), Brugada syndrome, stress cardiomyopathy, and early depression in localizing the site of myocardial ischaemia or
repolarization patterns.37 Prolonged new ST-segment elevation necrosis.39,40Supplementalleads,aswellasserialECGrecord-
(e.g. (cid:2)20 min), particularly when associated with reciprocal ings,shouldalwaysbeconsideredinpatientsthatpresentwith
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Thygesen et al ESC/ACCF/AHA/WHF Third Universal Definition of MI 2027
Table4. ECGChangesAssociatedWithPriorMyocardial Table5. CommonECGPitfallsinDiagnosingMyocardial
Infarction(inAbsenceofLVHandLBBB) Infarction
aThesamecriteriaareusedforsupplementalleadsV7–V9.
ischaemic chest pain and a non-diagnostic initial ECG.41,42
Electrocardiographic evidence of myocardial ischaemia in the
distributionofaleftcircumflexarteryisoftenoverlookedandis
bestcapturedusingposteriorleadsatthefifthintercostalspace
(V attheleftposterioraxillaryline,V attheleftmid-scapular
7 8
line, and V at the left paraspinal border). Recording of these
9
leads is strongly recommended in patients with high clinical
suspicion for acute circumflex occlusion (for example, initial
ECGnon-diagnostic,orST-segmentdepressioninleadsV ).41
1–3
Acut-pointof0.05mVSTelevationisrecommendedinleads
V –V ; specificity is increased at a cut-point (cid:2)0.1 mV ST
7 9
elevation and this cut-point should be used in men (cid:3)40 years such as the Minnesota Code and WHO MONICA, have been
old. ST depression in leads V –V may be suggestive of usedinepidemiologicalstudiesandclinicaltrials.3
1 3
infero-basal myocardial ischaemia (posterior infarction), espe-
Silent Myocardial Infarction
cially when the terminal T wave is positive (ST elevation
equivalent), however this is non-specific.41–43 In patients with AsymptomaticpatientswhodevelopnewpathologicQwave
criteria for MI detected during routine ECG follow-up, or
inferior and suspected right ventricular infarction, right pre-
reveal evidence of MI by cardiac imaging, that cannot be
cordial leads V R and V R should be recorded, since ST
3 4
elevation(cid:2)0.05mV((cid:2)0.1mVinmen(cid:3)30yearsold)provides directlyattributedtoacoronaryrevascularizationprocedure,
should be termed ‘si lent MI.’48–51 In studies, silent Q wave
supportivecriteriaforthediagnosis.42
MIaccountedfor9–37%ofallnon-fatalMIeventsandwere
During an episode of acute chest discomfort, pseudo-
associated with a significantly increased mortality risk.48,49
normalization of previously inverted T waves may indicate
Improper lead placement or QRS confounders may result in
acute myocardial ischaemia. Pulmonary embolism, intracra-
whatappeartobenewQwavesorQScomplexes,ascompared
nial processes, electrolyte abnormalities, hypothermia, or
toapriortracing.Thus,thediagnosisofanewsilentQwaveMI
peri-/myocarditis may also result in ST-T abnormalities
shouldbeconfirmedbyarepeatECGwithcorrectleadplace-
and should be considered in the differential diagnosis. The
ment,orbyanimagingstudy,andbyfocussedquestioningabout
diagnosisofMIismoredifficultinthepresenceofLBBB.44,45
potentialinterimischaemicsymptoms.
However,concordantST-segmentelevationorapreviousECG
may be helpful to determine the presence of acute MI in this Conditions That Confound the ECG Diagnosis
setting. In patients with right bundle branch block (RBBB),
of Myocardial Infarction
ST-T abnormalities in leads V1–V3 are common, making it AQScomplexinleadV isnormal.AQwave(cid:3)0.03secand
difficult to assess the presence of ischaemia in these leads: (cid:3)25%oftheRwaveamp1litudeinleadIIIisnormalifthefrontal
however, when new ST elevation or Q waves are found, QRS axis is between (cid:4)30° and 0°. A Q wave may also be
myocardialischaemiaorinfarctionshouldbeconsidered.
normalinaVLifthefrontalQRSaxisisbetween60°and90°.
SeptalQwavesaresmall,non-pathologicalQwaves(cid:3)0.03sec
Prior Myocardial Infarction and(cid:3)25%oftheR-waveamplitudeinleadsI,aVL,aVF,and
AsshowninTable4,QwavesorQScomplexesintheabsence
V –V . Pre-excitation, obstructive, dilated or stress cardiomy-
4 6
ofQRSconfoundersarepathognomonicofapriorMIinpatients opathy, cardiac amyloidosis, LBBB, left anterior hemiblock,
with ischaemic heart disease, regardless of symptoms.46,47 The LVH, right ventricular hypertrophy, myocarditis, acute cor
specificity of the ECG diagnosis for MI is greatest when Q pulmonale,orhyperkalaemiamaybeassociatedwithQwaves
waves occur in several leads or lead groupings. When the Q orQScomplexesintheabsenceofMI.ECGabnormalitiesthat
wavesareassociatedwithSTdeviationsorTwavechangesin mimicmyocardialischaemiaorMIarepresentedinTable5.
thesameleads,thelikelihoodofMIisincreased;forexample,
minorQwaves(cid:2)0.02secand(cid:3)0.03secthatare(cid:3)0.1mVdeep Imaging Techniques
aresuggestiveofpriorMIifaccompaniedbyinvertedTwaves Non-invasive imaging plays many roles in patients with
inthesameleadgroup.OthervalidatedMIcodingalgorithms, knownorsuspectedMI,butthissectionconcernsonlyitsrole
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2028 Circulation October 16, 2012
in the diagnosis and characterisation of MI. The underlying capability to echocardiography in suspected acute MI. Para-
rationaleisthatregionalmyocardialhypoperfusionandisch- magnetic contrast agents can be used to assess myocardial
aemia lead to a cascade of events, including myocardial perfusion and the increase in extracellular space that is
dysfunction, cell death and healing by fibrosis. Important associated with the fibrosis of prior MI. These techniques
imaging parameters are therefore perfusion, myocyte viabil- havebeenusedinthesettingofacuteMI,59,60andimagingof
ity, myocardial thickness, thickening and motion, and the myocardial fibrosis by delayed contrast enhancement is able
effects of fibrosis on the kinetics of paramagnetic or radio- todetectevensmallareasofsubendocardialMI.Itisalsoof
opaque contrast agents. value in detecting myocardial disease states that can mimic
Commonly used imaging techniques in acute and chronic MI, such as myocarditis.61
infarction are echocardiography, radionuclide ventriculogra-
phy, myocardial perfusion scintigraphy (MPS) using single Computed Tomography
photon emission computed tomography (SPECT), and mag- Infarcted myocardium is initially visible as a focal area of
netic resonance imaging (MRI). Positron emission tomogra- decreasedleftventricle(LV)enhancement,butlaterimaging
phy (PET) and X-ray computed tomography (CT) are less showshyper-enhancement,aswithlategadoliniumimaging
common.52Thereisconsiderableoverlapintheircapabilities byMRI.62Thisfindingisclinicallyrelevantbecausecontrast-
and each of the techniques can, to a greater or lesser extent, enhanced CT may be performed for suspected pulmonary
assessmyocardialviability,perfusion,andfunction.Onlythe embolism and aortic dissection—conditions with clinical
radionuclidetechniquesprovideadirectassessmentofmyo- features that overlap with those of acute MI—but the tech-
cyteviability,becauseoftheinherentpropertiesofthetracers nique is not used routinely. Similarly, CT assessment of
used.Othertechniquesprovideindirectassessmentsofmyo- myocardial perfusion is technically feasible but not yet fully
cardial viability, such as contractile response to dobutamine validated.
by echocardiography or myocardial fibrosis by MR.
Applying Imaging in Acute Myocardial Infarction
Echocardiography ImagingtechniquescanbeusefulinthediagnosisofacuteMI
Thestrengthofechocardiographyistheassessmentofcardiac becauseoftheirabilitytodetectwallmotionabnormalitiesor
structure and function, in particular myocardial thickness, lossofviablemyocardiuminthepresenceofelevatedcardiac
thickening and motion. Echocardiographic contrast agents biomarker values. If, for some reason, biomarkers have not
can improve visualisation of the endocardial border and can been measured or may have normalized, demonstration of
be used to assess myocardial perfusion and microvascular new loss of myocardial viability in the absence of non-
obstruction.TissueDopplerandstrainimagingpermitquan- ischaemic causes meets the criteria for MI. Normal function
tification of global and regional function.53 Intravascular and viability have a very high negative predictive value and
echocardiographic contrast agents have been developed that practicallyexcludeacuteMI.63Thus,imagingtechniquesare
targetspecificmolecularprocesses,butthesetechniqueshave useful for early triage and discharge of patients with sus-
not yet been applied in the setting of MI.54 pected MI. However, if biomarkers have been measured at
appropriate times and are normal, this excludes an acute MI
Radionuclide Imaging and takes precedence over the imaging criteria.
Several radionuclide tracers allow viable myocytes to be Abnormalregionalmyocardialmotionandthickeningmay
imaged directly, including the SPECT tracers thallium-201, be caused by acute MI or by one or more of several other
technetium-99m MIBI and tetrofosmin, and the PET tracers conditions, including prior MI, acute ischaemia, stunning or
F-2-fluorodeoxyglucose (FDG) and rubidium-82.18,52 The hibernation. Non-ischaemic conditions, such as cardiomyop-
strength of the SPECT techniques is that these are the only athyandinflammatoryorinfiltrativediseases,canalsoleadto
commonly available direct methods of assessing viability, regional loss of viable myocardium or functional abnormal-
although the relatively low resolution of the images leaves ity. Therefore, the positive predictive value of imaging for
them at a disadvantage for detecting small areas of MI. The acuteMIisnothighunlesstheseconditionscanbeexcluded,
common SPECT radiopharmaceuticals are also tracers of andunlessanewabnormalityisdetectedorcanbepresumed
myocardial perfusion and the techniques thereby readily to have arisen in the setting of other features of acute MI.
detect areas of MI and inducible perfusion abnormalities. Echocardiography provides an assessment of many non-
ECG-gated imaging provides a reliable assessment of myo- ischaemiccausesofacutechestpain,suchasperi-myocarditis,
cardial motion, thickening and global function. Evolving valvular heart disease, cardiomyopathy, pulmonary embo-
radionuclidetechniques that are relevant to the assessment lism or aortic dissection.53 It is the imaging technique of
of MI include imaging of sympathetic innervation using choice for detecting complications of acute MI, including
iodine-123-labelled meta-iodo-benzylguanidine (mIBG),55 myocardial free wall rupture, acute ventricular septal
imaging of matrix metalloproteinase activation in ventric- defect, and mitral regurgitation secondary to papillary
ular remodelling,56,57 and refined assessment of myocar- muscle rupture or ischaemia.
dial metabolism.58 Radionuclideimagingcanbeusedtoassesstheamountof
myocardium that is salvaged by acute revascularization.64
Magnetic Resonance Imaging Tracer is injected at the time of presentation, with imaging
The high tissue contrast of cardiovascular MRI provides an deferreduntilafterrevascularization,providingameasureof
accurateassessmentofmyocardialfunctionandithassimilar myocardium at risk. Before discharge, a second resting
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