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3:PatientAssessment

Overview
Thischapterprovidesabroadoverviewoftheclinicalexaminationandanupdateonthefundamentaldiagnostictestingthat providethebasisforevaluatingpatientswithcardiovasculardisease.Theperformanceofstressstudieswithandwithout imagingisoutlined.Emphasisisgiventotheappropriateuseandinterpretationofnoninvasiveimaging,including echocardiography/Doppler,cardiacmagneticresonanceimaging,cardiaccomputedtomographyandperipheralvascular studies.Cardiaccatheterizationdiagnosticmethodsincludeadiscussionoffundamentalhemodynamics,theinvasive evaluationofavarietyofdiseasestatesandtheclinicalvalueofthenewestintracoronaryimagingandflowassessment methods.Adiscussionofcontrastmediaandradiationsafetymeasurescompletesthiscomprehensivechapter.

Authors
PatrickT.O'Gara,MD,FACC EditorinChief ThomasM.Bashore,MD,FACC AssociateEditor JamesC.Fang,MD,FACC AssociateEditor GlennA.Hirsch,MD,MHS,FACC AssociateEditor JuliaH.Indik,MD,PhD,FACC AssociateEditor DonnaM.Polk,MD,MPH,FACC AssociateEditor SunilV.Rao,MD,FACC AssociateEditor

3.1:HistoryandPhysicalExam
Author(s): RichardA.Lange,MD,MBA,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Listthecommoncardiacsymptoms. 2. Recognizethevalueofabnormalphysicalexaminationfindingsforevaluationofalltypesofadultcardiovasculardisease (CVD). 3. Describethepathophysiologyofgalloprhythmanditsanalysisinpatientswithheartdisease. 4. Identifytheimportanceoffollowupcarebythecardiovascular(CV)specialisttoensureoptimaluseofmoderndiagnostic techniquesandtreatment.

Introduction
Adirectedhistoryandtargetedphysicalexaminationiscriticaltotheinitialevaluation ofthepatientwithknownorsuspectedCVD.Thehistorymayprovidecluesthat connectseeminglydisparatesymptoms,revealtheinfluencesofgeneticorother medicalconditions,andprovideinsightintothepatients'understandingoftheir conditionandcompliancewithprescribedtreatment.Thephysicalexamination providestheinitialbedsideevaluationofthepatientsandinformsclinicaldecision makinginrealtime. Thecardiacexaminationintegratesthepatient'shistorywithinspection,palpation, auscultationand,whenappropriate,maneuverstobringoutpathophysiologic findings.Eventhoughauscultatorytrainingininternalmedicineprogramshasbeen increasing,thereisagrowingbodyofliteraturedocumentingadisturbinglackof competencyincurrentmedicaltraineesandpracticingphysicians.Contributingto thedeteriorationofphysicalexaminationskillsisagrowingrelianceontechnology andtimeurgencyduringpatientencounters. Cardiacauscultatoryskillsamonghealthcareprofessionalsareextremelypoor, regardlessoftheleveloftraining.Lessthanafourthofinternalmedicineandfamily practiceresidentsrecognizeclassiccardiacfindings.1 Onlyonethirdofclinically importantheartsoundsandmurmursrecordedfrompatientswerecorrectly identifiedbyphysiciansattendingamedicaleducationconferenceoncardiac auscultation.2 Arecentstudyofcardiacexamskillcompetencyshowedthatcardiologists outperformedotherphysicians3 however,competencydiminishedwithmore recentlytrainedfaculty.Testscoresweresimilarformedicalstudents,residents, andprimarycarephysicians,whichconfirmedthelackofimprovementatany traininglevelpastmedicalschool.Unlesscorrected,cardiacexaminationskillswill continuetodeclineastheoldergenerationofmastercliniciansisreplacedby physicianswhoareinadequatelytrained. Educationaleffortstoimprovephysicalexaminationskillshaveincludedrepetition, patientcenteredteachingconferences,webbasedcurriculum,visualdisplay feedbackofauscultatoryandDopplerechocardiographicfindingsviatheuseof acousticcardiography(Figure1),4 andhandheldcardiacultrasound(HCU) devices.5 ThismodulewillreviewthefundamentalsoftheCVhistoryandphysical examination.

Figure1

AcousticCardiography(TimeFrequencyAnalysisofHeartSounds) Figure1 Asingleheartbeatshowingasimultaneouselectrocardiogram(ECG),soundrecording,andthetimefrequencyrepresentationoftheheart soundrecording(scalogram). A=aorticcomponentM=mitralcomponentP=pulmonarycomponentT=tricuspidcomponent. ModifiedwithpermissionfromErne,P.,Beyondauscultationacousticcardiographyinthediagnosisandassessmentofcardiacdisease.Swiss MedWkly2008138:43952.

History
Themajorsymptomsassociatedwithcardiacdiseaseincludechestdiscomfort, dyspnea,fatigue,edema,palpitations,andsyncope.Asemiquantitative assessmentofsymptomseverityisusefulforevaluatingfunctionallimitation, stabilityofsymptomsovertime,andtreatmentefficacy.Accordingly,cliniciansand researchersoftenuseactivityscales,ortheNewYorkHeartAssociation(NYHA)or CanadianCardiovascularSociety(CCS)functionalclassificationsystems(Table 1).6 Obtainingadetailedfamilyhistoryisalsoimportant,sincemanyCVdisordersare heritable(i.e.,HoltOramsyndrome,Carneycomplex,Marfansyndrome,aortic aneurysms,longQTsyndrome,atrialfibrillation,cardiomyopathies,etc.).Toolsare availablethatfacilitateorganizationofadetailedfamilyhistoryintheformofa pedigree(http://www.hhs.gov/familyhistory)andprovidethebasisforappropriate diagnostictestinginfamilymembers. ChestDiscomfort Anginaistypicallyaretrosternal,pressurelikediscomfortthatmayradiatetothejaw, neck,back,epigastrium,leftshoulder,orleftarm.Patientsoftenusevarious adjectivestodescribethepain,including"squeezing,""crushing,""gripping," "pressurelike,"and"suffocating,"andtheymayrefertoitas"heaviness."Not uncommonly,theyinsistthatitisa"discomfort,"nota"pain."Anginaisalmostnever sharporstabbinginquality,anditusuallydoesnotchangewithpositionor respiration.Atypicalpresentationsofanginamayincludeindigestion,belching,and dyspnea,andaremorecommoninwomen,olderpatients,anddiabetics. Anginaischaracterizedasstableorunstable.Stableanginausuallyisprecipitated byphysicalexertion,emotionalstress,eatingameal,orexposuretocold,anditis readilyrelievedbyrestornitroglycerin.Theanginalepisodetypicallylastsonlyafew minutesfleetingdiscomfortforafewsecondsoradullachelastingforhoursis rarelyangina.Theterm"chronicstableangina"referstoanginathathasbeenstable infrequencyandseverityforatleast2months.Chronicstableanginaistheinitial manifestationofcoronaryheartdiseaseinaboutonehalfofpatientstheotherhalf initiallyexperienceunstableangina,myocardialinfarction,orsuddendeath. Unstableanginawhichusuallyresultsfromplaquerupturewithsubsequent plateletaggregationandthrombusformationistypifiedbyprolongedchest discomfortatrestnewonsetanginathatissevere,prolonged,orfrequentor previouslystableanginathathasbecomemorefrequent,longerinduration,more easilyprovoked,andmoredifficulttorelieve. Dyspnea Cardiacrelateddyspneaisusuallydueto:1)anelevatedpulmonarycapillarywedge (PCW)pressurewithresultantstimulationofalveolarinterstitialJreceptorsand/or pulmonaryedema,2)lowcardiacoutput,or3)righttoleftshuntingofblood.Anyof theseconditionscancausedyspneawithexertion.Whendyspneaoccurswith recumbency(orthopnea),itisusuallyanindicationthatPCWpressureisincreased andisoftenaccompaniedbyparoxysmalnocturnaldyspnea,whichusuallyoccurs 24hoursaftertheonsetofsleepandsubsidesgraduallyoverseveralminutes whenthepatientsitsuprightorstands. Thepatientwithlowcardiacoutputtypicallyexperiencesdyspneaonexertionand fatigueintheabsenceoforthopneaorparoxysmalnocturnaldyspnea.Thepatient withdyspneaandcyanosisshouldbeevaluatedforthepresenceofrighttoleft shuntingofbloodifthisoccurswithstanding(platypnea),theshuntinglikelyoccurs throughaninteratrialcommunication(socalledorthodeoxiaplatypneasyndrome). Fatigue Fatigueisadifficultsymptomtoevaluatebecauseitisamanifestationofawide varietyofphysicalandpsychiatricdisorders.Chronicfatigueinapatientwithheart failureusuallyindicatesalowoutputstate.Conversely,thesuddenonsetof

Table1

Table2

unexplainedfatigueisacommonprecursorsymptomofacutecoronarysyndromes especiallysuddendeathandMI.Unexplainedfatigueinapatientwithknownor suspectedischemicheartdiseaserequiresfurtherevaluation. Edema Althoughdependentedemamaybeanindicationthatrightatrial(RA)filling pressuresareelevated,asanisolatedvariable,ithasalowpredictivediagnostic valuebecauseitcanbecausedbymanyotherconditions(i.e.,venousinsufficiency, renalinsufficiency,liverdisease,severeanemia,etc).Intheevaluationofthepatient withsuspectedcongestion,individualsymptomsorsignshavelimiteddiagnostic sensitivity,specificity,andpredictivevalue(Table2).7 Thediagnosticaccuracyofedemaforidentifyingcardiacdiseaseisimprovedifa combinationoffindings(i.e.,dyspnea,narrowpulsepressure,elevatedjugular venouspressure[JVP],rales,tachycardia,S3 ,andabdominojugularreflux)is present.Inedematouspatientswhoarenotknowntohaveleftventricular(LV) dysfunction,thepresenceofthreeormoresymptomsorsignspredictsincreased fillingpressureswith>90%likelihood.Incontrast,ifoneornonewerepresent,there is<10%likelihoodofincreasedLVfillingpressures.8 Palpitations Inthepatientwhocomplainsofpalpitations,thelikelihoodthatacardiacarrhythmia ispresentisincreasedifthereisaknownhistoryofcardiacdisease,palpitations areaffectedbysleeping,ortheyincreasewhilethepatientisatwork.9 Aknown historyofpanicdisorderorhavingpalpitationslastinglessthan5minutesmakes thediagnosisofcardiacarrhythmialesslikely.Thepresenceofaregularrapid poundingsensationintheneckorvisibleneckpulsationsinassociationwith palpitationsincreasesthelikelihoodofaspecifictypeofarrhythmia(atrioventricular nodalreentrytachycardia[AVNRT]).9 Syncope Syncopeandpresyncopemaybecardiac(i.e.,arrhythmicorvalvular[i.e.,aortic stenosis])orneurocardiogenicinorigin.Cardiacsyncopetypicallyoccurssuddenly andrestorationofconsciousnessoccursquickly.Conversely,patientswith neurocardiogenicsyncopemayhavepremonitorysymptoms(i.e.,nausea,yawning, visualimpairment),appearpaleanddiaphoretic,andrevivemoreslowly,albeit withoutseizureactivityoraprolongedpostictalstate. Inmostpatients,theetiologyofthesyncopalepisodecanbeestablishedfromthe history,physicalexam,andelectrocardiogram(ECG).Furthertestingisreservedfor thosewithevidenceofunderlyingheartdiseasebasedonthehistoryandclinical examination,orbecauseofanabruptsyncopalepisodewithoutobviouscause. Considerableresourcesarewastedpursuingunlikelycausesofsyncopewhenan adequateclinicalexaminationhasnotbeenperformed.

ActivityScalesUsedtoAssessFunctionalCapacity Table1 ReproducedwithpermissionfromGoldmanL,HashimotoB,CookEF,LoscalzoA.Comparativereproducibilityandvalidityofsystemsfor assessingcardiovascularfunctionalclass:advantagesofanewspecificactivityscale.Circulation198164:122734.

DiagnosticValueofClinicalMarkersofCongestion Table2 AdaptedwithpermissionfromChakkoS,WoskaD,MartinezH,etal.Clinical,radiographic,andhemodynamiccorrelationsinchroniccongestive heartfailure:conflictingresultsmayleadtoinappropriatecare.AmJMed199190:3539,andButmanSM,EwyGA,StandenJR,KernKB,Hahn E.Bedsidecardiovascularexaminationinpatientswithseverechronicheartfailure:importanceofrestorinduciblejugularvenousdistension.J AmCollCardiol199322:96874

PhysicalExamination (1of2)
Withtheexceptionofisolatedanginapectoris,mostcardiacconditionshave abnormalitiesonthephysicalexamination.Thissectionwillattempttohighlight importantphysicalexaminationfindings.Foracomprehensiveprogramthat integratescommonauscultatoryandrhythmabnormalitieswithotherphysicalexam findings,phonocardiograms,hemodynamicdata,andcomputeranimations,the readerisdirectedtotheprogrambyCrileyandcolleaguesat http://www.blaufuss.org. BasicMeasurements Simplebasicmeasurementssuchasheight,weight,bloodpressure,andheartrate containimportantclinicalinformation.Measurementofweightgainorlossis particularlyimportantinpatientswithovertorsuspectedheartfailure. Intheoverweightpatient,determinationofthebodymassindex(BMI)[weight (kg)/height2 (m2 )]andwaistcircumferencehavebecomeamoreimportantmeasure thanweightalone.InpersonswithaBMIbetween25and35(i.e.,overweightor obese),waistcircumferenceandwaisttohipratioshouldbemeasured.Waist circumferenceismeasuredeitheratthenarrowestcircumferenceofthetorsoorat themidpointbetweenthelowerribsandtheiliaccrest.Hipcircumferenceis measuredatthelevelofthelargestlateralextensionofthehipsoroverthebuttocks. Abdominalobesity,whichidentifiespersonsatriskforheartdisease,isdefinedas: 1)waistcircumference>102cm(40inches)inmenand88cm(35inches)in women,or2)waisttohipratio>1.0inmenand>0.85inwomen. Thebloodpressureisanessentialparameterinpatientswithknownorsuspected heartdisease."Whitecoathypertension"iscommonand,ifsuspected,may necessitatehavingthepatientmeasurehisorherbloodpressureonmultiple occasionsathomeorundergoambulatorymonitoring.Acommonsourceoferrorin clinicalpracticeistheuseofaninappropriatelysmallcuff,whichresultsin overestimationofthebloodpressure.Anarrowpulsepressureisindicativeofa reducedstrokevolume,whereasawidepulsepressureisseenwithvascular stiffness(duetoagingand/oratherosclerosis)andconditionscausingabrisk decreaseinaorticbloodvolume(i.e.,aorticregurgitationorpatentductus arteriosus).Theheartrateandrhythmwillindicatethepresenceofatrialfibrillation, prematurebeats,andtachyorbradyarrhythmias. Skin Centralcyanosisisindicativeofrighttoleftshuntingofbloodwhilecyanosislimited tothefingers,toes,nose,andears(socalled,acrocyanosis)reflectslowbloodflow becauseofvasoconstriction.Thelattermayoccurinshock,severeheartfailure,or severeperipheralvasculardisease.Differentialcyanosisaffectingthelowerbutnot theupperextremitiesmaybeobservedwithpatentductusarteriosusandrighttoleft shuntingatthegreatvessellevelduetopulmonaryarterialhypertension. Lentigines(darkbrownfrecklesthatdonotchangewithsunexposure)ontheface, neckandtrunkarepresentinseveralCVsyndromes(e.g.,LEOPARD,LAMB,NAME, Carneycomplex)withmultipleatrialmyxomas,atrialseptaldefect(ASD), hypertrophiccardiomyopathy,orvalvularstenoses. Incriticallyillpatients,paleskincolorandcoldskintemperature,aswellasthelevel ofalertness,providehighlyusefulestimatesoftheadequacyofthecardiacoutput. Manycliniciansdescribetheclinicalassessmentoftheheartfailurepatientbased ontheirhemodynamicsperfusionstatus(warmorcold)andvolumestatus(dryor wet)whichisusefulinassessingprognosisandguidingtherapy(Table3).10,11 JugularVenousPressure TheJVPisasurrogateoftheRApressureandcanbeestimatedwitheitherthe externalorinternaljugularvein.Eventhoughtheexternalljugularveiniseasierto visualizeandreliablydiscriminatesbetweenalowandhighcentralvenous

Table3

Figure2

Figure3

pressure,12itisnotthepreferredchoicebymanybecauseithasvalvesandisnot directlyinlinewiththesuperiorvenacavaandRA.AlthoughtheJVPassessesRA, notLApressure,DraznerandcolleaguesfoundthattheRApressurereliably predictedthePCWpressureinpatientswithadvancedheartfailurethepositive predictivevalueofanRApressure>10mmHgforaPCWpressure>22mmHgwas 88%.13 Conventionally,theJVPismeasuredastheverticaldistancebetweenthetopofthe jugularvenouspulsationandtheangleofLouis(thesternalinflectionpoint,where themanubriummeetsthesternum),withadistance>3cmconsideredabnormal. However,thedistancebetweentheangleofLouisandthemidRAvaries considerablyamongindividuals,sothattheuseofthesternalangleasareference leadstosystematicunderestimationofvenouspressure.14,15Instead,theclavicle canbeusedasareferencewiththepatientintheseatedposition.15Sincethe distancebetweentheRAandtheclavicleisatleast10cm,venouspulsationsabove theclavicleareclearlyabnormal. AlthoughthereiswidevariabilityamongobserversintheestimationoftheJVP, knowledgethatthepressureiselevated,andnotitsspecificvalue,issufficientfor diagnosisandmanagementinmostclinicalscenarios.Inpatientswithsymptomatic heartfailureorasymptomaticLVdysfunction,thepresenceofanelevatedJVP predictsheartfailurehospitalizationsanddeathfrompumpfailure(Figure2).16,17 Thevenouswaveformsincludethea,c,andvwaves(Figure3).Theawaveoccurs withRAcontractionitprecedesS1 andisprominentinpatientswithreducedright ventricular(RV)compliance."Cannon"awavesareseenwithAVdissociationwhen theRAcontractsagainstaclosedtricuspidvalve. WithcompletionofRAcontraction,thexdescentoccursandisinterruptedbythec wave,whichistheresultofventricularsystolepushingtheclosedtricuspidvalveinto theRA.Thex'descentfollowsfromtheatrialsuctioncreatedbyventricularsystole, pullingthetricuspidvalveandRAdownward.ThevwaveresultsfromRAfilling, whichoccursattheendofventricularsystole,anditpeaksjustafterS2 .Itsheightis determinedbytheRAcomplianceandvolumeofbloodfillingtheRAantegradeor retrograde(i.e.,fromthevenacavaeortricuspidregurgitation,respectively). Withseveretricuspidregurgitation,thevwaveisaccentuated.Theydescentfollows thevwavepeakandresultsfromthefallinRApressureaftertricuspidvalve opening.Ifthereisreducedventricularfillinginearlydiastole,theydescentwillbe blunted,asisthecasewithpericardialtamponadeortricuspidstenosis. Conversely,theydescentwillbesteepwhenventriculardiastolicfillingoccursearly andrapidly,aswithpericardialconstriction. Normally,JVPshouldfallbyatleast3mmHgwithinspiration.Ariseinvenous pressure,oritsfailuretodecreasewithinspirationisknownastheKussmaulsign, andisclassicallyassociatedwithconstrictivepericarditis,althoughithasbeen reportedinrestrictivecardiomyopathy,pulmonaryembolism,rightventricular(RV) infarction,advancedsystolicheartfailure,rightsidedvolumeoverload,andreduced RVcompliance. Venoushypertensioncanbeelicitedbytheabdominojugularreflex(describedlater) orpassivelegelevation.Thesesignsindicateavolumeoverloadedstateand limitedcomplianceofanoverdistendedorconstrictedvenoussystem.

SchematicforAssessmentofClinicalProfilesintheHeartFailurePatient Table3 Congestionisassessedbythepresenceoforthopnea,jugularvenousdistention,rales,abdominojugularreflux,ascites,peripheraledema,ora squarewavebloodpressureresponsetotheValsalvamaneuver.Compromisedperfusionisassessedbythepresenceofanarrowpulse pressure,pulsusalternans,symptomatichypotension(withoutorthostasis),coolextremities,and/orimpairedmentation.

PrognosticValueofElevatedJugularVenousPressureandS Figure2 KaplanMeierplotsdemonstratingtheprognosticvalueofanelevatedjugularvenouspressureandS3insymptomatic(PanelsAandB)and asymptomatic(PanelsCandD)heartfailurepatientswithsystolicdysfunction. PanelsAandB,reproducedwithpermissionfromDraznerMH,RameJE,StevensonLW,DriesDL.Prognosticimportanceofelevatedjugular venouspressureandathirdheartsoundinpatientswithheartfailure.NEnglJMed2001345:57481.PanelsCandD,reproducedwith permissionfromDraznerMH,RameJE,DriesDL.Thirdheartsoundandelevatedjugularvenouspressureasmarkersofthesubsequent developmentofheartfailureinpatientswithasymptomaticleftventriculardysfunction.AmJMed2003114:4317.

JugularVenousWaveForms Figure3 A.Normalvenouswaveformsincludethea,c ,andvwavesandthex ,x,andydescents,withcorrespondingheartsounds. B.Cannonawavesareseenwithatrioventriculardissociation. C.Thevwaveisaccentuatedwithseveretricuspidregurgitation. D.Steepydescentduetoearlyandrapidventriculardiastolicfilling,asoccurswithpericardialconstriction

PhysicalExamination (2of2)
Extremities Thetemperatureandcoloroftheextremities,presenceofclubbing,anddigitalfindingsmayimplythepresenceof cardiacdisease.Cool,clammyextremitiesthatarepaleorcyanoticsuggestthepresenceofamarkedlydiminished cardiacoutput.Clubbingisobservedwithrighttoleftshuntingofbloodandalsomayoccurwithendocarditis.The presenceofJanewaylesions(nontender,slightlyraisedhemorrhagesonthepalmsandsoles),Osler'snodes(tender, raisednodulesonthepadsofthefingersortoes),andsplinterhemorrhages(linearpetechiaeinthemidnailbed) supportthediagnosisofendocarditis. Arachnodactyly("spiderfingers")isseenwithMarfansyndrome.Anunapposable"fingerized"thumb(withorwithout radialulnarshortening)isafindingoftheautosomaldominantHoltOramsyndromeinwhichASDsandconduction abnormalitiesarefound. LowerextremityedemawithelevatedJVPoccursinmanyvolumeoverloadedstates,includingheartfailure.Edemainthe absenceofanelevatedJVPsuggestsanoncardiaccondition(i.e.,chronicvenousinsufficiency,dihydropyridinecalcium channelblockertherapy,hypoalbuminemia,deepveinthrombosis,lymphaticobstruction,hypothyroidism,etc.). ChestandAbdomen Therespiratorypatternshouldbenotedduringspontaneousbreathingwithattentiontorate,depth,audiblewheezing, andstridor.Palpation,percussion,andauscultationofthechestfollowsequentially. Athrillmaybepresentoverwelldevelopedintercostalarterialcollateralsinpatientswithhypertensionandsevereaortic coarctation.Ralesareoneofthesignscommonlyusedtopredictelevatedfillingpressurestheothersarepedaledema, jugularvenousdistention,abdominojugularreflux,andthepresenceofanS3 and/orS4 .Diagnosticaccuracyisimproved byusingacombinationoffindingsratherthanrelyingonanisolatedclinicalfinding(i.e.,rales)thathavelimited predictivevalue.8 Ascitesandanenlarged,tenderliverareoftennotedinpatientswithdecompensatedrightheartfailure,chronic constrictivepericarditis,orrestrictivecardiomyopathysystolichepaticpulsationsindicateseveretricuspidregurgitation. Palpationcandetect~40%ofabdominalaorticaneurysmsthatare>3.0cmindiameter. TheabdominojugularrefluxisusefulinpredictingheartfailureandaPCWpressurehigherthan15mmHg.Toassess forabdominojugularreflux,steadypressureisappliedovertheupperabdomenfor10secondsormorewhilecarefully observingthejugularvenouspulsation.ThenormalresponseisabriefriseandadeclineinthemeanJVP.Anabnormal resultconsistsofaprogressiveandsustainedriseof>3cmintheJVP.Thepatientshouldbeinstructedtorefrainfrom breathholdingorperformingaValsalvamaneuverthatcouldfalselyelevatethevenouspressure. PeripheralArterialExamination ThearterialpulsewavecharacteristicscanprovideacluetothepresenceofsevereLVdysfunction(pulsusalternans), hypertrophiccardiomyopathy(bifidpulse),pericardialtamponade(pulsusparadoxus),aorticstenosis(pulsusparvuset tardus),andaorticregurgitation(waterhammerpulse).Aboundingpulsemayoccurinhyperkineticstates(i.e.,fever, anemia,andthyrotoxicosis),andabifidpulsemayoccurwithfeverorafterexerciseinanormalindividual,andis consistentwithincreasedvascularcompliance.Inheartfailure,thepulsepressurecanbeareliablesignofstroke volumeandcardiacoutputapulsepressure<25%ofthesystolicpressureisassociatedwithacardiacindexof<2.2 L/min/m2 .18 Thepresenceofperipheralarterialdisease(PAD)isassociatedwithanincreasedriskofcoronaryarterydisease. Accordingly,allpatientsshouldhavepalpationandauscultationofthecarotidarteries,abdominalaorta,andfemoral arteriesandpalpationofthepopliteal,dorsalispedis,andposteriortibialpulses,evenintheabsenceofclaudication.In 510%ofsubjects,theposteriortibialordorsalpedalpulsemaynotbepalpablebecauseofunusualanatomy,buteach pairshouldbesymmetric. Inanasymptomaticpatient,thepresenceofafemoralbruit,anabsentorreducedpulse,orabnormalpulseoximetry(i.e., >2%differencebetweenfingerandtoeoxygensaturation)canindicatePAD.19,20Althoughthecorrelationbetweenthe presenceofabruitandthedegreeofvascularobstructionisweak,thepresenceofathrillorextensionofthebruitinto diastoleisindicativeofaseverestenosis.Thelossofhaironthelowerlegs,dependentrubor,andslowarterialfilling afterelevationofthelegisindicativeofPAD,whichcanbeconfirmedwiththeanklebrachialindex(ABI). AnABIof0.710.90indicatesthepresenceofmildPAD,anABIof0.410.70indicatesmoderatePAD,andanABIof0.40 orlessindicatesseverePAD.PainatresttypicallyoccurswithanABI<0.50,andischemicorgangrenousextremitiesare

associatedwithanABI<0.20. InspectionandPalpationoftheHeart AheaveintheleftanteriorchestwallmayoccurwithanenlargedandhyperdynamicLV,andaleftparasternalheave indicatesRVpressureorvolumeoverload.Pulsationslocatedintherightupperparasternalandsternoclavicularare suggestiveofanascendingaorticaneurysm,whilethoselocatedintheleftupperparasternalregionindicatepulmonary arterialhypertension.Systolicanddiastolicthrillssignifyturbulent,highvelocitybloodflow,andhelplocalizetheoriginsof heartmurmurs. Inthenormalpatient,thepointofmaximalimpulse(PMI)isovertheLVapexinthemidclavicularlineatthefifthintercostal spaceitis<2cmindiameter,movesquicklyawayfromthefingers,andisbestpalpatedatendexpiration,whenthe heartisclosesttothechestwall. WithLVdilatation,thePMIisdisplacedleftwardanddownward.WithLVpressureoverload,thePMIissustained.A prominent,rapid,earlyfillingwaveinpatientswithadvancedsystolicheartfailuremayresultinapalpablethirdheart sound(S3 ),eventhoughthegallopitselfisinaudible.Apalpable,presystolicimpulsecorrespondstoanS4 (i.e.,atrial contributiontodiastolicfillingofanoncompliantLV),andalargeLVaneurysmcanproduceapalpablesystolicimpulse discretefromtheapexbeat.

HeartSounds
FirstHeartSound(S1 ) Thefirstheartsound(S1 )occursatthebeginningofventricularsystole,coincident withtheclosureoftheAV(i.e.,mitralandtricuspid)valves.SplittingofS1 ismore appreciablewithrightbundlebranchblock.TheintensityofS1 variesasafunctionof themobilityoftheanteriormitralvalveleafletandthedistanceittravelstoreturntoits annularplaneattheonsetofsystole.Thus,S1 intensityisincreasedintheearly stagesofrheumaticmitralstenosis(i.e.,whenthevalveleafletsarepliable)andwith shortPRintervals(<160msec),andsofterinthelatestagesofmitralstenosis(i.e., whentheleafletsarerigid)andwithlongPRintervals(>200msec). SecondHeartSound(S2 ) Thesecondheartsound(S2 )occursattheendofventricularsystoleandis associatedwiththeclosureoftheaorticandpulmonicvalves.Withnormal, physiologicalsplitting,theA2 P2 intervalincreasesduringinspirationandnarrows withexhalation.TheA2 P2 intervalwidensifthereisdelayedpulmonicvalveclosure (asoccursinrightbundlebranchblock,pulmonicstenosis,orseverepulmonary hypertension)orprematureaorticvalveclosure(asoccurswithseveremitral regurgitation)(Table4). Conversely,paradoxicalsplitting(i.e.,A2 P2 splitsduringexpirationandnarrowswith inspiration)maybepresentwhenaorticvalveclosureisdelayed(asoccurswithleft bundlebranchblock,aorticstenosis,hypertrophicobstructivecardiomyopathy,or severehypertension)orpulmonicvalveclosureoccursprematurely(asoccurswith severetricuspidregurgitation).Wide,fixedsplitting(i.e.,theA2 P2 intervalis unchangedduringtherespiratorycycle)occursonlywithASD. A2 isnormallylouderthanP2 andcanbeheardacrosstheprecordiumP2 is typicallyonlyheardattheleftuppersternalborder.Whenbothcanbeheardatthe lowerleftsternalborderorapex,orwhenP2 canbepalpatedatthesecondleft interspace,pulmonaryhypertensionispresent.Inthepatientwithaorticorpulmonic stenosis,theintensityofA2 orP2 decreasesasthestenosisbecomesmoresevere untilasingleS2 results. SystolicSounds Anejectionclickisanearlysystolicsoundthatprecedestheupstrokeofthecarotid pulse(Figure4).Itmaybeappreciatedinthepatientwithaorticorpulmonicroot dilationorcongenitalbicuspidaorticorpulmonicvalvediseasewithpliablevalve leaflets.Ofnote,theejectionsoundthataccompaniespulmonicvalvestenosis decreasesinintensitywithinspiration,andistheonlyrightsidedcardiacsoundto doso.Ejectionsoundsdisappearastheculpritvalvelosesitspliabilityovertime. Thepatientwithmitralvalveprolapsetypicallyhasamidsystolicclick,whichmayor maynotbefollowedbyasystolicmurmur.Anymaneuverthatdecreasesventricular preload(i.e.,Valsalva,uprightposition)causesthemitralvalvetoprolapseearlier hence,theclickandmurmur(ifpresent)moveclosertoS1 .Conversely,ifventricular preloadisincreased(i.e.,withsquattingorhandgrip),themitralvalveprolapses laterinsystole,andtheclickandmurmurmoveawayfromS1 (Figure5). DiastolicSounds Athirdheartsound(S3 )isalowpitchedsoundthatoccursduringtherapidfilling phaseofventriculardiastole.AleftsidedS3 isbestheardovertheLVapexintheleft lateraldecubitusposition,whereasarightsidedS3 isusuallyheardatthelowerleft sternalborderandbecomeslouderwithinspiration.AnS3 maybenormallypresent inchildren,adolescents,andyoungadults,butinolderadultsitindicatesheart failure.
Figure7 Table4

Figure4

Figure5

Figure2

Figure6

Figure8

Figure9

S3 poorlypredictsventricularejectionfractionbecauseitreflectsearlydiastolicfilling ratherthansystolicperformance.Hence,inpatientswithheartfailure,S3 isequally prevalentinthosewithorwithoutLVsystolicdysfunction.21Inthepatientwithheart failureandknownLVdysfunction,thepresenceofanS3 isanindependentpredictor ofadverseoutcomeandindicatorofresponsivenesstodigitalistherapy(Figure 2).16,17 Afourthheartsound(S4 )isalowpitchedsoundthatoccursduringtheatrialfilling phaseofventriculardiastoleandindicatesdiminishedventricularcompliance,most oftenduetohypertrophyormyocardialischemia.AleftsidedS4 isbestheardover theLVapexintheleftlateraldecubitusposition,whereasarightsidedS4 isusually heardatthelowerleftsternalborderandbecomeslouderwithinspiration.Inmany individuals,itmayeasiertopalpateS4 thantohearit.Whenatrialcontractilefunction declinesasaresultoflongstandingatrialpressureorvolumeoverload,theS4 diminishesinintensityandtheelevatedatrialpressurecausestheS3 toincreasein intensity(Figure6).Whenatrialfibrillationdevelops,theS4 disappears. Thehighpitchedopeningsnap(OS)ofmitralstenosisoccursshortlyafterS2 (Figure7).TheA2 OSintervalisinverselyproportionaltotheLALVdiastolic pressuregradient.Asmitralstenosisworsens,theA2 OSintervalnarrows,andas themitralleafletsbecomeprogressivelyrigid,theOSandS1 becomesofter. Apericardialknockisahighpitchedearlydiastolicsound,whichcorrespondsin timingtotheabruptcessationofventricularexpansioninearlydiastoleinpatients withconstrictivepericarditis.Withatrialmyxoma,atumorplopisoccasionallyheard. Itisalowpitchedsoundthatarisesfromthediastolicprolapseofthetumoracross themitralvalveadiastolicmurmurisusuallynotpresent. Intermsofthetimingofearlydiastolicsounds,anOSoccursearlierthana pericardialknock(i.e.,mitralvalveopeningprecedesearlyLVdiastolicfilling),anda pericardialknockoccursearlierthananS3 ,becauseleftatrialpressureishigher andLVearlydiastolicfillingismorerapidwithconstrictionthanwithheartfailure. CardiacMurmurs Turbulentbloodflowandtheconsequentvibrationswithintheheartorgreatvessels isthebasisofmurmurs.Cardiacmurmursareproducedbypressuregradients acrossvalves,abnormalcommunicationsbetweenintracardiacstructures, regurgitantvalves,orexcessiveflow(i.e.,innocentmurmursofyoungpeople).The intensityofthemurmurreflectsthepressuregradientnotthemagnitudeofblood flowbetweencardiacchambersorgreatvessels.Thisexplainswhysevere,acute mitraloraorticregurgitationduetopapillarymuscleruptureorendocarditis, respectivelycanbealmostsilent,whereasasmallventricularseptaldefectmay produceaveryloudmurmur.Murmurintensityisgradedonascaleof16a palpablethrillispresentwithmurmursofgrade4orhigherintensity. Thetiming(i.e.,systolevs.diastole),location,andtonalqualityofthemurmuris importantinidentifyingitsetiology.Innocentsystolicmurmursareubiquitousin youth(until21years)andareduetohighbloodflow.Severalcharacteristicscanbe usedtodistinguishinnocentmurmursfromvalvularmurmurs.Theelderly(beyond 65yearsofage)oftenhaveamurmurduetoturbulencefromsclerosisoftheaortic valveortoaorticrootdilatation.Suchmurmursareusuallygrade12/6,short,and haveanearlypeaktherearenoaccompanyingabnormalheartsoundsor abnormalitiestopalpation. Aorticstenosisisinvariablyharshormusicalovertheaorticareaandleftsternal borderifnot,itusuallyindicatesalowcardiacoutput.Theharshmurmurofaortic stenosismaysoundlikeablowingmurmurofmitralregurgitationattheapex (Gallavardineffect)andmistakenfordoublevalvedisease.Mitralregurgitation murmursareusuallyblowing,butcanbeharshormusical(oftenwithalatepeak)if duetorupturedchordaetendinaeormitralvalveprolapse. Diastolicmurmursarealwayspathologicandareamongthemostdifficulttoidentify (Figure7).Identificationofaorticregurgitationoftenrequiresauscultationoverthe

upperleftsternalborderwiththepatientsittingandleaningforwardwithfull expiration.Themitralstenosisrumblemaybeaudibleonlydirectlyovertheapex usingthe"bell"ofthestethoscopewiththepatientintheleftlateraldecubitus position.Interestingly,alongaorticregurgitationmurmurmeanslesssevere regurgitation,whilealongdurationofamitraldiastolicrumblemeansmoresevere stenosis.Acontinuousmurmurwhichisduetoanarterialtovenousconnection, suchasapatentductusarteriosusbeginsearlyinsystole,peaksinintensitywhen S2 occurs,andcontinuesintodiastolebutstopspriortoS1 . Maneuvers TheValsalvamaneuvercanbeusedtoassessthepresenceofheartfailureandto identifythesourceofmurmurs.TheValsalvamaneuverhasfourphases,whichcan beassessedinvasivelywithanintraarteriallineornoninvasivelyusingablood pressurecuff.Anormalbloodpressureresponseissinusoidalinappearance (Figure8),withKorotkoffsoundsaudibleonlyduringphasesIandIV,becausethe systolicpressurenormallyrisesattheonsetandreleaseofthestrainphase.The patientwithheartfailuremayhaveabsenceofthephaseIVovershootorasquare waveresponsewithValsalva(Figure9).Theabsentovershootpatternindicates decreasedsystolicfunctionandthesquarewaveresponseindicateselevatedfilling pressures. Inthepatientwithaharshsystolicmurmur,thedifferentresponsestoValsalvacan distinguishaorticstenosisfromobstructivehypertrophiccardiomyopathy.LVfilling andvolumedeclinesduringthestrainphaseofValsalvawhichcausesthesystolic murmurofaorticstenosistodecreaseinintensityandthemurmurofobstructive hypertrophiccardiomyopathytoincreaseinintensity.Inthepatientwithmitralvalve prolapse,theassociatedclickoccursearlierinsystoleduringaValsalvamaneuver asaresultofsmallerLVvolume.

ConditionsThatAlterSplittingoftheSecondHeartSound Table4 AV=aorticvalveLBBB=leftbundlebranchblockPV=pulmonaryvalveRBBB=rightbundlebranchblock.

SystolicMurmurs Figure4 A.Ejectionclick(EC)andcrescendodecrescendomurmurofbicuspidaorticorpulmonicstenosis.Withrheumaticordegenerative,calcific stenosis,theclickisabsent. B.Holosystolicmurmurofchronicmitralortricuspidregurgitationorventricularseptaldefectwithoutpulmonaryhypertension. C.Midsystolicclickandmurmurofmitralvalveprolapse.

EffectofPositionalChangesonMitralValveProlapseClickandMurmur Figure5 ReproducedwithpermissionfromShaverJA,LeonardJJ,LeonDF.ExaminationoftheHeart.PartIV:AuscultationoftheHeart.Dallas:American HeartAssociation1990:13.Copyright1990.AmericanHeartAssociation.

PrognosticValueofElevatedJugularVenousPressureandS3 Figure2 KaplanMeierplotsdemonstratingtheprognosticvalueofanelevatedjugularvenouspressureandS3insymptomatic(PanelsAandB)and asymptomatic(PanelsCandD)heartfailurepatientswithsystolicdysfunction. PanelsAandB,reproducedwithpermissionfromDraznerMH,RameJE,StevensonLW,DriesDL.Prognosticimportanceofelevatedjugular venouspressureandathirdheartsoundinpatientswithheartfailure.NEnglJMed2001345:57481.PanelsCandD,reproducedwith permissionfromDraznerMH,RameJE,DriesDL.Thirdheartsoundandelevatedjugularvenouspressureasmarkersofthesubsequent developmentofheartfailureinpatientswithasymptomaticleftventriculardysfunction.AmJMed2003114:4317.

SchematicIllustrationoftheLAPressureandLVEndDiastolicPressureandPhonocardiograminChronicLVDiseaseAssociatedWithEithera PredominantS3orS4Gallop Figure6 WhenthereisapredominantS4,thereisapowerfulatrialsystoliccontraction(awave)producingaloudS4gallopandalowermeanleftatrial (LA)pressure.Whentheatriumfails,themeanLApressurerises,andtheVwaveheightincreases,resultinginahighleftventricular(LV)filling pressureinearlydiastole,producingaloudS3gallop. ModifiedwithpermissionfromLewisRP,LeierCV.Leftsidedheartfailure.In:CarlsonRW,GehebMA,eds.PrinciplesandPracticeofMedical IntensiveCare.Philadelphia:W.B.Saunders,1993:101524.

MurmursAudibleinDiastole Figure7 A.Earlydecrescendo,harshmurmurofaorticorpulmonicregurgitation. B.Openingsnap(OS)andmiddiastolicmurmurwithpresystolicaccentuationofmitralstenosisinsinusrhythm.Whenatrialfibrillationdevelops, thereisnopresystolicaccentuation. C.Continuousmurmurofarterialvenousconnections(i.e.,patentductusarteriosus,rupturedsinusofValsalvaaneurysm,arteriovenous malformation,coronaryfistula,etc.)thatpeaksatS2andcontinuesintodiastole.

AorticPressureDuringValsalvaManeuverinaNormalPatient Figure8 PhaseI,withinitiationofValsalva,theaorticpressureincreasestransientlybecauseofanincreaseinintrathoracicpressure. PhaseII,withmaintenanceofValsalva,theaorticpressureandpulsepressuredecreasebecauseofagradualdeclineinleftventricular(LV) preload.IfLVfillingpressureisnormal,reflextachycardiaoccursduetoactivationofthebaroreceptors. PhaseIII,withreleaseofValsalva,theaorticpressuredeclinesfurtherinresponsetodecreaseinintrathoracicpressure. PhaseIV,recoveryperiodwithincreaseinLVpreload,aorticpressure,andpulsepressure. ReproducedwithpermissionfromNishimuraRA,TajikAJ.TheValsalvamaneuver3centurieslater.MayoClinProc200479:5778.

AbnormalValsalvaResponsesasAssessedviatheKorotkoffSounds Figure9 A.NormalsinusoidalresponsewithKorotkoffsoundsaudibleduringstrain(PhaseI)andrelease(PhaseIV). B.Soundsaudibleduringinitialstrainphaseonly(PhaseI)suggestsimpairedsystolicfunctionintheabsenceoffluidoverload. C.PersistenceofKorotkoffsoundsthroughoutstrainphase(PhaseIandII)suggestselevatedleftventricularfillingpressures. BP=bloodpressure. ReproducedwithpermissionfromShamshamF,MitchellJ:Essentialsofthediagnosisofheartfailure.AmFamPhysician200061:131928.

ProstheticHeartValves
Centraltoanassessmentofprostheticvalvefunctionisanunderstandingofthe normalauscultatoryfindingsforeachtypeineachlocation.Valvedysfunctionmaybe suggestedbyachangeintheintensityorqualityofapreviouslyaudiblesound,the appearanceofanewmurmur,orachangeinthecharacteristicsofapreexisting murmur.Mechanicalvalvesproducecrispandhighpitchedopeningandclosing sounds,whereasbioprostheticvalvesproducesoundsthataresimilarinqualityto thoseofanativevalve.Withacagedballvalve,theopeningsoundislouderthanthe closingsoundtheoppositeistruewithatiltingdiskvalve.Thenormaland abnormalauscultatoryfindingsforeachtypeofprostheticvalveandforaorticand mitrallocationsareshowninFigure10.

Figure10

AuscultatoryCharacteristicsofVariousProstheticValvesintheAorticandMitralPositions,WithSchematicDiagramsofNormalFindingsand DescriptionsofAbnormalFindings Figure10 AC=aorticleafletclosureCC=closingclickDM=diastolicmurmurMC=mitralleafletclosingMO=mitralleafletopeningOC=openingclick SEM=systolicejectionmurmur. ReproducedwithfromVongpatanasinW,HillisLD,LangeRA.Prostheticheartvalves.NEnglJMed1996335:40716.

KeyPoints
Obtainingadetailedfamilyhistoryisimportant,sincemanyCVdisordersareheritable. Intheevaluationofthepatientwithsuspectedcongestion,asymptomorsigninisolationhaslimiteddiagnostic sensitivity,specificity,andpredictivevalue. InpatientswithsymptomaticheartfailureorasymptomaticLVdysfunction,thepresenceofanelevatedJVPorS3 predictsheartfailurehospitalizationsanddeathfrompumpfailure. Assessmentoftheheartfailurepatientbasedontheirhemodynamicsperfusionstatus(warmorcold)and volumestatus(dryorwet)isusefulinassessingprognosisandguidingtherapy. Theharshmurmurofaorticstenosismaysoundlikeablowingmurmurofmitralregurgitationattheapex (Gallavardineffect). Diastolicmurmursarealwayspathologic.

References
1. MangioneS.Cardiacauscultatoryskillsofphysiciansintraining:acomparisonofthreeEnglishspeaking countries.AmJMed2001110:2106. 2. MarchSK,BedynekJLJr,ChiznerMA.Teachingcardiacauscultation:effectivenessofapatientcenteredteaching conferenceonimprovingcardiacauscultatoryskills.MayoClinProc200580:14438. 3. VukanovicCrileyJM,HovanesyanA,CrileySR,etal.Confidentialtestingofcardiacexaminationcompetencyin cardiologyandnoncardiologyfacultyandtrainees:amulticenterstudy.ClinCardiol201033:73845. 4. ErneP.Beyondauscultationacousticcardiographyinthediagnosisandassessmentofcardiacdisease.Swiss MedWkly2008138:43952. 5. deGrootdeLaatLE,tenCateFJ,VourvouriEC,vanDomburgRT,RoelandtJR.Impactofhandcarriedcardiac ultrasoundondiagnosisandmanagementduringcardiacconsultationrounds.EurJEchocardiogr20056:196 201. 6. GoldmanL,HashimotoB,CookEF,LoscalzoA.Comparativereproducibilityandvalidityofsystemsforassessing cardiovascularfunctionalclass:advantagesofanewspecificactivityscale.Circulation198164:122734. 7. GheorghiadeM,FollathF,PonikowskiP,etal.Assessingandgradingcongestioninacuteheartfailure:a scientificstatementfromtheacuteheartfailurecommitteeoftheheartfailureassociationoftheEuropeanSociety ofCardiologyandendorsedbytheEuropeanSocietyofIntensiveCareMedicine.EurJHeartFail201012:42333. 8. RohdeLE,BeckdaSilvaL,GoldraichL,etal.Reliabilityandprognosticvalueoftraditionalsignsandsymptoms inoutpatientswithcongestiveheartfailure.CanJCardiol200420:697702. 9. ThavendiranathanP,BagaiA,KhooC,DorianP,ChoudhryNK.Doesthispatientwithpalpitationshaveacardiac arrhythmia?JAMA2009302:213543. 10. DraznerMH,HellkampAS,LeierCV,etal.Valueofclinicianassessmentofhemodynamicsinadvancedheart failure:theESCAPEtrial.CircHeartFail20081:1707. 11. NohriaA,TsangSW,FangJC,etal.Clinicalassessmentidentifieshemodynamicprofilesthatpredictoutcomes inpatientsadmittedwithheartfailure.JAmCollCardiol200341:1797804. 12. VinayakAG,LevittJ,GehlbachB,PohlmanAS,HallJB,KressJP.Usefulnessoftheexternaljugularvein examinationindetectingabnormalcentralvenouspressureincriticallyillpatients.ArchInternMed 2006166:21327. 13. DraznerMH,HamiltonMA,FonarowG,CreaserJ,FlavellC,StevensonLW.Relationshipbetweenrightandleft sidedfillingpressuresin1000patientswithadvancedheartfailure.JHeartLungTransplant199918:112632. 14. McGeeSR.Physicalexaminationofvenouspressure:acriticalreview.AmHeartJ1998136:108. 15. RamanaRK,SanagalaT,LichtenbergR.AnewangleontheAngleofLouis.CongestHeartFail200612:1969. 16. DraznerMH,RameJE,DriesDL.Thirdheartsoundandelevatedjugularvenouspressureasmarkersofthe subsequentdevelopmentofheartfailureinpatientswithasymptomaticleftventriculardysfunction.AmJMed 2003114:4317. 17. DraznerMH,RameJE,StevensonLW,DriesDL.Prognosticimportanceofelevatedjugularvenouspressureand athirdheartsoundinpatientswithheartfailure.NEnglJMed2001345:57481. 18. StevensonLW,PerloffJK.Thelimitedreliabilityofphysicalsignsforestimatinghemodynamicsinchronicheart failure.JAMA1989261:8848. 19. KhanNA,RahimSA,AnandSS,SimelDL,PanjuA.Doestheclinicalexaminationpredictlowerextremity peripheralarterialdisease?JAMA2006295:53646. 20. ParameswaranGI,BrandK,DolanJ.Pulseoximetryasapotentialscreeningtoolforlowerextremityarterial diseaseinasymptomaticpatientswithdiabetesmellitus.ArchInternMed2005165:4426. 21. MalkiQ,SharmaND,AfzalA,etal.Clinicalpresentation,hospitallengthofstay,andreadmissionrateinpatients withheartfailurewithpreservedanddecreasedleftventricularsystolicfunction.ClinCardiol200225:14952.

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3.2:ExerciseTesting
Author(s): ToddD.Miller,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. 2. 3. 4. Contrastthedifferencesbetweentheexercisetest'svaluefordiagnosticversusprognosticpurposes. Identifytheimpactofverificationbiasondiagnostictestperformance. Determinehowtoapplytheexercisetestforaccurateprognostication. Comparetheaccuracyofthestandardexercisetreadmilltest(ETT)versusstressimagingforconductingrisk stratificationinpatientswithanormalrestingelectrocardiogram(ECG).

Introduction
ECGmonitoringeitherduringorimmediatelyafterexercisetodiagnosis"coronary insufficiency"datesbackmorethan70years.Treadmilltestingistheexercise modalitymostoftenappliedintheUnitedStates.Themostcommonlyusedprotocol istheBruceprotocol,whichbeginsataworkloadofapproximately45metabolic equivalents(METs),andincreasestheworkloadinapproximately3METincrements every3minutes. IndicationsandContraindications ThetwomostcommonindicationstoperformanETTarefordiagnosticpurposes andprognosticpurposesforclinicallystablepatientswhoareundergoingevaluation ofpossibleorknowncoronaryarterydisease(CAD).1,2Historically,theETTwas commonlyrecommendedforriskstratificationintwospecialclinicalcircumstances: 1)preoperativeassessment,and2)acutecoronarysyndrome.3,4However,itisnow performedlessfrequentlyfortheseindications.Forasymptomaticindividuals,the ETT,withorwithoutimagingtoscreenforCAD,isgenerallydiscouragedby AmericanCollegeofCardiology/AmericanHeartAssociation(ACC/AHA)guidelines.5 TheETTplaysaminorroleintheassessmentofarrhythmias.Itcanbeusefulfor diagnosisintheindividualwhosehistorysuggestsanexerciseinduced tachyarrhythmia.Rarely,itisusedtooptimizethesettingofthemotionsensorina patientwithapacemaker.Infrequently,anETTisperformedforobjective hemodynamicandfunctionalassessmentinapatientwithstructuralheartdisease ofuncertainclinicalsignificance.Forexample,itcouldbeusedwithapatientwith hypertrophicobstructivecardiomyopathyorborderlinesevereaorticstenosiswho presentswithvaguesymptoms(e.g.,fatigue,lightheadedness). Contraindicationstoexercisecanbecategorizedasabsoluteorrelative(Table1).1 Mostoftheseconditionswillbereadilyapparentduringthepatient'spretestclinical assessment.However,therearetwouncommonentitiesthatcanmimicCADand aremorelikelytobeoverlooked,especiallyinasemiacutesettingsuchasan emergencyroomchestpainunit.Thesearepulmonaryembolusandaortic dissection. TheETTisgenerallyasafeprocedure,withariskofdeathormyocardialinfarction (MI)of1in2,500tests.Exerciseendpointsincludethefollowingspecificsymptoms orsigns:thepatient'sdesiretostop,moderateangina,centralnervoussystem symptoms,hypotension(definedasadecreaseinsystolicbloodpressure10mm Hgbelowbaseline),STsegmentelevation1.0mm,andseriousarrhythmias.Most laboratoriesstopexerciseonceSTsegmentdepressionreaches2.0mm. SpecialConsiderations Clinicianscommonlyorderastresstestforbothdiagnosticandprognosticreasons inthesamepatient.However,studiesthatanalyzetestperformanceapply significantlydifferentmethodologiesforassessingdiagnosticversusprognostic accuracy(Figure1).Diagnosticaccuracyisevaluatedintheminoritysubsetof patientswhoarereferredforcoronaryangiography,thelargemajorityofwhomhave positivetestresults.Conversely,prognosticstudiesmeasureclinicalendpointsin theentirestudypopulation,exceptforexcludingpatientswhoundergoearly revascularization.Mostpatientsinprognosticstudieshavenormaltestresults. Theseissuesareexploredingreaterdetailinthismodule. AppropriatenesscriteriadonotexistforthestandardETT,butareavailablefor stressradionuclideimagingandstressechocardiography.6,7Confusionoccurs whenguidelinesandappropriatenesscriteriaassignapparentlydiscrepantratings totestindicationsforthesameclinicalscenario.Theratingsystemappliedbythe ACC/AHAguidelines(i.e.,ClassI,II,III)isnotidenticaltothesystemusedby appropriatenesscriteria(i.e.,appropriate,uncertain,inappropriate).Anappropriate indicationisnotsynonymouswithaClassIindication.Theguidelinesprocess entailsamorerigorousreviewofthemedicalliteratureandismoreevidencebased.
Figure1

Table1

ContraindicationstoExercise Table1 AdaptedwithpermissionfromGibbonsRJ,BaladyGJ,BrickerJT,etal.,onbehalfoftheAmericanCollegeofCardiology/AmericanHeart AssociationTaskForceonPracticeGuidelines.CommitteetoUpdatethe1997ExerciseTestingGuidelines.ACC/AHA2002guidelineupdatefor exercisetesting:summaryarticle.AreportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines (CommitteetoUpdatethe1997ExerciseTestingGuidelines).JAmCollCardiol200240:153140.

PerformanceofDiagnosticandPrognosticStudies Figure1 Redbox=Diagnosticsubset Yellowbox=Patientsexcludedfromprognosticgroup Greenbox=Prognosticsubset CABG=coronaryarterybypassgraftingFU=followupPCI=percutaneouscoronaryintervention.

ExerciseTreadmillTestforDiagnosticPurposes
STSegmentDeflection Fordiagnosticpurposes,thehallmarkofanabnormaltestisSTsegment depression,analyzedasadichotomous(positiveornegative)variable.1 Most laboratoriesdefineanischemicresponseas1.0mmhorizontalordownsloping STsegmentdepressionthatismeasured60to80msecaftertheJpoint.Upsloping STsegmentdepressioncanincreasetestsensitivity,butdoessoattheexpenseof anunacceptabledecreaseintestspecificity. SeveralfeaturesconcerningSTsegmentdepressionincreasethelikelihoodofa truepositiveversusafalsepositivetest,including:occurrenceatalowexercise workload,involvementofseveralECGleads,greatermagnitudeofdepression,and longerpersistenceintherecoveryperiod.STsegmentdepressionthatdevelops onlyintherecoveryperiodhasthesamediagnosticaccuracyasSTsegment depressionthatoccursduringexercise.Thevastmajority(>90%)ofpositive responsesoccurinleadsV4 V6 ,regardlessofthesiteofanatomicalCAD.ST segmentdepressionthatisconfinedtotheinferiorleadsaloneusuallyrepresentsa falsepositivefinding. STsegmentelevationoccursmuchlesscommonlythanSTsegmentdepression.It canbearrhythmogenicifexercisecontinues.UnlikeSTsegmentdepression,ST segmentelevationcanlocalizethesiteofmyocardialischemia.Itusuallyreflectsa highgradestenosisinthecoronaryarterysupplyingthoseleadsinwhichtheST segmentelevationoccurs. Severalothermarkershavebeenproposedasindicatorsofischemiaoridentifiers ofspecificcoronaryanatomy(i.e.,leftmainorproximalCAD).Thesemarkershave included:anincreaseinRwavevoltage,developmentofinvertedUwaves,ST segmentelevationinleadaVR,andSTsegmentchangesintherightprecordial leads.Theseobservationsgenerallyhavenotwithstoodcarefulscrutiny.Currently, theydonotplayasignificantroleinassessmentoftheECGischemicresponse. DiagnosticTestAccuracy AllnoninvasivetestsusedforassessmentofCADareanalyzedagainstthegold standardofinvasivecoronaryangiography.Thefollowingtermsandtheirdefinitions areappliedtodescribetestaccuracy.
Figure2

Figure3

Figure4

Abbreviations:FP=falsepositiveFN=falsenegativeTP=truepositiveTN=true negative. ForthestandardETT,testsensitivityis68%andtestspecificityis77%.Sensitivityof theETTislowerthansensitivityofstressimaging.However,specificityis comparablewiththatofstressimaging(Figure2).1,8,9 VerificationBias/ReferralBias Thesevaluesfortestsensitivityandspecificityarenottrulyaccuratebecausethey aredistortedbyverificationbias.Verificationbiasdescribestheimpactonthe

reportingoftestsensitivityandspecificitywhencalculatedprimarilyusingpatients withpositivetestresults.Nearlyallstudiesexaminediagnostictestaccuracyinthe minorityofpatientsreferredforcoronaryangiography.Thisisasubsetofthe populationwhoaredominatedbypositivetestresults.Ifveryfewpatientswitha negativetestarereferredtoangiography,thensensitivity(TP/TP+FN)approaches 100%andspecificity(TN/TN+FP)approaches0%. Theonlypureapproachtomeasuringthediagnosticaccuracyofanoninvasivetest istocatheterizeallpatientsregardlessofthenoninvasivetestresults.Onlyone studyhasappliedthisdesign.ThisstudyreportedthesensitivityforETTat45%, whichissubstantiallylowerthanthevalueof68%reportedbymetaanalysis.10 Otherstudieshaveusedastatisticalapproachbyapplyingcomplexmathematical formulastoadjustfortheimpactofreferralbias(Figure3).1113Figure3highlights thelowadjustedsensitivityvalues,suggestingthatmanypatientswithCADgo undetected,evenbystressimagingprocedures. BayesTheorem Sincenoneofthenoninvasivetestscorrelateperfectlywiththeresultsofcoronary angiography,noneofthenoninvasivetestsaretruly"diagnostic."Instead,CAD probabilitysimplyshiftsaccordingtothetestresults.BayesTheoremstatesthatthe posttestprobabilityofCADdependsnotonlyonthetestresult,butalsoonthe pretestprobabilityofCAD(Figure4).Thepretestprobabilityiscalculatedfrom clinicalvariablesbaseduponage,gender,andcharacteristicsofchestpain.2 ETT hasmaximaldiagnosticvalueforpatientswithintermediate(i.e.,1090%)pretest probabilityofCAD.AccordingtoACC/AHAguidelines,itisaClassIindicationin thesepatients.1,2 ETTisoflittlediagnosticvalueforpatientsattheextremeendsofpretestprobability. Theseincludethosewithalow(<10%)pretestprobability,primarilywomenunder age60withnonanginalchestpain.Italsoincludesthosewithahigh(>90%)pretest probability,primarilymenoverage50withtypicalangina.Forthesepatientsubsets, ETTfordiagnosticpurposesisassignedaClassIIbindication. AdditionalAccuracyConsiderations CertainabnormalitiesontherestingECGprecludeinterpretationoftheexercise ECG.Theseincludeleftbundlebranchblock(LBBB)andpacedventricularrhythm. However,theexerciseECGcanbeinterpretedinthepresenceofrightbundle branchblock(RBBB)iftherightprecordialleads(i.e.,V1 V3 )areignoredand interpretationisconfinedtotheleftprecordialleads(i.e.,V4 V6 ). Certainfactorsreducetestsensitivity.Themostcommonfactoristheuseofbeta blockers.OtherfactorsthatreducetestspecificityincludeSTTabnormalitiesonthe restingECG,digoxinuse,andleftventricularhypertrophy.Testaccuracy(both sensitivityandspecificity)islowerinwomenthanmen.Thisisatleastpartiallydue toalowerprevalenceofCADinwomen.AlthoughETTaccuracyislowerinwomen, ACC/AHAguidelinesdonotconsidergendertobeadeterminantforselectinga specifictestmodalityinanindividualpatient.

DiagnosticAccuracyofETT,SPECT,andEcho Figure2 Echo=echocardiographyETT=exercisetreadmilltestSPECT=singlephotonemissioncomputedtomography. References 1. GibbonsRJ,BaladyGJ,BrickerJT,etal.,onbehalfoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceon PracticeGuidelines.CommitteetoUpdatethe1997ExerciseTestingGuidelines.ACC/AHA2002guidelineupdateforexercisetesting: summaryarticle.AreportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines (CommitteetoUpdatethe1997ExerciseTestingGuidelines).JAmCollCardiol200240:153140. 2. KlockeFJ,BairdMG,LorellBH,etal.ACC/AHA/ASNCguidelinesfortheclinicaluseofcardiacradionuclideimagingexecutivesummary: areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines(ACC/AHA/ASNC CommitteetoRevisethe1995GuidelinesfortheClinicalUseofRadionuclideImaging).JAmCollCardiol200342:131833. 3. CheitlinMD,ArmstrongWF,AurigemmaGP,etal.ACC/AHA/ASE2003guidelineupdatefortheclinicalapplicationofechocardiography summaryarticle:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines (ACC/AHA/ASECommitteetoUpdatethe1997GuidelinesfortheClinicalApplicationofEchocardiography).JAmCollCardiol 200342:95470.

ImpactofVerificationBias Figure3 Echo=echocardiographyETT=exercisetreadmilltestSPECT=singlephotonemissioncomputedtomography. References: 1. MoriseAP,DiamondGA.Comparisonofthesensitivityandspecificityofexerciseelectrocardiographyinbiasedandunbiased populationsofmenandwomen.AmHeartJ1995130:7417. 2. RogerVL,PellikkaPA,BellMR,ChowCW,BaileyKR,SewardJB.Sexandtestverificationbias:impactonthediagnosticvalueof exerciseechocardiography.Circulation199795:40510. 3. MillerTD,HodgeDO,ChristianTF,MilavetzJJ,BaileyKR,GibbonsRJ.Effectsofadjustmentforreferralbiasonthesensitivityand specificityofsinglephotonemissioncomputedtomographyforthediagnosisofcoronaryarterydisease.AmJMed2002112:2907.

BayesTheorem Figure4

ExerciseTreadmillTestforPrognosticPurposes(Risk Stratification)
DesignofPrognosticStudies ETTandstressimagingprognosticstudiesaredesignedtomeasuretwodifferent typesofendpoints.Themorecommontypeofstudymeasuresclinicalendpoints (e.g.,death,nonfatalMI).PatientswithknownCAD,includingthosewithprior revascularization,maybeincludedinthesestudies.Patientswhoundergo revascularizationwithinarelativelyshorttimeperiod(e.g.,23months)afterthe noninvasivetestarecommonlyexcludedfromfollowupinthesestudies.Thisis basedupontherationalethatthissubsetisreceivingatreatmentnotappliedtothe entirestudypopulation,whichmayaltertheirprognosis.Amajorgoalofthistypeof studyistodemonstratethatpatientscategorizedaslowriskonthebasisofthe stresstest,doturnouttohavealowclinicaleventrate.Themajorityofthesepatients donotundergoanyadditionalcardiactesting. Asecondtypeofriskstratificationstudyappliesanangiographicendpointtoassess howaccuratelystresstestingidentifiespatientswithsevereCAD.SevereCADis definedasleftmainorthreevesselCAD.SevereCADisoneofthestrongest cardiacprognosticvariables.Patientswiththeseanatomicalfindingshaveasurvival advantagewhentreatedwithcoronaryarterybypassgrafting(CABG). ClinicalRiskCategories ACC/AHAguidelinesidentifythreeclinicalCADriskcategoriesonthebasisof annualmortalityrates:lowriskis<1%,intermediateriskis1%3%,andhighriskis >3%.2 Theseriskthresholdsarebasedinpartonthenaturalhistoryofanatomical CAD(Figure5).14Theguidelinesprovidegeneralmanagementrecommendations thatfollowstresstesting,basedonriskclassification.Lowriskpatientsdonot requirefurthertestingandcanbetreatedmedically,andhighriskpatientsshouldbe referredtocoronaryangiography.Themanagementofintermediateriskpatientsis lesscertain. PrognosticVariablesandTreadmillScores ThemostimportantETTprognosticvariableisexercisecapacity.15Patientswith poorcapacityareatahighriskforleftmain/threevesselCADandhaveahigh clinicaleventrate.Othervariableswhichidentifyhigherriskpatientsincludeexercise hypotensionandimpairedheartrateresponse,eitherduringexercise(i.e., chronotropicincompetence)orafterexercise(i.e.,heartraterecovery).Insome studies,ventricularectopyidentifieshigherriskpatients.STdepressionalsoadds toprognosticassessmentbutisgenerallyweakerthantheseothervariables. McNeer,etal.performedthelandmarkstudydemonstratingthatthecombinationof exercisecapacityandexerciseECGresponsecanpredicttheriskofleftmain/three vesselCADatangiography(Table2).16Forpatientswithexercisestage1or2anda positiveECG,>60%hadthreevesselCADand>25%hadleftmainCAD. Conversely,forpatientswithexercisestage3or4andanegativeECG,only10% hadthreevesselCAD,andonly4%and1%,respectively,hadleftmainCAD.Other studieshavedemonstratedthatpatientswiththreevesselCADandexcellent exercisecapacityhaveaveryloweventratewhentreatedwithmedicaltherapy. Studiesmeasuringclinicalendpointshavereportedthatacombinationofvariables stratifiesriskmoreaccuratelythananysinglevariable.Themostwidelyutilized variablecombinationistheDuketreadmillscore,whichcanbecalculatedas follows: Score= exercisecapacity(timeinminutes,Bruceprotocol)5XmagnitudeofSTsegment deflection(mm)4Xanginaindex (AnginaIndex:0=none1=nonlimiting2=limiting) Whenappliedtoanoutpatientcohort,62%ofthepatientshadalowriskscore. Therewasanobservedannualmortalityofonly0.25%(Figure6).17
Figure5

Table2

Figure6

CADPrognosticIndex Figure5 CAD=coronaryarterydisease. AdaptedwithpermissionfromCaliffRM,ArmstrongPW,CarverJR,D'AgostinoRB,StraussWE.27thBethesdaConference:matchingthe intensityofriskfactormanagementwiththehazardforcoronarydiseaseevents.Taskforce5.Stratificationofpatientsintohigh,mediumand lowrisksubgroupsforpurposesofriskfactormanagement.JAmCollCardiol199627:100719.

RelationshipofExerciseStageandECGtoPresenceandExtentofSignificantCoronaryArteryDisease Table2 Theresultsareexpressedaspercentages.Thenumbersinparenthesesequalthenumberofpatientsinthatcategory. CAD=coronaryarterydiseaseECG=electrocardiogram. ReproducedwithpermissionfromMcNeerJ,MargolisJR,LeeKL,etal.Theroleoftheexercisetestintheevaluationofpatientsforischemic heartdisease.Circulation197857:6470.

DukeTreadmillScore Figure6 AdaptedwithpermissionfromMarkDB,ShawL,HarrellFEJr,et.al.Prognosticvalueofatreadmillexercisescoreinoutpatientswithsuspected coronaryarterydiseaseNEnglJMed1991325:84953.

StressTestingInSpecialClinicalSituations
PreoperativeEvaluation Formerly,stresstestingcomprisedamajorcomponentofpreoperativeevaluation.However,themostrecentACC/AHA guidelineonthistopicrecommendsstresstestingbeforenoncardiacsurgeryonlyinthefollowingsituations3 : ClassIpatientswithactivecardiacconditions(unstablecoronarysyndromes,decompensatedheartfailure, significantarrhythmias,severevalvulardisease). ClassIIapatientswith3riskfactors(CAD,historyofheartfailure,diabetes,renalinsufficiency,cerebrovascular disease)andpoorfunctionalcapacity(<4METs)priortovascularsurgery,iftheresultsoftestingwillchange management. ClassIIbpatientswithoneortwoclinicalriskfactorsandpoorfunctionalcapacitywhoarescheduledfor vascularorintermediaterisksurgery,iftheresultswillchangemanagement. Testingisnotrecommendedforpatientsundergoinglowrisksurgery,thosewithgoodfunctionalcapacity(i.e.,4METs), orthosewithnoclinicalriskfactorswhoareundergoingintermediaterisksurgery. PostMyocardialInfarction Historically,stresstestingalsoplayedamajorroleforriskstratificationpostMI.Stresstestingforthispurposehas substantiallydeclinedduetotheperformanceofearlycoronaryangiographyinmanypatients.Coronaryangiographyisa ClassIindicationforpatientswitheitherSTsegmentelevationmyocardialinfarction(STEMI)ornonSTsegment elevationmyocardialinfarction(NSTEMI).Additionally,inaclimatethatfinanciallyrewardsshorterhospitalduration, performingstresstestingduringthepatient'shospitalizationonlylengthensthehospitalstay.Nonetheless,ETTremains aClassIindicationforthestabilized,lowriskpatientwhoprefersaconservativeapproach.4

CardiopulmonaryExerciseTesting
CardiopulmonaryexercisetestingconsistsofperforminganETTorcycleergometryinconjunctionwithmeasurementof ventilatorygasexchange.18Themostcommonlymeasuredvariablesinclude: Maximal(peak)oxygenuptake(oxygenconsumption[VO2 ]max)theamountofoxygenconsumedduringa maximalexerciseeffort. Ventilatorythreshold(VT)theexerciselevelwhereventilationstartstoincreaseexponentiallyinrelationtothe increaseinVO2 .Itiscommonlyreferredtoasthe"anaerobic"threshold. Peakrespiratoryexchangerate(RER)theratioofcarbondioxideproduction,orVCO2 ,toVO2 . Theventilatoryequivalentforcarbondioxide(VE/VCO2 )theratioofminuteventilation,orVE,toVCO2 . ExercisebreathingreserveameasureofhowcloselyVEduringexerciseapproachesthemaximalvoluntary ventilation(MVV),oftenmeasuredduringpulmonaryfunctiontesting. Oxygensaturation,measuredwithapulseoximeter. Thesevariablescanindicateifacardiacorapulmonaryabnormalityisthelimitingfeatureofapatient'sexercisecapacity. VO2 maxcanbeestimatedfromexerciseworkload,butislesspreciseandmorevariablethandirectmeasurementof VO2 max,especiallyinpatientswithlimitedfunctionalcapacity.RERisanindicatorofexerciseeffort.Avalue<1.0is consistentwithasubmaximalcardiovasculareffort.VE/VCO2 reflectsventilatoryefficiency,andisabnormalinpatients withheartfailureandchroniclungdisease.Themostcommonclinicalapplicationsofcardiopulmonarytestingare unexplaineddyspneaandheartfailure.Inpatientswithheartfailure,VO2 ispredictiveofsurvivalandaidsintheselection ofcandidatesforcardiactransplantation.

ComparisonofStandardExerciseTreadmillTestandStress Imaging
Twoofthemostimportantcardiacprognosticfactorsaregloballeftventricular function,usuallymeasuredasleftventricularejectionfraction(LVEF),andsevere CAD,definedasleftmainand/orthreevesselCAD.Randomizedtrialscompared treatmentwithmedicaltherapyaloneversusrevascularization.Thesetrialsreported animprovementinsurvivalwithCABGonlyinthesubsetofpatientswithleftmain CADorthreevesselCAD,especiallyinthesettingofLVEF<50%. Otherrandomizedtrialshavereportedthatdefibrillatorsimprovesurvivalinpatients withseverelyreducedLVEF<35%.Basedonthesestudies,themostimportantgoal oftheinitialevaluationofapatientwithpossibleCADshouldbetheidentificationof severeCADorseverelydecreasedLVEF.Thesepatientsubsetsareeligibleforlife prolongingtherapiesthatarenotappliedtotheentirepatientpopulation. StudiesComparingApproaches Studieshavereportedthatstressimagingaddsincrementalprognosticinformation toclinicalandstandardETTvariables.19,20Thestatisticalmethodologyappliedin thesestudiescomparedtheglobalchisquaretestvaluesofamultivariablemodel thatcontainedonlyclinicalandETTvariables,versusamodelthatalsocontained theimagingvariables.Thisapproachdidnotprovideanyinformationonwhat percentageofapopulationiscorrectlyreclassifiedbyimaging. Toaddressthisissue,MayoClinicinvestigatorsperformedastudythatintentionally enrolledonlypatientswithanormalECG.21Thestudywasconductedtocompare theaccuracyofaclinicalETTmodel(i.e.,ETTmodel)versusaclinicalETTSPECT model(i.e.,imagingmodel)intheidentificationofpatientswithleftmainand/or threevesselCADatangiography.Thestudyalsocomparedthemodels'abilitiesto predictclinicaloutcomes.Therationaleforselectingonlypatientswithanormalrest ECGwastwofold:1)severalstudieshavereportedthat9298%ofpatientswho presentwithanormalrestingECGhaveanormalLVEFwhendirectlymeasuredby avarietyofimagingmethods2 and2)theaccuracyoftheexerciseECGisbetterdue tohigherspecificityinpatientswithanormalrestingECGversusthosewithSTT waveabnormalities.1 IntheMayoClinicstudy,only3%(i.e.,14outof411patients)werecorrectly reclassifiedbytheadditionofimaging(Figure7).Mostofthecorrect reclassificationsresultedfromshiftingpatientswhowerecategorizedas intermediateriskforsevereCADbytheETTmodelintothelowriskcategorybythe imagingmodel.Theimagingmodelfailedtocorrectlyidentifymorepatientswithleft mainorthreevesselCAD. AcostanalysisbasedonMedicarerelativevalueunits(RVUs)indicatedthatthecost foreachcorrectreclassificationexceeded$20,000.Theimagingmodelalsowasnot anymoreaccuratethantheETTmodelforpredictingclinicalevents.Otherstudies havealsoreportedaverylowyieldofimaginginpatientscategorizedaslowriskon thebasisofclinicaland/orETTvariables. GuidelinesRecommendations TheACC/AHAguidelinesrecommendstressimagingastheinitialtestingmodality inthreegroupsofpatientswhohave:1)aninabilitytoexercisewithrequirementfor pharmacologicstress2)significantabnormalitiesontherestingECGthatpreclude interpretationofthestressECGor3)priorrevascularizationwherelocalizationof ischemiaisfrequentlyanimportantclinicalissue(Table3).2 ForotherpatientswithanormalornearnormalrestingECGwhocanadequately exercise,thestandardETTisrecommendedastheinitialnoninvasivetest. Advantagesincludeitsgreateravailabilityandconsiderablylowercost.Mostofthese patientswillhavenormalLVfunctiononthebasisofanormalrestingECGanddo notrequireimagingformeasurementofLVEF.Also,themajoritywillhavealowrisk treadmillscoreanddonotrequirefurthertesting.

Figure7

Table3

Approximately2540%ofthesepatientswillhaveanintermediaterisktreadmilltest resultandmayrequirefurtherriskstratification,whichcouldincludeastress imagingprocedure.Thisstepwiseapproach(i.e.,standardETTfirst,followedby stressimagingifnecessary)islessefficientinthisintermediaterisksubsetof patients.However,itisconsiderablymorecosteffectivethanperformingstress imagingintheentirestudypopulation,sincepatientscategorizedaslowriskor highriskbytheETTalonewillnotrequireimaging.

ProbabilityofSevereCoronaryArteryDisease Figure7 ToppanelmodelcontainingclinicalvariablesonlymiddlepanelmodelcontainingclinicalandETTvariablesbottompanelmodelcontainingclinical, ETT,imagingvariables. ReproducedwithpermissionfromChristianTF,MillerTD,BaileyKR,GibbonsRJ.Exercisetomographicthallium201imaginginpatientswith severecoronaryarterydiseaseandnormalelectrocardiograms.AnnInternMed1994121:82532.

StandardETTVersusImaging,InitialTestSelection Table3 *LBBB,paced,WPW,1mmSTsegmentdepression. CABG=coronaryarterybypassgraftingECG=electrocardiogramETT=exercisetreadmilltestPCI=percutaneouscoronaryintervention. AdaptedwithpermissionfromAndersonJL,AdamsCD,AntmanEM,etal.ACC/AHA2007guidelinesforthemanagementofpatientswith unstableangina/nonSTelevationmyocardialinfarction:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForce onPracticeGuidelines(WritingCommitteetoRevisethe2002GuidelinesfortheManagementofPatientsWithUnstableAngina/NonSTElevation MyocardialInfarction)developedincollaborationwiththeAmericanCollegeofEmergencyPhysicians,theSocietyforCardiovascular AngiographyandInterventions,andtheSocietyofThoracicSurgeonsendorsedbytheAmericanAssociationofCardiovascularandPulmonary RehabilitationandtheSocietyforAcademicEmergencyMedicine.JAmCollCardiol200750:e1157.

Conclusions
Table4representsacondensedversionofACC/AHAguidelineindicationsforsome ofthemostcommonindicationsforETTwithoutimaging.Notethatratingindications maydifferifthetestisbeingdonefordiagnosticversusprognosticreasons,evenin thesamepatient.Forinstance,considerthecaseofa60yearoldmanwhohas typicalangina,isabletoexercise,andhasanormalrestingECG.ETTfordiagnosis ofCADisaClassIIbindication,sincethispatienthasahighpretestprobabilityof CADandthetestresultswillnotsubstantiallyalterthisprobability.Ontheother hand,ETTforriskstratificationisaClassIindication. Itisalsoimportanttonotetheapparentdiscrepanciesinratingindicationsassigned byACC/AHAguidelinesversusappropriatenesscriteriaforstressnuclearand stressechocardiographicimaging.Asageneralrule,theguidelinestendtobemore conservative.Forinstance,testinginasymptomaticpatientsisgenerallyassigneda ClassIIborIIIindicationbytheguidelines,whereas,accordingtoappropriateness criteria,someclinicalscenariosinselectedasymptomaticpatients(e.g.,screening forCADinhighriskasymptomaticpatients)areconsideredappropriateforstress imaging.

Table4

AmericanCollegeofCardiology/AmericanHeartAssociationGuidelineRecommendations Table4 CAD=coronaryarterydiseaseECG=electrocardiogramLBBB=leftbundlebranchblockLVH=leftventricularhypertrophyMI=myocardial infarctionWPW=WolffParkinsonWhitesyndrome. AdaptedwithpermissionfromAndersonJL,AdamsCD,AntmanEM,etal.ACC/AHA2007guidelinesforthemanagementofpatientswith unstableangina/nonSTelevationmyocardialinfarction:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForce

onPracticeGuidelines(WritingCommitteetoRevisethe2002GuidelinesfortheManagementofPatientsWithUnstableAngina/NonSTElevation MyocardialInfarction)developedincollaborationwiththeAmericanCollegeofEmergencyPhysicians,theSocietyforCardiovascular AngiographyandInterventions,andtheSocietyofThoracicSurgeonsendorsedbytheAmericanAssociationofCardiovascularandPulmonary RehabilitationandtheSocietyforAcademicEmergencyMedicine.JAmCollCardiol200750:e1157.

KeyPoints
TwomostpotentiallyseriouscontraindicationstoETTthatcansometimesbeoverlookedareaorticdissection andpulmonaryembolus. Forexercisetestdiagnosticaccuracy,themajorvariableanalyzedisSTsegmentdepression.Ischemicresponse isconventionallydefinedas1.0mmhorizontalordownslopingSTsegmentdepressionmeasured0.08 secondsaftertheJpoint. BayesTheoremstatesthattheposttestprobabilitythatapatienthasCADdependsnotonlyuponthetestresults, butalsothepatient'spretestprobabilityofCAD. Themajorimpactofverificationbias(i.e.,posttestreferral)onexercisetestaccuracyisanartifactualincreasein testsensitivityandadecreaseintestspecificity. Thestrongestprognosticexercisetestvariableisexerciseduration. Severalexercisetestscoreshavebeendevelopedforriskstratification,andthemostcommonlyappliedscoreis theDuketreadmillscore. Thetwomostcommonapplicationsofcardiopulmonaryexercisetestingare:1)identificationofunderlyingcardiac orpulmonarydiseaseinapatientwithunexplaineddyspneaandprognosticassessment,and2)assessmentof candidacyforcardiactransplantationinapatientwithcongestiveheartfailure. ThestandardETTistheprocedureofchoice,ratherthanstressimaging,fornoninvasiveassessmentofCADina patientwithoutpriorcoronaryrevascularizationwhoiscapableofadequateexerciseandwhohasanormalor nearnormalrestingECG.

References
1. GibbonsRJ,BaladyGJ,BrickerJT,etal.,onbehalfoftheAmericanCollegeofCardiology/AmericanHeart AssociationTaskForceonPracticeGuidelines.CommitteetoUpdatethe1997ExerciseTestingGuidelines. ACC/AHA2002guidelineupdateforexercisetesting:summaryarticle.AreportoftheAmericanCollegeof Cardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines(CommitteetoUpdatethe1997 ExerciseTestingGuidelines).JAmCollCardiol200240:153140. 2. GibbonsRJ,AbramsJ,ChatterjeeK,etal.ACC/AHA2002guidelineupdateforthemanagementofpatientswith chronicstableanginasummaryarticle:areportoftheAmericanCollegeofCardiology/AmericanHeart AssociationTaskForceonpracticeguidelines(CommitteeontheManagementofPatientsWithChronicStable Angina).JAmCollCardiol200341:15968. 3. FleisherLA,Beckman,JA,Brown,KA,etal.ACC/AHA2007guidelinesonperioperativecardiovascularevaluation andcarefornoncardiacsurgery:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTask ForceonPracticeGuidelines(WritingCommitteetoRevisethe2002GuidelinesonPerioperativeCardiovascular EvaluationforNoncardiacSurgery)developedincollaborationwiththeAmericanSocietyofEchocardiography, AmericanSocietyofNuclearCardiology,HeartRhythmSociety,SocietyofCardiovascularAnesthesiologists, SocietyforCardiovascularAngiographyandInterventions,SocietyforVascularMedicineandBiology,andSociety forVascularSurgery.JAmCollCardiol200750:e159241. 4. AndersonJL,AdamsCD,AntmanEM,etal.ACC/AHA2007guidelinesforthemanagementofpatientswith unstableangina/nonSTelevationmyocardialinfarction:areportoftheAmericanCollegeofCardiology/American HeartAssociationTaskForceonPracticeGuidelines(WritingCommitteetoRevisethe2002Guidelinesforthe ManagementofPatientsWithUnstableAngina/NonSTElevationMyocardialInfarction)developedincollaboration withtheAmericanCollegeofEmergencyPhysicians,theSocietyforCardiovascularAngiographyand Interventions,andtheSocietyofThoracicSurgeonsendorsedbytheAmericanAssociationofCardiovascularand PulmonaryRehabilitationandtheSocietyforAcademicEmergencyMedicine.JAmCollCardiol200750:e1157. 5. GreenlandP,AlpertJS,BellerGA,etal.2010ACCF/AHAguidelineforassessmentofcardiovascularriskin asymptomaticadults:areportoftheAmericanCollegeofCardiologyFoundation/AmericanHeartAssociation TaskForceonPracticeGuidelines.JAmCollCardiol201056:e50103. 6. HendelRC,BermanDS,DiCarliMF,etal.ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM2009AppropriateUse CriteriaforCardiacRadionuclideImaging:AReportoftheAmericanCollegeofCardiologyFoundationAppropriate UseCriteriaTaskForce,theAmericanSocietyofNuclearCardiology,theAmericanCollegeofRadiology,the AmericanHeartAssociation,theAmericanSocietyofEchocardiography,theSocietyofCardiovascularComputed Tomography,theSocietyforCardiovascularMagneticResonance,andtheSocietyofNuclearMedicine.JAmColl Cardiol200953:220129. 7. DouglasPS,KhandheriaB,StainbackRF,etal.ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR2008 appropriatenesscriteriaforstressechocardiography:areportoftheAmericanCollegeofCardiologyFoundation AppropriatenessCriteriaTaskForce,AmericanSocietyofEchocardiography,AmericanCollegeofEmergency Physicians,AmericanHeartAssociation,AmericanSocietyofNuclearCardiology,SocietyforCardiovascular AngiographyandInterventions,SocietyofCardiovascularComputedTomography,andSocietyforCardiovascular MagneticResonanceendorsedbytheHeartRhythmSocietyandtheSocietyofCriticalCareMedicine.JAmColl Cardiol200851:112747. 8. KlockeFJ,BairdMG,LorellBH,etal.ACC/AHA/ASNCguidelinesfortheclinicaluseofcardiacradionuclide imagingexecutivesummary:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTask ForceonPracticeGuidelines(ACC/AHA/ASNCCommitteetoRevisethe1995GuidelinesfortheClinicalUseof RadionuclideImaging).JAmCollCardiol200342:131833. 9. CheitlinMD,ArmstrongWF,AurigemmaGP,etal.ACC/AHA/ASE2003guidelineupdatefortheclinicalapplication ofechocardiographysummaryarticle:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociation TaskForceonPracticeGuidelines(ACC/AHA/ASECommitteetoUpdatethe1997GuidelinesfortheClinical ApplicationofEchocardiography).JAmCollCardiol200342:95470. 10. FroelicherVF,LehmannKG,ThomasR,etal.Theelectrocardiographicexercisetestinapopulationwithreduced workupbias:diagnosticperformance,computerizedinterpretation,andmultivariableprediction.VeteransAffairs CooperativeStudyinHealthServices#016(QUEXTA)StudyGroup.QuantitativeExerciseTestingand Angiography.AnnInternMed1998128:96574. 11. MoriseAP,DiamondGA.Comparisonofthesensitivityandspecificityofexerciseelectrocardiographyinbiased andunbiasedpopulationsofmenandwomen.AmHeartJ1995130:7417. 12. RogerVL,PellikkaPA,BellMR,ChowCW,BaileyKR,SewardJB.Sexandtestverificationbias:impactonthe diagnosticvalueofexerciseechocardiography.Circulation199795:40510. 13. MillerTD,HodgeDO,ChristianTF,MilavetzJJ,BaileyKR,GibbonsRJ.Effectsofadjustmentforreferralbiason thesensitivityandspecificityofsinglephotonemissioncomputedtomographyforthediagnosisofcoronaryartery disease.AmJMed2002112:2907. 14. CaliffRM,ArmstrongPW,CarverJR,D'AgostinoRB,StraussWE.27thBethesdaConference:matchingthe intensityofriskfactormanagementwiththehazardforcoronarydiseaseevents.TaskForce5.Stratificationof patientsintohigh,mediumandlowrisksubgroupsforpurposesofriskfactormanagement.JAmCollCardiol

199627:100719. 15. KligfieldP,LauerMS.Exerciseelectrocardiogramtesting:beyondtheSTsegment.Circulation2006114:207082. 16. McNeerJ,MargolisJ,LeeK,etal.Theroleoftheexercisetestintheevaluationofpatientsforischemicheart disease.Circulation197857:6470. 17. MarkDB,ShawL,HarrellFEJr,etal.Prognosticvalueofatreadmillexercisescoreinoutpatientswithsuspected coronaryarterydisease.NEnglJMed1991325:84953. 18. BaladyGJ,ArenaR,SietsemaK,etal.,onbehalfoftheAmericanHeartAssociationExercise,Cardiac Rehabilitation,andPreventionCommitteeoftheCouncilonClinicalCardiologyCouncilonEpidemiologyand PreventionCouncilonPeripheralVascularDiseaseInterdisciplinaryCouncilonQualityofCareandOutcomes Research.Clinician'sGuidetoCardiopulmonaryExerciseTestinginAdults:AScientificStatementFromthe AmericanHeartAssociation.Circulation2010122:191225. 19. HachamovitchR,BermanDS,KiatH,etal.ExercisemyocardialperfusionSPECTinpatientswithoutknown coronaryarterydisease:incrementalprognosticvalueanduseinriskstratification.Circulation199693:90514. 20. MarwickT,MehtaR,ArheartK,LauerM.Useofexerciseechocardiographyforprognosticevaluationofpatients withknownorsuspectedcoronaryarterydisease.JAmCollCardiol199730:8390. 21. ChristianTF,MillerTD,BaileyKR,GibbonsRJ.Exercisetomographicthallium201imaginginpatientswith severecoronaryarterydiseaseandnormalelectrocardiograms.AnnInternMed1994121:82532.

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3.3:Echocardiography
Author(s): TheodoreP.Abraham,MBBS,FACC AllisonHays,MD

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Reviewtheechocardiographicmethodsavailabletoevaluateglobalandregionalleftventricular(LV)function. 2. Describethesensitivity,specificity,andoverallaccuracyofvariousstresstestmodalitiesfordetectionofsignificant coronaryarterystenoses. 3. Discussthemethodsandapplicationsinvolvedincontrastechocardiographyforimagingperfusion. 4. Demonstratetheincrementalvalueofstressechoimagingoverelectrocardiogram(ECG)stresstestingalonefor detectionofcoronaryarterydisease(CAD)inpatientspresentingwithchestpain. 5. Discussnovelmethodsandapplicationsofechocardiography,includingthreedimensional(3D)echoandstrain imaging.

Introduction
Twodimensional(2D)echocardiographycanimagetheleftventricle(LV)inreal timeatmultiplelevels,anditiscommonlyusedforassessmentofglobaland regionalLVsystolicfunction(Figure1).Theadvantagesof2Dechocardiographyare thatitisportable,lowrisk,inexpensive,andreadilyavailable.1 Thereareboth qualitativeandquantitativemethodsusing2DechotoestimateglobalEF,regional function,andwallthickening. Astandardized17segmentmodelbasedonmultiplanarimaginghasbeen developedforapplicationto2Dechocardiography,aswellasnuclearandcardiac magneticresonance(CMR)techniques.2 LVvolumescanbeestimatedusing formulasbasedonmeasurementsintwoorfourchamberlongaxisviews. Additionalinformation,alongwiththeassessmentofcardiacstructureandfunction, includestheevaluationofvalvular,pericardial,andintraandextramyocardial abnormalities. 2Dechocardiographyisfrequentlyusedintheassessmentofventricularfunctionin thesettingofknownorsuspectedLVdysfunction,acutemyocardialinfarction(AMI), andotheracuteischemicsyndromes.2Dechocardiographyhasbeencarefully validatedasareliablemeasureofLVmassanditsregressioninhypertensiveheart disease.3 Onerequirementisgoodacousticwindows. AccurateassessmentofLVcavitysizeandregionalsystolicthickeningrequires visualizationoftheendocardialborders.Althoughadvancesinimagingtechnology, suchassecondharmonicimaging,haveimprovedborderdelineation,adequate evaluationisstillnotpossibleinupto15%ofpatients,primarilyduetoobesity,lung disease,orchestsurgery.Intravenous(IV)contrastagentshavebeendevelopedto improveLVcavityopacification(Figure2).4 Theuseofcontrastinthestress laboratorysettingcansignificantlyimprovewallsegmentvisualizationandimage qualityatrest,aswellasatpeakstress,resultinginimprovedconfidenceof interpretation.5 Usingendocardialborderdetectiontechniquessuchascolorkinesis,asshownin Figure3,normalvaluesforLVsystolicfunctionhavebeendeveloped.6 Othernovel applicationssuchasrealtimethreedimensionalechocardiography(3DE)are evolvingintoclinicallyusefultools(Figure4).7 3DEhasbeenvalidatedasan accuratemeasureofLVmassandvolumes,andismoreaccuratethan2Decho, withgoodcorrelationwithCMR.8 InadditiontoglobalLVfunctionandvolumes, regionalvolumesareobtained,whichallowquantitationofLVdyssynchrony.911The preciseroleof3DEindaytodayclinicalechocardiographyremainstobedefined. TissueDopplerisemergingasaclinicallyusefulmeansofassessingLVdiastolic function(Figure5),12helpingtodistinguishbetweennormalandabnormalfilling. Thisinformationcandifferentiatenormalfrompseudonormalfillingwhencombined withDopplerLVfillingindices.ThetissueDopplervelocityofthemitralannulusis loadindependent,whereasDopplerLVfillingindicesarenot. TissueDopplerimaging(TDI)providesimportantprognosticvalueforpatientsina varietyofclinicalsettings.Lowearlydiastolictissuevelocity(e')predictsmortalityin patientswithLVsystolicdysfunctionandhypertensivepatients.13,14Theratioof mitralinflowvelocity(E)toe'velocitycorrelateswellwithinvasivemeasurementsof LVfillingpressure,13andhasincrementalvalueinpredictingheartfailureevents.15 TheE/e'ratioalsopredictssurvivalafterAMI.Inonestudyofpostinfarctionpatients, anE/e'ratio>15wasthestrongestpredictoroffuturecardiovascularevents,and contributedadditivevaluetostandardclinicalassessmentandtoconventional echocardiographicmeasuresofsystolicdysfunction.16 TissueDopplervelocitiesinthewalloftheheartcanalsobeusedtomeasure myocardialstrainandstrainrate,indicesofintramyocardialfunction.Strainor deformationisproducedbyapplicationofastress(forceperunitcrosssectional

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Figure6

Figure7

area).Deformationisexpressedaseitherfractionalorpercentchangefromthe originaldimension.Strainandstrainratearepotentiallymorepowerfultechniques toassesscontractilitybecausetheyareindependentofpassivetranslationofthe wall(Figure6).17,18 StrainimagingwasinitiallydevelopedfromTDIpostprocessing,withvelocity informationconvertedtobothstrainandstrainrate.Mostechocardiography laboratoriescontinuetoemploysubjectivevisualevaluationofregionalwallmotion, andstrainimaginghasmoreoftenbeenregardedasaresearchtool.However, significantinsightsintothepathophysiologyofischemicheartdiseasehaveresulted fromechocardiographicstrainimaging.1921 Previously,theclinicalassessmentofwallmotionabnormalitiesatrestorwith stresshasconsistedofqualitativevisualevaluationofwallmotionandthickening. Theadditionofstrainimaginghasrefinedandcomplementedtheabilityof echocardiographytomoreobjectivelymeasurespecificpatternsofischemiaand infarction.Becauseischemicwallmotionabnormalitiesareoftenassociatedwith passivemotion,oneadvantageofstrainimagingisthatitcandistinguishbetween activecontractionandpassivemotion,whichisoftendifficulttoappreciatevisually.22 Onestudyshowedthatnovelstraintechniquesevaluatingmyocardialmechanics canpredictregionalperfusionchangesduringdobutaminestressechocardiography (DSE).23Anotherimportantapplicationofstrainimaginghasbeenasanadjunctto lowdoseDSEtoassessmyocardialviability. Inonestudy,over50patientswithischemicheartdiseasewerestudiedbyDSEwith bothvisualwallmotionassessmentandstrain/strainrateimaging,followedby revascularizationwithpercutaneousinterventionorcoronarybypass.24Thetestwas repeated9monthslatertodeterminemyocardialfunctionalrecoveryafter revascularizationasevidenceofviability.Visualwallmotionassessmentalonehad asensitivityof71%andaspecificityof77%fordetectingviablesegmentsbyDSE. Sensitivitywassignificantlyimprovedwithlongitudinalstrain/strainrateimaging, withthemostfavorableresultsachievedbyacombinationofvisualassessmentand strainimaging,withasensitivityof84%andaspecificityof80%. Thesestudiesillustratehowquantitativestrainanalysismaycomplementthe standardechocardiographicevaluationofischemiaandpotentiallyimprovethe diagnosticaccuracyofstressechocardiography.Strainimaginghasbecome establishedasarobustresearchtoolandhasgreatpotentialtoplaymanyrolesto advancethecareofthecardiovascularpatient. Onelimitationofstrainimagingtechniquesisnoiseofthemeasurement.Another limitationisthattheangleoftheDopplermustbeappliedasparallelaspossibleto themyocardium,andtherefore,isonlyusefulinthelongaxis.Impairmentof longitudinalmyocardialfibermotionisasensitivemarkerofearlymyocardial dysfunction,ischemia,andviability,andthus,thesetechniquesmaydevelopinto clinicallyusefulmeasures. Speckletrackingisanovelechocardiographictechniqueusedtomeasure intramyocardialfunction(Figure7),andisderivedfromspeckletrackingcomputer processingmethods.25,26Speckletrackinghasbeenappliedinpatientswith hypertensionandLVhypertrophytodemonstratereducedanddelayeduntwisting rate,andtodistinguishbetweenpathologicandphysiologichypertrophy.27This techniqueisalsoprovingusefulintheassessmentofLVdyssychronybymeasuring radial,circumferential,andlongitudinalstraininCHFpatients.28

LongAxis2DEchocardiographicViews Figure1 Shownherearelongaxistwodimensionalechocardiographicviews,aparasternalviewontheleft,andanapicalfourchamberviewonthe rightinanormalsubject.Intheparasternallongaxisview,theseptumandposteriorwall,aswellasmitralandaorticvalves,areclearlyseen. Theapicalfourchamberviewdemonstratesbothventriclesandatria,aswellasthemitralandtricuspidvalves.

EndDiastolicApicalFourChamberEchocardiographicImages Figure2 Enddiastolicapicalfourchamberechocardiographicimagesdemonstratingimprovedendocardialvisualizationafterintravenousinfusionof microbubblecontrastagentintheimageontheright. ReproducedwithpermissionfromElsevierScience.LindnerJR,WeiK.Contrastechocardiography.CurrProblCardiol200227:454519.

ColorKinesisImagesoftheLVObtainedinaNormalSubject Figure3 Exampleofcolorkinesisimagesoftheleftventricle(LV)obtainedinanormalsubjectinfourstandardechocardiographicviewswith segmentationschemesusedforanalysisofendocardialmotion. PanelA:Parasternalshortaxisview:ant=anteriorasp=anteroseptalsp=septalinf=inferiorpst=posteriorlat=lateral. PanelB:Parasternallongaxisview:basp=basalanteroseptalmasp=midanteroseptalmpst=midposteriorbpst=basalposterior. PanelC:Apicalfourchamberview:blt=basallateralmlt=midlateralalt=apicallateralasp=apicalseptalmsp=midseptalbsp=basal septal. PanelD:Apicaltwochamberview:ban=basalanteriorman=midanterioraan=apicalanteriorain=apicalinferiormin=midinferiorbin =basalinferior.Normalvaluesforthetimingandmagnitudeofsystolicwallthickeninganddiastolicfunctioncanbedevelopedusingsuch techniques. ReproducedwithpermissionfromtheAmericanPhysiologicalSociety.MorAviV,SpencerK,GorcsanJ,etal.Normalvaluesofregionalleft ventricularendocardialmotion:multicentercolorkinesisstudy.AmJPhysiolHeartCircPhysiol2000279:H246476.

MethodofSemiautomaticContourDetectionfor3DEchocardiography Figure4 Showninthisfigureisamethodofsemiautomaticcontourdetectionfor3Dechocardiography.Ahighresolutionrealtime3DEtransducerallows acquisitionof3DEdatasetswithhighqualityfromasingleacousticwindow.Acomputerizedcontourtrackingalgorithmenablessemiautomated dataanalysiswithonlyminimalinteractionbytheinvestigator.Astackofeightrotatedlongaxisimagesisautomaticallyselectedfromthe3DE dataset(leftpanel).Ineachoftheselongaxiscrosssections(onlyoneisshown),theLVapexandmitralannulusarechoseninanend diastolic(middleupperpanel)andendsystolic(middlelowerpanel)stopframe.Themarkersatthemitralannulusaresubsequentlyusedbythe algorithmtosetthemitralvalveplaneandtotruncatethecontoursoftheLVcavity.Thereafter,anellipseisplacedineachoftheenddiastolic andendsystolicframestocreatethemodel.Thisellipseismanuallyadapted(length,width,androtationangle)tofitascloselytotheendocardial borderaspossible.Thecontoursaresubsequentlydetectedautomaticallybythealgorithm(rightupperandlowerpanelsforenddiastolicand endsystolicstopframes,respectively,withdetectedcontour). ReproducedwithpermissionfromKuhlHP,SchreckenbergM,RulandsD,etal.Highresolutiontransthoracicrealtimethreedimensional echocardiography:quantitationofcardiacvolumesandfunctionusingsemiautomaticborderdetectionandcomparisonwithcardiacmagnetic resonanceimaging.JAmCollCardiol200443:208390.

DopplerInflowandDopplerTissueVelocities Figure5 TheseexamplesofDopplerinflow(ontop)andDopplertissuevelocities(onbottom)arefromtwopatientswithnormalsystolicfunctionand similarmitralinflowsignals.Ontheleft,anormalmitralannularvelocityandE/e'ratioindicatenormalfillingpressures.Ontheright,themitral annulare'velocityisreducedandtheE/e'ratioelevatedinapatientwithhighLApressure. A=mitralfillingatatrialcontractiona'=latemitralannulusdiastolicvelocityE=mitralearlyfillingwavee'=earlymitralannulusdiastolicvelocity E/e'=ratioofmitralearlyfillingwavetoearlymitralannulusvelocityLAp=LApressure. ReproducedwithpermissionfromOmmenSR,NishimuraRA.Aclinicalapproachtotheassessmentofleftventriculardiastolicfunctionby Dopplerechocardiography:update2003.Heart200389:iii1823.

LongitudinalStrainRateMapsinApicalLongAxisViewatBaselineandDuringAcuteIschemia Figure6 Exampleoflongitudinalstrainrate(SR)mapsinapicallongaxisview,atbaseline(A)andduringacuteischemia(B)inananimalafterLAD occlusion.Strainratesarereconstructedascolorcodedmaps(right),withhorizontalaxisrepresentingtimeandverticalaxisrepresentingthe unfoldedLVcircumference.NegativeSR(longitudinalshortening)iscolorcodedinyelloworangeandpositiveSR(longitudinallengthening)in cyanblue.Atbaseline,SRsarehomogeneouslydistributedfromapextobase.Duringischemia,delayedonset(whitearrows)andreduced systolicSRs,postsystolicshortening,andpostsystolicshorteninganddelayedonsetoflocallengthening(blackarrows)arereadilyvisible.IVRT =isovolumicrelaxationtime. ReproducedwithpermissionfromPislaruC,BelohlavekM,BaeRY,etal.Regionalasynchronyduringacutemyocardialischemiaquantifiedby ultrasoundstrainrateimaging.JAmCollCardiol200137:11418.

TwoChamberLongAxisImageinEarlySystoleWith2DEchocardiogaphicSpeckleTracking Figure7 Longitudinalisovolumicdeformationoftheleftventricular(LV)wallseenonultrasonographicspeckletracking(twodimensionalstrain).Onsetof contraction(redcolor)occursneartheapicalsegment. ReproducedwithpermissionfromSenguptaPP,KorinekJ,BelohlavekM,etal.Leftventricularstructureandfunction:basicscienceforthe clinician.JAmCollCardiol200648:19882001,Figure2.

StressEchocardiography
Stressechocardiographycanbeperformedwithtreadmill,uprightbicycle,orsupine bicycleexercise,orbyusingpharmacologicstressorssuchasdobutamineor dipyridamole.1 DSEhasahighersensitivitythandoesvasodilatorstress.Figure8 showstheweightedmeansensitivity,specificity,andoverallaccuracyforexercise echocardiographyfromapooledanalysisofthedataintheliterature,whichwere 86%,81%,and85%,respectively.1 Figure8alsoshowsthatthesensitivityand specificityforDSEiscomparabletoexerciseechocardiography,withaslightlylower sensitivityandslightlyhigherspecificity. Somestudieshavedirectlycomparedstressmyocardialperfusionimaging(MPI) andstressechocardiography.Figure9showsthisdirectcomparisonin1,405 patientsfromstudiesintheliterature.29ThesensitivityofMPIishigher,but specificityislowerthanstressechocardiography.Itshouldbepointedoutthatwhen anormalcyrateisemployedasasubstituteforspecificity,whichrequirescoronary angiography,thefalsepositiverateisonly10%. Thesensitivityofexerciseechocardiographymaybediminishedifsubmaximal exerciseheartratesareattained.Marwicketal.30reportedthatwhenexerciseheart rateswere<85%ofmaximumpredictedheartrate,thesensitivityofexercise echocardiographicstresstestswasonly42%.AswithstressMPI,stress echocardiographyismoresensitiveandspecificfordetectinginducibleischemia thanisexerciseECGtestingalone.Sensitivityishigherinmultivesseldisease patientsthaninsinglevesseldiseasepatients,andinpatientswith>70%stenoses versus5070%stenoses.1

Figure8

Figure9

SensitivityandSpecificityforAllStudiesPublishedUpto2002 Figure8 Sensitivityandspecificityforallexerciseanddobutamineechocardiographystudiespublishedupto2002.Noteaslightlyhighersensitivityfor exerciseechocomparedtodobutamineecho. ReproducedwithpermissionfromCheitlinMD,ArmstrongWF,AurigemmaGP,etal.ACC/AHA/ASE2003guidelineupdatefortheclinical applicationofechocardiographysummaryarticle:areportoftheAmericanCollegeofCardiology/AmericanHeartAssociationTaskForceon PracticeGuidelines(ACC/AHA/ASECommitteetoUpdatethe1997GuidelinesfortheClinicalApplicationofEchocardiography).JAmCollCardiol 200342:95470.

DirectComparisonofStressMPIandStressEchoin1,405Patients Figure9 Directcomparisonofstressmyocardialperfusionimaging(MPI)andstressechocardiography(ECHO)in405patientspooledforanalysis.Note the84%sensitivityforMPIishigherthanthesensitivityforECHO,whereasspecificityislower. ReproducedwithpermissionfromElsevierScience.SchinkelAF,BaxJJ,GeleijnseML,etal.Noninvasiveevaluationofischaemicheartdisease: myocardialperfusionimagingorstressechocardiography?EurHeartJ200324:789800.

ComparisonofStressEchoandStressMyocardialPerfusion Imaging
WhencomparedtoMPIwithnucleartracers,advantagesofstressechocardiography are:1)thetechniqueistotallynoninvasive,safe,andrepeatable2)noradiation exposureisinvolved3)thetimeforacompleteexaminationisshortcomparedto stress/restperfusionimaging4)thetechniqueisportableandrequiresnohighly sophisticatedinstrumentation5)ithastheconcomitantabilitytoidentifystructural abnormalitiesoftheheart,includingcoexistingvalvulardisease,LVhypertrophy,and pericardialabnormalitiesand6)imagequalityisincreasedusingcontrast echocardiographyversusconventionalstressechocardiography,permitting simultaneousassessmentofperfusionandfunction. Somelimitationsofstressechocardiographyarethat:1)imagesaredifficultto acquireatpeakexercisebecauseofexertionalhyperpneaandmarkedcardiac excursion2)anischemicresponseisrequiredfortheelucidationofabnormalwall motionandinadequateheartrateresponses,particularlywithdobutamine echocardiography,whichreducessensitivity3)rapidrecoveryofwallmotion abnormalitiescanoccurwithmildischemia,whichmayleadtoafalsenegativetest result4)imagesmustbeacquiredrapidlyafterexercise5)detectionofresidual ischemiawithinaninfarctzoneisdifficultbecauseofrestingakinesis6)stress echocardiographyishighlyoperatordependentfordatacollectionimageanalysis, withconsiderableinterindividualvariabilityininterpretingstressimages7)good qualitycompletestudiesareachievedinonly70%ofpatientsaninabilitytoimage alloftheLVmyocardiumoccursinapproximately15%ofpatientsand8)a quantitativemeasurementofLVejectionfractionisdifficultandoperatordependent. DobutamineEchocardiography Dobutamineechocardiographyhasbeenusedextensivelytoassessthelikelihood offunctionalrecoveryinchronicischemicheartdiseaseandafterAMI.Typically,a biphasicresponsewithinadysfunctionalsegment(increasedthickeningatlow dosesofdobutaminefollowedbydysfunctionathigherdoses)isconsideredtobe themostspecificfindingforviability(Figure10).31Wallthicknessatrestisalso predictiveoffunctionalrecovery,assegments<6mmthickaretypicallynonviable.32 Bypathology,apositivedobutamineresponserequiresatleast50%viable myocytesinagivensegment.33 Morethanjustrecoveryofrestfunctionlateafterrevascularizationhasbeenshown tobeimportant,specificallyrecoveryofcontractilereserve(i.e.,dobutamine responseafterrevascularization)inhibernatingmyocardium.31Thenumberof viablesegmentsonadobutamineechocardiographyrelatestolongtermoutcome inpatientswithischemiccardiomyopathy.34 ContrastEchocardiography Contrastechocardiographycanbeusedtoassessresidualmyocardialviabilityin thesettingofacuteorchronicischemicheartdisease.InAMI,thepresenceof preservedmyocardialperfusion,asassessedbycontrastechobeforeprimary coronaryintervention,isassociatedwithmaintainedorimprovedperfusionatday3 5postMI,andeventualrecoveryofrestingfunctionintheinfarctedterritory(Figure 11).35 In20patientswithchronicischemicheartdiseasewhounderwentrevascularization, thesensitivityofcontrastechoforrecoveryoffunctionwas92%comparedto92%for thallium201singlephotonemissioncomputedtomography(201TISPECT),and 80%fordobutamineecho.36Specificitywashighestwithcontrastecho(63%,45%, and54%,respectively).ArecentpostMIstudyof99patientsdemonstratedthatthe lackofresidualviability,asidentifiedbycontrastecho,wasanindependentpredictor ofcardiacdeathandrecurrentMI.37 StressEchocardiographyandPrognosis

Figure10

Figure11

Figure12

Figure13

Stressechocardiographyisalsousefultodetermineprognosis.Onerecentstudy examinedoutcomesin1,874patientswithknownorsuspectedCADwhohad normalexercisecapacity,butabnormalexerciseechocardiograms.Predictorsof cardiacdeathornonfatalMIincludeddiabetesmellitus,historyofMI,andlackof decreaseinendsystolicsizeinresponsetoexercise.Theriskofcardiacdeathor nonfatalMIwas1.6%peryearforthosewhohadadecreaseinLVendsystolicsize withexercise,and1.2%peryearforthosewhodidnothaveanyseverelyabnormal segmentsimmediatelyafterexercise(Figure12).38 Similarly,inastudyof1,500patientswhounderwentexercisestress(34%of patients)ordobutaminestress(66%ofpatients),anormalstressstudywas associatedwithabenignprognosis(0.9%/yearcardiaceventrate)(Figure13).39 Althoughtheprognosticcapabilitiesofstressechocardiographyinpatientswith knownorsuspectedCADhavebeenwellrecognized,40,41itsroleinpredicting clinicalimprovementwithcoronaryrevascularizationislessestablished.Onestudy of3,121patientsundergoingstressechocardiographyfoundthatpatientswith increasedpeakwallmotionscoreindex(>1.7)showedsignificantbenefitfrom revascularizationwithreducedcardiaceventrates.42 Amorerecentrandomizedcontrolledtrialfoundthatthepresenceofviable myocardium(usingdobutamineechocardiographyorSPECT)wasassociatedwith improvedsurvivalinpatientswithCADandLVdysfunction,butthatthisrelationship wasnotsignificantafteradjustingforotherbaselineclinicalvariables.43The measurementofmyocardialviabilitydidnotidentifypatientswithadifferential survivalbenefitfromcoronaryarterybypasssurgery,ascomparedwithmedical therapyalone. NovelApplicationsofStressEchocardiography Recentdatashowedthatinpatientswithanegativestressechocardiogrambywall motioncriteria,reducedcoronaryflowreserve(CFR)intheleftanteriordescending artery(LAD)hasbeenassociatedwithfutureadversecardiacevents.44Therefore, themeasurementofCFRmayimprovetheprognosticabilityofstress echocardiographyinpatientswithanegativestudybytraditionalwallmotion analysis. MPIcombinedwithstressechocardiographycanassessforregionaldifferencesin coronaryperfusioninadditiontoischemicwallmotionchanges. Inaprospectiveseries,patientswerereferredforadenosineSPECTandalso underwentmyocardialcontrastechocardiography.Contrastechocardiography demonstrated88%sensitivityand85%specificitycomparedwithSPECTMPI.45 Perfusionimagingisalsofeasiblewith3Dechocardiography.Inastudyof30 patientsundergoingadenosineSPECT,3Dmyocardialcontrastechocardiography, and2Dmyocardialcontrastechocardiography,allechocontrastperfusion modalitiesdemonstratedsimilarsensitivity(9092%)andspecificity(6979%) comparedwithSPECTMPI.46Thesestudiessuggestagrowingroleformyocardial contrastperfusionechocardiographyintheassessmentofpatientswithoratriskfor CAD. Finally,exerciseparametersofdiastolicfunctionmayalsoprovideimportant prognosticinformation.Inaseriesof522patientswithnormalsystolicfunctionand normalrestingE/e',thosewithanelevatedexerciseE/e'demonstratedincreased riskforadversecardiovasculareventscomparedwiththosewithnormaldiastolic responsetoexercise.47 PrognosticValueofLeftAtrialSize Accuratemeasurementsofleftatrial(LA)volumeareimportantinquantifyingLA function,andareavaluabletoolinclinicalpractice.EnlargementoftheLAcavityhas beenshowntocorrelatewithincreasedmortality,andisavaluablemarkerofthe presenceandseverityofheartdisease.48Transthoracicechocardiographyprovides anaccuratemethodtoquantifyLAvolumecomparedwithreferencestandardssuch asMRIandcineCT.49

OnestudyshowedthatLAvolume,asmeasuredonechocardiogram,isasuperior markerofcardiovasculareventsthaneitherLAareaordiameterinpatientsin normalsinusrhythm.50AlthoughLAsizedeterminationbyanyparameterwas predictiveoffuturecardiovascularevents,LAvolumeyieldedthebestresultsin predictingcardiovascularevents(areaunderreceiveroperatorcharacteristiccurve= 0.71). LAvolumemayalsohavesignificantclinicalvalueinpredictingtheoccurrenceof postoperativeatrialfibrillation(AF).Osraneketal.examined205patients undergoingcardiacsurgery,andfoundthatonlyageandLAvolumewere independentpredictorsofpostoperativeAF,andthatpatientswithLAvolume>32 ml/m2 hadafivefoldincreasedriskofAF.51InlightofthefactthatpostoperativeAF frequentlyresultsinincreasedmorbidity,mortality,andprolongedhospitalstay,the abilitytopredictpatientsathighriskofthiscomplicationbymeasuringLAvolume couldbeofsignificantclinicalvalue.Becauseoftheseemergingclinical applications,theAmericanSocietyofEchocardiographyhasrecommendedroutine quantificationofLAvolumebybiplane2Dechocardiographyusingeitherthemethod ofdiscs(bySimpson'srule)orthearealengthmethod.52

SensitivityandSpecificityofDobutamineEchocardiographyforDetectionofMyocardialHibernation Figure10 Bargraphshowingsensitivityandspecificityofdobutamineechocardiographyfordetectionofmyocardialhibernationusingabiphasicresponse andcombinedbiphasicorworseningresponsestodobutamine.Theanalysiswasperformedbothonapersegmentandperpatientbasis. ReproducedwithpermissionfromLippincott,Williams&Wilkins.AfridiI,KleimanNS,RaiznerAE,ZoghbiWA.Dobutamineechocardiographyin myocardialhibernation.Optimaldoseandaccuracyinpredictingrecoveryofventricularfunctionaftercoronaryangioplasty.Circulation 199591:66370.

ImageofPatientPresentingWithAcuteAnteriorMIFromTotalOcclusionofLAD Figure11 Inthisfigure,apatientpresentingwithanacuteanteriormyocardialinfarction(MI)fromtotalocclusionoftheleftanteriordescendingartery (LAD)wasimagedpriortocoronarystentingontheleft,demonstratingabsenttissuelevelperfusion,andaftercoronarystentingontheright, withrestoredperfusion,saveforasmallareainthedistalseptum. ReproducedwithpermissionfromBalcellsE,PowersER,LepperW,etal.Detectionofmyocardialviabilitybycontrastechocardiographyinacute infarctionpredictsrecoveryofrestingfunctionandcontractilereserve.JAmCollCardiol200341:82733.Copyright2003,AmericanCollegeof CardiologyFoundation.

EventRatesperPersonYearofFollowUpforPatientsWithNormalExerciseEchocardiographyandforPatientsWith0%,1%to25%,and>25% ofLVSegmentsSeverelyAbnormalImmediatelyAfterExercise Figure12 Thegraphdemonstrateseventratesperpersonyearoffollowupforpatientswithnormalexerciseechocardiographyandforpatientswith0%, 1%to25%,and>25%ofleftventricular(LV)segmentsseverelyabnormalimmediatelyafterexercise. ReproducedwithpermissionfromMcCullyRB,RogerVl,MahoneyDW,etal.Outcomeafterabnormalexerciseechocardiographyforpatients withgoodexercisecapacity:prognosticimportanceoftheextentandseverityofexerciserelatedleftventriculardysfunction.JAmCollCardiol 200239:134552.Copyright2002,AmericanCollegeofCardiologyFoundation.

CumulativeSurvivalasFunctionofWallMotionScoreIndexFromStressEchocardiographyUsingCardiacEventsasanEndpoint Figure13 Cumulativesurvivalasafunctionofwallmotionscoreindex(WMSI)fromstressechocardiographyusingcardiaceventsasanendpoint.Note theexcellentprognosisinthosepatientswithanormalwallmotionscoreindex(WMSI=1). ReproducedwithpermissionfromYaoSS,QureshiE,SherridMV,ChaudryFA.Practicalapplicationsinstressechocardiography:risk stratificationandprognosisinpatientswithknownorsuspectedischemicheartdisease.JAmCollCardiol200342:108490.Copyright2003, AmericanCollegeofCardiologyFoundation.

KeyPoints
Astandardized17segmentmodelbasedonmultiplaneimaginghasbeendevelopedandisappliedforLVwall motionassessmentto2Dechocardiography. TDIisemergingasaclinicallyusefulmeansofassessingLVdiastolicfunction,andprovidesimportant prognosticvalueforpatientsinavarietyofclinicalsettings.Itisimportanttoknowhowtoreadandinterpretmitral inflowvelocitiesandtissueDopplertracingsfortheassessmentofimpairedrelaxationusingechocardiography. Stressechocardiographyismorespecificandlesssensitivefordetectinginducibleischemiathanisnuclear perfusiontesting.Stressechocardiographyisusefultodetermineprognosisinavarietyofpatientpopulations, andcanbeenhancedbytheconcomitantuseofechocontrast.

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AfridiI,QureshiU,KopelenHA,WintersWL,ZoghbiWA.Serialchangesinresponseofhibernatingmyocardiumto inotropicstimulationafterrevascularization:adobutamineechocardiographicstudy.JAmCollCardiol 199730:123340. 32. CwajgJM,CwajgE,NaguehSF,etal.Enddiastolicwallthicknessasapredictorofrecoveryoffunctionin myocardialhibernation:relationtorestredistributionT1201tomographyanddobutaminestress echocardiography.JAmCollCardiol200035:115261. 33. BaumgartnerH,PorentaG,LauYK,etal.Assessmentofmyocardialviabilitybydobutamineechocardiography, positronemissiontomographyandthallium201SPECT:correlationwithhistopathologyinexplantedhearts.JAm CollCardiol199832:17018. 34. SeniorR,KaulS,LahiriA.Myocardialviabilityonechocardiographypredictslongtermsurvivalafter revascularizationinpatientswithischemiccongestiveheartfailure.JAmCollCardiol199933:184854. 35. BalcellsE,PowersER,LepperW,etal.Detectionofmyocardialviabilitybycontrastechocardiographyinacute infarctionpredictsrecoveryofrestingfunctionandcontractilereserve.JAmCollCardiol200341:82733. 36. ShimoniS,FrangogiannisNG,AggeliCJ,tal.Identificationofhibernatingmyocardiumwithquantitative intravenousmyocardialcontrastechocardiography:comparisonwithdobutamineechocardiographyandthallium 201scintigraphy.Circulation2003107:53844. 37. DwivediG,JanardhananR,HayatSA,SwinburnJM,SeniorR.Prognosticvalueofmyocardialviabilitydetectedby myocardialcontrastechocardiographyearlyafteracutemyocardialinfarction.JAmCollCardiol200750:32734. 38. McCullyRB,RogerVL,MahoneyDW,etal.Outcomeafterabnormalexerciseechocardiographyforpatientswith goodexercisecapacity:prognosticimportanceoftheextentandseverityofexerciserelatedleftventricular dysfunction.JAmCollCardiol200239:134552. 39. YaoSS,QureshiE,SherridMV,ChaudhryFA.Practicalapplicationsinstressechocardiography:riskstratification andprognosisinpatientswithknownorsuspectedischemicheartdisease.JAmCollCardiol200342:108490. 40. ChuahSC,PellikkaPA,RogerVL,McCullyRB,SewardJB.Roleofdobutaminestressechocardiographyin predictingoutcomein860patientswithknownorsuspectedcoronaryarterydisease.Circulation199897:1474 80. 41. MarwickTH,MehtaR,ArheartK,LauerMS.Useofexerciseechocardiographyforprognosticevaluationofpatients withknownorsuspectedcoronaryarterydisease.JAmCollCardiol199730:8390. 42. YaoSS,BangaloreS,ChaudhryFA.Prognosticimplicationsofstressechocardiographyandimpactonpatient outcomes:aneffectivegatekeeperforcoronaryangiographyandrevascularization.JAmSocEchocardiogr 201023:8329. 43. BonowRO,MaurerG,LeeKL,etal.Myocardialviabilityandsurvivalinischemicleftventriculardysfunction.NEngl JMed2011364:161725. 44. CortigianiL,RigoF,SicariR,GherardiS,BovenziF,PicanoE.Prognosticcorrelatesofcombinedcoronaryflow reserveassessmentonleftanteriordescendingandrightcoronaryarteryinpatientswithnegativestress echocardiographybywallmotioncriteria.Heart200995:14238. 45. AbdelmoneimSS,BernierM,DhobleA,etal.Diagnosticaccuracyofcontrastechocardiographyduringadenosine stressfordetectionofabnormalmyocardialperfusion:aprospectivecomparisonwithtechnetium99msestamibi singlephotonemissioncomputedtomography.HeartVessels201025:12130. 46. AbdelmoneimSS,BernierM,DhobleA,etal.Assessmentofmyocardialperfusionduringadenosinestressusing realtimethreedimensionalandtwodimensionalmyocardialcontrastechocardiography:comparisonwithsingle photonemissioncomputedtomography.Echocardiography201027:4219. 47. HollandDJ,PrasadSB,MarwickTH.Prognosticimplicationsofleftventricularfillingpressurewithexercise.Circ CardiovascImaging20103:14956. 48. BenjaminEJ,D'AgostinoRB,BelangerAJ,WolfPA,LevyD.Leftatrialsizeandtheriskofstrokeanddeath.The FraminghamHeartStudy.Circulation199592:83541. 49. RodevanO,BjornerheimR,LjoslandM,MaehleJ,SmithHJ,IhlenH.Leftatrialvolumesassessedbythreeand twodimensionalechocardiographycomparedtoMRIestimates.IntJCardImaging199915:397410. 50. TsangTS,AbhayaratnaWP,BarnesME,etal.Predictionofcardiovascularoutcomeswithleftatrialsize:isvolume superiortoareaordiameter?JAmCollCardiol200647:101823. 51. OsranekM,FatemaK,QaddouraF,etal.Leftatrialvolumepredictstheriskofatrialfibrillationaftercardiac surgery:aprospectivestudy.JAmCollCardiol200648:77986. 52. LangRM,BierigM,DevereuxRB,etal.Recommendationsforchamberquantification:areportfromtheAmerican SocietyofEchocardiography'sGuidelinesandStandardsCommitteeandtheChamberQuantificationWriting

Group,developedinconjunctionwiththeEuropeanAssociationofEchocardiography,abranchoftheEuropean SocietyofCardiology.JAmSocEchocardiogr200518:144063.

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3.4:NuclearCardiology&PositronEmissionTomography
Author(s): KarthikeyanAnanthasubramaniam,MD,FACC MouazAlMallah,MD,MSc,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Explaintheconceptsoffirstpassradionuclideangiocardiography(FPRNA)andequilibriumradionuclide angiocardiography(ERNAorMUGA)inregardtotheassessmentofventricularfunction. 2. Describetheroleofsinglephotonemissioncomputedtomography(SPECT)inevaluationofventricularfunction. 3. Outlinetheemergingroleofpositronemissiontomography(PET)inevaluationofventricularfunction. 4. IdentifythediagnosticvalueofSPECTandPETmyocardialperfusionimaging(MPI)inthediagnosisofcoronaryartery disease(CAD). 5. DiscussthebasicsofSPECTinterpretationandlimitations. 6. DeterminetheroleofSPECTandPETinspecialpatientpopulations. 7. Understandtheproblemofischemiccardiomyopathyandexplaintheterminologyofdefiningviablemyocardiumandits prevalence. 8. ReviewthevariousSPECTtechniquesforassessmentofmyocardialviability,withfocusonthalliumandtechnetium basedisotopes. 9. ExplainthebasicsofPETcardiacimagingforviabilityanddataforPETcomparedtoothertechniquesforviability assessment.

Introduction
Thismoduleisdividedintofoursectionscoveringpertinentaspectsofnuclearcardiology/PETinpatientassessment. Thesectionsare: 1. EvaluationofVentricularFunctionWithNuclearImaging. 2. DiagnosisofCoronaryArteryDiseasebySinglePhotonEmissionComputedTomographyandPositronEmission Tomography. 3. TheRoleofSinglePhotonEmissionComputedTomographyinPrognosisandRiskStratification. 4. MyocardialViabilityAssessmentbySinglePhotonEmissionComputedTomographyandPositronEmission TomographyImaging. Currentnuclearcardiologypracticefacilitatesleftventricularfunction(LVF)tobeevaluatedbythreemaintechniques: 1. Radionuclideangiocardiography(RNA) 2. ElectrocardiographicgatedSPECT,and 3. GatedPET.

EvaluationofVentricularFunctionWithNuclearImaging (1of2)
RadionuclideAngiocardiography RNA,firstintroducedinthe1970s,isahighlyaccuratetechniqueforLVejection fraction(EF)assessment.Ithasveryhighcorrelationtocontrastventriculography(r= 0.94).1,2Oneofitsmainadvantagesishighreproducibilityandlowinterand intraobservervariabilityof<5%.3,4 RNAcanbeperformedeitherasFPRNAorERNA.FPRNAusesthefirsttransitofa radionuclidebolusoftechnetium(Tc)99mradiolabeledredbloodcellsthroughthe centralcirculation.Itwaswidelyusedtoevaluateintracardiacshunts,LVF,andright ventricularfunction(RVF),buthasnowbeensupplantedbyechocardiographyand magneticresonanceimaging(MRI). AdvantagesofFPRNAtechniqueinclude:1)dataacquisitionin<30seconds,2)RVF assessmentwithlessoverlapofactivityinotherchambers,5 3)useofmultiple radiopharmaceuticalsforimageacquisition(bone,renal,andmyocardial scintigraphicagents),4)provenrobustmethodologyofpeakventricularfunctionwith exercise,and5)prognosticinformationderivedfromexerciseFPRNA.6 Inparticular, anexerciseEFof50%byFPRNAseemstobeaspecificcutoffpointbelowwhich patientswithCADdemonstrateanincreasingprobabilityofdeath. Disadvantagesinclude:1)needforlargeboreintravenousline,2)highcount dedicatedgammacamera,and3)requirementofabsenceofsignificanttricuspid regurgitation.Figure1showsthetypicaltransitofradioisotopeaspartofanFPRNA study.7 ERNAalsoutilizesaradionuclidebolusoftechnetiumTc99mradiolabeledred bloodcellspreparedbyinvitro,invivo,ormodifiedinvivotechnique.Once equilibriumfollowinginjectionisachieved,themeasuredradioactivityisproportional tovolumeandallowsrepeatedimagingoverseveralhours. Figure2illustratestheconceptofERNAacquisitionshownasadiagrammatic representation.Eachcardiaccycleisdividedinto28equalsegments.Foreach heartbeat,dataareaccumulated,thenstoredinaseparatefile.Totheright,these dataforthe28portionsofthecyclearedisplayedasasinglesummedventricular volumecurve.Thenumbers128refertotemporalsequencewithinthecardiac cycle.8 EFiscalculatedbyplanarERNAbythefollowingformula: ((Enddiastoliccounts[BGC]endsystoliccounts[BGC])/Enddiastoliccounts [BGC])x100% whereBGCstandsforbackgroundcorrection. Placementofregionofinterestforbackgroundcorrectioniscritical.Highbackground activityincreasesthecalculatedEF,andlowbackgroundcountsdecreasethe calculatedEF. PlanarERNAiswidelyusedtoevaluateLVFfollowingacutemyocardialinfarction (AMI),valvularheartdisease,andtofollowpatientsreceivingcardiotoxic chemotherapy.9 Table1highlightsthemajorusesofERNA,andTable2highlights theadvantagesanddisadvantagesofERNA. OneofthemainusesofplanarERNAistomonitorEFinpatientsreceiving cardiotoxicchemotherapy.Table3summarizesthewidelyusedrecommendations incorporatingERNAestimationofEFandsubsequentmanagementof chemotherapyusingdoxorubicin(althoughthisisapplicabletomanynewer cardiotoxicchemotherapyagents).10 AssessmentofDiastolicFunction
Figure1

Figure2

Table1

Table2

Table3

AssessmentofdiastolicfunctionwithRNAinvolvestheevaluationofrateofchange (firstderivative)ofcountsinthediastolicvolumecurvetocalculateindicesof diastolicfilling,includepeakLVfillingrate(normal>2.4enddiastolic volumes/second)andtimetopeakfillingrate(normal<180msec)andatrial contributionoffilling.11Sincelargestudieswithageandsexadjustedcriteriafor normaldiastolicvaluesinRNAhavenotbeenpublishedandsinceDoppler echocardiographyprovidesamorereadilyavailabletoolwithnormaldataforage andsexspecificdiastolicvalues,12thelatterislikelytobethemainstayfor noninvasivediastolicfunctionassessment.

TypicalTransitofRadioisotopeasPartofanFPRNAStudy Figure1 FPRNA=firstpassradionuclideangiocardiographySVC=superiorvenacavaRA=rightatriumRV=rightventricle. ReproducedwithpermissionfromCrawfordES,HusainSS.NuclearCardiacImaging:TerminologyandTechnicalAspects.Reston,VA:Society ofNuclearMedicine2002.

ConceptofERNAAcquisitionShownasaDiagrammaticRepresentation Figure2 Eachcardiaccycleisdividedinto28equalsegments.Foreachheartbeat,dataareaccumulated,thenstoredinaseparatefile.Totheright,these dataforthe28portionsofthecyclearedisplayedasasinglesummedventricularvolumecurve.Thenumbers128refertotemporalsequence withinthecardiaccycle. ReproducedwithpermissionfromWackersFJ,SouferR,ZaretBL.Nuclearcardiology.In:BraunwaldE,ZipesDP,LibbyP,eds.Heartdisease: ATextbookofCardiovascularMedicine.Philadelphia:Saunders2001:273.

CommonUsesofPlanarERNA Table1 ERNA=equilibriumradionuclideangiocardiography.

MajorAdvantagesandDisadvantagesofERNA Table2 EF=ejectionfractionERNA=equilibriumradionuclideangiocardiography.

UseofERNAinPatientsUndergoingChemotherapy Table3 ECG=electrocardiogramEF=ejectionfractionERNA=equilibriumradionuclideangiocardiographyLV=leftventricular.

EvaluationofVentricularFunctionWithNuclearImaging (2of2)
SinglePhotonEmissionComputedTomographyEquilibriumRadionuclide Angiocardiography ERNAcanalsobeperformedwithSPECT(alsoreferredtoasgatedbloodpool SPECT),andcorrelateswellwithplanarERNA.13ThemajorstrengthofSPECT ERNAisthatiteliminatesoverlapofstructuresseenwithplanarERNAand facilitatesbetterassessmentofLVFandmorphology.Figure3showsplanarand SPECTERNAatrestinapatientwithabasalinferioraneurysm.Earlierstudieshave showngoodcorrelationofSPECTERNAwithMRI.14Thereisincreasinginterestin alsoadoptingSPECTERNAmethodologyforassessmentofRVFandEF.14,15 GatedSinglePhotonEmissionComputedTomography Electrocardiography(ECG)gatedSPECTMPIiscurrentlythestandardofpracticein mostinstitutionsperformingSPECTimaging.Theabilitytomeasurenumerous ancillaryparametersinadditiontoperfusionaddssubstantialdiagnosticand prognosticinformationinSPECTimaging.LVEF,enddiastolicandendsystolic volumes,andthetransientischemicdilationratioaresomeofthestandard parametersobtainablebygatedSPECT. Figure4showsdiagnosticparametersderivablefromgatedmyocardialperfusion study.ThecalculationofEFbygatedSPECTisavolumebasedratherthancount basedtechnique.ThetimevolumecurvedepictedinFigure5allowsestimationof EFusingthefollowingformula16: EF%=enddiastolicvolumeendsystolicvolume/enddiastolicvolumex100% AlthoughgatedSPECTderivedLVparameterswerewidelythoughttobeapplicable onlyinconjunctionwithTc99msestamibiortetrofosminSPECTimaging,multiple subsequentstudieshaveshownthatreliablegatedSPECTderivedLVparameters alsoarefeasiblewiththallium201(Tl201)SPECT(particularlywhenmultidetector camerasareused).17TheuseofgatingbasedassessmentofLVwallmotionand thickeningwheninterpretingnuclearperfusionimaginghasimprovedspecificityfor CADdetection(Figure6).18 Ingeneral,fixeddefectswithnormalwallmotionarethoughttobeattenuation artifactsandfixeddefectswithabnormalwallmotiondesignatedasscar.19 However,itshouldbenotedthatgiventhatthecollimatedspatialresolutionof SPECTrangesfrom915mm,smallsubendocardialinfarctsmaybemissedby SPECTwhencomparedtoothertechniqueswithhigherspatialresolutionsuchas cardiacMRI(Figure7).20 GatedSPECTutilizesthesamefundamentalprinciplesofacquisitionofcounts basedonaregularRRinterval.Usually8or16framegatingisused(Figure8).In general,anEFof45%isconsideredthelowerlimitsofnormalfor8framegated SPECT.21 AswithanymodalitythatusesECGsynchronizedgating,aregularrhythmis essentialforaccuratedataacquisitionandprocessing.Markedvariationofrhythms (e.g.,ectopy,atrialfibrillation,sinusarrhythmia)caninterferewithaccuracyofgating. Wallthickeningaccuracyisaffectedthemost,followedbywallmotionandEF.Gated SPECTalsotendstohavegreatervariabilityinaccuracyofvolumesandEFinvery deformedandaneurysmalventricles,andinbothextremesofLVsize. PertheAmericanSocietyofNuclearCardiology(ASNC)SPECTguidelines,21itis recommendedthatacquisitionofbothrestandstressimagesusegating.Studies haveshownthatapoststressEFdrop(>5EFpoints)suggestsstressinduced ischemiainaterritorysubtendedbycriticalstenosis(>90%).22Thus,comparing poststressEFwithrestEFistheonlywaytodetectsuchachange,whichcould otherwisebemissed.

Figure3

Figure4

Figure5

Figure6

Figure7

Figure8

Figure9

Furthermore,theincrementalprognosticvalueofpoststressSPECTEFand systolicvolumeiswellestablishedandaddsincrementalvaluetotheperfusion analysis.23,24Gatinghasalsobeenshowntoincreasediagnosticaccuracyof SPECTinwomenaddingincrementalvaluetoperfusionandimprovingspecificity.25 Differentiationofischemicandnonischemiccardiomyopathyisalsofacilitatedby integratingperfusionandfunctioninformationtogether,ratherthaneitheralone.The combinationofhighsummedstressscoreandregionalvarianceinwallmotion helpsdifferentiateischemicfromnonischemiccardiomyopathy(Figure9).26 Leftmainorthreevesseldiseaseisunderdiagnosedbyperfusionanalysisalone duetobalancedreductionofisotopeuptakeinsignificantmultivesseldisease, leadingtoanoverall"apparent"normalperfusionpattern.2729GatedSPECTmay helptoimprovedetectionofischemiamorespecificallyinthesesituationsby demonstratingadropinpoststressEF,thepresenceofpostischemicstunning,or transientischemicdilationallofwhichmayserveasvaluablecluestothepresence ofCADnotappreciatedotherwise. CorrelationofGatedSPECTEjectionFractionandVolumesWithOther Modalities GatedSPECTassessmentofvolumeshasbeenvalidatedwithechocardiography, gatedRNA,30,31andMRI.3234However,somerecentstudieshaveshown underestimationofvolumesandincreasedvariabilityinEFestimationcomparedto contemporaryMRImethods.35 PositronEmissionTomographyEvaluationofLeftVentricularFunction Inrecentyears,withtheincreasinguseofPETandPET/CTscannersfordetection andstagingofcancersandtumors,thecardiacapplicationsofPEThavealso increaseddramatically.PEThasinherentadvantagescomparedtoSPECT,withits superiorspatialresolution,inherentattenuationcorrection,andhigherenergy positronemittersresultinginbetterimagequality,alongwithmorerapidimaging protocols. Withtheuseofgatedacquisitionprotocols,PETlendsitselftoestimationofLVEF andvolumes.However,PETperfusionandgatedfunctionarecurrentlylimitedto onlypharmacologicstress,giventhatthecommonlyusedperfusiontracers(N13 ammoniaandrubidium82[Rb82])havesuchshorthalflivesthatacquisitionduring exerciseisnotfeasible.However,duetotheshorthalflifeofPETperfusiontracers, theEFpoststressisacquiredatpeakstresswhenthereismaximalcoronary hyperemia,ratherthanduringthedelayedacquisitionrequiredbySPECTimaging. SeveralstudieshaveevaluatedtheaccuracyofPETbasedautomatedLVFand volumeassessment.Schaeferetal.36,37showedanexcellentcorrelationbetween F18fluorodeoxyglucose(FDG)gatedPETderivedEFandvolumescomparedto MRI.TheEFwasslightlyunderestimatedbyPETduetounderestimationofend diastolicandoverestimationofendsystolicvolumes. LimiteddataarealsoavailableforN13ammoniaPETbasedEFandvolume estimationsoftheLV,withgoodcorrelationsreportedbetweenFDGPET38and contrastventriculography.39 Finally,dataonLVEFareemergingwithgeneratorproducedRb82basedPETMPI. Lertsburapaetal.40demonstratedthatstressPETEFwithRb82carried independentpredictivevalueforallcausemortality.Dorbalaetal.41alsoshowed similarfindings,and,inaddition,demonstratedthatlowerEFreserve%(stressrest EF)predictedincrementallyhighermortalityrelativetotheperfusionfindings. FuturePerspectives TherehasbeenaresurgenceofinterestinFPRNAatleastinpartbecauseofthe availabilityofTc99mlabeledradiotracers,whichallowsimultaneousevaluationof myocardialperfusion(SPECT)andgatedfunction(RNA)inthesamesetting. AnotherexcitingdevelopmentingatedSPECTistheevaluationofdyssynchrony usingtherestinggatedSPECTdata.PhaseanalysisofgatedSPECTdatausing

FourieranalysishasbeenshowntobeareliablemethodforLVdyssynchrony assessment.42Specificparameterssuchashistogrambandwidthandhistogram bandwidthstandarddeviationhavebeenshowntoberelatedtoadverseevents independentofEFwhenabnormal.43 SPECTERNAhasalsobeenrecentlystudiedwithexcellentresults,usingphase analysistoevaluatemechanicaldyssynchrony.44Finally,newflatpanelSPECT detectorsystemsshowtremendouspromiseindeliveringhighqualityperfusionand functionanalysisatlowradiationdoses,whichcouldbeasubstantialbreakthrough forpatientcare.45

PlanarandSPECTERNAatRestinaPatientWithaBasalInferiorAneurysm Figure3 Planarandsinglephotonemissioncomputedtomography(SPECT)equilibriumradionuclideangiocardiography(ERNA)atrestinapatientwitha basalinferioraneurysm.Planarimagesintheleftanterioroblique(LAO),anterior(ANT),andleftlateral(LLAT)views(top).Thebasalinferior aneurysmisbestappreciatedintheLLAT(arrow).SPECTimagesinthesamepatient(bottom).Shortaxis(SA),verticallongaxis(VLA),and horizontallongaxis(HLA)slicesareshown.Thebasalinferioraneurysmisappreciatedonmultiplereconstructiveslices(arrows).Aschematic drawingoftheanatomyisshownontheright. ReproducedwithpermissionfromWackersFJ,SouferR,ZaretBL.Nuclearcardiology.In:BraunwaldE,ZipesDP,LibbyP,eds.Braunwalds HeartDisease:ATextbookofCardiovascularMedicine.6thed.Philadelphia:W.B.Saunders2001:273.

DiagnosticParametersDerivableFromGatedMyocardialPerfusionStudy Figure4 CalculationofEFbygatedSPECTisavolumebasedratherthancountbasedtechnique. ED=enddiastolicEF=ejectionfractionES=endsystolicLV=leftventricularSDS=summeddifferencescoreSRS=summedrestscore SSS=summedstressscoreTID=transientischemicdilation. ReproducedwithpermissionfromGermanoG,BermanDS.ClinicalGatedCardiacSPECT.2nded.Malden,MA:BlackwellFutura1999.

TimeVolumeCurve Figure5 ThetimevolumecurveallowsestimationofEFusingthefollowingformula: EF%=enddiastolicvolumeendsystolicvolume/enddiastolicvolumex100% ReproducedwithpermissionfromGermanoG,BermanDS.ClinicalGatedCardiacSPECT.2nded.Malden,MA:BlackwellFutura1999.

GatingBasedAssessmentofLVWallMotionandThickening Figure6 Theuseofgatingbasedassessmentofleftventricular(LV)wallmotionandthickeningwheninterpretingnuclearperfusionimaginghas improvedspecificityforcoronaryarterydiseasedetection. ReproducedwithpermissionfromJonesRH,JohnsonSH,BigelowC,etal.Exerciseradionuclideangiocardiographypredictscardiacdeathin patientswithcoronaryarterydisease.Circulation199184(3Suppl):I528.

LimitationsinSpatialResolutionofSPECT Figure7 Giventhatthecollimatedspatialresolutionofsinglephotonemissioncomputedtomography(SPECT)rangesfrom915mm,smallsubendocardial infarctsmaybemissedbySPECTwhencomparedtoothertechniqueswithhigherspatialresolutionsuchascardiacmagneticresonance imaging. ReproducedwithpermissionfromWagnerA,MahrholdtH,HollyTA,etal.ContrastenhancedMRIandroutinesinglephotonemissioncomputed tomography(SPECT)perfusionimagingfordetectionofsubendocardialmyocardialinfarcts:animagingstudy.Lancet2003361:3749.

PrinciplesinEFAcquisitionbySPECT Figure8 Gatedsinglephotonemissioncomputedtomography(SPECT)utilizesthesamefundamentalprinciplesofacquisitionofcountsbasedonaregular RRinterval.Usually8or16framegatingisused.Ingeneral,anejectionfraction(EF)of45%isconsideredthelowerlimitsofnormalfor8 framegatedSPECT. ReproducedwithpermissionfromHollyTA,AbbottBG,AlMallahM,etal.Singlephotonemissioncomputedtomography.JNuclCardiol 201017:94173.

RoleofGatedSPECTinDifferentiatingCardiomyopathyEtiology Figure9 Differentiationofischemicandnonischemiccardiomyopathyisfacilitatedbyintegratingperfusionandfunctioninformationtogether,ratherthan eitheralone.Thecombinationofhighsummedstressscoreandregionalvarianceinwallmotionhelpsdifferentiateischemicfromnonischemic cardiomyopathy. ReproducedwithpermissionfromDaniasPG,PapaioannouGI,AhlbergAW,etal.Usefulnessofelectrocardiographicgatedstresstechnetium 99msestamibisinglephotonemissioncomputedtomographytodifferentiateischemicfromnonischemiccardiomyopathy.AmJCardiol 200494:149.

DiagnosisofCoronaryArteryDiseasebySinglePhotonEmission ComputedTomographyandPositronEmissionTomography
RoleofSPECTintheDiagnosisofCoronaryArteryDisease SPECTMPIisacommonlyusedtestforthediagnosisofCAD.Thalliumand technetiumarethecommonlyusedradioisotopes.Thalliumhasalowerenergy window,butmuchlongerhalflife,resultinginhigherradiationexposure.A comparisonofthesetwoisotopesisshowninTable4. ImagingandStressProtocols Differentimagingprotocolscanbeused.Thesecanbecombinedwithdifferent modalitiesofstresstestingincludingexercise,vasodilators,ordobutaminestress protocols.ThephysiologicprincipleinCADdiagnosisbystressSPECTisa challengetothecoronaryflowreserveleadingtodifferentialuptakeofisotopebased onregionalheterogeneityofflowinstenosedandnonstenosedterritories. TheadenosineA2areceptorprimarilymediatescoronaryvasodilation,andisthe maintargetofnonselectivepharmacologicvasodilators(adenosine,dipyridamole). However,stimulationofA1receptorsbytheseagentscausesatrioventricular(AV) block,andA2b/A3receptorscausesbronchoconstriction.Morerecently,selective A2areceptoragonistssuchasregadenosonhavebecomeavailablefor pharmacologicSPECT.Thechoiceofthestressmodalityshouldbeguidedbythe followingprinciples: 1. Patientswhocanexerciseshouldexerciseintheabsenceofactiveangina. 2. Inpatientswithleftbundlebranchblock,vasodilatorstressisthepreferred modeofstresstestingtoavoidpartiallyreversibleorfixedseptaldefectson theperfusionimage. 3. InpatientswitharecentMI,vasodilatorstressshouldbeused. 4. Inpatientswithactivewheezing,dobutaminestressisthepreferredmodeof stresstestingovertheuseofadenosineorexercise.21 AsummaryoftheimagingprotocolsisshowninFigures10a,b,c,d,e,f.Notethatin comparisontoTc99basedimaging,Tl201imagingshouldbeginapproximately 1015minutesafterstresstesting.Ingeneral,therestdoseisonethirdthestress doseinsamedayimagingprotocols.21 Interpretation TheinterpretationofmyocardialperfusionSPECTimagesshouldbeasystematic processthatroutinelyincludesevaluationoftherawimages,perfusionimages (location,size,severity,andreversibilityofperfusiondefectscardiacchambersizes andpresenceorabsenceofincreasedpulmonaryuptake),andgatedimagesfor globalandregionalventricularfunction.21 PerfusionDefects Myocardialperfusiondefectsshouldbeidentifiedbytheuseofvisualanalysisofthe reconstructedslices.Theperfusiondefectsshouldbecharacterizedbytheirlocation astheyrelatetospecificmyocardialwalls,perthe17segmentmodel(Figure11).46 Defectseverityistypicallyexpressedqualitativelyasmild,moderate,orsevere. Defectextentmaybequalitativelydescribedassmall,medium,orlarge. Defectswhoseseverityandextentdonotchangebetweenstressandrestimages arecategorizedas"fixed"or"nonreversible."Whenperfusiondefectsaremore severeand/orextensiveonstresscomparedtorestingimages,aqualitative descriptionofthedegreeofreversibilityisrequired.Reversibledefectsdenote ischemia,whereasfixeddefectsaretheresultofscaringorartifacts.Examplesof normalandabnormalnuclearscansareshowninFigures12and13,respectively. Inaddition,useofthesemiquantitativesegmentalscoringsystemimprovesthe accuracy,reducesthelikelihoodofoverlookingsignificantdefects,andprovidesan
Figure10f Figure10e Figure10a Table4

Figure10b

Figure10c

Figure10d

Figure11

Figure12

importantindexthatisapplicabletodiagnosticandprognosticassessments.Itis recommendedthattheinterpretationandsemiquantificationofregionaltracer uptakefollowtheAmericanHeartAssociation(AHA)17segmentmodel.The recommended4pointscoringsystemisasfollows:normal=0,milddefect=1, moderatedefect=2,severedefect=3,anddefectequaltobackgroundactivity=4. Theseregionalscoresarethensummedintoglobalscoresasfollows:summed stressscore(SSStotalperfusiondefectduringstressreflectingscarplus ischemia),summedrestscore(SRStotalperfusiondefectatrestreflectingscar), andsummeddifferencescore(SDSdifferencebetweenstressandrestreflecting ischemia). Theglobalscorescanalsobeexpressedaspercentmyocardiumabnormal, scarredorischemicbydividingthecorrespondingsummedscoresby68,whichis themaximumpossiblescore(17segmentsx4).Thesesemiquantitativescoresare helpfultodefineapatient'ssubsequentriskofdeathorMI. Othernonperfusionhighriskmarkersthatshouldbeidentifiedinclude: Ventriculardilation:LVenlargementatrestand/orpoststressisahighrisk marker.Inparticular,stresstorestLVcavityratio,alsoreferredtoas transientcavitydilatation(TCD)ortransientischemicdilation(TID),hasbeen describedasamarkerforhighriskcoronarydisease.ATIDratioof>1.2is associatedwithworseoutcomeseveninpatientswithnormalperfusion. ThisreversibleLVdilationisthoughttobesecondarytoischemiainduced subendocardialhypoperfusion,yieldinganapparentincreaseintheLVcavity sizeonstressscintigramscomparedwiththerestimagesinwhich resolutionofsuchischemiahasoccurred.Thisfindingisassociatedwitha higherincidenceofmultivesselCADandaworseoutcomethaninpatients notdemonstratingthisfinding.47 Lunguptake:Thepresenceofincreasedlunguptakeafterthalliumperfusion imaging(lung/heartratio>0.5)isanindicatorofpoorprognosis. RVuptakeandRVdilation:ThenormalmyocardialintensityoftheRVis approximately50%ofpeakLVintensity.IncreasedRVuptakehasbeen associatedwiththepresenceofpoorlongtermoutcomes. Gating Gatingrequiresastableandconsistentheartrhythmaswellassufficienttemporal resolutiontocorrectlycharacterizethecardiaccycle.Usuallyan8or16frameperR Rintervalgatingmethodisused.RegionalandglobalLVfunctionisthenevaluated fromthegatedimages.Inaddition,gatingprovidesinformationaboutLVend systolicvolumeandenddiastolicvolume,andthesedataaddincremental diagnosticandprognosticinformation,asdiscussedlater. DiagnosticAccuracy ThesensitivityfordetectingCAD(50%stenosis)averages87%in33studies pooledfromtheliterature.Specificity,derivedfrompatientsreferredforcardiac catheterizationthathadnormalangiograms,averages73%.Thenormalcyrateis 91%inthispooledanalysis.Thenormalcyrateisavariablethatreducesthereferral biasinherentinspecificitydeterminationsthatusepatientswithangiographically normalcoronaryarteriesatcatheterization.Thenormalcyrateisdefinedasthe percentageofpatientswitha<5%pretestlikelihoodofCADwhohavenormalMPI studies. Inaddition,thereisnodifferenceobservedbetweenthediagnosticaccuracyof exerciseorvasodilatorMPI.Thesensitivityandspecificityofpharmacologic vasodilatorstressimagingarecomparabletothoseofexercisestressimaging,with asensitivityof89%andaspecificityof75%.48 Attenuation Attenuationartifactscausedbybreasttissuearerelatedtoacombinationofbreast sizeandthedegreeofoverlapovertheLV,aswellasbreasttissuedensity. Diaphragmaticattenuationcanbeseeninmenorwomen.Itismorefrequentlyseen inpatientswithabdominalobesityduetoelevationofthelefthemidiaphragm,with theheartadoptingamorehorizontalpositionwithinthechest.

Figure13

Acutegastricdilatationcanoccasionallycauseasimilarartifact.Diaphragmatic attenuationusually(althoughnotalways)showsasafixedperfusiondefect.The gatedimagesareextremelyhelpfulfordifferentiatingattenuationartifactsfromscar. Inpatientswithmarkeddiaphragmaticattenuation,proneimagingcanalsobe helpful. Proneimagingisusuallyusedinpatientswithmotionand/orinferiorwall attenuation.Attenuationcorrectionwiththeuseofanexternalradionuclidesourceor CTisaneffectivewaytotroubleshootattenuationartifactsinordertoimprovethe specificityandnormalcyrate. PositronEmissionTomographicPerfusionImaging PETperfusionimagingisanalternativetoSPECTimaging.Inmostimaging laboratories,PETperfusionimagingisperformedwithRb82,apotassiumanalog thatistransportedintracellularlyviathesarcolemmamembrane.Thetraceriseluted fromageneratoranddirectlyinfusedintothepatient.Ithasaveryshorthalflifeof75 seconds,permittingrapidsequentialimaging.Becauseoftheshorthalflife,only vasodilatorstresscanbeused. ThesensitivityandspecificityofRb82PETfordetectionofCADare89%and86%, respectively.49WhenCTisusedforattenuationcorrectionforRb82emission images,thesensitivityis93%,withan83%specificity.UsingPET,thedetectionrate formultivesseldiseaseis95%.50 ThereareseveraladvantagesofPEToverSPECTimaging.Attenuationcorrectionis moreeasilyperformed.PETischaracterizedbyhighspatialandcontrastresolution, andyieldsbetterspecificitythanobservedwithSPECT.Multivesseldisease identificationisbetterachieved. Inonestudy,PETcorrectlyidentified71%ofpatientswithanatomicmultivessel disease,whereasSPECTonlypredicted48%ofpatientswhohadmultivesselCAD atcardiaccatheterization.AnotheradvantageofPETisthatmyocardialbloodflow canbequantitatedinmilliliters/minute/gramorthecoronaryflowreservecanbe assessed.ThispermitsbetteridentificationofdiffuseCADbecausetraceruptake canbehomogeneous,reflectiveofbalancedischemia.50 PatientPopulationBenefittingFromSPECT ThehighestclinicalbenefitofSPECTMPIwouldbeseenifpatientswith intermediatepretestlikelihoodofcoronarydiseaseareevaluated.Toguide utilizationofimaging,theAmericanCollegeofCardiologyFoundation(ACCF),along withotherprofessionalsocieties,issuedthe2005ACCF/ASNCSPECTMPI appropriatenesscriteria,whichwerelaterupdatedin2010.51Usingthesecriteria, studiesareclassifiedasappropriate,inappropriate,oruncertain.Arecent multicenterstudysuggestedthatinthecurrentclinicalpractice,nearly13%of studiesareinappropriate.52 Thetopfiveinappropriateindicationswere: 1. DetectionofCADinanasymptomatic,lowCADriskpatient. 2. Asymptomatic,postrevascularization,<2yearsafterPCI,symptomsbefore PCI. 3. Evaluationofchestpain,lowprobabilitypatient,interpretableECG,andable toexercise. 4. Asymptomaticorstablesymptoms,knownCAD,<1yearaftercatheterization, orabnormalpriorSPECT. 5. Preoperativeassessment,lowriskforsurgery.

CharacteristicsofSPECTPerfusionTracers Table4

SameDayRestStressTc99mProtocol(1of6) Figure10a Tc=technetium.

SameDayStressRestTc99mProtocol(2of6) Figure10b Tc=technetium.

TwoDayStressTc99mProtocol Figure10c Tc=technetium.

SameDayStressReinjectionRedistributionTl201(4of6) Figure10d Tl=thallium.

SameDayDualIsotope(5of6) Figure10e

SameDayStressRedistributionTl201(6of6) Figure10f Tl=thallium.

The17SegmentModel Figure11 The17segmentmodeloftheleftventricle,assuggestedbytheAmericanHeartAssociation. ReproducedwithpermissionfromCerqueiraMD,WeissmanNJ,DilsizianV,etal.Standardizedmyocardialsegmentationandnomenclaturefor tomographicimagingoftheheart:astatementforhealthcareprofessionalsfromtheCardiacImagingCommitteeoftheCouncilonClinical CardiologyoftheAmericanHeartAssociation.Circulation2002105:53942.

NormalSPECTMyocardialPerfusionImaging Figure12 Anexampleofnormalsinglephotonemissioncomputedtomography(SPECT)myocardialperfusionimaging(MPI).Thereisnoevidenceof decreaseduptakeinanywall.

AbnormalSPECT Figure13 Anexampleofabnormalscaninapatientwithchestpainandlongstandingdiabetes.Notethedecreasedperfusionintheanterior,septal,and apicalwallonstressandtransientischemicdilatation. SPECT=singlephotonemissioncomputedtomography.

TheRoleofSPECTinPrognosisandRiskStratification
ThemaingoalsofriskstratificationinCADareasfollows: Improveclinicaloutcomesandlowercosts. Identifyhighriskpatientswhowouldbenefitfromspecial procedures/therapiesthatmayoffsetsignificantmortalityandmorbidity. Riskstratificationmaybeusedasamethodtoallocateresourcestothosein greatestneed. AnimportantprincipleinriskstratificationinMPIistointerpretboththestressand imagingpartsofthetesttogether.Highriskexerciseorstressmarkersshouldnot beignored,eveninthesettingofnormalperfusion.Thesehighriskmarkers include: Durationofsymptomlimitingexercise<6METs Failuretoincreasesystolicbloodpressure>120mmHgorasustained decrease10mmHgbelowrestduringprogressiveexercise STdepression2mm(Figure14) ExerciseinducedSTsegmentelevation Anginaatlowworkload Sustained(>30seconds)orsymptomaticventriculartachycardia Poorheartraterecovery(<12bpm) Chronotropicincompetence(failuretoachieve85%ofagepredicted maximalheartrate) PrognosticValueofNormalSPECTMyocardialPerfusionImaging AnormalMPIisreassuring.Thereisconsistentevidencethatanormalmyocardial perfusionscanisgenerallyassociatedwithanexcellentprognosis.Anannualevent rateof<1%hasbeenreported.Inapooledanalysisof19publishedserieson normalorlowriskSPECTperfusionstudiescomprising39,173patients,the medianrateofmajoradversecardiacevents(MACE)was0.6%/year(Figure15). However,theeventrateishigherthanthisinpatientswithanormalMPIstudyand oneormoreofthefollowing: Submaximalheartrateresponsetoexercise Pharmacologicalstress Advancedage Diabetesmellitus PriorCAD HighDuketreadmillscore TIDoftheLV Chronickidneydisease53 Ontheotherhand,inpatientswithabnormalscans,theriskvariesbythelevelofthe abnormality.Inriskadjustedanalysis,patientswithmildormoderateischemiahave alowtointermediateclinicalrisk,whereaspatientswithseverescarand/or ischemiaareathighriskofdeathorMI. Inalandmarkstudy,Hachomovitchandcolleagueshaveshowninmorethan 10,000patientsthattheriskofcardiacdeathandMIincreasesexponentiallyasthe sizeoftheperfusiondefectincreases.54Itisimportanttonotethoughthatpatients withmildperfusionabnormalitieshavenoincreaseintheriskofcardiacdeath,but therewasanincreaseintheriskofnonfatalMI(Figure15).Inaddition,ancillary findingsincludingTID,increasedRVtraceruptake,abnormalvasodilatorstress ECG,andincreasedpulmonaryuptakearealsomarkersofincreasedclinicalrisk (Figure16).47 SinglePhotonEmissionComputedTomographyMyocardialPerfusionImaging asaGuideforTherapeuticDecisions Inariskbasedapproachtomanagement,patientswithmildlyormoderately abnormalscansgenerallyfarebetterwithmedicaltherapy(unlesstheirsymptoms
Figure22 Figure14

Figure15

Figure16

Figure17

Figure18

Figure19

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Figure21

arepoorlycontrolled),whereaspatientswithseverelyabnormalscansshowing extensiveischemiahaveimprovedoutcomeswithrevascularization(Figure17).55 ThisriskbasedapproachtomanagementofCADbasedonmyocardialperfusion resultsisalsocosteffective,asconfirmedintheEND(EconomicsofNoninvasive Diagnosis)study.Astrategyofinitialscreeningwithexercisetreadmilltest,followed byMPIandasubsequentselectiveangiogramappearstobemostcosteffective (Figure18).56 Inaddition,manystudieshaveshownthatMPIprovidesindependentand incrementalvalueoverclinicalvariables,treadmillvariables,andevencoronary angiography(Figure19).Also,gatedSPECThasincrementalvalueoverperfusion imaginginassessingprognosis.LVEF)hasbeenshowntoriskstratifypatientsfor subsequentcardiacdeath.PoststressLVEF,asmeasuredbygatedSPECT,also providessignificantprognosticinformationovertheextentandseverityofperfusion defectinthepredictionofcardiacdeath.Finally,LVendsystolicvolumeprovides addedinformationoverpoststressLVEFforpredictionofcardiacdeath(Figure 20).24 PrognosticValueofExerciseVersusPharmacologicalSinglePhotonEmission ComputedTomographyMyocardialPerfusionImaging MultiplestudieshaveconfirmedtheexcellentprognosticvalueofnormalSPECTMPI inallpatients.However,patientswhoundergopharmacologicalstresstestinghave higherincidenceofcardiacdeathornonfatalMIateverylevelofabnormality comparedtopatientswhoundergoexercisestress(Figure21).Thisismostlikely duetothehigherriskprofileofpatientswhoundergopharmacologicalstress testing.54 PrognosticValueofSinglePhotonEmissionComputedTomographyMyocardial PerfusionImaginginSpecialPopulations Women:Despiteslightlylowerspecificityinwomen(duetopotential artifacts),multiplestudieshaveconfirmedthatSPECTmyocardialperfusion hasthesameprognosticvalueinbothmenandwomen.57Also,a decreasedsensitivityforCADdetectioninwomenisobservedinthosewith verysmallventricles(Figure22).58 Thereareseveralmethodologicalissuesthatareimportanttoconsider whenimagingwomen.First,itisimportanttonotethatTc99mlabeled imagingagentsarepreferabletoTl201inwomenbecauseofless attenuationandfewerimageartifacts.Second,gatedSPECTenhances specificityovernongatedSPECTbecauseareassuspectedofbeingadefect duetobreastattenuationshouldshownormalsystolicthickening,whereasa myocardialscarwouldshowawallmotionorthickeningabnormalityinthe anteriorwall.Third,a2dayprotocolwhererestandstressimagesare separatedby24hoursisindicatedinveryobesewomen.Thispermitsmore highqualityrestimagesbecausea2.53timeshigherdosecanbegiven comparedtothedosegivenonasamedayrest/stressprotocol.Fourth, attenuationcorrectionalgorithmsmightenhancespecificityandsensitivityof SPECTimaginginwomen. Diabetics:Cardiovasculardeathisthemostcommoncauseofmortalityin thepopulation.CADaccountsfor6580%ofdeathsindiabeticpatients. SeveralstudieshaveconfirmedthattheaccuracyofSPECTisnotdifferent betweenpatientswithandwithoutdiabetes.Despitethat,diabeticpatients haveahighereventratecomparedtonondiabeticsateveryabnormalitylevel. Inaddition,patientswithinsulindependentdiabetesmellitusdoworsethan patientswithnoninsulindependentdiabetesmellitus(Figure23).58 ThecurrentevidencedoesnotsupportroutinescreeningforsilentCADin diabeticpatients.Wackersetal.conductedtheDIAD(DetectionofIschemia inAsymptomaticDiabetics)study,whichincludedmorethan1,000patients whowererandomizedtoscreeningversusnoscreeningbySPECTMPI.Five hundredandtwentytwopatientswerescreenedbyMPI.Ofthese,22%had

Figure23

anabnormalstresstestresult.Cardiacautonomicneuropathyturnedoutto betheonlyindependentpredictorofanabnormalMPI.However,onfollowup (mean4.80.8years),ascreeningstrategydidnotimproveeventfree survivalinthiswelltreatedcohortthecumulativecardiaceventratewas 2.8%(0.5%/year).59,60 Preoperativeriskassessment:SPECTMPIshouldonlybeusedinpatients inwhomthepreoperativeguidelinesrecommendstresstesting.Anormal stresstestinthispopulationhasanexcellentnegativepredictivevalueof 99%forperioperativecardiacevents.However,thepositivepredictivevalueof abnormalSPECTMPIisintherangeof525%.Thus,itisnotnecessaryto revascularizeallpatientswithabnormalSPECTMPIpriortononcardiac surgery.Thedecisiontorevascularizeshouldbepersonalizedandbasedon thedegreeofischemia.Itisimportanttonotethattheriskofperioperative eventwithfixeddefectsishigherthanthatofnormalMPI,butitisstill significantlylowerthantheriskinpatientswithreversibledefects.

IncidenceofNonfatalMIorDeathRelativetoExerciseDurationinPatientsWith2mmofSTSegmentDepression Figure14 Notethattheeventrateisthreetimeshigherinpatientswhocouldnotachieveatleast6minutesofexerciseandwhohad2mmofST depression. MI=myocardialinfarction. ReproducedwithpermissionfromThompsonCA,JabbourS,GoldbergRJ,etal.Exerciseperformancebasedoutcomesofmedicallytreated patientswithcoronaryarterydiseaseandprofoundSTsegmentdepression.JAmCollCardiol200036:21405.Copyright2000American CollegeofCardiologyFoundation.

RatesofCardiacDeathandMyocardialInfarctionperYearasaFunctionofScanResult Figure15 Thenumbersareshownunderneaththecolumns.*Statisticallysignificantincreaseasafunctionofscanresult.**Statisticallysignificantincrease inrateofmyocardialinfarction(MI)vs.cardiacdeath(CD)withinscancategory. ReproducedwithpermissionfromHachamovitchR,BermanDS,ShawLJ,etal.Incrementalprognosticvalueofmyocardialperfusionsingle photonemissioncomputedtomographyforthepredictionofcardiacdeath:differentialstratificationforriskofcardiacdeathandmyocardial infarction.Circulation199897:53543.

AnnualEventRateinPatientsWithNormalPerfusionandTransientLVDilation Figure16 Annualeventrateinpatientswithnormalperfusionandtransientleftventricular(LV)dilation(bluebars)comparedtopatientswithnormal perfusionscansandabsenceoftransientLVdilation(yellowbars).Notethatwithvasodilatorstress,theeventrateis3.2%/yearinpatientswith normalscansandtransientischemiccavitydilationcomparedto1%annuallyforpatientswithnormalperfusionandnotransientischemicdilation. ReproducedwithpermissionfromAbidovA,BaxJJ,HayesSW,etal.TransientischemicdilationratiooftheLVisasignificantpredictorof futurecardiaceventsinpatientswithotherwisenormalmyocardialperfusionSPECT.JAmCollCardiol200342:181825.Copyright2003 AmericanCollegeofCardiologyFoundation.

AdjustedRiskofCardiacDeathvs.Ischemia Figure17 Loghazardratioforrevascularization(Revasc)vs.medicaltherapy(MedicalRx)asafunctionof%myocardiumischemic.Therelationship between%myocardiumischemicandoutcomesrevealedthatinthesettingofnoormildamountsofinducibleischemia,patientsundergoing medicaltherapyhadasurvivaladvantageoverpatientsundergoingrevascularization.Thesetwolinesintersectatavalueof10%to12.5% myocardiumischemic,abovewhichthesurvivalbenefitforrevascularizationovermedicaltherapyincreasesasafunctionofincreasing amountsofinducibleischemia. ReproducedwithpermissionfromHachamovitchR,HayesSW,FriedmanJD,CohenI,BermanDS.Comparisonoftheshorttermsurvivalbenefit associatedwithrevascularizationcomparedwithmedicaltherapyinpatientswithnopriorcoronaryarterydiseaseundergoingstressmyocardial perfusionsinglephotonemissioncomputedtomography.Circulation2003107:29007.

CostsofCareforDirectCathvs.InitialMyocardialPerfusionImagingforStableAngina Figure18 Thecostsofcareforthedirectcatheterizationgroupversusthegroupthatunderwentinitialmyocardialperfusionimagingplusselective catheterizationforevaluationofstableangina.Notethatthediagnosticcostandfollowupcostwerehigherforpatientswitheitheralow, intermediate(Int),orhighpretestlikelihoodofclinicalriskwhohadcatheterizationasthefirststepinevaluation. ReproducedwithpermissionfromShawLJ,HachamovitchR,BermanDS,etal.Theeconomicconsequencesofavailablediagnosticand prognosticstrategiesfortheevaluationofstableanginapatients:anobservationalassessmentofthevalueofprecatheterizationischemia. EconomicsofNoninvasiveDiagnosis(END)MulticenterStudyGroup.JAmCollCardiol199933:6619.

AnnualizedRatesofHardEventsinPatientsWithaNormalRestingECGvs.ResultsofStressSestamibiScansandtheDTS Figure19 Annualizedratesofdeathand/orMI(hardevents)inpatientswithanormalrestingECGrelatedtoresultsofstress99mTcsestamibiscansand theDuketreadmillscore(DTS).NotethatthepatientswithintermediateDuketreadmillscoreswerefurthersuccessfullyriskstratifiedbythe extentoftheperfusionabnormalities.Patientswithmoderatetosevere(ModSev)abnormalitieshadasubstantiallyhighereventratethan patientswithlessseveredefects. ReproducedwithpermissionfromLippincott,Williams,&Wilkins.HachamovitchR,BermanDS,KiatH,CohenI,FriedmanJD,ShawLJ.Valueof stressmyocardialperfusionsinglephotonemissioncomputedtomographyinpatientswithnormalrestingelectrocardiograms:anevaluationof incrementalprognosticvalueandcosteffectiveness.Circulation2002105:8239.

CumulativeSurvival:StratificationbyEndSystolicVolumeandEjectionFraction Figure20 Cumulativesurvivalofpatientswith(A)EF45%and(B)EF<45%,stratifiedbyendsystolicvolume.Cumulativesurvivalwasprogressively lowerwithincreasingendsystolicvolume. ReproducedwithpermissionfromSharirT,GermanoG,KavanaghPB,etal.Incrementalprognosticvalueofpoststressleftventricularejection fractionandvolumebygatedmyocardialperfusionsinglephotonemissioncomputedtomography.Circulation1999100:103542.

PrognosticValueofExercisevs.PharmacologicSPECT Figure21 Pharmacologicstressmyocardialperfusionimaging(MPI)hasanexcellentprognosticvaluesimilartoexerciseMPI.However,asshowninthese twographs,foranydegreeofscanabnormality,subjectswithpharmacologicstresshaveahighereventratethanthosewhoexercised.This highereventrateinpharmacologicstressgroupreflectstheimportanceoffunctionalcapacityandcomorbiditiesasanimportantdeterminantof prognosisincoronaryarterydisease. SPECT=singlephotonemissioncomputedtomography. ReproducedwithpermissionfromHachamovitchR,BermanDS,ShawLJ,etal.Incrementalprognosticvalueofmyocardialperfusionsingle photonemissioncomputedtomographyforthepredictionofcardiacdeath:differentialstratificationforriskofcardiacdeathandmyocardial infarction.Circulation199897:53543.

RatesofCardiacDeathandNonfatalMIRelatedtoAdenosine99mTcSPECTDefectsinWomen Figure22 MI=myocardialinfarctionSPECT=singlephotonemissioncomputedtomographyTc=technetium. ReproducedwithpermissionfromElsevier.AmanullahAM,BermanDS,ErelJ,etal.Incrementalprognosticvalueofadenosinemyocardial perfusionsinglephotonemissioncomputedtomographyinwomenwithsuspectedcoronaryarterydisease.AmJCardiol199882:72530.

RiskStratificationinDiabetes Figure23 Relationshipbetweenlogrelativehazardforpredictedcardiacmortalityandsummedstressscoreininsulindependentdiabetesmellitus(IDDM), noninsulindependentdiabetesmellitus(NIDDM),andnondiabetics.TherewasaveryhighrateofcardiacdeathinpatientswithIDDMand abnormalscans. ReproducedwithpermissionfromBermanDS,KangX,HayesSW,etal.Adenosinemyocardialperfusionsinglephotonemissioncomputed tomographyinwomencomparedwithmen.Impactofdiabetesmellitusonincrementalprognosticvalueandeffectonpatientmanagement.JAm CollCardiol200341:112533.

MyocardialViabilityAssessmentbySinglePhotonEmission ComputedTomographyandPositronEmissionTomography Imaging


Background Ischemicheartdiseasecontributestoabout70%oftheetiologyforchronicheart failure(CHF).61LVdysfunctionisoneofthemostimportantdeterminantsof prognosisinpatientswithCAD,andmortalityinCADincreasesastheseverityof dysfunctionincreasesparticularlywithmedicaltherapy(Figure24).62,63 Furthermore,itisestimatedthat2540%ofpatientswithchronicCADandLV dysfunctionhavethepotentialforsignificantimprovementinLVFafter revascularization(Figure25).Figure25displaysLVEFatrestbyradionuclide ventriculographybefore(Preop)andafter(Postop)coronaryarterybypasssurgeryin patientswithpreoperativeLVdysfunctionintwosurgicalseries.Althoughsurgery resultedinonlyasmallincreaseinmeanEF,substantialincreaseswereobserved incertainsubsetsofpatients,withnormalizationofEFoccurringinmany patients.64,65 ItisnowunderstoodthatmostpatientswithCHFresultingfromischemic cardiomyopathyhaveanadmixtureofareaswithregionalnecrosis,repetitive stunning,ormyocardialhibernation.66Theterm"hibernating"wasintroducedby Diamondetal.67andexpandedbyRahimtoolaetal.,todescribeaprocessof chronicyetpotentiallyreversiblecontractiledysfunctionafterrestorationof myocardialbloodflowinischemiccardiomyopathy.68 Thedevelopmentofhibernatingmyocardiuminischemiccardiomyopathyisa complexprocessstemmingfromrepeatedboutsofischemiacausingmyocardial stunninginthesettingofobstructivecoronarydiseaseprogression.Thisleadsto ultrastructuralchangesatthecellularlevel,culminatinginmyocardialcontractile dysfunction(Figure26).69
Figure27 Figure25 Figure24

Figure26

Table5

Understandingthespecificcharacteristicsofthesedifferenttypesofabnormal myocardialtissue(hibernation,stunning,andscar)helpsunderstandingofthe responseorlackthereofofLVregionalandglobalfunctiontorevascularization (Table5). Patientswithsubstantialischemicandviablemyocardiumhaveabettersurvivalwith revascularizationthanwithmedicaltherapy.66,7073However,amajordeterminantof LVFimprovementisthepresenceofasubstantialamountofviablemyocardiumto ensurefunctionalrecoveryandprognosticbenefitfollowingrevascularization. InaTlSPECTviabilitystudybyRagostaetal.,usinga15segmentmodel,presence of7dysfunctionalsegmentsshowingviabilitypredictedincreasesinpreoperative EF8weeksafterrevascularizationcomparedtonochangeinEFpost revascularizationinpatientswith<7segmentsofviablemyocardium(Figure 27).74,75 InametaanalysisbyAllmanetal.,patientswithsubstantialamountsofviable myocardiumshowedthatpatientswithviablemyocardiumonmedicaltherapyhada 16.5%annualcardiacdeathratecomparedto3.2%inpatientswithviable myocardiumundergoingrevascularization(Figure28).66 Numerousotherfactorsapartfromthepresenceofviabilitymayalsodictatewhether regionalandglobalLVFwillimprove(Table6).76 Manyreadilyavailablemethodsofviabilitysuchasthepresenceorabsenceof electrocardiographicQwaves,severehypokinesisorakinesis,andthinningof regionalcoronaryterritoryventricularwallsserveassimpleinitialcluestothe clinician,butunfortunatelyarenotrobustenoughtoconfidentlyexcludethepresence orabsenceofhibernatingmyocardium.77
Table7

Figure28

Table6

Figure29

Thus,noninvasiveimagingtechniquesformanimportantpartoftheassessmentof myocardialviability.Thevaryingcharacteristicsofdysfunctionalyetviable myocardiumandthebasisofdifferentimagingtestingwithwidelyusedviability criteriaareillustratedinTable7.78 AssessmentofMyocardialViabilitybySinglePhotonEmissionComputed Tomography Thallium201Imaging Tlisapotassiumanaloguethatwasfirstusedfortheevaluationofviabilitywith SPECT.ItisactivelytransportedbytheNa+/K+ATPasepumpthroughanintactcell membraneofthemyocardialcells.Itsinitialuptakeisusedtoevaluateperfusion, whereaslateaccumulationevaluatescellintegrity. IncontrasttoTc99mtracers,uptakeofTlisnotirreversible,butisinfluencedby gradientconcentrationacrossthecellmembrane.Therefore,areasofdysfunctional hypoperfusedyetviablemyocardiumwhereuptakeofTlisinitiallyreduced comparedtonormallyperfusedmyocardiummayshowenhanceduptakeatlater imaging(usuallyatleast34hoursfollowinginitialadministration)duetoslow accumulationofTlwithpartialorcompletedisappearanceoftheinitialperfusion defect.Thisphenomenon,pertainingonlytoTl,istermed"redistribution"and representsthebasisforviabilityevaluationusingthistracer.Thetwomostused protocolstoevaluateviabilityarerepresentedbystressredistributionreinjectionand restredistributionimaging. StressRedistributionReinjection Withthisprotocol,imagesareacquiredimmediatelyafterpharmacologicorphysical stressandagainafter34hours.Ifinthislastsetofimagespersistentfixedand severedefectsareobserved,aseconddoseofTlisadministeredandathirdsetof imagesisacquiredimmediatelythereafter.Afinalsetofimagesat24hoursfor furtherevaluationofviabilityisalsoanoption(Figure29). Thisapproachwasdevelopedfromtheobservationthatfixeddefectsat34hoursof redistributionmaynotnecessarilyrepresentnecroticmyocardium,astheyfrequently showpreservedmetabolicactivitybyPETorresidualcontractionwiththepotential forrecoveryoffunctionfollowingrevascularization.19Theidentificationofviability usingthisprotocolisbasedonthedemonstrationofsignificantredistribution (usuallyanincreaseofatleast10%frominitialuptake)oronthepresenceofat least>50%ofmaximaltraceruptakeinadysfunctionalsegment. Datafrom11studiesenrolling301patientsusingthisprotocolreportedhigh sensitivity(weightedmean86%,range33100%),butreducedspecificity(weighted mean50%,range1680%),80indicatinganoverestimationoffunctionalrecoveryina substantialnumberofdysfunctionalsegments.Similarly,highsensitivitybut suboptimalspecificityhasbeenreportedwhenimprovementofglobalEFhasbeen considered.Theadvantageofthisapproachisthatitalsotakesintoaccountthe presenceofinducibleischemiathatprovidesanadditionaldeterminantof prognosis. Figure30ashowsarepresentativepatient.Itshowsstress(top)rest(middle) redistributionwithanitrateenhancedreinjection(bottom)studydoneina77year oldpatientwithapriorinferiorinfarctpresentingwithheartfailuresymptoms followingalargeanteriorMIsustained2weeksprior,whichwastreatedwith thrombolytictherapy.The2DechocardiogramrevealsanEFof18%withan aneurysmalapex.ImageswithTlrevealatransmuralinfarctionoftheentireinferior wall,aneurysmalapex,distalseptum,andperiapicalwallsindicativeofno significantviabilitywithredistributionandnitrateenhancement.Thepatientwas continuedonacourseofmedicalmanagementandreferredforimplantable defibrillatorplacement.InFigure30b,thestressrestreinjectionstudyshows substantialviabilityintheleftanteriordescending(LAD)territory. RestRedistribution
Figure32 Figure30a

Figure30b

Figure31

Figure33

Figure34

Table8

Figure35

Figure36

Usingthisapproach,Tlisinjectedatrestandimagesareacquiredimmediatelyand following34hoursofredistribution.Therefore,inducibleischemiaisnotevaluated. Viabilityisdefinedwhenadysfunctionalsegmentshowssignificantredistribution (>10%increaseinTluptake)orarelativeuptake>50%ofmaximalactivity.With thesecriteria,meansensitivityforpredictionofregionalfunctionalrecoveryaveraged 88%(range44100%)andmeanspecificitywas59%(range2292%)inapooled analysisof22studiesreporting557patients.80However,asubstantialnumberof apparentfixeddefects(2530%)at4hoursmayshowuptakewithadditional imaging.81ThevalueofthisprotocoltopredictchangesinglobalEFhasbeen investigatedinfewclinicalstudiesreportinghighsensitivity,butsuboptimal specificity.TheprognosticvalueofrestingTlimaginghasbeentestedinsmall clinicalstudiesinwhichboththeamountofviablemyocardiumandthatofnecrotic myocardiumwerefoundtoinfluencebothmortalityandmorbidityinpatientswith ischemicLVdysfunction.66 Figure31isanexampleofarest,4hourredistributionTlscanindicatingtransmural infarctionpatterninRCAterritory. Technetium99mLabeledAgents Twocompounds,TcsestamibiandTctetrofosmin,arecurrentlyusedforclinical purposes,althoughonlytheformerhasbeenadequatelytestedforviability evaluation.IncontrasttoTl,Tcagentsaretrappedalmostirreversiblyin mitochondriaafterintravenousinjectionandflowdependentdistributionto myocardialcells,andtheydonotundergoaclinicallysignificantredistribution process.Therefore,theimagesreflecttheuptakeofthetraceratthetimeofinjection andnotatthetimeofacquisition,aswithTl. Whenonlyviabilityneedstobeevaluated,asinglesetofimagesissufficient, usuallyobtainedaftersublingualnitrateadministrationtomaximallyenhanceuptake inhypoperfusedmyocardium.However,foramorecomprehensiveevaluationof viabilityandischemia,twosetsofimages,andthereforetwoseparateinjectionsof thetracerareneededoneduringmaximalphysicalorpharmacologicstressanda secondoneatrestorafternitrateadministration.Thecriterionfordefiningviabilityis representedbyarelativeuptake>50%ofmaximaltraceractivityinadysfunctional segment. Apooledanalysisof13studiesusingthisapproachandenrolling308patientshas reportedanaveragesensitivityof79%(range62100%)andaveragespecificityof 58%.80Sevenstudies(reporting180patients)inwhichtraceruptakewas supplementedwithnitrateadministrationreportedasensitivityof86%and increasedspecificityof83%ofpredictingregionalfunctionalimprovement.82 AlthoughdataonTc99mtetrofosminarelimited,thereisgoodagreementbetween theTctetrofosminandTcsestamibistudies,withsimilaraccuracyfortheprediction offunctionalrecoveryafterrevascularization.80 NitrateEnhancedViabilityImaging TheadditionofnitratestoviabilityassessmentbyTlorTc99mbasedisotopeshas beenshowntoenhancedetectionofviabilitybyfacilitatingdeliveryoftheisotopeto thehypoperfusedmyocyte.StudieswithnitrateenhancedTlhaveshownenhanced detectionofviablemyocardiumandimprovedprognosticationcomparedtonon nitrateenhancedimages.83Similarly,studieswithnitrateenhancedTc99mhave shownagreaterabilitypredictimprovementinregionalfunction84andin prognostication.85 Anadditionalrelevantadvantagederivedfromfavorablephysicalpropertiesofthese Tc99mcomparedtoTlagentsistheopportunitytoacquireECGgatedimages.This allowsfortheevaluationofregionalandglobalfunction,particularlyregionalwall thickening,endsystolicandenddiastolicvolumes,andLVEF. TheaccuracyofthisapproachtopredictrecoveryofglobalLVfunctionhasbeen evaluatedinasinglecenterstudyreportingapromising79%sensitivityand78% specificity.80StudiescomparingviabilitydetectionofTlandTcbasedassessment ofviabilityhaveshowngoodagreementbetweentheseagentswithregardto

Figure37

Figure38

Figure39

predictingtheamountofviablemyocardiumandtherecoveryofLVfunction(Figure 32).86 MyocardialViabilityAssessmentbyPositronEmissionTomography PETisawellestablishednoninvasivetechniqueforevaluationofmyocardial perfusionandviability.87PETiswidelyregardedasthenoninvasivegoldstandard forassessingmyocardialviability.ThePETperfusiontracersusedinclinical practiceareN13ammonia,Rb82andF18FDG,thelatterbeingthemost commonlyusedmetabolictracerforcardiacapplications. InpatientswithCAD,astheseverityofstenosisprogresses,thereisconcomitant reductioninmyocardialbloodflowleadingtoultrastructuralchangesatthecellular levelandultimatelycontractiledysfunction.Althoughnormallyperfusedmyocardium utilizesfreefattyacidsasitsmetabolicfuel,ischemicmyocardiumpreferentially switchestoglucoseutilization(Figure33).88 Thecommonthemeinnoninvasivediagnosticevaluationofhibernatingmyocardium isbasedonthefactthatthereissignificantreductionincoronaryflowreserve. Indeed,recoveryofhibernatingmyocardiumrequirescoronaryrevascularization, whichinturnnormalizesflowreserve(Figure34).89 Uptakeofaglucoseanalogue,F18FDG,bydysfunctionalmyocardiumindicates metabolicactivityand,inturn,myocardialviability.Regionalmyocardialperfusion canbesimultaneouslyassessedwithanagentthatremainsinthevascularspace (N13ammoniaorRb82).Usingthecombinedperfusionandmetabolic information,PETimagingcandistinguishbetweennormal,stunnedischemic (hibernating)andscarredmyocardium(Table8).88 TheassessmentofviabilitybyPETinvolveseitherastressrestRb82orN13 ammoniaperfusionscanfollowedbyF18FDGmetabolicscan(providingischemia andviabilityinformation)orarestRb82orN13ammoniaperfusion/F18FDG metabolicscan(providingviabilityinformationalone).Carefulpatientpreparationis essentialtogetdiagnosticFDGimages,particularlyindiabeticpatients.90Atypical PETviabilityprotocolisshowninFigure35(toprow:stressrestperfusion metabolismPET,bottomrow:restperfusionmetabolismPET). Myocardialsegmentswithsignificantreductionsinperfusionandmetabolism(scar) haveonlya20%chanceoffunctionalimprovementwithrevascularization.Prior studieswithFDGPEThaveshownthatscarsizeisanindependentpredictorof improvementinEFpostrevascularization(Figure36).91 Ontheotherhand,dysfunctionalsegmentswithischemicandviablemyocardium (hibernating)havea8085%chanceofimprovingafterrevascularization.92,93An exampleofsubstantialperfusionmetabolismmismatch(hibernatingmyocardium) withanRb82(toprows)andF18FDG(bottomrows)restPETviabilitystudyis showninFigure37inapatientwithsevereischemiccardiomyopathy(EF22%)and 100%LADocclusivedisease.Basedonthescanresults,thepatientunderwent revascularizationoftheLADwitha6monthimprovementinEFto40%. QuantitativePETimagingofF18FDGuptakehasbeenshowntoprovidehigh sensitivityandspecificityforpredictingimprovedfunctionafterrevascularization (Figure38).88 Inparticular,segmentsshowing50%FDGuptakeareassociatedwitha93% sensitivityand85%specificityforpredictingfunctionalimprovementinasynergic segmentsafterrevascularization.94 Thegreatertheamountofischemicviablemyocardiumdetectedonviability evaluation,thegreateristhelikelihoodofbenefitfromrevascularization.Ingeneral,a 7%orgreaterburdenofviablemyocardiumseemstobeassociatedwithareduction inadverseeventsfollowingrevascularization.95Priorstudieshavealsoshownthat byincorporatingPETderivedviabilityinformationinadditiontoclinicaland angiographicdata,outcomesaftercoronarybypassgraftingcouldbepredicted. Nonfataleventsoccurredin48%ofmedicallytreatedFDGpositivepatients(positive forhibernatingmyocardium)comparedtoonly8%inFDGpositiverevascularized

patients.However,mortalitywassimilarinbothFDGpositiveandFDGnegative groups. Morerecently,thePARR2(PositronEmissionTomographyandRecoveryfollowing Revascularization)randomizedtrialexaminedtheimpactofPETinrevascularization decisionmakinginpatientswithCADandsevereLVdysfunctionwithEF<35% comparedtoastandardofcarewherePETinformationwasnotavailable.96 AlthoughthePETarmshowedatrendtobetteroutcomestheprimaryendpointwas notstatisticallydifferentbetweenthe2groups(Figure39).96However,the investigatorssuggestedthatthestudyendpointscouldhavebeenaffectedby nonadherenceofPETbasedrecommendationsbyclinicianscaringforthepatients.

MedicalVersusSurgicalTherapyandOutcomesinCoronaryArteryDiseaseSubcategorizedbyEjectionFraction Figure24 ReproducedwithpermissionfromMuhlbaierLH,PryorDB,RankinJS,etal.Observationalcomparisonofeventfreesurvivalwithmedicaland surgicaltherapyinpatientswithcoronaryarterydisease.20yearsoffollowup.Circulation199286(5Suppl):II198204.

EffectofSurgicalRevascularizationonLVDysfunction Figure25 Leftventricular(LV)ejectionfractionatrestshownbyradionuclideventriculographybefore(Preop)andafter(Postop)coronaryarterybypass surgeryinpatientswithpreoperativeLVdysfunctionintwosurgicalseries. Althoughsurgeryresultedinonlyasmallincreaseinmeanejectionfraction,substantialincreaseswereobservedinasubstantialsubsetof patients,withnormalizationofejectionfractionoccurringinmanypatients. ReproducedwithpermissionfromElefteriadesJA,TolisGJr,LeviE,MillsLK,ZaretBL.Coronaryarterybypassgraftinginsevereleftventricular dysfunction:excellentsurvivalwithimprovedejectionfractionandfunctionalstate.JAmCollCardiol199322:14117andBonowRO,DilsizianV. Thallium201forassessmentofmyocardialviability.SeminNuclMed199121:23041.

ConsequencesofChronicRepetitiveIschemia Figure26 ReproducedwithpermissionfromCantyJMJr.Coronarybloodflowandmyocardialischemia.In:LibbyP,BonowRO,MannDL,ZipesDP. BraunwaldsHeartDisease:ATextbookofCardiovascularMedicine.8thed.Philadelphia:Saunders2007:116794.

PatternsandPropertiesofDysfunctionalMyocardiuminCoronaryArteryDisease Table5

PostoperativeEjectionFractionRelatedtoPreoperativeViabilitybyThallium201Criteria Figure27 ReproducedwithpermissionfromRagostaM,BellerGA,WatsonDD,KaulS,GimpleLW.Quantitativeplanarrestredistribution201Tlimagingin detectionofmyocardialviabilityandpredictionofimprovementinleftventricularfunctionaftercoronarybypasssurgeryinpatientswithseverely depressedleftventricularfunction.Circulation199387:163041.

DeathRatesforPatientsWithIschemicLVDysfunctionUndergoingMedicalTherapyorRevascularization Figure28 Deathratesforpatientswithischemicleftventricular(LV)dysfunctionundergoingmedicaltherapyorrevascularization,subgroupedaccording tothepresenceofviableornonviablemyocardium.Revascularizationofpatientswithviabilityisassociatedwitha79%yearlydifferencein mortality. ReproducedwithpermissionfromAllmanKC,ShawLJ,HachamovitchR,UdelsonJE.Myocardialviabilitytestingandimpactofrevascularization onprognosisinpatientswithcoronaryarterydiseaseandleftventriculardysfunction:ametaanalysis.JAmCollCardiol200239:11518.

FactorsInfluencingRecoveryAfterRevascularization Table6 ReproducedwithpermissionfromSchinkelAF,BaxJJ,DelgadoV,PoldermansD,RahimtoolaSH.Clinicalrelevanceofhibernatingmyocardiumin ischemicleftventriculardysfunction.AmJMed2010123:97886.

ImagingTechniquesinViabilityAssessment Table7 BMIPP=methylp[123I]iodophenylpentadecanoicacidFDG=fluorodeoxyglucoseMRI=magneticresonanceimagingPET=positron emissiontomographySPECT=singlephotonemissioncomputedtomography. ModifiedwithpermissionfromBaxJJ,BoogersMM,SchuijfJD.Nuclearimaginginheartfailure.CardiolClin200927:26576.

Thallium201StressRestReinjectionProtocol:IschemiaandViabilityAssessment Figure29 SPECT=singlephotonemissioncomputedtomographyTl=thalliumTM=treadmillstress.

Stress(top)RestRedistribution(middle)WithaNitrateenhancedReinjection(bottom)Study(1of2) Figure30a Stress(top)restredistribution(middle)withanitrateenhancedreinjection(bottom)studydoneina77yearoldpatientwithapriorinferior infarctpresentingwithheartfailuresymptomsfollowingalargeanteriorMIsustained2weeksprior,whichwastreatedwiththrombolytic therapy.The2DechocardiogramrevealsanEFof18%withananeurysmalapex.ImageswithTlrevealatransmuralinfarctionoftheentire inferiorwall,aneurysmalapex,distalseptum,andperiapicalwallsindicativeofnosignificantviabilitywithredistributionandnitrateenhancement.

ExampleofStressRestThalliumProtocolWithReinjection(2of2) Figure30b Stressrestreinjectionstudyshowingsubstantialviabilityintheleftanteriordescending(LAD)territory. ReproducedwithpermissionfromDilsizianV,RoccoTP,FreedmanNM,LeonMB,BonowRO.Enhanceddetectionofischemicbutviable myocardiumbythereinjectionofthalliumafterstressredistributionimaging.NEnglJMed1990323:1416.

ExampleofRestThalliumViabilityProtocolWith0and4HourInjections Figure31 A66yearoldmalewithlatepresentationinferiorSTelevationmyocardialinfarctionundergoesviabilityimagingwiththallium201withrestand4 houracquisition.Alargefixedtransmuralinfarctionpatternisnotedinrightcoronaryarteryterritorywithnoapparentimprovementinthedelayed images.However,thisprotocolisnolongerrecommendedforviabilityimaging,asitunderestimatesdysfunctionalviablemyocardium. Approximately2530%offixeddefectsat4hoursmayredistributeat1224hours.

ThalliumVersusSestamibiforViabilityAssessment Figure32 ReproducedwithpermissionfromUdelsonJE,ColemanPS,MetherallJ,etal.Predictingrecoveryofsevereregionalventriculardysfunction. Comparisonofrestingscintigraphywith201Tland99mTcsestamibi.Circulation199489:255261.

MyocyteEnergyMetabolism Figure33 ReproducedwithpermissionfromGhoshN,RimoldiOE,BeanlandsRS,CamiciPG.Assessmentofmyocardialischaemiaandviability:roleof positronemissiontomography.EurHeartJ201031:298495.

PerfusionDataOn163HibernatingMyocardialSegmentsBefore(baseline)andAfterCoronaryRevascularisation Figure34 MBF=myocardialbloodflowMBFdip=postdipyridamolemyocardialbloodflowCVR=coronaryvasodilatorreserve. ***p<0.0001. ReproducedwithpermissionfromPaganoD,FathOrdoubadiF,BeattKJ,TownendJN,BonserRS,CamiciPG.Effectsofcoronary revascularisationonmyocardialbloodflowandcoronaryvasodilatorreserveinhibernatingmyocardium.Heart200185:20812.

SimpliedApproachtoPerfusionMetabolsimPatternsSeeninPositronEmissionTomographyViabilityImaging Table8 ReproducedwithpermissionfromGhoshN,RimoldiOE,BeanlandsRS,CamiciPG.Assessmentofmyocardialischaemiaandviability:roleof positronemissiontomography.EurHeartJ201031:298495.

MyocardialViabilityProtocol Figure35 Typicalpositronemissiontomography(PET)viabilityprotocol(toprow:stressrestperfusionmetabolismPET,bottomrow:restperfusion metabolismPET). FDG=fluorodeoxyglucose. ModifiedwithpermissionfromZaretBL,BellerGA.ClinicalNuclearCardiology:StateoftheArtandFutureDirections.3rded.Philadelphia: Mosby2005:Chapter33.

AbsoluteChangeinEjectionFractionvs.ScarScores Figure36 Small(016%ofleftventricle[LV]),moderate(1627.5%ofLV),andlarge(27.547%ofLV)*p=0.002,smallversuslargescarscore. EF=ejectionfraction. ReproducedwithpermissionfromBeanlandsRS,RuddyTD,deKempRA,etal.,onbehalfofthePARRInvestigators.Positronemission tomographyandrecoveryfollowingrevascularization(PARR1):theimportanceofscarandthedevelopmentofapredictionruleforthedegree ofrecoveryofleftventricularfunction.JAmCollCardiol200240:173543.

ExampleofPerfusionMetabolismMismatchbyF18FDGPET Figure37 Exampleofsubstantialperfusionmetabolismmismatch(hibernatingmyocardium)witharubidium82(toprows)andF18fluorodeoxyglucose (FDG)(bottomrows)restpositronemissiontomography(PET)viabilitystudyinapatientwithsevereischemiccardiomyopathy(ejectionfraction [EF]22%)and100%leftanteriordescending(LAD)occlusivedisease.Basedonthescanresults,thepatientunderwentrevascularizationofthe LADwitha6monthimprovementinEFto41%. ReproducedwithpermissionfromAnanthasubramaniamK,DharR,CavalcanteJL.Roleofmultimodalityimaginginischemicandnonischemic cardiomyopathy.HeartFailRev201116:35167.

ExampleofPerfusionMetabolismMismatchbyF18FDGPETWithQuantificationofExtentofMismatchandScar Figure38
18Ffluorodeoxyglucosepositronemissiontomographymyocardialviabilityscanshowingmismatchpattern.(A)Therestrubidiumperfusion

images.Thereisreductioninuptakeintheanteriorwallandapex(toprow).The18Ffluorodeoxyglucosemetabolismimages(middlerow)show significant18Ffluorodeoxyglucoseuptakeintheanteriorwallandapex,indicatingthereissignificantperfusionmetabolismmismatch,or hibernatingmyocardiumintheseregionsasisseenmoreclearlyinthemergedimages(bottomrow).(B)Thequantifiedmismatchscore(31%of theleftventricle)andmatchscore(6%oftheleftventricle). ReproducedwithpermissionfromGhoshN,RimoldiOE,BeanlandsRS,CamiciPG.Assessmentofmyocardialischaemiaandviability:roleof positronemissiontomography.EurHeartJ201031:298495.

ClinicalImpactof18FFluorodeoxyglucoseViabilityStudiesinthePARR2Study Figure39 Survivalcurvesforthecompositeoutcome(acompositeofcardiacdeath,myocardialinfarction,orrecurrenthospitalstayforcardiaccause), within1yearintheoverallstudy(A)andintheposthocanalysiscomparingpatientswherepositronemissiontomographyrecommendations wereadheredto,versusthestandardarm(B).Thehazardratio(HR)forthecompositeoutcome,positronemissiontomographyvs.standard care,was0.78(95%confidenceinterval[CI],0.581.1p=0.15)forpatientsthatadheredtopositronemissiontomographyrecommendations forrevascularization,revascularizationworkup,orneither,HR=0.62(95%CI,0.420.93p=0.019)inthosewithoutrecentangiography,for cardiacdeath,HR=0.4(95%CI,0.170.96p=0.035). ReproducedwithpermissionfromGhoshN,RimoldiOE,BeanlandsRS,CamiciPG.Assessmentofmyocardialischaemiaandviability:roleof positronemissiontomography.EurHeartJ201031:298495,Figure10.

ComparisonofViabilityTechniques
NucleartechniquesemployingSPECTandPETenjoythehighestsensitivity amongstalltechniquesforviabilityassessment,withechocardiographyhavingthe highestspecificityforpredictingrecoveryforregionalandglobalcontractilefunction postrevascularization(Figure40predictsofregionalLVFpostrevascularization, andFigure41predictsglobalLVFpostrevascularization).97 WhethercardiacPETissuperiortoSPECTinassessingmyocardialviability remainsunclear,withonerandomizedtrialshowingnodifferenceinoutcomes betweentwotechniques,98althoughotherstudieshaveshownbenefitofPETin patientswithsevereLVdysfunction.99

Figure40

Figure41

ComparisonofViabilityTechniques Figure40 Comparisonofsensitivitiesandspecificitieswith95%confidenceintervalsofthevarioustechniquesforthepredictionofrecoveryofregional functionafterrevascularization.T1201,thallium201Tc99m,technetium99mlabeledtracersFDGPET,F18fluorodeoxyglucoseandpositron emissiontomography. ReproducedwithpermissionfromSchinkelAF,BaxJJ,PoldermansD,ElhendyA,FerrariR,RahimtoolaSH.Hibernatingmyocardium:diagnosis andpatientoutcomes.CurrProblCardiol200732:375410.

VariabilityTechniquesandRecoveryofFunction Figure41 Comparisonofsensitivitiesandspecificitieswith95%confidenceintervalsofthevarioustechniquesforthepredictionofrecoveryofglobalLV functionafterrevascularization.Thenumberofavailablestudiesandpatientsareindicatedpertechnique.T1201,thallium201Tc99m, technetium99mlabeledtracersFDGPET,F18fluorodeoxyglucoseandpositronemissiontomography. ReproducedwithpermissionfromSchinkelAF,BaxJJ,PoldermansD,ElhendyA,FerrariR,RahimtoolaSH.Hibernatingmyocardium:diagnosis andpatientoutcomes.CurrProblCardiol200732:375410.

NewPerspectives
TheresultsofthemyocardialviabilityarmoftheSTICH(SurgicalTreatmentforIschemicHeartFailure)trialsuggestthat assessmentofmyocardialviabilitydoesnotconfersurvivalbenefitfromcoronaryarterybypassgrafting(CABG) comparedwithmedicaltherapy.100However,cautionisrecommendedinevaluatingtheseresultsasassignmentof viabilitytestingwasnotrandomized,modalitychoicewasbasedonthecenterandphysicianpreference,andwaslimited toSPECTordobutamineecho.Mortalityinthemedicalarmwasalsolowerthanexpectedandonly19%ofpatientshad nonviablemyocardium,thuslimitingcomparisons.Finally,biastowardstreatmentoptionsbyphysicians(basedonthe viabilitytesting)cannotbeexcluded.

KeyPoints
RNA(FPRNAandERNA)isanexcellent,reproduciblenucleartechniqueforevaluationofLVandRVfunction. SPECTassessmentofLVfunctionisanintegralandrecommendedpartoftheassessmentofmyocardial perfusion.Itprovidesawealthofnonperfusionvariables,whichhelpindiagnosisandprognosisforCAD. GatedPETisrapidlygainingrecognitionasavaluableadjuncttointerpretationofPETmyocardialperfusion.Its uniqueadvantageoverSPECTisthatthestressEFisobtainedatpeakpharmacologicstressratherthanina poststresssituation,aswithSPECT.ThedisadvantageofPETEFisthatitislimitedtopharmacologicstress onlywithcurrentPETisotopes. ExerciseandpharmacologicSPECTarewellvalidatedmethodsfordiagnosisofCAD. Acombinationofperfusionandfunctioninformationprovidesrobustprognosticvalueandservestoguidemedical andrevascularizationstrategies. SPECTiswidelyusedinnumerouspatientpopulationsforriskstratificationsuchaswomen,diabetics,chronic kidneydisease,andpreoperativeassessment. UseofoptimalmedicaltherapyandSPECTbasedonpublishedappropriateusecriteriacouldhelpguide effectivemanagementofCAD. Availabledataregardingdetectionandinterventionforhibernatingmyocardiumhavelargelybeenbasedonmeta analysisandobservationalstudies.Thesesuggestthatthepresenceofsubstantialhibernatingmyocardiumin patientswithischemicheartfailureisassociatedwithimprovementofLVfunctionandbettersurvivalwhen revascularizedcomparedtomedicaltherapy. Recentrandomizedtrials(i.e.,thePARR2andSTICHviabilityarm)havelargelybeenneutralwithregardtothe roleofviabilityinrevascularizationdecisionmaking,althoughtheyhadtheirownlimitations. BothTlandTc99mradiotracersappeartobecomparableintheirabilitytoevaluateformyocardialviability,and nitrateenhancementshouldroutinelybeusedtoenhancedetectionofviablemyocardium. Nuclearimagingtechniqueshavehighersensitivity,whereascontractiletechniques(suchasdobutamineecho) havehigherspecificityforpredictingLVfunctionimprovementpostrevascularization.

References
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3.5:CardiacComputedTomographyTechnology
Author(s): AllenJ.Taylor,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Identifyacquisitionmodesandscansettingsduringcardiaccomputedtomography(CT)thatleadtogreaterpatientsafety throughreductionsinradiationexposure. 2. SelectpatientseligibleforreferralwithoutcontraindicationstocardiacCT. 3. RecognizeasymptomaticandsymptomaticpatientsinwhichcalciumscanningorCTangiographyareappropriate modesoftesting.

Introduction
ProgressinthetechnicaldevelopmentsofcardiovascularCTtechnologyoverthe pastdecadenowenablesrapidandaccurateimagingofthecardiovascularsystem, includingcoronaryarteries,coronaryarterialwall,cardiacvalves,myocardium,and associatedstructures.ThebasicprincipleofCTtechnologyistheuseofionizing radiationwithinagantryrotatingaroundthepatientinwhichXraysaredetectedona detectorarray(Figure1)andconvertedthroughreconstructionalgorithmstoimages. Severaltechnicaladvancesenableaccurate,motionfreeimagingoftheheart: Increaseinthenumberofdetectorrows(or"slices"). Eachrowisanarrowchannel,approximately0.625mminwidth, throughwhichXraysaredetectedonscintillationcrystals.The increaseinthenumberofrowsleadstomoreoftheheartviewed simultaneouslyforexample,64rowsof0.625mmwidthproduces approximately4cmofcoverage. Imagedata(voxels)ofequalsidesonallsizes,or"isotropism." Leadstodistortionfree,multiplanarimaging. Increasedtemporalresolution. Temporalresolutionisdeterminedbythetimerequiredforthegantry torotatearoundthepatient,typicallyabout300ms.Although improvementsintemporalresolutionhavebeenobtainedthrough novelscannerdesigns(e.g.,dualsourceCT,orsimultaneous imagingwithtwosourcedetectorarraysleadingtotemporal resolutionsof83ms),thetemporalresolutionofcardiacCTisbelow thatobtainedwithinvasivecoronaryangiography.

Figure1

ViewWithintheRotatingMultidetectorComputedTomographyGantry Figure1 KeyelementsincludetheXraytubeorsource,acollimatortoaligntheXraybeam,andthedetectorarrayconsistingofnarrowchannelsfor detectionofXrayphotons.Thenumberofdetectorchannels(e.g.,64)determinesthenomenclatureof64rowmultidetectorCT.Presently,the maximumnumberofdetectorswithinacommerciallyavailablemultidetectorCTscanneris320. CT=computedtomography.

ScanModes
TherearetwobasicscanmodesincardiacCThelicalandaxialscanning(Table 1).1 BothmodesproducesimilarqualityimageswithequalaccuracyforCT angiography. Helicalscanninginvolvescontinuousradiationexposureandtable movement(thepatientismovedthroughtherotatingXraybeam).Thisrelies oncollectionofaredundantoroverlappingdatasetsothatcompleteimage datacanbereconstructedusingthetimingoftheelectrocardiogram(ECG) afterCTdataacquisition("retrospective"reconstruction). Pro:Continuousdataacquisitionenablesreconstructionofcine imagesforevaluationofmotion(e.g.,ventricularsystolicfunction). Con:TheXraysourceiscontinuously"on,"leadingtohigherradiation exposure. Axialimaginginvolvessequentialscanner"snapshots,"inbetweenwhichthe Xraytubeisturnedoffandthetableismovedtoadifferentpositionforthe nextimagetobeacquired.TheCTdataarethenreconstructedinaseriesof slicesakintoslicesofaloafofbread. Pro:ThemajorrelativemeritofaxialCTacquisitionistheon/off natureofXrayexposure,leadingtomarked(80%)reductionsinXray exposure. Ventricularfunctioncannotbeevaluatedduetotheon/offnatureofthe Xraybeam. Anewmodeofimaginginvolvinghelicalacquisitionwithhighpitch(no overlap)hasbeendeveloped.2,3Preliminarydataindicatethepotentialfor verylowradiationexposure<12mSv,butmoredataonimagequalityand diagnosticaccuracyareneeded.

Table1

ComparisonofHelicalandAxialComputedTomographyScanAcquisition Table1 CT=computedtomographyECG=electrocardiogram.

RadiationExposure
RadiationdosinginCTismeasuredusingtheCTdoseindexanddoselengthproduct(mGyxcm).Effectiveradiation (Sieverts)exposureentailstheapplicationofaconstantdeterminedbytherelativeradiationsensitivityofthetissue. Radiationexposuremustbekepttotheminimumachievablethatretainsdiagnosticimagequality.Factorsthatcan reduceradiationexposureinclude: Limitingtheamountoftissuescanned. Reducingtubesettings(current,voltage). 100kVimagingcanbeusedforsmallerpatients(<8090kg). Preferentialuseofaxialscanmode. Randomizedtrialdatashowthatwhenusedappropriately,typicalreductioninradiationexposureis90%foracombined axialscanmodeusingatubepotentialof100kV.

PatientPreparationandScanningSequence
TheabsoluterequirementsforpatientstoundergocontrastenhancedcardiacCT angiographyincludetheabilitytoreceiveintravenouscontrast(5080cccontrast allergy,renalfunction),andcooperatewithbreathinginstructionsandholdtheir breathforapproximately1020seconds.Relativecontraindicationsincludehighor irregularheartrates(particularlyatrialfibrillation),morbidobesity(>40kg/m2 ),or severecoronarycalcium(calciumscoresabove6001000dependingonthe distributionofcalciumdeposits).Toimproveimagequality,patientsroutinelyreceive abetablockertocontrolandregularizeheartrate(optimallyto<6065bpm, dependingonthetemporalresolutionofthescanner),andnitroglycerin400800 mcgsublingually.Othercommonimagingartifactsincludescatterfrommetallic objects(Figure2).

Figure2

CommonImagingArtifactsorNondiagnosticImagingonCardiacComputedTomography Figure2 Theimagingincludes:(A)registrationerrorseenashorizontallinesintheimage,(B)respiratorymotionseenasdiscontinuityofthesternum,(C) poorcontrastopacificationofthecoronaryartery,(D)coronaryduplicationartifactfromanectopicbeat,(E)poorsignaltonoiseratio(grainy image)duetoobesity,(F)severecoronarycalcification,and(G)streakartifactfromanimplantablebiventricularpacemaker. ReproducedwithpermissionfromDr.JohnLesser,MinneapolisHeartInstitute.

CardiacComputedTomographyAnatomy
Cardiacchambers,coronaryvessels,greatvessels,andothersurroundingcardiac andmediastinalstructurescanbeimagedinamultiplanarfashion(Figure3). Formsofimagedisplayinclude(Figure4): Orthogonalplanes(axial,coronal,sagittal)orobliqueplanarreformats. Thinorthicksliceimagesusuallydisplayedasmaximumintensity projectionsinwhichthebrightestpixelisviewedwithinaslabthickness. Curvedstructurescanbeviewedthroughtheuseofcurvedmultiplanar reformationsconstructedwiththeuseofcenterlinetechniques.
Figure4

Figure3

OverviewofCardiacComputedTomographyCrossSectionalAnatomyFromAxialImages Figure3 (A)ThinsliceaxialprojectionattheleveloftheSVCandRVOTshowingrelationshipsofthestructuresatthebaseoftheheart.(B)Thickslice axialmaximumintensityprojectionshowingtheoriginoftheLMCAandtheLAD(arrow).(C)Midlevelfourchamberventricularviewshowingthe RA,RV,LA,andLV,andthenormalPc.(D)ThickslicemaximumintensityprojectionshowingthedistalRCAandthenearbycoronarysinus (arrow). Ao=aortaLA=leftatriumLAD=leftanteriordescendingLMCA=leftmaincoronaryarteryLV=leftventriclePc=pericardiumPV= pulmonaryveinRA=rightatriumRAA=rightatrialappendageRCA=rightcoronaryarteryRV=rightventricleRVOT=rightventricular outflowtractSVC=superiorvenacava.

ThreeCommonDisplayModesforCardiacComputedTomography Figure4 (A)Obliqueanglemultiplanarreformatdisplayedasathickslidemaximumintensityprojectionusefulforaligningtheimageplanetocardiac structures.(B)Centerlinecurvedmultiplanarreformatdisplayedasamultiplanarreformatusefulfordisplayingcurvedstructuresinatwo dimensionalimageplane.(C)Athreedimensional(3D)volumerenderedformatusefulforshowinggeneralanatomicoverview.

ClinicalIndicationsforCardiacComputedTomography
ClinicalindicationsforcardiovascularCTencompassabroadrangeofpotential anatomicimagingtargetsandclinicalscenarios.CardiacCTisconsideredmost appropriateinsettingsinwhichthereisagenerallyloworintermediatepretest likelihoodofcoronaryarterydiseasebeingpresent,andinwhichthetestresults wouldleadtoalteredpatientmanagement.Recommendationsontheappropriate useofcardiacCTarelargelyguidedbyexpertopinionthroughAppropriateUse Criteria.4 CoronaryArteryCalciumScanning Coronarycalciumtestingisusedinasymptomaticpatientstorefinetheirclinically predictedriskofincidentcoronaryheartdisease(CHD)beyondthatpredictedby standardcardiacriskfactors.Coronaryarterycalciumistypicallypresentindirect proportiontotheoverallextentofatherosclerosis,althoughtypicallyonlyaminority (approximately20%)ofplaqueiscalcified.Coronarycalciumisdetectedusinga standardizedprotocolthatshouldresultinacceptablylowlevelsofradiation exposure(<1.5mSv)andpotentiallylowerwiththeevolutionoflower100kVp imagingprotocols.5 Thesumoftheareaanddensityweightingsacrossthecoronaryarteries(Figure5) istheunitless"calciumscore"originallydefinedbyAgatstonandcolleaguesusing electronbeamCT,andnowadaptedtomodernmultidetectorCTsystems.Coronary calciumpresenceanditsextentusingtheareadensityscoringmethodis dependentonage,gender,ethnicity,andstandardcardiacriskfactors.Calcium scoresarehigherforagivenageandgenderamongCaucasians. Itiswellestablishedthatthedetectionofcoronarycalciumindicatesanincreased riskofincidentCHDoverthatpredictedbystandardriskfactors,rangingfromtwofold forscoresofupto100,increasingto11foldforscoresabove1,000(Figure6).6 SimilarfindingsareshownforgenderandethnicityfromtheMultiEthnicStudyof Atherosclerosis(MESA),7 andamongbothyoung(ages4050years)8 andolder9 patientpopulations. MiddleagedwomenwithanydetectablecoronaryarterycalciumexperienceaCHD eventriskthatexceeds2%peryear.10Multivesselcoronarycalcium,11thenumber ofcalcifiedlesions,12ordiffusespotty(smallfoci<3mm)13areassociatedwitha higherclinicalrisk(Figure7).Conversely,datafrom13studiesinvolving75,000 patientsover4yearsshowthatacalciumscoreof0isassociatedwithaveryhigh eventfreeprobability(99.9%peryear).14 Therearenodatademonstratingthatastrategyofcoronarycalciumscreening improvescardiovascularoutcomes.However,communitybasedscreening cohorts15,16haveshownuptothreefoldgreateruseofaspirin,statincholesterol medications,andothercardiovascularriskreductioninterventionsinthesettingof coronarycalcium.SerialcalciumscanningformonitoringCHDriskisnot recommended.Althoughcalciumscoreprogression<15%peryearhasbeen associatedwithincreasedcardiovascularrisk,theimpactonmanagementand outcomesisunknown. Guidelines Appropriateusecriteriasupporttheuseofcoronarycalciumscanningasa riskstratificationtoolwhenaninitialevaluationofclinicalriskusingrisk predictiontoolsindicatesanintermediatelevelofCHDrisk(1020%over10 years)orinthesettingoflowriskpatientswithafamilyhistoryofpremature CHD.4 Areasofuncertaintyincludepatientswithlowintermediaterisk(6%10% risk),particularlyamongwomenandyoungermeninwhomrelativeriskand lifetimeCHDriskmaybeunacceptablyincreased.
Figure6

Figure5

Figure7

Figure8

Figure9

Figure10

BoththeNationalCholesterolEducationProgram17andtheClinicalExpert ConsensusoftheAmericanCollegeofCardiologyFoundation6 indicated thattheperformanceofcoronarycalciumscanningisareasonabletesting optionamongsuchpatientsbasedonthepossibilitythatsuchpatientsmight bereclassifiedtoahigherriskstatusbasedonahighcoronaryartery calciumscore,andsubsequentpatientmanagementmaybemodified. CoronaryComputedTomographyAngiography TheprimaryclinicalapplicationofcardiacCTistheperformanceofnoninvasive coronaryCTangiographyamongpatientswithsymptomssuggestiveofmyocardial ischemia.Stenosisseverityissemiquantitativelygraded(Figure8).Metaanalysisof primarilysinglecenterstudiesfromsymptomaticpatients(prevalenceofcoronary arterydisease64%)showthattheoverallaccuracyof64rowCTangiography includedasensitivityof8799%andspecificityof9396%.18 AccurateperformanceofcardiacCTrequiresproperattentiontotechnicalmethods andpatientpreparation.However,evenunderoptimalconditions,somecoronary segments(~4%)willbeuninterpretableduetopatientortechnicalfactors.Several recentmulticentertrialssupportthehighsensitivityofcoronaryCTangiography1921 however,specificitywillbereduced,particularlyamongpatientswithseverecoronary arterycalcification(whichcanrenderCTangiographyuninterpretableparticularlyat calciumscoresabove4001,000)orobesity(duetoexcessimagenoise). Comparedwithgradingbyquantitativeinvasivecoronaryangiography,CT angiographicstenosisseveritytendstobesomewhatworseandwithonlyamodest correlation(r=0.50.6),butcorrelatesverywellwithintravascularultrasound,likely asaconsequenceofbettervisualizationofthearterialwall.22Similartoresultswith invasivecoronaryangiography,thedeterminationofananatomicstenosisisonly modestlypredictiveofinducibleischemia.A50%orgreaterstenosisoncardiacCT hasa3050%likelihoodofdemonstrableischemiaonmyocardialperfusion imaging,23,24underscoringtheneedforamultimodalityapproachtoimagingto guidesubsequentpatienttreatment. AcuteChestPain GiventhehighnegativepredictivevalueofcardiacCT,thetesthasbeenstudiedas amethodtoexcludecoronaryarterydiseaseamongpatientspresentingwithacute chestpain.ArandomizedclinicaltrialshowedthattheuseofcardiacCTamong patientspresentingtotheemergencydepartmentwithchestpainandanormalECG andinitialcardiacbiomarkersledtomorerapiddischargeandcostsavings comparedwithaconventionalserialbiomarkerevaluation.25Amajorityofpatients havenormalCTangiogramsandcanbesafelydischarged,whereasapproximately 2050%mayhavesomeplaqueidentifiedandrequirefurtherevaluation.26 ThePostrevascularizationPatient Ingeneral,patientswithknowncoronaryarterydiseasearepresentlynottheoptimal candidatesfornoninvasiveangiographyduetothehighpretestlikelihoodof coronaryatherosclerosis.However,someconditionsmaybefavorableforscanning. Evaluationofcoronarybypassgraftpatencyishighlyaccuratewithsensitivitiesand specificitiesofnear100%,27duetothelargesizeandlimitedmobilityofthese structures(Figure9).Priortoreoperativecoronarysurgery,cardiacCTcanbeused todefinetherelationshipofsternalwirestocardiacandgraftstructuresforthe purposeofplanningsurgicalreentrytechniques.Highriskfindingsincludecardiac structuresadjacenttooradherenttothesternum,orcoronarybypassgraftswhich crossintothemidline(Figure10).28 Imageartifactfrommetallicstentslimitstheapplicationinpatientswithprior coronarystentprocedures,suchthatstents<3mmindiameteraredifficultto evaluateandarepronetononinterpretability.However,moderatetohighaccuracy, approximately90%,29canbeobtainedinstents3mmorindiameter.

ExampleofCoronaryArteryCalciumScoringinWhichCalcifiedFociAreIdentifiedWithintheLAD(orange)andLeftCircumflex(pinkoutlinedin blue)CoronaryArteries Figure5 TheRAranditsRAvaredisplayedandusedintheareadensitycalciumscoringcalculation. LAD=leftanteriordescendingRAr=regionsareaRAv=averagedensityinHounsfieldunits.

DataFromtheMultiethnicStudyofAtherosclerosisRegardingtheDistributionofCoronaryCalciumScoresAmongMenRelativetoAgeand Ethnicity,andMajorCardiovascularOutcomesObservedintheStudyinAssociationWithHigherThresholdsofCoronaryCalciumScores Figure6 References: 1. McClellandRL,ChungH,DetranoR,PostW,KronmalRA.Distributionofcoronaryarterycalciumbyrace,gender,andage:resultsfrom theMultiEthnicStudyofAtherosclerosis(MESA).Circulation2006113:307. 2. DetranoR,GuerciAD,CarrJJ,etal.Coronarycalciumasapredictorofcoronaryeventsinfourracialorethnicgroups.NEnglJMed 2008358:133645.

DistributionsofCoronaryCalcium Figure7 Thedistributionsofcoronarycalciumincludes(A)Nodetectablecoronarycalcium(B)coronarycalciuminallthreeepicardialcoronaryarteries including(clockwise)therightcoronaryartery(arrow),leftanteriordescending,andleftcircumflexcoronaryarteries(C)aspottyordiffuse patternofcoronarycalciumwithmultiplesmall(<3mm)fociofcoronarycalciumand(D)alargecalcifiedlesionintheleftanteriordescending coronaryartery.

DifferentSeverityGradesofCoronaryArteryLesionsasDepictedonCardiacComputedTomography Figure8 (A)Largemixedplaquewithoutsignificantstenosisintheproximalleftanteriordescendingcoronaryartery(curvedmultiplanarreformat)with outwardarterialremodeling(arrow),asshowninthecrosssectionalimage(inset).(B)Largenoncalcifiedplaquewithoutwardarterial remodelingintherightcoronaryarterywithmildluminalstenosis(<25%).(C)Moderatestenosis(50%)intheproximalleftcircumflexcoronary arterywithamixedplaque.(D)Highgrade(>70%)stenosisofthemidleftanteriordescendingcoronaryarterywithanoncalcifiedplaque.(E) Totalocclusionofthedistalleftcircumflexcoronaryartery.

CardiacComputedTomographyProvidesHighAccuracyforEvaluationofCoronaryBypassGraftsDuetoTheirLargeSize,TypicallyTheir LimitedExtentofCalcifiedAtherosclerosis,andLimitedMobilityintheCardiacCycle Figure9 Saphenousveingraftsareshowninan(A)obliquemultiplanarreformat(saphenousveingraft=arrowhead,calcifiedatherosclerosisinthe nativecoronaryartery=arrow)and(B)threedimensionalvolumerenderedreformatofasaphenousveingraftinaYconfiguration.

ReproducedwithpermissionfromDr.StephanAchenbach,Erlangen,

HighRiskSubsternalReoperativeAnatomyinaPatientWithPriorCoronaryBypassSurgeryIncludingaCoronaryBypassGraftImmediately BeneaththeSternum Figure10 Shownin:(A)axialand(B)sagittalimages.(C)Therightventricleisimmediatelyadjacentandadherenttothesternalwire.

VentricularMorphologyandFunction
Helicalscanacquisitionspermitadequatespatialresolutionforadequatestructural detailforaccuratedeterminationofleft30andrightventricular31,32ejectionfraction andvolumes.Myocardialmorphologycanalsobereliablyassessedforfindingsof priormyocardialinfarction,suchaswallthinning,calcification,orfattymyocardial replacement(indicatedbynegativeHounsfieldunitdensitieswithinthe myocardium).Atrialmorphologyandvolumecanalsobeassessed.Clotintheleft atrialappendagecanbeidentifiedwithhighnegativepredictivevalue,although delayedmixinginthesettingofpoorflowmayresultinadiagnosisof pseudothrombus. Evolvingmyocardialapplicationsincludethedetectionofmyocardialscar,viability, andperfusion.Scarringmaybedetectedbyregionsofmyocardialhypoattenuation onfirstpassimaging,andwhenparticularlynotedwithmyocardialthickness<5mm suggestspriormyocardialinfarctionandnonviablemyocardium.Latemyocardial hyperenhancementimaginginvolvesspecificcardiacCTacquisitionwithboththe infusionofadditionalcontrastmedium,andadelayofapproximately10minutesto permitslowaccumulationofcontrastcomparablewiththeapproachwithcardiac magneticresonanceimagingandgadolinium(Figure11). Usingcoronaryvasodilators,firstpassCTstressperfusionimagingisbeing developedwithinitialdataindicatingapervesselsensitivityof96%,specificityof 73%,andnegativepredictivevalueof98%forthedetectionofstenosisof70%or withradiationexposurecomparablewithstressradionuclideimaging.33Themost recentdevelopmentsincardiacCTangiographyincludeattenuationgradient mappinginthecoronaryarteries,whichmaypermitnoninvasivedeterminationof flowdynamicscomparablewithfractionalflowreserve.

Figure11

TheSpectrumofChronicMyocardialInfarctionasSeenonCardiacComputedTomgraphy Figure11 (A)Thinnedmyocardiumfollowinganteroseptalmyocardialinfarction(arrow).(B)Hypoattenuation(Hounsfieldunits<0)oftheventricularseptum indicativeofchronicmyocardialinfarctionandfibrofattychange(arrow).(C)Calcificationoftheleftventricularapex(arrow).(D)Delayed enhancementimaging(10minutes)showinglateenhancementoftheanteroapexindicativeofchronicscarringandnonviablemyocardium. RA=rightatrium.

IncidentalScanFindings
IncidentalscanfindingsduringcardiacCTspanabroadspectrumfromnoncardiacvascularstructures(aorta,pulmonary artery,andpulmonaryveins),thelungs,mediastinum,musculoskeletalandsofttissuestructures,andgastrointestinal tract.InaseriesofsubjectsstudiedwithmultidetectorCT,incidentalscanfindingswerecommon(4050%).Althoughthe majorityofpatientsdonotrequirefurtherevaluation,aminority(510%)willrequiresecondimagingtestsorclinical followup.Presentpracticerequirestheevaluationofincidentalscanfindingsusingafullfieldofreviewreconstructions bycardiovascularimagers,withexpertiseinevaluationofotherthoracicpathology.34

Training,Competency,andCertification
CardiacCTrepresentsanewimagingmodalityformanycardiovascularspecialists.Competency35andtraining34 standardsforcardiacCThavebeenpublishedforcardiovascularspecialistsandbroadlyrequireaknowledgebasein CTmethodsandcaseexperiencefrom150cardiacCTangiographycases,whichcanbeobtainedfrombothlive(50 cases)andworkstationreviewexperiencetoachieveLevel2status.BoardcertificationisgovernedbytheCertification BoardinCardiovascularComputedTomography,36withboardeligibilitycloselymatchingthecompetencystandardsof theAmericanCollegeofCardiology.

KeyPoints
Theevolutioninscannertemporalandspatialresolutionhasledtoimprovedaccuracyandclinicalapplicabilityof cardiacCT. MajorreductionsinradiationexposuremaybeachievedthroughselectionofanaxialscanmodewiththeXray tubepotentialoptimizedtobodysize. ConsiderationsintheselectionofpatientsforcardiacCTincluderenalfunctionduetotheneedforiodinated contrast,bodysizeduetoimpactonimagequality,andacontrolledheartrate(typically<6065bpm)during normalsinusrhythm. Calciumscanningdetectssubclinicalatherosclerosisthatmaybequantitatedusingtheage/gender/ethnicity dependentcalciumscore,whichindependentlyandstronglypredictsfutureCHDoutcomes. CalciumscanningisappropriateforCHDriskpredictioninthosewithintermediatepretestCHDriskorafamily historyofCHD. CardiacCTangiographyismostappropriatelyperformedinsymptomaticpatientswithloworintermediatepretest probabilityforcoronaryarterydisease,andishighlyaccurateforthedetectionofobstructivecoronaryartery diseaseinnativecoronaryarteriesandbypassgrafts.

References
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3.6:CardiovascularMagneticResonanceImaging
Author(s): LowieM.R.VanAssche,MD HanW.Kim,MD IgorKlem,MD RaymondJ.Kim,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. 2. 3. 4. Describethebasicsofimageacquisition,signalprocessing,andimagecontrast. Recognizeimportantsafetymeasureswhenworkinginacardiacmagneticresonance(CMR)environment. Listthepulsesequencestructureandthestepsofthecorecardiovascularexam. DiscusstheclinicalapplicationsofCMRinvariouscardiacpathophysiologicconditions.

BasicPrinciples
Preface TheaimofthismoduleistoprovideanintroductiontoCMRandtoprovidean overviewoftheclinicalapplicationsthatareavailabletoclinicianstoday. Similartoothermedicalimagingtechniques,magneticresonanceimaging(MRI) acquiresimagesthroughthetransmissionandreceivingofenergy.However,unlike othermodalities,MRIoffersthecapabilitytomodulateboththeemittedandreceived signalssothatamultitudeoftissuecharacteristicscanbeexaminedand differentiatedwithouttheneedtochangescannerhardware.Asaresult,froma singleimagingsession,onecouldobtainawealthofinformationregardingcardiac functionandmorphology,myocardialperfusionandviability,hemodynamics,large vesselanatomy,andsoforth.Thisinformation,however,isgatherednotfroma singlelongacquisition,butratherfrommultipleshortacquisitions,eachrequiring differentpulsesequences(softwareprogramsthatdrivethescanner)withspecific operationalparametersandoptimalsettings. Unfortunately,magneticresonance(MR)vendorsmayuseproprietarynamesforthe sameimagingmethodsandsettings.1,2Thus,thegoalofthissectionwillbeto clarifytheseissuesandtoprovideasimpleframeworkofthetechnicalaspectsof MRI.Whereappropriate,issuesspecifictoCMRwillbediscussed. MagneticResonancePhysics AnMRIscannerperformsthreebasicoperations(Figure1):a)generationofastatic magneticfield,b)transmissionofenergywithintheradiofrequency(RF)rangetothe patient,andc)receivingtheMRsignalfollowingthetransmissionofRFenergy.Most clinicalCMRscannerstodayhaveastaticmagneticfieldstrength(Bo )of1.5Tesla, whichis30,000timesstrongerthantheearth'smagneticfield.Thishighmagnetic fieldstrengthisgeneratedbyasuperconductingmagnetthatishousedwithinthe MRIscanneritself.Whenapatientisplacedwithintheboreofthescanner,most protonsalignparalleltothefield,leadingtoasmallnetmagnetizationvector(Figure 1,panelA). Thenextsteptowardimagegenerationisthetransmissionofenergytotheregionof interest.WiththeabsorptionoftheenergyfromtheRFpulse,thenetmagnetization vectoristiltedfromitsequilibriumorientationparalleltothestaticmagneticfield (longitudinaldirection)intothetransverseplane.Theangleofdisplacementofthe netmagnetizationvectorisknownastheflipangle(Figure1,panelB),andmaybe varieddependingonthepulsesequence.Rotationoftheprecessingnet magnetizationvectorintothetransverseplaneresultsinthecreationofatime varyingmagneticfield.ThesignalcreatedfromasingleRFexcitationisillustratedin Figure1,panelC,andisknownasafreeinductiondecay(FID). FollowingtheRFexcitation,twoindependentrelaxationprocessesreturnthenet magnetizationvectortoitsthermalequilibrium(realignedwiththestaticmagnetic fieldFigure2).Thefirstprocess,knownaslongitudinalorspinlatticerelaxation, describestheregrowthofthemagnetizationvectorparalleltothestaticmagnetic field(Figure2,panelA).Longitudinalrelaxationresultsfromthetransferofenergy fromtheexcitedprotonstosurroundingmoleculesinthelocalenvironment.The timeconstantT1describestheexponentialregrowthoflongitudinalmagnetization. Thesecondprocess,knownastransverseorspinspinrelaxation,describesthe decayofthemagnetizationvectorinthetransverse(XY)plane(Figure2,panelB). Transverserelaxationmaytakeplacewithorwithoutenergydissipation.For example,thetransferofenergyleadingtolongitudinalrelaxationalsoresultsin transverserelaxation. Additionally,processesthatsimplycauseprotonspinstolosephasecoherence withoutenergydissipationleadtotransverserelaxationaswell.Thelatter mechanismmostcommonlyresultsfromstaticorslowlyfluctuatingvariationsinthe magneticfieldwithintheimagedsample.ThetimeconstantT2describesthe exponentialdecayoftransversemagnetization.TheT1andT2areintrinsic
Figure4 Figure1

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Figure5

propertiesofanygiventissue.PulsesequencesutilizedifferencesinT1andT2to generateimagecontrastbetweentissues. ImageAcquisitionandSignalProcessing TheMRsignalsfollowingRFexcitationarelocalizedinthreedimensionalspaceby theuseofmagneticfieldsgeneratedbythreesetsofgradientcoils(Figure3).These gradientcoilsalterthestrengthofthestaticmagneticfieldasalinearfunctionof distancefromtheisocenterofthemagnetineachofthreeorthogonaldirections(X, Y,orZaxes).Thevariationinfieldstrengthsacrossspaceproducesdifferencesin protonprecessionalfrequenciesalongeachaxis. Specifically,toformatwodimensionalimage,thegradientsallowtheselectionof thesliceofinterest(e.g.,sliceencodingdirection)andalsomodulatetheMR signalstoprovideinplanespatialinformationalongthefrequencyencoding directionandthephaseencodingdirection.Forsliceselection,thesliceencoding gradient(Zaxisgradientforatransaxialslice)isplayedduringRFexcitation(Figure 3,panelB).Sinceenergydepositionisonlypossibleonresonance,alteringthe centerfrequencyoftheRFpulsevariestheslicelocation.Increasingordecreasing thebandwidthoffrequenciesinthetransmittedRFpulseincreasesordecreases thethicknessoftheimagedslice. Forspatiallocalizationinthefrequencyencodingdirection,theXaxisgradient(fora transaxialslice)isplayedduringMRsignalreceive(Figure3,panelC).Asaresult, specificfrequencycomponentsoftheMRsignalarisedirectlyfromspecificspatial locationsalongtheXaxis.Spatiallocalizationinthephaseencodingdirectionis moredifficultconceptually.TheYaxisgradient(foratransaxialslice)isplayedfora finitetimebeforeMRsignalreceive.Thisresultsinaphaseshiftintheprecessing protonsthatvarieswithlocationalongtheYaxis.Importantly,eachimageisthe resultofmultipleMRsignalreadouts,eachofwhichwereprecededbyaphase encodinggradientstep,withslightdifferencesinthestrength(amplitude)oftheY axisgradient. Afterallthephaseencodingstepsarecompleted,therawdatafromthescanner consistsofatwodimensionalgridofdata(alsoknownaskspace),whichis convertedtoanMRimagebyaninversetwodimensionalFouriertransformbythe imagereconstructioncomputer. CreatingContrastinMagneticResonanceImages OneoftheimportantadvantagesofMRIistheabilitytogeneratesubstantialsoft tissuecontrastbytheuseofpulsesequencesandtheadministrationofcontrast media.Ingeneral,pulsesequencesareadjustedtoemphasizedifferencesin tissueT1andT2,whichmaybeinherentoralteredbythepresenceofcontrast media.Forinstance,onpulsesequencesthatareT1weighted,tissueswithshort T1,suchasfat,appearbright. Traditionally,T1weightingisaccomplishedbyimagingwithshortRFrepetition times(TR),whichmagnifydifferencesinlongitudinalrecoverybetweentissues. Newersequencesutilizemagnetizationpreparationpulses,suchassaturationor inversionpulses,tocreateimprovedT1contrast(Figure4).Aninversion(180) comparedwithsaturation(90)prepulseprovidesgreaterT1weighting,butthe sequenceismorepronetoartifactswhengatingisirregular(eitherbecauseof electrocardiogram[ECG]artifactorarrhythmia). T2weightedpulsesequencesaretraditionallycreatedusingrelativelylongecho times(TE).WithlongTE(ontheorderoftissueT2),thereisincreasedseparationof differentT2relaxationcurves,whichtranslatesintolargerdifferencesinimage intensity. Theadministrationofintravenouscontrastagentscanalsobeusedtoaffectimage contrastbyalteringtissueT1and/orT2.ThemagnitudeofT1and/orT2change dependsonthespecificrelaxivitiesofthecontrastmedia,thedistribution characteristics(i.e.,intravascular,extracellular,ortargetedtoaspecifictissue),and tissueperfusion.GadoliniumbasedcontrastmediaiscommonlyusedinCMR. Gadoliniumisalanthanidemetalwithsevenunpairedelectrons,makingitstrongly paramagnetic.Whenadministered,itprimarilyshortenstheT1inthetissueswhere itisdistributed(Figure5).

CardiacMagneticResonanceSafety TheCMRenvironmenthasthepotentialtoposeseriousriskstopatientsandfacility staffinseveralways.Injuriesmayresultfromthestaticmagneticfield(projectile impactinjuries),veryrapidgradientfieldswitching(inductionofelectriccurrents leadingtoperipheralnervestimulation),RFenergydeposition(heatingofthe imagedportionofthebody),andacousticnoise. Therisksofprojectileinjuriesfromthestaticmagneticfieldareminimizedbythe institutionofpoliciesthatstrictlylimitaccesstothemagnetroom.Forinstance, patientsareextensivelyscreenedpriortoimaging,andallfacilitypersonnelundergo dedicatedtraininginMRsafety.TheuseofMR"safe"orcompatibleequipment(e.g., stethoscopes,wheelchairs,gurneys,oxygentanks,infusionpumps,monitors,etc.) withclearlabelingofsuchinthescannerareareducesthisriskfurther. TheFoodandDrugAdministration(FDA)hasplacedlimitsontherateofchangeof gradientmagneticfields(e.g.,theslewrate)andtheamountofRFenergy(e.g., specificabsorptionrate[SAR])thatcanbetransmittedtopatients.Allscanners monitortheslewrateandcalculatetheSARtohelppreventnervestimulationand heating.Acousticnoiseof100dBormoreisgeneratedfromthevibrationormotion ofthegradientcoilsduringimageacquisition.Theuseofprotectivehearingdevices, suchasheadphonesorearplugs,reducesnoisetolevelsthatdonotresultin hearingimpairmentorpatientdiscomfort.Inpractice,continuouscommunication withthepatientthroughouttheexamisimportantforpatientcomfortandsafety. Patientswithmedicaldevicesorimplantsmayfaceadditionalpotentialhazards, includingdeviceheating,movement,ormalfunction.Forexample,ferromagnetic aneurysmclipsorelectronicmedicaldevices(e.g.,neuralstimulators,insulin pumps)arestrictcontraindicationstoMRI.However,thereisaspecificsubsetof patientswithmetallicimplants/devicesthatmaysafelyundergoMRI.A comprehensivelistofdevices/implantsthatarecompatiblewithundergoingMRI scanningmaybefoundelsewhere.3,4 Regardingcardiacdevices,itisimportanttonotethatprostheticvalvesandcoronary arterystentsarenowconsideredsafeforMRIscanning.35Indeed,recently,theFDA approvedtheuseofMRIimmediatelyaftertheimplantationofpaclitaxeland sirolimusdrugelutingstents.Atmostinstitutions,MRIscansarenotperformedin patientswithimplantedpacemakersordefibrillatorsbecauseofthepotentialriskof devicemalfunction,excessivedeviceorleadheating,orinductionofcurrentswithin theleads.Recently,however,afewpreliminaryreportshaveemerged,suggesting thatMRImaybepossibleinpatientswithmodernpacemakersanddefibrillatorsin whomthebenefitsaredeemedgreaterthantherisks.610Inpatientsinwhom deviceshavebeenextracted,butwiththeleadsremaining(bothtransvenousor epicardial),MRIiscontraindicated,astheriskofheatingorinductionofcurrentsmay behigher. Recently,itwasreportedthatasmallsubsetofpatientswithendstagerenal diseasereceivinggadoliniumcontrastmaybeatriskfordevelopingnephrogenic systemicfibrosis(NSF).1115NSFischaracterizedbyanincreasedtissue depositionofcollagen,oftenresultinginthickeningandtighteningoftheskinand predominantlyinvolvingthedistalextremities.Additionally,fibrosismayaffectother organs,includingskeletalmuscles,lungs,pulmonaryvasculature,heart,and diaphragm.Thus,gadoliniumcontrastagentsshouldbeutilizedcautiously(and alternativetestsshouldbeconsidered)inpatientswithseverechronicrenaldisease (e.g.,glomerularfiltrationrates[GRF]30ml/min/1.73m2 ),particularlythose undergoingperitonealdialysisorhemodialysis. Otheratriskgroupsincludepatientswithacuterenalfailure(whereestimatedGFR maynotaccuratelyreflectrenalfunction),patientswithhepatorenalsyndrome,and patientsintheperitransplantperiodafterlivertransplantation.Apolicystatement regardingtheuseofgadoliniumcontrastagentsinthesettingofrenaldiseasehas beenpublishedbytheAmericanCollegeofRadiology.12

BasicOperationsoftheMRIScanner Figure1 (A)Thestaticmagneticfield(Bo).Theprotonsalignparallelorantiparalleltothestaticmagneticfield,creatingasmallnetmagnetizationvector. Whilealignedtothemagneticfield,theprotonsprecessattheLarmorfrequency. (B)Transmissionofradiofrequencyenergy(RF).EnergyistransmittedtotherotatingprotonsbyaRFpulseattheLarmorfrequency.RFpulses thatresultinaflipangleof90and180areshown(topandbottom,respectively).Thefiguresarepresentedintherotatingframeofreference, wheretheXYaxesarerotatingattheLarmorfrequencyandthusappearstationary. (C)Generationofthemagneticresonance(MR)signal.Rotationofthenetmagnetizationvectorintothetransverseplaneresultsinthecreationof atimevaryingmagneticfield,whichinturninducesanalternatingcurrentinthereceivercoilarray,whichistheMRsignal.

LongitudinalRecoveryandTransverseDecayFollowinga90FlipAngleExcitation Figure2 A)Longitudinalmagnetizationrecovery(T1relaxation).Thegreengrowthcurvedemonstratestheexponentialregrowthofthelongitudinal componentofthenetmagnetizationvector. (B)Transversemagnetizationdecay(T2relaxation).Thereddecaycurveillustratestheexponentialdeclineofthetransversecomponentofthe netmagnetizationvector. (C)Thenetmagnetizationvector.Thevectorsumofthelongitudinalandtransversecomponentsthatcomprisethenetmagnetizationvectoris shown.

SpatialLocalizationoftheMRSignal Figure3 (A)Orthogonalmagneticfieldgradientsareusedtolocalizethemagneticresonance(MR)signal.Thegradientsareshownorientedfora transaxialimagingplanehowever,theaxesmaybeorientedorthogonallyinanyarbitrarydirection. (B)Sliceselection.Theradiofrequency(RF)pulsewithcenterfrequencywoexcitesprotonspinslocatedatpositionzoalongthedirectionofthe gradientwhenappliedinthepresenceofthelinearsliceselectmagneticfieldgradient.ChangingtheRFpulsecenterfrequencytow1orw2 shiftsthelocationoftheimagingslicetoz1orz2,respectively. (C)Frequencyencoding.DuringMRsignalreceive,thefrequencyencodinggradientaltersthefrequencyoftheMRsignaldependinguponits positionalongthedirectionofthegradient.TheMRsignalfromanygivenpositionhasauniquefrequency.Intheexampleshown,frequencywL (orwH )isanMRsignalfrompositionXL(orXH ).

MagnetizationPreparationPulsestoCreateT1Contrast Figure4 (A)Saturationrecovery.A90radiofrequency(RF)pulsefollowedbystronggradientspoilersreducesthenetmagnetizationtozero. MagnetizationrecoversdependingontissueT1.Forinstance,immediatelyfollowingintravenousbolusadministrationofgadoliniumcontrast, myocardiumwithnormalperfusionhassubstantialuptakeofgadolinium,thushasshortT1,andappearsbrightonsaturationrecoveryperfusion magneticresonanceimaging(MRI).Incomparison,myocardiumwithreducedperfusionhasdiminisheduptakeofgadolinium,longerT1,and appearsdark.Ideally,datareadoutshouldfollowthesaturationpulseataspecifictime(timepointbratherthantimepointaorc)toachieve maximumseparationbetweentheT1relaxationcurvesofnormalandabnormalmyocardium. (B)Inversionrecovery.An180RFpulseinvertsthelongitudinalmagnetizationfromthe+zaxistothezaxis.Oftenusedininfarctimaging,the timebetweentheinversionpulseandthecenterofdatareadout(inversiontimeorIT)isselectedtoaccentuatethedifferencesofgadolinium uptakeinnormalandinfarctedmyocardium.Specifically,theinversiontimeischosensothatthecenterofimagereadout(forlinearkspace acquisition)occurswhentheT1relaxationcurveofnormalmyocardiumcrosseszero(e.g.,nulled).Notethatwiththisinversiontime,theT1 relaxationcurveofinfarctedmyocardiumisabovethezerocrossing,andinfarctedtissueisbright.

TheEffectofGadoliniumContrastonT1andT2WeightedImaging Figure5 Priortocontrastadministration,thereareminimaldifferencesininherenttissueT1andT2betweennormalandinfarctedmyocardiumthus, infarctionispoorlydelineated(toppanel).Aftergadoliniumadministration,theT1ofinfarction(althoughnotT2)ismarkedlyshortened,leadingto cleardelineationontheT1weightedimage(bottompanel).T1weightedimageswereacquiredusinganinversionrecoverygradientecho sequence.T2weightedimageswereacquiredusingadarkbloodturbospinechosequence.ApproximateT1andT2timesarefor1.5T scanners.

TheCardiovascularExam
PulseSequenceStructure AnindividualpulsesequenceisacombinationofRFpulses,magneticgradientfield switches,andtimeddataacquisitions,allappliedinapreciseorder,whichresults ineitheraccentuationorsuppressionofspecificbiologicalparameters.Asimple waytoconceptualizepulsesequencesistoconsiderthemasconsistingoftwo separateelements:1)theimagingengine,and2)associatedmodifiers.16The imagingengineisarequiredcomponentthatprovidesinformationregardingthe spatialrelationshipofobjectswithintheimagingfield(i.e.,isthemaincomponent thatproducestheimage).Modifiersareoptionalcomponentsthatcanbeaddedto theimagingengineeitherindividuallyorincombination,toprovidespecific informationregardingtissuecharacteristicsortospeedimaging.Figure6lists someofthemorecommonlyusedimagingenginesandmodifiersinCMR. TheCoreExam Figure7depictstheprotocolstepsassociatedpulsesequences,andthetimelineof atypicalcoreexamthatincludesstresstesting.DependingontheCMRstudy indicationandthefindingsduringthecourseoftheexamination,additional elementsmaybeaddedtofullyinvestigatetheclinicalquestion. Function/Volumes Thegoalofcineimagingistocaptureamovieofthebeatingheartinorderto visualizeitscontractilefunction.Typically,between20and25cineframesis acquiredpercardiaccycle,witheachframecomprising3545ms.CineMRImaybe acquiredineithera"realtime"singleshotmodeorviaasegmentedkspacedata acquisitionapproach(Figure6).RealtimecineMRIcanbeperformedduringfree breathingandwithminimalpatientcooperation,makingitidealforchildrenor patientswhohavedifficultyfollowingbreathinginstructions.SegmentedcineMRIis performedduringabreathholdandofferssubstantialimprovementinimagequality withsuperiorspatialandtemporalresolutioncomparedtorealtimeimaging.Thus, inclinicalpractice,segmentedimagingisusuallypreferred.17,18 Insegmentedacquisition,dataarecollectedovermultipleconsecutiveheartbeats (typically510).Duringeachheartbeat,blocksofdata(segments)areacquiredwith referencetoECGtiming,whichrepresenttheseparatephasesorframesofthe cardiaccycle.Followingthefullacquisition,datafromagivenphase,collectedfrom themultipleheartbeats,arecombinedtoformthecompleteimageoftheparticular cineframe. PerfusionatStressandRest Thegoalofperfusionimagingistocreateamovieofthetransitofcontrastmedia (typicallygadoliniumbased)withthebloodduringitsinitialpassthroughtheleft ventricular(LV)myocardium(i.e.,firstpasscontrastenhancement).Usually45 shortaxisviewsareobtainedeveryheartbeat,withatotalof4060heartbeats consistingoftheentirefirstpass(Figure8). AvarietyofpulsesequencesareinusetodayforperfusionMRI,andthepaceof developmentisrapid.Commonimagingenginesaresteadystatefreeprecession (SSFP),gradientrecalledecho(GRE),andGREechoplanarimaging(GREEPI) hybridsequences(Figure6).Virtuallyallsequencesincludeasaturationprepulse modifiertoprovideT1weightingandtoaccentuateregionaldifferencesin myocardialgadoliniumconcentration(Figure4,panelA).Sinceimagesareacquired insingleshotmode,aparallelimaging19,20modifierisessentialtospeedimaging andallowadequateLVcoverageaswellasreducedmotionartifacts.21Ingeneral, imagereadouttimesmorethan~120mscanleadtosubstantialmotionartifactsin imagesacquiredduringperiodsofthecardiaccycleinwhichthereisrapidLV motion. ViabilityandInfarction
Figure7 Figure5

Figure6

Figure8

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Table1

ThegoalofdelayedenhancementMRI(DEMRI)istocreateimageswithhigh contrastbetweenabnormalmyocardialtissue,whichgenerallyaccumulatesexcess gadolinium(followingintravenousadministration),andnormaltissueinwhich gadoliniumconcentrationislow.Thisiscurrentlybestachievedusingasegmented GREimagingenginewithinversionrecoveryprepulsemodifiertoprovideverystrong T1weighting.2226Aparallelimaging19,20modifiercanbeusedtoshorten acquisitiontime.Imagingisperformedapproximately5minutesafterrestperfusion imagingor1015minutesafteraonetimeintravenousgadoliniumdoseof~0.15 mmol/kgifstressrestperfusionimagingisnotperformed.Shortandlongaxis viewsintheidenticalplanesusedforcineimagingareobtainedduringrepeated6 10secondbreathholds.Dataacquisition(readoutperiod)istimedwiththeECGin middiastoletominimizecardiacmotion.Onlyeveryotherheartbeatisusedfordata collectiontoallowforadequaterecoveryoflongitudinalrelaxationbetweeninversion pulses(ifbradycardiaispresent,imagingcanoccureveryheartbeat).27 Followinganintravenousbolus,gadoliniumdistributesthroughouttheintravascular andinterstitialspace,whilesimultaneouslybeingclearedbythekidneys.Innormal myocardium,wherethemyocytesaredenselypacked,tissuevolumeis predominatelyintracellular(~7580%ofthewaterspace28).Sincegadoliniumis unabletopenetrateintactsarcolemmalmembranes,29thevolumeofdistributionis small,andonecanconsiderviablemyocytesasactivelyexcludinggadolinium media. Inacutemyocardialinfarction(MI),myocytemembranesareruptured,allowing gadoliniumtopassivelydiffuseintotheintracellularspace.Thisresultsinan increasedvolumeofdistributionforgadolinium,andthusincreasedtissue concentrationcomparedwithnormalmyocardium.3032Similarly,inchronic infarction,asnecrotictissueisreplacedbycollagenousscar,theinterstitialspaceis expandedandgadoliniumtissueconcentrationisincreased.32 HighertissueconcentrationsofgadoliniumleadtoshortenedT1relaxation.Thus, whentheparametersaresetproperly,T1weightedsequencessuchasthoseused forDEMRIcandepictinfarctedregionsasbrightor"hyperenhanced,"whereas viableregionsappearblackor"nulled"(Figure5).Oneofthemostimportant parameterstosetcorrectlyisthetimebetweentheinversionprepulseanddata readout,knownastheinversiontime.Theacronymcommonlyusedis"TI",butto avoidconfusionwith"T1"(longitudinalrelaxationtime),theauthorsprefertheuseof "IT." Figure4,panelBdemonstratesthattomaximizecontrastbetweeninfarctedand viablemyocardium,ITshouldbesettowhentherelaxationcurveofviable myocardiumcrosseszero.Ingeneral,oncetheoptimalIThasbeendetermined,no adjustmentisnecessaryifDEMRIiscompletedinapproximately5minutes. However,itisimportanttokeepinmindthatgadoliniumgraduallywashesoutof viablemyocardium,andITwillneedtobeadjustedupwardifDEMRIisperformedat multipletimepointsaftercontrastadministration.27 Comparedwithotherimagingtechniquesthatarecurrentlyusedtoassess myocardialviability,animportantadvantageofDEMRIisthehighspatialresolution. Withastandardimplementation,agroupof10hyperenhancedpixels(voxel resolution1.9x1.4x6mm)inaDEMRIimagewouldrepresentaninfarctionof0.16 g,oraregion1,000thoftheLVmass.26Thislevelofresolution,whichismorethan 40foldhigherthansinglephotonemissioncomputedtomography(SPECT),allows visualizationofevenmicroinfarctsthatcannotbedetectedbyotherimaging methods.25,33 Recentlyanultrafast,realtimeversionofDEMRIhasbeendevelopedthatcan acquiresnapshotimagesduringfreebreathing.34,35Thistechniqueutilizesan SSFPimagingengineinsingleshotmodewithparallelimagingacceleration,and providescompleteLVcoverageinunder30seconds.Thistechniquecouldbe consideredthepreferredapproachinmoreacutelyillpatientswhoareunableto breathhold,orwhohaveanirregularheartrhythm.However,comparedwith standardsegmentedDEMRI,sensitivityfordetectingMIismildlyreduced,andthe transmuralextentofinfarctionmaybeunderestimated.35

AdditionalImaging Morphology Occasionally,additionalstructural/anatomicalinformationisnecessarytofully investigatetheclinicalquestion,suchasinthesettingofcongenitalheartdisease, cardiacmasses,orpatientswithaorticrootdilationoninitialthreechambercine MRI.Ingeneral,a"morphology"scanconsistsofaseriesofparallelslices,which "breadloaf"theanatomicalregionofinterest.Althoughanyorientationmaybe imaged,usuallyaxial,sagittal,orcoronalplanes(orallthree)arechosenfirst. Inordertoquicklyprovidesubstantialanatomicalcoverage,morphologyimagingis primarilyperformedinsingleshotmodeusingeitheranSSFPorTSEimaging engine.TheSSFPsequenceissimilartothatusedforrealtimecineMRI,butithas beenalteredtoproduceastackofimagesthatprogressesthroughspacerather thanacinemovieloopatasinglelocation.Initsnativeform(withoutadditional modifiers),SSFPproducesimagesinwhichbloodinthecardiacchambersand vasculatureappearbrightthus,itisknownasa"brightblood"technique. Tofirstorder,SSFPimagesareT2/T1weighted.24Incontrast,spinechobased sequencessuchasTSEproduceimagesinwhichflowingbloodisdarkthus,these areknownas"blackblood"techniques.However,bloodsignalsuppressionmaybe incomplete,andablackbloodmodifier,whichconsistsofadoubleinversion prepulse,36isoftenaddedtoimprovebloodnullingorblackening.Asingleshot versionofTSEthatiscommonlyusedincardiovascularimagingisblackblood HASTE(halfFouriersingleshotTSE).WithSSFPorHASTEmorphologicimaging, theentirethoraxcanbeimagedinmultipleorthogonalviewsinlessthan2minutes withoutbreathholding. T2Weighted"Edema"Imaging T2weightedimaginghasshownpromiseinassessingacuteinflammatory processes.37Inthesettingofmyocardialnecrosis,suchasinacuteMIor myocarditis,tissuemyocardialwatercontentincreasessubstantiallywithinthe regionofnecrosis.38ThepresenceoftissueedemaresultsinalongerintrinsicT2 forinfarctedmyocardium(6065ms)comparedtothatofnormal(4550ms).39 Thus,thegoalofT2weightedimagingistoutilizethedifferencesinT2between normalandnecroticmyocardiumtocreatetissuecontrast. Flow/Velocity Dependingontheclinicalquestion,thecoreexammayincludevelocityencoded cineimaging(VENCMRI)tomeasurebloodvelocitiesandflowsinarteriesand veins,andacrossvalvesandshunts.Alsoknownasphasecontrastvelocity mapping,theunderlyingprincipleisthatsignalfrommovingbloodortissuewill undergoaphaseshiftrelativetostationarytissue,ifamagneticfieldgradientis appliedinthedirectionofmotion. ThegoalofVENCMRIistoproduceacineloopacrossthecardiaccycle,whereon anygivenframe,pixelintensityisproportionaltobloodvelocity.Generallydisplayed usingagreyscale,whitecorrespondstomaximumflowinonedirection,blackto maximumflowintheoppositedirection,andmidgreyindicatesthatflowisabsent (Figure9).Althoughbloodvelocitycanbemeasuredinanyarbitrarydirection,itis usuallyassessedinreferencetotheimagingplane.Encodingvelocityintheslice gradientdirectionallowsmeasurementofthroughplanevelocities,andencodingin eitherthefrequencyorphaseencodegradientdirectionsallowsinplane measurementofvelocitycomponentsdirectedeitherverticallyorhorizontallywithin theimageplane. VENCMRIiscommonlyperformedusingasegmentedGREimagingengineduring apatientbreathhold.Thesequence,however,ismodifiedtomeasuretheeffectsof amagneticfieldgradientontheprecessingprotonswithinflowingblood.Optimizing themaximumvelocitythatcanbemeasuredwhichisinverselyrelatedtogradient strength(foraconstantapplicationtime)isimportant.Settingthemaximum velocitytoolowwillleadtoaliasing,whereassettingittohighwillleadtomorenoise orinaccuracyinthevelocitymeasurement.Retrospectiveratherthanprospective ECGgatingispreferredtoallowdatacollectionthroughouttheentirecardiaccycle,

includingenddiastole. AlthoughVENCMRIappearsanalogoustoDopplerechocardiography,thereare importantdifferences(Table1).Forinstance,anadvantageofVENCMRIisthat bloodflowthroughanorificeisdirectlymeasuredonanenfaceimageoftheorifice withthroughplanevelocityencoding.Withechocardiography,therearetwo limitations.First,thebloodflowprofileisnotdirectlymeasured,butassumedtobe flat(i.e.,velocityinthecenteroftheorificeisthesameasneartheedges)sothat, hopefully,onesamplingvelocitywouldindicateaveragevelocity.Second,thecross sectionalareaoftheorificeisestimatedfromadiametermeasurementoftheorifice atadifferenttimefromwhenDopplervelocitywasrecordedusingadifferent examination(Mmodeor2Dimaging). Ontheotherhand,VENCMRIhassomedisadvantages.Perhapsmostimportantly, VENCMRIisnotperformedinrealtimeandrequiresbreathholdingtominimize artifactsfromrespiratorymotion.Oneconsequenceisthatitisdifficulttomeasure changesinflowthatoccurwithrespiration. CoronaryMagneticResonanceAngiography CoronaryMRangiography(MRA)maybeusedtodirectlyvisualizecoronaryanatomy andmorphology.However,coronaryMRAistechnicallydemandingforseveral reasons.Thecoronaryarteriesaresmall(35mm)andtortuouscomparedwith othervascularbedsthatareimagedbyMRA,andthereisnearlyconstantmotion duringboththerespiratoryandcardiaccycles.Thus,preciseassessmentof stenosisseverityandvisualizationofdistalsegmentsaredifficult,leadingto intermediatesensitivityandspecificityvaluesforthedetectionofcoronaryartery disease(CAD)invalidationstudies.40Currently,theonlyclinicalindicationthatis consideredappropriateforcoronaryMRAistheevaluationofpatientswith suspectedcoronaryanomalies.41

TheEffectofGadoliniumContrastonT1andT2WeightedImaging Figure5 Priortocontrastadministration,thereareminimaldifferencesininherenttissueT1andT2betweennormalandinfarctedmyocardiumthus, infarctionispoorlydelineated(toppanel).Aftergadoliniumadministration,theT1ofinfarction(althoughnotT2)ismarkedlyshortened,leadingto cleardelineationontheT1weightedimage(bottompanel).T1weightedimageswereacquiredusinganinversionrecoverygradientecho sequence.T2weightedimageswereacquiredusingadarkbloodturbospinechosequence.ApproximateT1andT2timesarefor1.5T scanners.

MRIPulseSequenceStructure Figure6 Themagneticresonanceimaging(MRI)pulsesequencecanbeconsideredascomposedoftwoseparateelements:theimagingengineand modifiers.Typicalimagesusingdifferentimagingenginesandmodifiersareshownatthebottom.Allimagesareofthesameshortaxisspatial location.Seetextforfurtherinformation. ModifiedwithpermissionfromShahDJ,JuddRM,KimRJ.Technologyinsight:MRIofthemyocardium.NatClinPractCardiovascMed20052:597 605.

TimelineandPotentialComponentsofaMultiTechniqueCMRExaminationforCardiacImaging Figure7 CMR=cardiacmagneticresonanceMI=myocardialinfarctionMRA=magneticresonanceangiographySNR=signaltonoiseratio. ReproducedwithpermissionfromKimHW,FarzanehFarA,KimRJ.Cardiovascularmagneticresonanceinpatientswithmyocardialinfarction: currentandemergingapplications.JAmCollCardiol200955:116.

FirstPassPerfusionMRIImageAcquisition Figure8 Imagesareacquiredseriallyatmultipleslicelocations(usually45shortaxisviewsforleftventricularcoverage)everyheartbeattodepictthe passageofacompactcontrastbolusasittransitstheheart.Exampleimagesofoneslicelocationareshownatseveralrepresentativetime points:beforearrivalofcontrast(frame1)contrastinRVcavity(frame12)contrastinLVcavity(frame22)peakcontrastinLVmyocardium (frame30),showingnormalperfusionintheseptum(openarrowhead)andabnormalperfusionintheinferolateralwall(solidarrowhead)and thecontrastwashoutphase(frame50).

MagnetizationPreparationPulsestoCreateT1Contrast Figure4 (A)Saturationrecovery.A90radiofrequency(RF)pulsefollowedbystronggradientspoilersreducesthenetmagnetizationtozero. MagnetizationrecoversdependingontissueT1.Forinstance,immediatelyfollowingintravenousbolusadministrationofgadoliniumcontrast, myocardiumwithnormalperfusionhassubstantialuptakeofgadolinium,thushasshortT1,andappearsbrightonsaturationrecoveryperfusion magneticresonanceimaging(MRI).Incomparison,myocardiumwithreducedperfusionhasdiminisheduptakeofgadolinium,longerT1,and appearsdark.Ideally,datareadoutshouldfollowthesaturationpulseataspecifictime(timepointbratherthantimepointaorc)toachieve maximumseparationbetweentheT1relaxationcurvesofnormalandabnormalmyocardium. (B)Inversionrecovery.An180RFpulseinvertsthelongitudinalmagnetizationfromthe+zaxistothezaxis.Oftenusedininfarctimaging,the timebetweentheinversionpulseandthecenterofdatareadout(inversiontimeorIT)isselectedtoaccentuatethedifferencesofgadolinium uptakeinnormalandinfarctedmyocardium.Specifically,theinversiontimeischosensothatthecenterofimagereadout(forlinearkspace acquisition)occurswhentheT1relaxationcurveofnormalmyocardiumcrosseszero(e.g.,nulled).Notethatwiththisinversiontime,theT1 relaxationcurveofinfarctedmyocardiumisabovethezerocrossing,andinfarctedtissueisbright.

ECGGatedVelocityEncodingMRI Figure9 Analogoustocineimaging,eachvelocityencodedimage(toprowofimages)correspondstoacardiacphase,andgatingtothe electrocardiogram(ECG)isnecessary.Ontheimages,whiterepresentsmaximalvelocity(inthiscaseacrosstheaorticvalve,redarrow).Black representsflowintheoppositedirection(inthedescendingthoracicaorta,bluearrow).Greyrepresentsnoflow.Thebottomrowdemonstrates thecorrespondingcineMRIimages.MRI=magneticresonanceimaging.

ComparisonofVelocityEncodedMRIandDopplerEchocardiography Table1 *Giventemporalresolutionisforbreathholdimaging.Temporalresolutionmaybesignificantlyimprovedfornonbreathholdimaging,butartifacts duetorespiratorymotionartifactmaybeprominent. Conduitcrosssectionalareaisestimatedfromdiametermeasurement. CW=continuouswaveMRI=magneticresonanceimaging.

ClinicalApplications (1of2)
CoronaryArteryDiseaseandIschemia AnumberofCMRapproachesexistforthedetectionofCAD.42Eachofthese techniquesexploitsspecificanatomicalorphysiologicalpropertiesthatoccurasa resultofCAD(Table2).However,clinically,themostwidespreadapproachfor evaluatingCADisstresstestingwithimagingofeithermyocardialcontractionor perfusion. Analogoustoechocardiography,cineMRIduringdobutaminestimulationcanbe usedtodetectischemiainducedwallmotionabnormalities.DobutaminecineMRI mayyieldhigherdiagnosticaccuracythandobutamineechocardiography,43andcan beeffectiveinpatientsnotsuitedforechocardiographyduetopooracoustic windows.44 Recentdatasuggestthatthepresenceofinducibleischemiabythistechnique predictssubsequentcardiacmortality.4549Asaresult,the2006appropriateness criteriaforcardiaccomputedtomographyandcardiacMRIfromtheAmerican CollegeofCardiologyFoundationandothersocietieshasspecifiedthattheuseof dobutaminecineMRIisappropriateforthedetectionofCADinsymptomaticpatients withintermediatepretestprobability,whohaveuninterpretableECGsorareunable toexercise.41Fromapracticalstandpoint,severallogisticalissuesregarding patientsafetyandadequatemonitoringrequirethoroughplanningandexperienced personnel.Perhapsinpartbecauseoftheseissues,onlyafewcentersworldwide routinelyperformthistechnique. FirstpassperfusionMRIduringadenosinevasodilationisrapidlybecomingthe stresstestofchoiceinclinicalCMRcenters.PerfusionMRIispromisingforseveral reasons.Decreasedperfusionisthefirststepintheischemiccascade.Therefore, techniquesthatassessperfusionhavethepotentialtobemoresensitivethan techniquesthatassesslatersteps.5054 Logistically,stressperfusionimagingisquickandsimple.Thedurationof adenosineinfusionisshort(~3minutes),anddirectaccesstothepatientislimited onlyduringimagingofthefirstpass(~45seconds).Comparedwithcompeting technologiessuchasradionuclideimaging,perfusionMRIhasmanypotential advantages:morethananorderofmagnitudeimprovementinspatialresolution (typicalvoxeldimensions,MRI3.0x1.8x8mm=43mm3 vs.SPECT10x10x10 mm=1000mm3 Figure10)theabilitytoidentifyregionaldifferencesinflowover thefullrangeofcoronaryvasodilation(i.e.,noplateauinsignalathighflowrates,as seenwithradionuclidetracers55,56Figure11)thelackofionizingradiationandan examinationtimeof3045minutesversus23hours. ThediagnosticperformanceofstressperfusionMRIhasbeenevaluatedina numberofstudiesinhumans.5775Overall,thesestudieshaveshowngood correlationswithradionuclideimagingandxraycoronaryangiography.Tables3a, b,andcsummarizethepublishedstressperfusionMRIstudiesinhumanswith coronaryangiographycomparison.Atotalof34studieshavebeencompleted, consistingofover2,800patientswithknownorsuspectedCAD.Onaverage,the sensitivityandspecificityofperfusionMRIfordetectingobstructiveCADwere85% and81%,respectively.The2006appropriatenesscriteriaforcardiaccomputed tomographyandcardiacMRIfromtheAmericanCollegeofCardiologyFoundation andothersocietieshasindicatedthattheuseofstressperfusionMRIisappropriate fordetectionofCADinsymptomaticpatientswithintermediatepretestprobability andwhohaveuninterpretableECGsorareunabletoexercise.41 Despitethemostlyfavorableresultsofthesestudies,anumberofissuesshouldbe considered.Somestudiesareoflimitedclinicalapplicabilitybecausetheyrequired centralvenouscatheters,61imagedonly1sliceperheartbeat,61,65orexcluded patientswithdiabetes.70Manystudieshadsmallsamplesizes11had30orfewer
Table2

Figure10

Figure11

Table3a

Table3b

Table3c

Figure12

Figure13

Figure14

patients.MostincludedpatientsalreadyknowntohaveCADorknowntohaveprior MI.Inthesestudies,thereispretestreferralor"spectrum"bias,whichcanartificially raisetestsensitivityand/orspecificity.76,77Importantly,inmanystudiesafterthe datawerecollected,severalmethodsofanalysisweretestedanddifferent thresholdsfortestabnormalitywereappraised.Forthesestudies,thereported sensitivityandspecificityvaluesareoptimisticsincetheendpointswerechosen retrospectivelyandtheyrepresentoptimizedvalues. Severalpracticalissuesshouldalsobeconsideredwhenevaluatingthesestudies. ThestudiesinTables3a,b,andcarefairlyheterogeneousintermsoftheprotocols andmethodsemployed.Inpart,thisisareflectionoftherapidpaceofpulse sequencedevelopmentoverthistimeframe.Thus,earlierstudiesmayhaveutilized pulsesequencesand/orimagingprotocolsthatarenolongercommonlyusedina clinicalsetting,andsomereportsmaynotbedirectlycomparable.Forinstance,the doseofgadoliniumcontrastadministeredhasbeenvariable(overasixfoldrange 0.0250.15mmol/kg).Second,severalstudiesusedaquantitativeapproach(i.e., regionsofinterestaredrawnontheimagesandimageintensitiesaremeasured) fordiagnosticassessment. Althoughaquantitativeapproachhasthepotentialadvantageofallowingthe measurementofabsolutebloodflow,theapproachrequiresextensiveinteractive postprocessingandistimeconsuming.Asaresult,aquantitativeapproachhas notbeenfeasibleforgeneralclinicaluseandisuncommonlyutilizedoutsideofthe researchsetting. Incontrast,imageinterpretationbysimplevisualassessmentwouldbearealistic approachforaclinicalCMRpractice.Unfortunately,theresultsintheliterature regardingvisualassessmentofperfusionMRIaremixed,generallydemonstrating adequatesensitivity,butrelativelypoorspecificityforthedetectionofCAD.Inlarge part,imageartifactsareresponsibleforreducedspecificity.However,thereisno reasontointerpretthestressperfusionimagesinisolation. The"core"examisamulticomponentprotocolthatincludescineandDEMRIin additiontostressandrestperfusion.Inthiscontext,itisnoteworthythatan interpretationalgorithmthatcombinesdatafromperfusionMRIandDEMRIhas beenintroduced,whichsubstantiallyimprovesthespecificityandaccuracyofrapid visualassessmentforthedetectionofCAD(Figure12).75 Thealgorithmisbasedontwosimpleprinciples.First,withperfusionMRIandDE MRI,therearetwoindependentmethodstoobtaininformationregardingthe presenceorabsenceofMI.Thus,onemethodcouldbeusedtoconfirmtheresults oftheother.Second,DEMRIimagequality(e.g.,signaltonoiseratio)isfarbetter thanperfusionMRIbecauseitislessdemandingintermsofscannerhardware (DEMRIimagescanbebuiltupoverseveralsecondsratherthanin0.1second,as isrequiredforfirstpassperfusion).78Thus,DEMRIshouldbemoreaccuratefor thediagnosisofMI.78 Conceptually,itthenfollowsthatperfusiondefectsthathavesimilarintensityand extentduringbothstressandrest("matcheddefect"),butdonothaveinfarctionon DEMRI,areartifactualandshouldnotbeconsideredpositiveforCAD.Conversely, thepresenceofinfarctiononDEMRIfavorsthediagnosisofCAD,eveniftheresults ofperfusionimagingareequivocal. Thismulticomponentapproachtoimageinterpretationhasbeenstudiedinavariety ofpatientcohorts,includingthoseatintermediateriskforCAD,75,79withknownor suspectedCAD,80,81withhistoryofrevascularization,82andundergoingrisk stratificationaftersuccessfulthrombolytictherapyforSTsegmentelevationMI.83 Althoughdirectheadtoheaddataarelacking,thesestudiessuggestthatrapid visualassessmentusingthiscombinationprotocolprovidesresultsthatare comparable,ifnotbetterthancompetingtechnologies.Asaresult,manyclinical laboratorieshaveadoptedthismethodology. ViabilityandInfarction AlthoughavarietyofMRItechniqueshavebeenutilizedtoassessmyocardial viability,currently,onlydobutaminecineMRIandDEMRIareusedclinically.In

Figure15

general,DEMRIispreferredoverdobutaminecineMRIbecauseDEMRImaybe performedwithouttheuseofinotropicagentsorspecialmonitoringequipment.84 Notsurprisingly,thevastmajorityofclinicalsitesperformDEMRIratherthan dobutaminecineMRIforviabilityassessmentthus,thefollowingdiscussionwill focusonDEMRI. ValidationStudies ThereisanabundanceofvalidationdatainanimalmodelsinwhichDEMRIhas beendirectlycomparedtothehistopathology.22,23,32Thesedatademonstratea nearlyexactrelationshipbetweenthesizeandshapeofinfarctedmyocardiumby DEMRItothatbyhistopathology(Figure13).HumanstudiesdemonstratethatDE MRIiseffectiveinidentifyingthepresence,location,andextentofMIinboththeacute andchronicsettings.24,26TypicalDEMRIimagesinpatientswithlargeandsmall MIsareshowninFigure14.DEMRIprovidesscarsizemeasurementsthatare closelycorrelatedwithpositronemissiontomography(PET)inpatientswith ischemiccardiomyopathy,85andprovidesresultssuperiorto(SPECT)inpatients withsubendocardialinfarctions.25 Recently,DEMRIwasevaluatedinaninternationalmulticentertrialforthedetection ofMI.86Intotal,282patientswithacuteand284withfirsttimeMIwerescannedin 26centersthroughouttheUnitedStates,Europe,andSouthAmerica.Thestudy demonstratedthatthesensitivityofDEMRIincreasedwithrisinggadoliniumdose, reaching99%and94%inacuteandchronicMI,respectively,withthe0.3mmol/kg dose(Figure15).Furthermore,withdoses0.2mmol/kgorhigher,whenMIwas identified,itwasinthecorrectlocationinmorethan97%ofpatients(i.e.,thelocation ofhyperenhancementmatchedtheperfusionterritoryoftheinfarctrelatedartery). Importantly,thisstudyrepresentsthefirstmulticentertrialdesignedtoevaluatean imagingapproachfordetectingMI.Althoughmulticentertrialshaveusedinfarctsize measurementsbySPECTasasurrogateendpointtoassesstheefficacyofan investigativetherapy,87thesetrialswerenotdesignedtoevaluateSPECT,and limitedmulticenterdataonthesensitivityoraccuracyofradionuclideimagingfor detectingorlocalizingMIhavebeenreported. Inaddition,theDEMRItrialtestedthesensitivityofimagingforbothacuteand chronicMI.Thisisnotablebecausetherearefarlessclinicaltrialdataonthe detectionofchronicMIbyimagingmethods,andchronicinfarctsaregenerallymore difficulttodetectthanacuteinfarctsbecausesubstantialshrinkagecanoccurduring healing.23Thus,insummary,thedataindicatethatDEMRIisawellvalidated, robusttechniquethatcanbeeasilyimplementedonscannersthatarecommonly availableworldwide,withaneffectivenessthatrivalsthebestavailableimaging techniquesforthedetectionandassessmentofMI. AssessingViability AstraightforwardclinicalapplicationofDEMRIistodifferentiatepatientswith potentiallyreversibleventriculardysfunctionfromthosewithirreversibledysfunction. Inthesettingofischemicheartdisease,itisprimarilytheformergroupthatwill benefitfromcoronaryrevascularization.TheuseofDEMRIforthispurposeisfurther discussedinthemoduleonHibernation,Stunning/ViabilityinChapter7.

CardiovascularMagneticResonanceTechniquesfortheDetectionofCoronaryArteryDisease Table2 MRI=magneticresonanceimagingMRA=magneticresonanceangiographyBOLD=bloodoxygenationleveldependentATP=adenosine triphosphate.


1Reststudiesalonemayprovidesomeinformationregardingthepresenceofcoronaryarterydisease. 2Forassessmentofcoronaryanomaliesandpatencyofcoronarybypassgrafts. 3Recentstudiessuggestpotentialutilityforassessmentofcoronarybypasspatencyandinstentrestenosis.

ImportanceofSpatialResolutioninStressPerfusionImaging Figure10 Patienthasaninducibleperfusiondefectlimitedtothesubendocardialportionoftheseptalwall(blackarrow)causedbyanostialstenosis (whitearrow)ofaseptalbranchoftheleftanteriordescendingcoronaryartery.

ComparisonsofPerfusionMRI,Radionuclide,andMicrosphereFlows Figure11 Magneticresonanceimaging(MRI)signalintensitytimecurveswerelinearlyrelatedtoreferencemicrosphereflowsoverthefullrangeof vasodilation.Relationshipsbetween99mtechnetium(Tc)sestamibiand201thallium(Tl)activityandmicrosphereflowswerecurvilinear,plateauing asflowsincreased.DatasuggestthatperfusionMRI,unlikeradionuclideimaging,hasthepotentialfordetectingstenoses,producingonly moderatelimitationsinflowreserve.(A)Normalizedmagneticresonancefirstpassperfusion(MRFP)imagingandfullthicknessmicrosphere relativeregionalflows(RRF).(B)Normalized99mTcsestamibiandfullthicknessmicrosphereRRFs.(C)Normalized201Tlandfullthickness microsphereRRFs.(D)Invivosinglephotonemissioncomputedtomography(SPECT)andexvivowellcountingvaluesof99mTcsestamibi versusmicrosphereRRFs. ReproducedwithpermissionfromLeeDC,SimonettiOP,HarrisKR,etal.Magneticresonanceversusradionuclidepharmacologicalstress perfusionimagingforflowlimitingstenosesofvaryingseverity.Circulation2004110:5865.

StressPerfusionMRIStudiesinHumansWithCoronaryAngiographyComparison(1of3) Table3a CAD=coronaryarterydiseaseDEMRI=delayedenhancementmagneticresonanceimagingEPI=echoplanarimagingGRE=gradientrecalled echoIR=inversionrecoveryprepulseMRI,magneticresonanceimagingSR=saturationrecoveryprepulseSSFP=steadystatefree precessionNS=notstated. *Numbersbasedonaregionalratherthanperpatientanalysis.


1Whenbothrestandstressimagingwereperformed,theorderisaslisted. 2Prospectivestudieswerethoseinwhichthecriteriafortestabnormalitywereprespecifiedbeforedataanalysis. 3Pilotstudyperformedfirsttodeterminethebestthresholdfortestabnormality. 4Atenrollment,allpatientshadtheclinicaldiagnosisofSTelevation,nonSTelevationmyocardialinfarction,oracutecoronarysyndrome. 5Reportedsensitivityandspecificityarefromafractionofthetotalcohort,asubgroupwiththebestresults. 6Withparallelimagingacceleration. 7Allpatientshadrelevantaorticstenosis. 8Multicentertrialwithfivedifferentcontrastdosesthesensitivity/specificityareestimatesfromreceiveroperatingcharacteristicanalysis,which

isbasedontheresultsfromthegroupwiththeoptimumcontrastdose(n=45). Sensitivity/specificityafterincorporatingDEMRIwere89%and87%,respectively. Sensitivity/specificityafterincorporatingDEMRIwere87%and89%,respectively. #Representsaveragevaluesofthetwoobserversaveragesensitivity/specificityafterincorporatingDEMRIwere92%and54%,respectively. ||Representsaveragesensitivity/specificityoftheentirestudypopulationafterincorporatingDEMRI(algorithmA).

DEMRIwasincorporatedinimageanalysis. References: 1. KleinMA,CollierBD,HellmanRS,BamrahVS.Detectionofchroniccoronaryarterydisease:valueofpharmacologicallystressed, dynamicallyenhancedturbofastlowangleshotMRimages.AJRAmJRoentgenol1993161:25763. 2. HartnellG,CerelA,KamaleshM,etal.Detectionofmyocardialischemia:valueofcombinedmyocardialperfusionandcineangiographic MRimaging.AJRAmJRoentgenol1994163:10617. 3. EichenbergerAC,SchuikiE,KochliVD,AmannFW,McKinnonGC,vonSchulthessGK.Ischemicheartdisease:assessmentwith gadoliniumenhancedultrafastMRimaginganddipyridamolestress.JMagnResonImaging19944:42531. 4. AlSaadiN,NagelE,GrossM,etal.Noninvasivedetectionofmyocardialischemiafromperfusionreservebasedoncardiovascular magneticresonance.Circulation2000101:137983. 5. BertschingerKM,NanzD,BuechiM,etal.Magneticresonancemyocardialfirstpassperfusionimaging:parameteroptimizationforsignal responseandcardiaccoverage.JMagnResonImaging200114:55662. 6. SchwitterJ,NanzD,KneifelS,etal.Assessmentofmyocardialperfusionincoronaryarterydiseasebymagneticresonance:a comparisonwithpositronemissiontomographyandcoronaryangiography.Circulation2001103:22305. 7. PantingJR,GatehousePD,YangGZ,etal.Echoplanarmagneticresonancemyocardialperfusionimaging:parametricmapanalysisand comparisonwiththalliumSPECT.JMagnResonImaging200113:192200. 8. SenskyPR,SamaniNJ,ReekC,CherrymanGR.Magneticresonanceperfusionimaginginpatientswithcoronaryarterydisease:a qualitativeapproach.IntJCardiovascImaging200218:37383. 9. IbrahimT,NekollaSG,SchreiberK,etal.Assessmentofcoronaryflowreserve:comparisonbetweencontrastenhancedmagnetic resonanceimagingandpositronemissiontomography.JAmCollCardiol200239:86470. 10. ChiuCW,SoNM,LamWW,ChanKY,SandersonJE.CombinedfirstpassperfusionandviabilitystudyatMRimaginginpatientswithnon STsegmentelevationacutecoronarysyndromes:feasibilitystudy.Radiology2003226:71722. 11. IshidaN,SakumaH,MotoyasuM,etal.Noninfarctedmyocardium:correlationbetweendynamicfirstpasscontrastenhancedmyocardial MRimagingandquantitativecoronaryangiography.Radiology2003229:20916. 12. NagelE,KleinC,PaetschI,etal.Magneticresonanceperfusionmeasurementsforthenoninvasivedetectionofcoronaryarterydisease. Circulation2003108:4327. 13. DoyleM,FuiszA,KortrightE,etal.Theimpactofmyocardialflowreserveonthedetectionofcoronaryarterydiseasebyperfusion imagingmethods:anNHLBIWISEstudy.JCardiovascMagnReson20035:47585.

StressPerfusionMRIStudiesinHumansWithCoronaryAngiographyComparison(2of3) Table3b

CAD=coronaryarterydiseaseDEMRI=delayedenhancementmagneticresonanceimagingEPI=echoplanarimagingGRE=gradientrecalled echoIR=inversionrecoveryprepulseMRI,magneticresonanceimagingSR=saturationrecoveryprepulseSSFP=steadystatefree precessionNS=notstated.*Numbersbasedonaregionalratherthanperpatientanalysis.


1Whenbothrestandstressimagingwereperformed,theorderisaslisted. 2Prospectivestudieswerethoseinwhichthecriteriafortestabnormalitywereprespecifiedbeforedataanalysis. 3Pilotstudyperformedfirsttodeterminethebestthresholdfortestabnormality. 4Atenrollment,allpatientshadtheclinicaldiagnosisofSTelevation,nonSTelevationmyocardialinfarction,oracutecoronarysyndrome. 5Reportedsensitivityandspecificityarefromafractionofthetotalcohort,asubgroupwiththebestresults. 6Withparallelimagingacceleration. 7Allpatientshadrelevantaorticstenosis. 8Multicentertrialwithfivedifferentcontrastdosesthesensitivity/specificityareestimatesfromreceiveroperatingcharacteristicanalysis,which

isbasedontheresultsfromthegroupwiththeoptimumcontrastdose(n=45). Sensitivity/specificityafterincorporatingDEMRIwere89%and87%,respectively. Sensitivity/specificityafterincorporatingDEMRIwere87%and89%,respectively. #Representsaveragevaluesofthetwoobserversaveragesensitivity/specificityafterincorporatingDEMRIwere92%and54%,respectively. ||Representsaveragesensitivity/specificityoftheentirestudypopulationafterincorporatingDEMRI(algorithmA). DEMRIwasincorporatedinimageanalysis. References: 14. WolffSD,SchwitterJ,CouldenR,etal.Myocardialfirstpassperfusionmagneticresonanceimaging:amulticenterdoserangingstudy. Circulation2004110:7327. 15. GiangTH,NanzD,CouldenR,etal.Detectionofcoronaryarterydiseasebymagneticresonancemyocardialperfusionimagingwith variouscontrastmediumdoses:firstEuropeanmulticentreexperience.EurHeartJ200425:165765. 16. PaetschI,JahnkeC,WahlA,etal.Comparisonofdobutaminestressmagneticresonance,adenosinestressmagneticresonance,and adenosinestressmagneticresonanceperfusion.Circulation2004110:83542. 17. ThieleH,PleinS,BreeuwerM,etal.Colorencodedsemiautomaticanalysisofmultislicefirstpassmagneticresonanceperfusion: comparisontotetrofosminsinglephotonemissioncomputedtomographyperfusionandXrayangiography.IntJCardiovascImaging 200420:37184discussion857. 18. PleinS,GreenwoodJP,RidgwayJP,CrannyG,BallSG,SivananthanMU.AssessmentofnonSTsegmentelevationacutecoronary syndromeswithcardiacmagneticresonanceimaging.JAmCollCardiol200444:217381. 19. PleinS,RadjenovicA,RidgwayJP,etal.Coronaryarterydisease:myocardialperfusionMRimagingwithsensitivityencodingversus conventionalangiography.Radiology2005235:42330. 20. SakumaH,SuzawaN,IchikawaY,etal.DiagnosticaccuracyofstressfirstpasscontrastenhancedmyocardialperfusionMRI comparedwithstressmyocardialperfusionscintigraphy.AJRAmJRoentgenol2005185:95102. 21. KlemI,HeitnerJF,ShahDJ,etal.Improveddetectionofcoronaryarterydiseasebystressperfusioncardiovascularmagneticresonance withtheuseofdelayedenhancementinfarctionimaging.JAmCollCardiol200647:16308. 22. CuryRC,CattaniCA,GabureLA,etal.DiagnosticperformanceofstressperfusionanddelayedenhancementMRimaginginpatients withcoronaryarterydisease.Radiology2006240:3945. 23. RieberJ,HuberA,ErhardI,etal.Cardiacmagneticresonanceperfusionimagingforthefunctionalassessmentofcoronaryartery disease:acomparisonwithcoronaryangiographyandfractionalflowreserve.EurHeartJ200627:146571. 24. PilzG,BernhardtP,KlosM,AliE,WildM,HoflingB.Clinicalimplicationofadenosinestresscardiacmagneticresonanceimagingas potentialgatekeeperpriortoinvasiveexaminationinpatientswithAHA/ACCclassIIindicationforcoronaryangiography.ClinResCardiol 200695:5318. 25. GreenwoodJP,YoungerJF,RidgwayJP,SivananthanMU,BallSG,PleinS.Safetyanddiagnosticaccuracyofstresscardiacmagnetic resonanceimagingvsexercisetolerancetestingearlyafteracuteSTelevationmyocardialinfarction.Heart200793:13638. 26. ChengAS,PeggTJ,KaramitsosTD,etal.Cardiovascularmagneticresonanceperfusionimagingat3teslaforthedetectionofcoronary arterydisease:acomparisonwith1.5tesla.JAmCollCardiol200749:24409. 27. CostaMA,ShoemakerS,FutamatsuH,etal.Quantitativemagneticresonanceperfusionimagingdetectsanatomicandphysiologic coronaryarterydiseaseasmeasuredbycoronaryangiographyandfractionalflowreserve.JAmCollCardiol200750:51422.

StressPerfusionMRIStudiesinHumansWithCoronaryAngiographyComparison(3of3) Table3c CAD=coronaryarterydiseaseDEMRI=delayedenhancementmagneticresonanceimagingEPI=echoplanarimagingGRE=gradientrecalled echoIR=inversionrecoveryprepulseMRI,magneticresonanceimagingSR=saturationrecoveryprepulseSSFP=steadystatefree precessionNS=notstated.*Numbersbasedonaregionalratherthanperpatientanalysis.


1Whenbothrestandstressimagingwereperformed,theorderisaslisted. 2Prospectivestudieswerethoseinwhichthecriteriafortestabnormalitywereprespecifiedbeforedataanalysis. 3Pilotstudyperformedfirsttodeterminethebestthresholdfortestabnormality. 4Atenrollment,allpatientshadtheclinicaldiagnosisofSTelevation,nonSTelevationmyocardialinfarction,oracutecoronarysyndrome. 5Reportedsensitivityandspecificityarefromafractionofthetotalcohort,asubgroupwiththebestresults. 6Withparallelimagingacceleration. 7Allpatientshadrelevantaorticstenosis. 8Multicentertrialwithfivedifferentcontrastdosesthesensitivity/specificityareestimatesfromreceiveroperatingcharacteristicanalysis,which

isbasedontheresultsfromthegroupwiththeoptimumcontrastdose(n=45). Sensitivity/specificityafterincorporatingDEMRIwere89%and87%,respectively. Sensitivity/specificityafterincorporatingDEMRIwere87%and89%,respectively. #Representsaveragevaluesofthetwoobserversaveragesensitivity/specificityafterincorporatingDEMRIwere92%and54%,respectively. ||Representsaveragesensitivity/specificityoftheentirestudypopulationafterincorporatingDEMRI(algorithmA). DEMRIwasincorporatedinimageanalysis.

References: 28. BurgstahlerC,KunzeM,GawazMP,etal.Adenosinestressfirstpassperfusionforthedetectionofcoronaryarterydiseaseinpatients withaorticstenosis:afeasibilitystudy.IntJCardiovascImaging200824:195200. 29. KleinC,GebkerR,KokocinskiT,etal.Combinedmagneticresonancecoronaryarteryimaging,myocardialperfusionandlategadolinium enhancementinpatientswithsuspectedcoronaryarterydisease.JCardiovascMagnReson200810:45. 30. DoeschC,SeegerA,HoevelbornT,etal.Adenosinestresscardiacmagneticresonanceimagingfortheassessmentofischemicheart disease.ClinResCardiol200897:90512. 31. SchwitterJ,WackerCM,vanRossumAC,etal.MRIMPACT:comparisonofperfusioncardiacmagneticresonancewithsinglephoton emissioncomputed.tomographyforthedetectionofcoronaryarterydiseaseinamulticentre,multivendor,randomizedtrial.EurHeartJ 200829:4809. 32. KlemI,GreulichS,HeitnerJF,etal.Valueofcardiovascularmagneticresonancestressperfusiontestingforthedetectionofcoronary arterydiseaseinwomen.JACCCardiovascImaging20081:43645. 33. KitagawaK,SakumaH,NagataM,etal.DiagnosticaccuracyofstressmyocardialperfusionMRIandlategadoliniumenhancedMRIfor detectingflowlimitingcoronaryarterydisease:amulticenterstudy.EurRadiol200818:280816. 34. BernhardtP,SpiessJ,LevensonB,etal.Combinedassessmentofmyocardialperfusionandlategadoliniumenhancementinpatients afterpercutaneouscoronaryinterventionorbypassgrafts:amulticenterstudyofanintegratedcardiovascularmagneticresonance protocol.JACCCardiovascImaging20092:1292300.

InterpretationAlgorithmforIncorporatingDEMRIWithStressandRestPerfusionMRIfortheDetectionofCAD Figure12 (A)Schemaoftheinterpretationalgorithm.(1)Positivedelayedenhancementmagneticresonanceimaging(DEMRI)study.Hyperenhanced myocardiumconsistentwithapriormyocardialinfarction(MI)isdetected.Doesnotincludeisolatedmidwallorepicardialhyperenhancement, whichcanoccurinnonischemicdisorders.(2)Standardnegativestressstudy.NoevidenceofpriorMIorinducibleperfusiondefects.(3) Standardpositivestressstudy:NoevidenceofpriorMI,butperfusiondefectsarepresentwithadenosinethatareabsentorreducedatrest.(4) Artifactualperfusiondefect:MatchedstressandrestperfusiondefectswithoutevidenceofpriorMIonDEMRI.

(B)Patientexamples.Toprow:PatientwithapositiveDEMRIstudydemonstratinganinfarctintheinferolateralwall(redarrow),although perfusionMRIisnegative.Theinterpretationalgorithm(step1)classifiedthispatientaspositiveforcoronaryarterydisease(CAD).Coronary angiographyverifieddiseaseinacircumflexmarginalartery.CineMRIdemonstratednormalcontractility.Middlerow:PatientwithanegativeDE MRIstudy,butwithaprominentreversibledefectintheanteroseptalwallonperfusionMRI(redarrow).Theinterpretationalgorithm(step3)

classifiedthispatientaspositiveforCAD.Coronaryangiographydemonstratedaproximal95%leftanteriordescendingarterystenosis.Bottom row:Patientwithamatchedstressrestperfusiondefect(bluearrows),butwithoutevidenceofpriorMIonDEMRI.Theinterpretationalgorithm (step4)classifiedtheperfusiondefectsasartifactual.Coronaryangiographydemonstratednormalcoronaryarteries. ReproducedwithpermissionfromKlemI,HeitnerJF,ShahDJ,etal.Improveddetectionofcoronaryarterydiseasebystressperfusion cardiovascularmagneticresonancewiththeuseofdelayedenhancementinfarctionimaging.JAmCollCardiol200647:16308.

ComparisonofExVivo,HighResolutionDelayedEnhancementMRImagesWithAcuteMyocardialNecrosis Figure13 Comparisonofexvivo,highresolutiondelayedenhancementmagneticresonance(MR)imageswithacutemyocardialnecrosisdefined histologicallybytriphenyltetrazoliumchloride(TTC)staining.Notethatthesizeandshapeoftheinfarctedregion(yellowishwhiteregion)defined histologicallybyTTCstainingisnearlyexactlymatchedbythesizeandshapeofthehyperenhanced(bright)regiononthedelayedenhancement image. ModifiedwithpermissionfromKimRJ,FienoDS,ParrishTB,etal.RelationshipofMRIdelayedcontrastenhancementtoirreversibleinjury,infarct age,andcontractilefunction.Circulation1999100:19922002.

RepresentativeDEMRIImagesinPatientsWithChronicMyocardialInfarction Figure14 Bothlarge(toprow)andsmall(bottomrow)infarctsareshown. DEMRI=delayedenhancementmagneticresonanceimaging. ModifiedwithpermissionfromWuE,JuddRM,VargasJD,KlockeFJ,BonowRO,KimRJ.Visualisationofpresence,location,andtransmural extentofhealedQwaveandnonQwavemyocardialinfarction.Lancet2001357:218.

SensitivityofDEMRIforAcuteandChronicMyocardialInfarction Figure15 Thediagnosticsensitivityofdetectingmyocardialinfarction(MI)issummarizedaccordingtogadoversetamidedosegroupandimagingtimepoint. Numbersinparenthesesare95%condenceintervals. DEMRI=delayedenhancementmagneticresonanceimaging. ModifiedwithpermissionfromKimRJ,AlbertTS,WibleJH,etal.Performanceofdelayedenhancementmagneticresonanceimagingwith gadoversetamidecontrastforthedetectionandassessmentofmyocardialinfarction:aninternational,multicenter,doubleblinded,randomized trial.Circulation2008117:62937.

ClinicalApplications (2of2)
HeartFailureandCardiomyopathies Inpatientswithheartfailure,itisimportanttodeterminetheetiologyofheartfailure inordertoappropriatelyplantherapyandprovideprognosticinformation.88Evenin asymptomaticpatientsinwhomsystolicdysfunctionisnotyetevident,early diagnosismayallowpreventivemeasuresthatcanchangethenaturalhistoryofthe disease,andcantriggerfamilyscreeningproceduresingeneticdisorders. Unfortunately,theetiologyofcardiomyopathyisoftendifficulttoascertain,and standardnoninvasiveimagingmaynotbedefinitive. DEMRIisusefulnotonlyfordetectingacuteandchronicMI,andforpredicting functionalimprovementafterrevascularization,butalsoforcharacterizingan extensivearrayofcardiomyopathies.TheutilityofDEMRIinthesettingof cardiomyopathyisbasedontheunderstandingthatratherthansimplymeasuring viability,thepresenceandpatternofhyperenhancementholdsadditional information. Recently,asystematicapproachtointerpretingDEMRIimagesinpatientswith heartfailureorcardiomyopathyhasbeenproposed.89,90Thisapproachisbasedon thefollowingthreesteps: Step1:Thepresenceorabsenceofhyperenhancementisdetermined.Inthesubset ofpatientswithlongstandingsevereischemiccardiomyopathy,thedataindicatethat virtuallyallpatientshavepriorMI.91Theimplicationisthatinpatientswithsevere cardiomyopathy,butwithouthyperenhancement,thediagnosisofidiopathicdilated cardiomyopathyshouldbestronglyconsidered. (Step2):Ifhyperenhancementispresent,thelocationanddistributionof hyperenhancementshouldbeclassifiedasaCADornonCADpattern.To distinguishthesepatterns,theconceptthatischemicinjuryprogressesasa "wavefront"fromthesubendocardiumtotheepicardiumisfundamental.92For example,hyperenhancementpatternsthatsparethesubendocardiumandare limitedtothemiddleorepicardialportionoftheLVwallshouldgenerallybe consideredasnonCAD. (Step3):IfhyperenhancementispresentinanonCADpattern,furtherclassification shouldbeconsidered.Therearenowconsiderabledata,whichdemonstratethat certainnonischemiccardiomyopathieshavepredilectionforspecificscarpatterns. Forinstance,inthesettingofLVhypertrophy,thepresenceofmidwall hyperenhancementinoneorbothjunctionsoftheinterventricularseptumandRV freewallishighlysuggestiveofhypertrophiccardiomyopathy,whereasmidwallor epicardialhyperenhancementintheinferolateralwallisconsistentwithAnderson Fabrydisease.Moreover,insteadofaninfinitevarietyofhyperenhancementpatterns, itappearsthatabroadstratificationispossibleintoalimitednumberofcommon DEMRIphenotypes.Figures16and17illustratepotentialhyperenhancement patternsthatmaybeencounteredinclinicalpractice,alongwithapartiallistoftheir differentialdiagnoses. PericardialDiseaseandCardiacMasses ConstrictivePericarditis Currently,pericardialconstrictionisbestassessedusingacombinationofturbo spinecho93morphologyandSSFPcineimaging(Figure18).Inadditionto conventionalcineimaging,taggedcineMRIandrealtimecineMRImayprovide supplementaryinformation.Withcardiactagging,discretetissuepointscanbe trackedthroughoutthecardiaccycle.ThisisaccomplishedusingRFprepulsesto labeltissue(usuallyatenddiastole)withadarkgridpattern(Figure6).Normally, gridlinesattheinterfacebetweenpericardiumandepicardium(actuallybetween parietalandvisceralpericardium,asthelatterisattachedtotheepicardium)should shearduringsystolesincethetwosurfacesmoveindependentlyandslideduring
Figure16

Figure17

Figure18

Figure6

Figure19

contraction.Conversely,inthesettingofpericardialadhesions,gridlinesatthe interfaceshouldremainintact,asmotionofthetwosurfaceswouldbeconcordant. RealtimecineMRIcanbeusedtodemonstrateincreasedventricular interdependence,ahemodynamichallmarkofpericardialconstriction.94Specifically, abnormalventricularseptalmotiontowardtheLVinearlydiastoleisseenduringthe onsetofinspiration(Figure18).Althoughthenumberofpatientsthathasbeen studiedisquitesmall,thisfindingappearshelpfulindistinguishingbetween constrictivepericarditisandrestrictivecardiomyopathy.94 Masses AlargebodyofliteratureaddressestheutilityofCMRfortheevaluationofcardiac masses.Muchofthisliteratureconcernsattemptstocharacterizedifferenttissues bycomparingimageintensitiesonT1T2,andprotondensityweightedimages. Differentiatingbetweenbenignandmalignantmassesbyimageintensities, however,wasusuallypoor.95Thisapproachtocardiacmasses,whichrelied primarilyonolderSEsequences,shouldnolongerbeusedinclinicalpractice. Instead,atpresent,atypicalprotocolfortheevaluationofacardiacmassshould consistofmultiplepulsesequenceswheretheaimistoassessmorphology, motion,perfusion,anddelayedenhancement,inadditiontoinherentdifferencesin T1andT2(Figure19).Thiscomprehensiveprotocolidentifiesbothnormalvariants oftenmistakenforcardiacmasses(e.g.,eustachianvalve,lipomatousseptal hypertrophy,warfarinridge)andabnormalphysiologicalcharacteristicsofmasses, whichmaypointtoaspecificdiagnosis.Forinstance,perfusionMRImay demonstrateincreasedvascularity,whichmaybeprominentinmalignanciessuch asangiosarcomaDEMRImayidentifyareasoftissuenecrosiswithinthecoreofa malignanttumor,whichappearasareasofhyperenhancement. Othersequencesmayalsobehelpful.Fatcanbeverifiedbyimagingfirstwithout andthenwithfatsaturationtechniques.Simplecystscanbeidentifiedby characteristichighimageintensityonSSFPsequencesorbyDEMRIinamanner similartothatusedtodetectpericardialfluid.Finally,othermorphological characteristicssuchastissueinvasionorcompression,flowobstruction,and associatedpericardialeffusionareimagedbythisprotocol. LeftVentricularThrombus LVthrombusrepresentsanimportantsubsetofcardiacmasses.Althoughmost commonintheLVapex,thrombusmayoccurelsewhere,withpredilectionfor locationswithstagnantbloodflowsuchasadjacenttoakineticinfarcted myocardium.ThepresenceofLVthrombusmaybeapparentoncineMRI,ifthe thrombusisclearlyintracavitary.However,layeredmuralthrombusmaybedifficultto detectsinceimageintensitydifferencesbetweenthrombusandmyocardiumare minimal.9699 RecentstudiessuggestthatDEMRIfollowingcontrastadministrationmaybean improvedmethodfordetectingLVthrombus.Molletetal.reportedthatDEMRI identifiedLVthrombusinsubstantiallymorepatientsthancineMRIortransthoracic echocardiographyhowever,areferencestandardwasnotavailable.96Srichaietal. evaluatedaprotocolcombiningcineMRIandDEMRIforthediagnosisofLV thrombusinpatientswithadvancedischemiccardiomyopathyundergoingsurgical LVreconstruction.97Among160patients(usingareferencestandardthatconsisted ofdirectvisualizationoftheLVcavityduringsurgeryand/orpathological confirmation),CMRshowedhighersensitivityandspecificity(88%and99%, respectively)thantransthoracic(23%,96%)andtransesophagealechocardiography (40%,96%)forthediagnosisofLVthrombus. Weinsaftetal.assessedtheprevalenceofLVthrombusbycineandDEMRIin784 consecutivepatientswithsystolicdysfunction(LVejectionfraction[EF]<50%).98 Amongthisbroadpopulation,DEMRIdetectedthrombusin7%(55patients)and cineMRIin4.7%(37patients),andclinicalfollowupforemboliceventsor pathologicalconfirmationwasconsistentwithDEMRIasabetterreference standardthancineMRI.Interestingly,patientswithischemiccardiomyopathywere morethan5timesmorelikelytohavethrombusthanthosewithnonischemic cardiomyopathydespitesimilarmeanLVEF.Additionally,myocardialscarring,also

detectedbyDEMRI,wasidentifiedasanovelriskfactorforthrombus.Inasecond study,Weinsaftetal.showedthatevenwhensonographiccontrastisroutinely utilized,echocardiographymayfailtoidentifyupto39%ofthrombidetectedbyDE MRI.99Basedonthesedata,DEMRImayrepresentanemerging"goldstandard"for thediagnosisofLVthrombus.

HyperenhancementPatternsThatMayBeEncounteredinClinicalPractice Figure16 Sincemyocardialnecrosisduetocoronaryarterydisease(CAD)progressesasawavefrontfromthesubendocardiumtotheepicardium, hyperenhancement(HE)(ifpresent)shouldalwaysinvolvethesubendocardiuminpatientswithischemicdisease.Isolatedmidwallorepicardial HEstronglysuggestsanonischemicetiology.Additionally,endocardialHEthatoccursglobally(i.e.,throughouttheleftventricle)isuncommon evenwithdiffuseCAD,andtherefore,anonischemicetiologyshouldbeconsidered.HE=hyperenhancement. ReproducedwithpermissionfromShahDJ,KimRJ.MagneticResonanceofMyocardialViability.In:EdelmanRR,HesselinkJ,ZlatkinM.Clinical MagneticResonanceImaging.3rded.NewYork:Elsevier2005.

RepresentativeDelayedEnhancementImagesinPatientsWithVariousNonischemicCardiomyopathies Figure17 Thehyperenhancementpatternsinallpatientsaredistinctlynoncoronaryarterydiseasetype. Dilatedcardiomyopathy(DCM).Arrowspointtoalinearstripeofhyperenhancementthatislimitedtothemidwalloftheinterventricular septum.Hypertrophiccardiomyopathy(HCM).Arrowspointtomultiplefociofhyperenhancement,whicharepredominantlymidmyocardial inlocationandoccurinthehypertrophiedseptumandnotinthelateralleftventricular(LV)freewall.Thejunctionsoftherightventricularfree wallandinterventricularseptumarecommonlyinvolved.Myocarditis.Arrowspointtotwoseparateregionsofhyperenhancement:alinear midwallstripeintheinterventricularseptum,andalargeconfluentregionaffectingtheepicardialhalfoftheLVlateralwall.Amyloidosis. ArrowspointtohyperenhancementaffectingthesubendocardialhalfofthemyocardialwalldiffuselythroughouttheentireLV.

RepresentativeImagesFromaPatientwithPericardialConstriction Figure18 BreathholdcineMRI(singlephaseshown)andT2weightedturbospinecho(TSE)imagingshowsmarkedpericardialthickening(orange arrowheads).RealtimecineMRIdemonstratesdisplacementoftheinterventricularseptum(orangearrows)towardstheleftventricleduring earlyinspiration,consistentwithventricularinterdependence.Thedottedorangelinehighlightsthemovementofthediaphragm.

MRIPulseSequenceStructure Figure6 Themagneticresonanceimaging(MRI)pulsesequencecanbeconsideredascomposedoftwoseparateelements:theimagingengineand modifiers.Typicalimagesusingdifferentimagingenginesandmodifiersareshownatthebottom.Allimagesareofthesameshortaxisspatial location.Seetextforfurtherinformation. ModifiedwithpermissionfromShahDJ,JuddRM,KimRJ.Technologyinsight:MRIofthemyocardium.NatClinPractCardiovascMed20052:597 605.permission.

EvaluationofaCardiacMass Figure19 Theprotocolconsistsof(a)oneormorestacksofsingleshotimagingthatcombinesrapidimageacquisitionwithcomprehensiveanatomic coveragetoquicklydelineatemorphology(b)cineimagingtoviewmotionduringthecardiaccycle(c)firstpassperfusionimagingduringthe transitofanintravenousbolusofgadoliniumcontrastand(d)postcontrastdelayedenhancementmagneticresonanceimaging(DEMRI),which accentuatesdifferencesincontrastuptakebetweenthemassandnormalmyocardiumandbetweendifferentregionsofthemass.Inthispatient withaleftatrialmass(arrows),biopsydemonstratedrecurrentinvasivethymoma(notethatseveralextracardiacmassesarealsopresent). Perfusionisreducedcomparedwithleftventricularmyocardium.Hyperenhancementispresentinaheterogeneousfashion. ReproducedwithpermissionfromFusterV,KimRJ.Frontiersincardiovascularmagneticresonance.Circulation2005112:13544.

KeyPoints
CMRhastheabilitytogeneratesubstantialsofttissuecontrastbecauseofdifferencesintissueT1andT2 (inherentoralteredbycontrastmedia). WorkinginaCMRenvironmentcanposepotentialriskstopatientsandstaff(CMRunsafedevices,nephrogenic systemicfibrosis). AninterpretationalgorithmthatcombinesdatafromperfusionMRIandDEMRIhasbeenintroducedthat substantiallyimprovesthespecificityandaccuracyofrapidvisualassessmentforthedetectionofCAD. CMRprovidesamultifacetedapproachtodiagnosisofvariouscardiacpathophysiologicconditionsbyenabling theassessmentofmorphology,function,perfusion,viability,tissuecharacterization,andbloodflowduringa singlecomprehensiveexamination.

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3.7:HemodynamicEvaluationintheCardiacCatheterizationLaboratory
Author(s): ToddL.Kiefer,MD,PhD J.KevinHarrison,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. 2. 3. 4. 5. Applyprinciplesofhemodynamicevaluationinthecatheterizationlaboratory. Discussnormalhemodynamics. Definehemodynamicevaluationofpathologicstates. Identifyprinciplesforcardiacoutput(CO)evaluation. Describemethodsfordetectingandquantitatingintracardiacshunts.

Introduction
Hemodynamicevaluationofindividualswithcardiacdiseasehasbeenamainstayofcardiaccatheterizationsincethe originaldescriptionsoftheprocedure.1 Overthelastseveraldecades,someoftheoriginaldetailandinsighthastakena secondseattoimaging,specificallytheimagingofcoronaryarteryanatomy.WiththedescriptionbyDr.DeWoodofacute myocardialinfarctioncoronaryangiography,andthesubsequentdevelopmentofpercutaneouscoronaryangioplastyand stenting,theseprocedureshavedominatedthecatheterizationsperformed.2 Detailedhemodynamicevaluationofallpatientshasalwaysbeenimportant,butsomeoperatorslookatthisinformation infrequentlyandbecomeuncomfortablewithanalysisofsuchpatients.Thisbecomesparticularlyproblematicwhen patientspresentwithcomplexformsofheartdiseaseinvolvingbiventricularheartfailureandintracardiacshunts. Hemodynamicsinthecoronarydiseasearenaincludepressuremeasurementsmadeinthedownstreamcoronary vesselsusingthetechniqueoffractionalflowreserve(FFR).HemodynamicandCOinformationremainsthemainstayof stenoticvalvediseaseassessmentandiscriticallyimportantintheevaluationofmyocardialdiseases,including restrictivecardiomyopathiesandhypertrophicobstructivecardiomyopathies.Hemodynamicdataarealsocritically importantintheevaluationofpatientswithprimaryrightheartfailureduetopulmonaryhypertension,whererightheart catheterizationisrequiredfordiagnosis,andwherethecorrectassessmentofpulmonaryvascularresistance(PVR)and rightheartfailureseverityisparticularlyimportantnowthatbettertreatmentsexistforpatientswithpulmonaryarterial hypertension. Theevaluationofpericardialdiseasehasalwaysreliedonhemodynamicevaluation.Overthelastdecade, improvementsinourabilitytodistinguishthisfrommyocardialdiseaseasacauseofheartfailurehasimprovedby notingthechangesinintracardiacpressuresduringtherespiratorycycle.3 Finally,newerpercutaneoustreatmentsfocusingonlessinvasivetreatmentofstructuralheartdiseasedependonthe operatorunderstandingthehemodynamicdetails.Forexample,theappropriatenessandevaluationoftranscatheter valveimplantationforindividualswithaorticvalvestenosis(AS)relyonanindividualoperatorunderstandingthe hemodynamicabnormalities.Estimationoftheseverityofaorticvalveregurgitation(AR)immediatelyfollowingvalve implantationisacriticalstepinthecompletionofthisprocedureandreliesonthehemodynamicevaluationin combinationwithotherimagingtechniques. Thepurposeofthisdiscussionistomakethereaderappreciatethetypicalhemodynamicevaluationofthepatientinthe catheterizationlaboratory,andlearnthenormalmeasurementsaswellasdataonemightobtaininspecificdisease states.Wherepossible,examplesofthesehemodynamicdatawillbeshownintherepresentativefigures.Thelastpart ofthemodulewilloutlinemeasurementsofcardiacflowincludingmeasurementtechniquesforobtainingCO,suchas evaluatingandquantitatingflowmeasurementsinpatientswithintracardiacshunts.

HemodynamicMeasurementTechniques
Theoverwhelmingmajorityofhemodynamicmeasurementstodayareobtainedthroughfluidfilledcatheters.These catheterscanbespecificallyplacedinthevariouscardiacchambers,andinthevenousandarterialsystem,tomake detailedandspecificmeasurements.Thesecatheterstransmittheenergyatthedistalendofthecatheterbackthrough thehydraulicmediumofthesalinecolumnwithinthelumenofthecatheter.Theproximalportofthecatheteristypically attachedbyanotherlengthoffluidfilledtubingtotransmittheintracardiacwaveformenergybacktoatransducer.This transduceristypicallymountedonthesideofthecatheterizationtable.Thetransducerchangesthemechanicalenergyto anelectricalsignal,whichisthereaftersenttoacomputerfordisplayonamonitor.Thisinformationcanthenbedigitally storedand/orprintedforahardcopyreport. Becauseofthelengthofthefluidfilledcathetersystem,thereisaninherentdelayintherecordingofthesepressuresit takessomeshort,butfinitetime,fortheenergytobetransmittedbacktothetransducer.Thisdelaycanberecognizedif onesimultaneouslycomparesthefluidfilledcatheter,withonehavingadirectpressuretransduceratthedistaltipofa catheter.Simultaneousrecordingfromthetwocatheterswillallowonetoquantitatethisdelayintime.Fromapractical pointofview,thisdoesnotaltertheclinicalassessmentofthepatient.However,somethingthatinterfereswiththe transmissionoftheenergytothetransducerwillinterferewiththesepressuremeasurements.Thisismostcommonly seenwhenasmallamountofairispresentwithinthefluidfilledsystemanywherebetweenthedistalcatheterandthe transducer,resultinginadampingofthesubsequentwaveforms. Similarly,ifoneleavescontrastinthecatheterlumen,theviscousnatureofthisfluidwilldampenthephasicresponseof thehemodynamicsignalobtained.Attimes,cathetermovementwithintheheartcanresultinnonphysiologicswingsin thepressuresignal.Someoperatorswillpurposelyusecontrastmediatoartificiallydampenthisfluctuation.Inmost monitoringsystems,therearelowpasselectronicfiltersonthecomputersystemswhichelectronicallysmooththesignal byremovinghigherfrequencynoise.Theoperatorneedstobeawarewhenthesefiltersarebeingusedsothattrue phasicchangesinthepressuresarenoterroneouslysmoothedbysuchanelectronicfilter. Thesetupofthetransducersisalsoimportantinmakingsurethattheabsolutequantitativemeasurementsareaccurate. Thisinvolvesmakingsurethatthetransducersareproperlysealedandzeroed.Forfluidfilledsystems,thisis accomplishedbyplacingthetransducerheightattheleveloftheaxillaryline(rightatrium[RA])onthecatheterization table.Theoperatorshouldthenpositionthefluidfilledtubingfromthetransduceratthelevelofthemidaxillaryline.At thislevel,thetransducerlinesshouldbeopentotheatmosphere,andthispressurevalueshouldbenormalizedtobe zeropressure.Whenoneisusingmultipletransducers,allofthetransducersshouldbesimultaneouslyzeroedinthis fashionatthelevelofthemidaxillaryline. Forcasesthatarelengthy,forexamplelongerthan1hour,itisoftenusefultomakesurethatthereisnotadriftofthis zeropointbyoccasionallyrecheckingthezeropointforthetransducersbeingused.Thisisparticularlyimportantwhen smallchangesinthepressurearecriticaltotheevaluationofthepatient,suchasevaluationofapatientwithmitralvalve stenosis.Forthesepatients,simultaneousmeasurementofleftatrial(LA)orpulmonarycapillarywedgepressure (PCWP)andtheleftventricular(LV)diastolicpressuresoftendifferbyonlyafewmillimetersofmercury,andsmallerrors canresultinadifferenceinthegradientsobtainedandintheclinicaldecisionmaking. Theotheralternativeinsuchcasesistoswitchtransducersbetweenthetwocathetersbeingevaluated.Ifswitchingthe cathetersgivesanidenticalpressuredifference,theoperatorcanbereassuredthatthepressuremeasurementsare accurate.Forexample,inthepatientwithmitralstenosis(MS),iftheoperatorisusingtransducer#1ontheLVpigtail catheterandtransducer#2ontheLAcatheter,thenswitchingtransducer#2totheLVpigtailcatheterandtransducer#1 totheLAcathetershouldyieldthesamepressuredifferenceifthetransducersareaccuratelyzeroed. Directtransductionoftheintracardiacandintravascularpressurescanbeobtainedbycathetersthataremanufactured withatransducerimplantedonthedistaltipofthecatheter.Thistypeofacathetereliminatesthedelayinthetransduction oftheenergytotheelectricalsignal.Italsoeliminatestheissueofcatheterwhipandotherartifactsencounteredinthe fluidfilledsystems.Despitetheseadvantages,suchcathetersarerarelyusedinclinicalpractice,astheyarelargerin diameter,requiringlargersheathsforinsertion,andaremoreexpensivethanthedisposablecathetersineveryday clinicaluse.Forthisreason,thesehighfidelitytransducertippedcathetersaretypicallyreservedforresearchpurposes, whenextremelyaccuratehemodynamicmeasurementsarerequired. Overthelastseveralyears,thefourteenthousandths(0.014)inchcoronarypressurewirehasgainedcommonclinical useinthecatheterizationlaboratory.Thiswireemploysadistaltippedtransducer,whichusesanonfluidfilledsystemto obtainepicardialintracoronarypressures.Thiswirecontainsanopticalmicrofiber,whichrunsthroughouttheinnercore ofthewire.Mechanicalenergyintheformofpressurefromthevascularspace,wherethedistaltipofthewireresides, alterstheopticalsignalinthemicrofiber,andthisalterationinopticalenergyistransducedintoapressuresignalandis displayedontheoutputmonitor. Toaccuratelyusethissystem,onemustnormalizethesignalagainstaknownpressuresignal.Thisnormalizationis accomplishedbyadjustingthispressuresignaltobeequaltoasimultaneouslyobtainedpressuresignalinthesame

location.Asapracticalexample,themostcommonwayofachievingnormalizationistoplacethecoronarypressurewire withinacoronaryguidecatheter.Thecoronarypressurewireisadvancedtothetipofthecoronaryguidecatheterwhile bothareresidingintheascendingaorta.Thecoronarywirepressuresignalisthencomparedtothefluidfilledguide catheterpressuresignal,andthecoronarypressurewiresignalisadjustedor"normalized"tobeidenticaltothefluid filledguidecatheterpressuresignal.Afterthisisaccomplished,the0.014inchpressureguidewirecanbeadvancedinto thecoronaryarteryinquestionandtheFFRmeasurementscanbeobtained.4,5 Last,this0.014inchpressurewirecanbeusedformeasurementofpressureselsewhereinthevascularspace,outside ofthecoronaryvascularbed.Forexample,itsusehasbeendescribedinthemeasurementofprostheticvalve gradients.6 Theoperatorshouldbespecificallycautionedthatthetechniquespublishedforthisuseneedtobe specificallyfollowedinordertoobtainaccuratemeasurementsofprostheticvalvegradientswiththiswiretransducer. Additionally,thecommerciallyavailablesoftwareoutputisirrelevantoutsidetheuseinthecoronaryvascularbedandcan beclinicallymisleadingiftheoperatorweretointerpretmeanpressuredifferencesonthesoftwareoutputscreenas beingrelatedtomeanpressuredifferencesinvalvegradients.

NormalIntracardiacPressureMeasurements
Cardiaccatheterizationallowstheoperatortoplacethedistaltipofthecatheterina specificvascularlocation,andtherefore,obtaindetailedpressuremeasurementsat thatparticularplace.Thebasicpremiseofintracardiacpressuresisthatanytimea chamberisfillingwithbloodvolumeordecreasingincapacityduringcontraction,the pressureinthatchamberwillincrease.Conversely,whenthepressureinaspecific chamberisdecreasing,thisisduetothechamberhavinglessbloodvolumeor whenthechambersizeisincreasingincapacityduetomyocardialrelaxation.The phasicchangesinthefourchambersoftheheartwillbedescribedbrieflytoexplain thephysiologicalterationsinthesepressures(Figure1). Normally,theRApressuretracinghasthreepositivedeflectionsandtwonegative inflections.ThepositivedeflectionsaretypicallydescribedasA,C,andVwaves.The Awaverepresentsatrialcontraction,whichtransientlyincreasesthepressureinthe RAduetoatrialsystole.TheCwavepositivepressuredeflectionoccursatthe beginningofventricularsystolewithtricuspidvalve(TV)closureduetoaslight decreaseintheRAchambercapacityastheTVannulusmovestowardtheRA inflow. Thelastpositivedeflection,theVwave,isduetotheRAfillingwithbloodfromthe venacavaeandthecoronarysinus.ThisincreaseinbloodvolumeintheRAduring ventricularsystolecausesanincreaseintheRApressure,theVwave,justpriorto theTVopening.WhentheTVopens,thereisarapidinfluxofbloodintotheright ventricle(RV),causingamarkeddecreaseofbloodvolumeintheRAchamberand resultinginthenegativedeflectionintheRApressureknownastheYdescent.The othernegativedeflectionintheRAtracing,theXdescent,occursimmediately followingtheAandCpositivedeflectionsintheRApressuretracing.TheXdescent intheRApressuretracingisduetothechamberenlargementduringatrialdiastole andthemovementoftheatrialannulustowardtheRVduringventricularsystole. IntheLA,fillingoftheatriumisduetopulmonaryvenous,ratherthancaval,return, andemptyingoftheLAisthroughthemitralvalve(MV)ratherthantheTV. Nevertheless,thephasicdeflectionsarequitesimilar.Theabsolutemagnitudeof theLApressureisnormallyhigherthantheRApressures.MeanRApressuresof5 mmHgarenormal,whereasmeanLApressuresof12mmHgarenormal.The higherpressuresintheLAareprimarilyduetothedecreasedcomplianceoftheLA comparedtotheRA.Inturn,theRApressuretracingsareprimarilygovernedbythe diastoliccapacitance/complianceoftherespectiveventricles,theRVbeingmore compliantthantheLV. Inaddition,theLAcapacitance/complianceisinfluencedbyanatomyitisconfined morethantheRA.TheLAispositionedasthemostposteriorstructurewithinthe heart,confinedanteriorlyandinferiorlybythegreatvesselsandtheLV,respectively, andconfinedposteriorlybytheposteriorchestwallandspine.Thiscompliance differenceisreflectedinalargerVwaveintheLAversustheRA.Normally,theA waveisgreaterthantheVwaveintheRApressuretracing,withtheopposite occurringintheLApressuretracing. Theventricularpressurechambertracingshaveaveryrecognizablemarkedly positivedeflectionduringsystolicventricularejection.Thepressureisisovolumic oncetheventricularpressureexceedstheatrialpressureandcontinuestoriseuntil thesemilunarvalveopensintotherespectivepulmonaryartery(PA)oraorticartery. Normally,intheRV,thispressurerisestoapproximately20mmHgfromtheend diastolicpressure(EDP)ofapproximately5mmHg.ThesystolicejectionintheRV continuesthroughoutventricularejectionandthen,withtheonsetofventricular diastole,theRVpressureplummetsbacktonearzeroduringearlydiastole. Ventriculardiastolecanbecharacterizedbyanearlyfillingphase(primarilygoverned byactiverelaxation)andalatefillingphase(primarilyrelatedtoventricular compliance).Duringventriculardiastole,theRVisfillingviatheTVinflowand,after therapidearlyfilling,theRVdiastolicpressuregraduallyincreases.Thereisasmall positivedeflection(Awave)inlatediastole,representingthepressuregenerated fromtheRAcontraction.Immediatelythereafter,ventricularsystoleensuesandthe cyclerepeats.

Figure1

TheLVpressuretracingissimilarinmorphologytotheRVpressuretracingbut differsintermsofthemagnitudeofthepressure.ThemaximalLVsystolicpressure normallyexceeds100mmHg,andtheLVdiastolicpressureisnormally1012mm HgcomparedtoanEDPofapproximately5mmHgintheRV.Thedurationofthe systolicejectionperiodislonger,comparingtheRVtracingstotheLVtracings, owingtothePVRbeingapproximately10%ofthesystemic.TheRVbeginstoeject earlier(duetotheearlieropeningofthepulmonaryvalve[PV]atlowerpressure)and continuestoejectlongerthantheLV(duetocontinuationofforwardflowintothe pulmonarycircuitevenasRVdiastolebegins). ThiscontinuationofforwardpulmonaryflowisduetotheextremelylowPVR.This continuationofflowcausesadifferencebetweentheclosuretimingofthePVand aorticvalve(AV).Thegapistermed"hangout,"anditresultsinthefamiliar auscultatoryP2 followingA2 ornormalsplittingofthesecondheartsound. Furthermore,thehigherdiastolicpressuresoftheLVcomparedtotheRVaredueto thedecreasedcomplianceoftheLVcomparedtotheRV.

NormalHemodynamics Figure1 AoS=aorticsystolicpressureAoD=aorticdiastolicpressureESP=endsystolicpressureLA=leftatriumPA=pulmonaryarteryPAD= pulmonaryarterydiastolicPAS=pulmonaryarterysystolicPCW=pulmonarycapillarywedgeRA=rightatriumRV=rightventricle. ModifiedwithpermissionfromBashoreTM.Clinicalhemodynamicsinvalvulardisease.In:WangA,BashoreTM,eds.ContemporaryCardiology: ValvularHeartDisease.NewYork:HumanaPress2009:93122.

ValvularHeartDisease (1of2)
Hemodynamicevaluationofvalvularheartdisease,especiallystenoticvalve disease,hasservedasthe"goldstandard"forseverityquantification.Thissection willdescribethecommonvalvularlesionsandthehemodynamicfindingstypically associatedwiththoseconditions. RegurgitantValveDisease Regurgitantvalvelesionsaretypicallyassessedusingacombinationof hemodynamicsandimagingtechniquesincludingcineangiography.The angiographicassessmentoftheseverityofregurgitationisgenerallypoor.Two methodsareinuse,includingavisualmethodandasemiquantitativemethod. Thetraditionalvisualmethodutilizestherelativecontrastdensityobservedbetween thechamberorvesselinjectedandthechamberorvesselintowhichthe regurgitationflows.Forinstance,inAR,theaorticrootisinjectedandtheLVreceives theregurgitantflow.Usingthismethod,theseverityofregurgitationisgradedfrom 1+to4+.Ifatanytimeduringthecardiaccycle,thedensityofcontrastisequalin boththeinjectedandreceivingimages,theamountofregurgitationisgraded3+. Theamountofregurgitationisgradedas4+ifthereceivingchamberopacificationis greaterthantheinjectedchamber.Grade1+suggestsatrivialamountand2+refers toanamountbetween1+and3+.Thisisobviouslyaverygrossmeasureand dependsonmanyfactorsbesidestheseverityofregurgitation,includingrateof injection,theamountofcontrast,thesizeoftheinjectedandrecipientchambers,the presenceofothervalvularlesions,andtheCO. Thesecondmethodofestimatingregurgitantflowinthecardiaccatheterization reliesontheangiographicmeasurementoftheLVstrokevolume.Bycomparingthe LVangiographicstrokevolumewiththecalculatedstrokevolumefromeitherthe thermodilutionorFickoutputs,onecandeterminearegurgitantfraction.For instance,inAR,iftheforwardstrokevolumeis200ccbyFickandtheangiographic strokevolumeis300cc,thentheregurgitantvolumeis100ccandtheregurgitant fraction=100/300or33%.Thesemeasurementsrequireangiographicvolume determinationsandcanonlybeappliedifthereisasingleregurgitantvalve,asitis notpossibletoseparatetheamountsofregurgitationpervalvewhentwovalvesare leaking. Fromhereon,themodulewillfocusonthehemodynamicconsequencesofvalvular disease.Forexample,ARoftenwillelevatetheLVfillingpressures.Theregurgitant bloodenteringtheLVfromtheaortaindiastoleincreasesthebloodvolumeintheLV chamber,andthus,theLVEDPincreases.Themagnitudeofthiselevationdepends onthemagnitudeoftheARandalsoonthecapacitanceoftheLV(Figure2). AcuteARmaymarkedlyelevatetheLVEDP.ThesamemagnitudeofARmayonly mildlyelevatetheLVdiastolicpressureinthechronicsetting.Inthelattersituation, theLVchamberincreasesinvolume,anditscapacitance/compliancethereforeis greater.ThewideaorticpulsepressuretypicalofpatientswithchronicARisoften absentinindividualswithacuteAR.InchronicAR,theforwardstrokevolumeis maintainedwithLVdilationsuchthatthetotalstrokevolumeejectedintothe ascendingaortaislarge.Thiscausesamarkedincreaseintheaorticsystolic pressure,followedbyarapiddeclineinpressureindiastoleastheincompetentAV allowsbloodtoflowbackintotheLV.Resultantaorticpressuresof160/40mmHg arenotuncommon. Peripheralpressures,suchasfemoralarterypressuresorradialarterypressures, measuredinsuchindividualsmayevenbemoremarkedlyabnormal,withsystolic pressuresinthedistalsystemicvasculatureexceedingsystolicpressurescentrally byasmuchas40mmHg(Hill'ssign).Thisisduetothelargestrokevolumeadding tothereflectedwavesfromtheperipheralvascularbedduringsystole.InacuteAR, suchmarkedpulsepressurefluctuationsintheaortaareuncommon,astheheart hasnotcompensatedandstrokevolumeisonlymarginallyincreased.WhenAR occursacutely,thehearttypicallycompensatesforthisproblembyincreasingheart rates.Insuchpatients,narrowpulsepressuresintheaortictracingmaybepresent,

Figure2

Figure3

Figure4

andthisshouldnotdissuadetheoperatorfromunderestimatingthetruemagnitude oftheAR. Thehemodynamicsofmitralregurgitation(MR)aremostreadilyapparentby examiningLAtracings.Mostoften,operatorsuseasurrogateoftheLApressure,the PCWP.Thecharacteristicfindingisalargeor"giant"Vwave.Thesemarkedpositive pressuredeflectionsoccurringduringventricularsystoleareduetotheejectionofLV bloodfromtheLVintotheLA(Figure3).When"giant"Vwavesarepresentdueto MR,theCandVwavesfusetoformonelargepositivedeflection.Themagnitudeof theVwavedoesnotdependsolelyonthemagnitudeofMR.Itisalsodependenton thecomplianceoftheLA.ForagivenamountofMR,theVwaveismuchgreaterina patientwithanoncompliantLAthanitisinapatientwithacomplaintLAchamber. SimilartoAR,thecomplianceoftheLAmay,inpart,berelatedtotheacuityofthe MR.ApatientwithsevereacuteMRtypicallyexhibitsaverylargeVwaveintheLAor thePCWtracing,reflectingthefactthattheLAhashadinsufficienttimetodilateand enlargetoincreaseitscompliance. ThesamemagnitudeofMRinapatientwithchronicregurgitation,maynot demonstratemuchofaVwaveatallduetoamarkedlyenlargedandmore compliantLA.ThisLAcomplianceisalsogovernedinlargepartbytheLV compliance.Thus,thepatientwithalowLVEDPmayhavearelativelymodestV waveinthepresenceofsevereMR,whereasthepatientwithhighLVEDPcausing poorLAcompliancemayhaveamuchmoreimpressiveVwaveintheLApressure tracing.DiuresisthatdecreasestheLVEDP,increasesthecomplianceoftheleft heart,andmaydecreasethemagnitudeoftheVwave.Volumeloadinginthesame individualmayincreasethemagnitudeoftheVwavebydecreasingthecompliance ofthiscircuitandcausingamuchlargermagnitudeVwaveforagivenamountof MR. AtrialfibrillationisanothercommonscenariothatwillalterthemagnitudeoftheV wavewithoutchangingthemagnitudeoftheMR.Patientsinatrialfibrillationtendto haveamuchlargermagnitudeVwaveforagivenamountofMRthanpatientsin sinusrhythm.Inatrialfibrillation,thereisnoatrialsystole,andtherefore,noatrial diastolethus,theatriumislesscompliant.Specifically,duringventricularsystole whenMRisoccurring,thoseindividualsinsinusrhythmhavejustdecreasedtheir atrialvolumetoaminimumasatrialsystoleandcontractionhasjustoccurred,and theatriumisgoingintoactivediastolicrelaxation.Thisdoesnothappeninpatients withatrialfibrillation,astheatriumisalreadyfilledandlesscompliantduring ventricularsystole.ThisresultsinahigherVwaveforagivenamountofMRin individualsinatrialfibrillation. Theoperatorshouldalsorealizethata"giant"Vwavecanoccasionallybepresent evenintheabsenceofMR.Themostcommonexampleofthisisacuteventricular septalruptureduetoacutemyocardialinfarction.Inthissituation,theLVhashigh diastolicfillingpressuresduetoacombinationoftheischemiceventandacute volumeloadontheventricle.Acutely,thismakesthecombinedLVandLA compliancepoor.Thisoccursinthesettingofhighpulmonarybloodflowduetothe ventricularseptaldefect,whichreturnstheshuntedbloodtothepulmonaryvenous circuitandtheLA,andconsequently,increasespressureswithintheLA,causing marked"giant"VwavesintheLApressuretracingsintheabsenceofMR. RegurgitantlesionsoftheTVandPVareevaluatedlessfrequentlyinthe catheterizationlaboratory,butthereareimportantspecificissuestodiscusswith respecttotheselesions.Severepulmonaryvalveregurgitation(PR)maysometimes bebestappreciatedinthecatheterizationlaboratory.IfRVcomplianceispoor(asin tetralogyofFallot),PRmaygorelativelyundetectedbyphysicalexaminationand echocardiographicevaluationduetotherapidequalizationofpressuresbetween thePAandtheRV. TheevaluationofPRrequirestheplacementoftworightheartcatheters simultaneously.OnecatheterispositionedinthePAcephalicofthePVandthe secondcatheterisplacedintheRV.ThisallowstheoperatortolookforanyRV outflowtractobstructionbeloworatinsystolethelevelofthePV.Moreimportantly, however,theoperatorcancomparethesimultaneouslyobtaineddiastolicpressures carefully.DuringdiastoleinanormallyfunctioningPV,therewillbepreservationof thepressuredifferencebetweenthePAtracingandtheRVtracing.Thatis,thePA diastolicpressurewillbenormallylowat1015mmHg,buttherewillbearapid

separationofthePAandtheRVpressurecurvesduringearlydiastole,whichwillbe maintainedthroughoutthediastolicinterval(Figure4).InpatientswithseverePR, thesepressuresduringlatediastolewillbenearlyidentical.Thisfindingistypically associatedwithanincreaseintheRVEDP>10mmHgandisdiagnosticofsevere PRandRVfailure. Thehemodynamicevaluationoftricuspidregurgitation(TR)reliesonthe examinationoftheRApressuretracing.Intheseindividuals,alargeVwaveinthe RApressuretracingisindicativeofTR.LikeMR,themagnitudeofVwaveintheRA pressuretracingisrelatedtothemagnitudeofthevalveregurgitation,butalsois influencedbythevolumestatusofthepatientandthepresenceorabsenceofatrial fibrillation.WhenalargeVwaveispresentintheRApressuretracing,especially whenassociatedwithanoverallincreaseinthemagnitudeofthemeanRA pressure,thisisindicativeofTRassociatedwithRVfailure. RVfunctionisdifficulttoassessclinically,andincreasesinRVdiastolicpressures areimportanttonote.IncreasesinRVdiastolicpressuresoverthenormal5mmHg indicatethatanormallyverycompliantRVisfailing.WhenisolatedTRresultsinRV failure,theelevationoftheRApressureisapoorprognosticsignandisan indicationforaggressivetreatmentofthislesion.IsolatedTRmayoccurdueto dilationoftheatriumthatstretchesthetricuspidannulus.TRresultsinavolume overloadtotheRV.RVdilationfromthevolumeoverloadcausesafurtherincrease inTRseverity,whichcanresultinamalignantcycleculminatinginworseningTR andRVfailure.Fromahemodynamicpointofview,themainissuestonotewithTR arethemagnitudeoftheVwave,theoverallmagnitudeoftheRApressure,andthe RVEDP. StenoticValvularDisease Theseverityofstenoticvalvularlesionsisoftenestimatedbycardiac echocardiography,includingDopplervelocitymeasurements.Thesemeasurements haveimprovedoverthelasttwodecades.Nevertheless,thetrueevaluationofvalve stenosisseverityismostaccuratelyassessedbyhemodynamicevaluationinthe catheterizationlaboratory.Leftsidedstenoticvalvegradientsareassessedin additiontotheassociatedhemodynamicchangeswithintheheartduetothese lesions,themagnitudeofthePVRandassociatedpulmonaryhypertension,andthe presenceofRVfailure. WithAS,theseverityofthisvalvelesionisassessedbydirectmeasurementofthe LVpressurecomparedtotheascendingaorticpressure.Thiscanbemeasured usingtwocatheters,iftwoarterialaccesssitesarepresent.Alternatively,thefemoral arterypressurecanbecomparedtotheLVpressure.Thisisasurrogatefor simultaneousLVandascendingaorticpressuretracings.Mostcommonly,an operatorwillcompareLVpressuretracingtoafemoralarterypressuretracing obtainedthroughthevascularinsertionsheath.Ifoneusesthistechnique,the operatormustensurethesheathlumenisnotobstructedbythecatheterthatis insertedthroughit.Thisistypicallyaccomplishedbyusingasheaththatisone FrenchsizegreaterthanthecathetermeasuringtheLVpressure. WhenmeasuringLVversusfemoralarterypressure,theoperatorshouldalso realizethatthereisatemporaldelayinthefemoralarterytracingcomparedtotheLV tracing.ThefemoraltracingmustthereforebealignedwiththeupstrokeoftheLV tracingtoallowforthisdelay.Thereisalsoperipheralpulseamplificationdueto reflectedwaves,whichtendstomakethefemoralarterypeaksystolicpressure greaterthantheascendingaorticsystolicpressure.Thistendstounderestimatethe trueAVpressuregradientduringmidtolatesystole. IftheoperatorusesthetechniqueofcomparingthefemoralarterypressuretotheLV pressure,themostaccuratewayofdeterminingthetruepressuregradientisto subsequentlypullbackthepigtailcatheterintotheascendingaortaandrecordthe simultaneousascendingaorticpressureandfemoralarterypressurewithnotation ofthegradientfromthefemoralarterytotheascendingaorta.Thisallowsthe operator,attheendoftheprocedure,totransposethetwosetsofpressuresusinga transparencytogetanestimateoftheLVpressureversusascendingaortic pressuregradient. Finally,someoperatorsdonotmeasuresimultaneouspressuresatall,butsimply

doapullbackfromtheLVtotheascendingaorta.Ifthistechniqueisdone,then transposingtheaorticpressuregradientagainsttheLVpressuretracingis necessarytodocumenttheAVpressuregradient.

AcuteandChronicAorticRegurgitation Figure2 Theleftpanelschematicallydemonstrateschronicaorticregurgitationwithawideaorticpulsepressureandnormalleftventricleendsystolic pressure(LVEDP).Therightpaneldemonstratesacuteaorticregurgitationwithanormalpulsepressure,amarkedlyelevatedLVEDPand narrowingoftheaorticdiastolicpressureandtheLVEDP. Ao=aortaLV=leftventricleLVEDP=leftventricleendsystolicpressure.

AcuteandChronicMitralRegurgitation Figure3 Inchronicmitralregurgitation(rightpanel)theVwaveintheleftatrium(LA)maynotbehighduetochronicLAenlargementandimproved compliancefromremodeling.TheLVEDPisoftennormalaswellduetosimilarleftventricle(LV)compensationforthevolumeoverload.Inacute mitralregurgitation(leftpanel),neithertheLAortheLVhashadtimetocompensate,andboththeVwaveandtheLVEDPareelevated. Ao=aortaLA=leftatrialLV=leftventricleLVEDP=leftventricleendsystolicpressureMR=mitralregurgitation.

LowPressurePulmonaryRegurgitation Figure4 Severepulmonaryregurgitationisnotedwithequalizationoftherightventricleandpulmonaryarteryenddiastolicpressuresfromacasewith tetralogyofFallotstatuspostatransannularpatchandfreeflowingpulmonaryregurgitation.Someresidualpulmonarygradientisalsoevident. PA=pulmonaryarteryRV=rightventricle.

ValvularHeartDisease (2of2)
Morecommonly,aduallumenfluidfilledcatheterisclinicallyemployed,which allowsfortheascendingaortaLVgradienttobesimultaneouslydefined.Thisis accomplishedbyusinga6Frenchcatheter,whichhasanendholeandsideholes atthedistalpigtailtip.Asecondlumenwithinthis6Frenchcatheterhasasingle sideholeapproximately10cmproximaltothedistalpigtailtip.Thislumenallowsa separate,independentpressuremeasurement.Oncethiscatheterisinsertedinto theLVacrossastenoticAV,theoperatorcanmeasuresimultaneousLVandaortic pressuremeasurementsusingtwofluidfilledtransducers. Finally,themostaccuratemeasurementofthisvalvegradientisaccomplishedby highfidelitypressuretransducersthataremountedonasinglecatheter.These typesofcatheters,manufacturedbyMillar,areavailable,butnotroutinelyused.This catheterhastwotransducersonemountednearthetipofthepigtail,whichcanbe positionedintheLV,andonemountedmoreproximallyonthecathetersuchthatits transducersitsintheascendingaorta.Thisallowstheoperatortogetverydetailed measurementsoftheLVoutflowpressuregradient. ExaminingthispressuredifferenceinsystoleinpatientswithASyieldsthree differentcommonlyreportedpressuredifferences(Figure5).Thefirstisthepeakto peakpressuregradient.Thismeasurementcanbeobtainedbysimplynotingthe peakLVpressureinsystoleandthepeakascendingaorticpressureduringsystole. Thepeaktopeakgradientisnotatruephysiologicgradientaspeakaorticandpeak LVpressuresdonotoccursimultaneously,butitcameintousewhenaortic gradientswereassessedmostlyviathepullbackmethoddescribedearlier. Thesecondmeasurementisthepeakinstantaneouspressuredifferenceduring ventricularsystole.Thisisthegreatestmagnitudeofthepressuredifference betweentheLVandtheaortaatasingleinstantduringventricularsystoleandis relatedtothepeakinstantaneousormaximumDopplervelocitymeasuredby echocardiographictechniques. Thethirdmeasurementisthemeanvalvegradient.Thisresultscomesfrom integrationoftheinstantaneouspressuresduringthetimeofsystolicejection.This iscloselyrelatedtothemeanpressureestimatedbyDopplerechocardiography.7 InadditiontorecordingaccuratetransvalvulargradientsacrossastenoticAV, catheterizationyieldsdataforcalculationstoprovideanestimateoftheaffectedvalve area.Toconvertthepressuregradientdatatovalvearea,onemustestimatetheCO. Thiscanbeestimatedbymeasuringthearterialvenousoxygendifference(Fick method)orbythermodilution. OncetheCOisdetermined,thenthegoldstandardforcalculatingtheaffectedvalve areaistousetheGorlinequation.8 Theamountofflowacrossthevalveduring1 minuteisthenumeratorofthisequationandisdeterminedbytheCOin liters/minutedividedbytheproductoftheheartratetimesthesystolicejectiontime. Thisresultisthendividedbyagravitationalconstant(44.3)timesthesquarerootof themeantransvalvulargradient.InMS,thediastolicflowisrequiredin1minuteand isdefinedbytheCOinliters/minutedividedbytheproductoftheheartratetimesthe diastolicfillingtime.Whentested,a"fudgefactor"wasrequiredtomaketheMSdata moreaccurate,andthe44.3constantwaschangedto0.85x44.3(37.7). AsimpleralternativetotheGorlinequationistheHakkiequation.9 TheHakki equationalsorequiresanestimateoftheCOtypicallymadebyaFickmethod calculationorathermodilutionestimate.Thisisthenumeratorandtheonlyother variableinthedenominatoristhesquarerootofthemeantransvalvularpressure gradient.TheoriginalHakkiequationusedapeaktopeakgradientmeasuredat catheterization,butthemeanpressuregradientispreferred.TheGorlinvalvearea measurementandtheHakkivalveareameasurementarequitecloseintermsof theirestimateofaorticvalvearea.Aorticvalveareacalculations<0.8cm2 or<0.6 cm2 /m2 aretypicallyconsideredindicativeofsevereAS.10Valveareas0.81.2cm2 aretypicallyconsideredmoderateAS.Valveareas>1.2cm2 areconsidered

Figure5

Figure6

indicativeofmildAS.Meanwhile,forMS,valveareas11.5cm2 areconsidered moderatestenosisand<1cm2 areconsideredseverestenosis.10 AcoupleofpracticalconsiderationsareworthnotingwithregardtoAS.Thefirstis thatthetechniqueofcrossingstenoticAVsisundertaught.Overthelastdecade, therehavebeenreportsofadverseeventswithcrossingstenoticAVs.11Inaddition, echocardiographicpredictorsofASseverityhaveimprovedusingDoppler techniques.Oneshouldemphasize,however,thattherearetechniquesforsafe, rapid,andeffectivecrossingofstenoticAVs.12Thisinvolvestheuseofastraight, softtipped0.035inchguidewiredirectedinadeliberatefashionthroughthestenotic valveusingmanipulationofanAL1oraJR4coronarycatheter.Occasionally,larger ALcurvesarehelpfulinpatientswithdilationoftheascendingaorta. Whileechocardiographyhasshowngreatclinicalutilityforthediagnosisand estimationofASseverity,echocardiographyoftenunderestimatesthetrueaortic valveareabasedontechnicallimitationsandmathematicalconsiderations.13There arealsotimeswhenmeasurementsofLVpressures(e.g.,concomitantMS)are critical,orcomplimentaryimagingofMRisrequiredwithleftventriculographyin patientswithAS.Catheterizationexpertsshouldbeskilledinthetechniqueof retrogradecrossingforpatientswithstenoticAVsandinvasiveevaluation consideredforpatientswherethestenosisseverityisinquestionbasedonDoppler echocardiography,orisdiscordantwiththepatient'slevelofsymptomatic impairmentorotherdata. MostcasesofobstructiontoLVoutflowareduetovalvularaorticstenosis.However, thereareothersituationswhereobstructionofLVoutflowispresentdespitenormal AVfunction.Themostcommonoftheseinvolveshypertrophicobstructive cardiomyopathywheremuscularobstructiontoLVoutflowispresentduringsystole. Lesscommonly,membranousobstruction,beloworabovetheAVplane,maybe presentinpatientswithcongenitaldisease.Intheseinstances,itisimportantto measuresimultaneouspressurescaudaltoandcephaladtothelevelofthe stenosis.PullbackmeasurementsfromtheLVapextotheascendingaortaare helpfulindocumentingthelevelandtheseverityoftheobstruction.Forfluidfilled disposablecatheters,itisimportanttouseendholecatheterstodocumentthelevel ofobstruction.Pigtailcatheterswithmultiplesideholesmaycauseinaccurate pressuregradients,astheymaygiveamixedpressuremeasurement,including pressuresaboveandbelowthelevelofthestenoticlesion. MSishemodynamicallyevaluatedinasimilarfashiontoAS.Anestimateofmitral valveorificeareacanalsobemadeusingtheGorlinequationortheHakkiequation estimatedasnotedabove.Typically,thehemodynamicpressuregradientis measuredbetweenthePCWPandtheLVpressure.Inthesecases,thediastolic interval(diastolicfillingperiod)istheintervalofinterest.WithoutMS,theLApressure oritssurrogate,thePCWP,shoulddroppromptlyindiastoleandfollowtheLVEDP. InthepresenceofMS,themeanLApressureiselevated,andapressuredifference persistsindiastolebetweentheLAandtheLV. Intermsofpracticalconsiderations,thePCWPmeasurementismucheasierto achievethanadirectmeasurementoftheLApressure.Inrarecases,transseptal needlepunctureoftheLAisrequiredifdirectLApressuremeasurementisneeded. WhileLApressuremeasurementsaremoreaccurateinthedeterminationofthe severityofmitralvalvepressuregradients,PCWPsaremeasuredmuchmore commonly.PCWPtimingisslightlylaterthanLAtimingandincreasesthearea betweentheLVpressureversusthePCWP,leadingtooverestimationofMSseverity unlessthepressuretracingissetback.ThisisusuallydonebyaligningthePCWP tracingVwavewiththedownslopeoftheLVpressuretracing. Ifthereisadiscrepancybetweentheclinicaland/orechocardiographicassessment ofMSandwhatisbeingdeterminedbyPCWPversusLVdiastolicpressures,then transseptalcatheterizationanddirectmeasurementoftheLApressureiscritical (Figure6).ThisisalsoimportantinpatientswherethePCWPtracingisa suboptimaltracing.Themostcommonscenarioforthistohappenisinapatient withseverepulmonaryhypertensionanddilationofthePAswhereidealwedge pressuretracingscanbechallengingtoobtain.Transseptalcatheterizationofthe LAbyoperatorstrainedandexperiencedinthistechniqueallowsresolutionofthese questionsviadirectmeasurementofLApressure.

Asapracticalconsideration,itisimportanttonotethatsmallerrorsinthe transvalvularpressuregradientinMScanresultinerrorsthatareclinically significant.Forexample,a5mmHgerrorinanAVpressuredeterminationmight resultinanapproximate10%errorinvalveseverityestimation,whereasa5mmHg pressuredifferenceinaMVdeterminationmightresultina50%changeinthe estimationofMSseverity. Rightsidedstenoticvalvediseasesarelesscommonlyencountered.Pulmonary valvestenosis(PS)requiressimultaneousmeasurementoftheRVandthePA pressures.Twocathetersarethebestwayofobtainingthesesimultaneous measurements.Thisistypicallynotdifficulttoachieveinthecatheterization laboratory,asthecathetersareinsertedinthevenousratherthanthearterial system.Oncethetwocathetersarepositionedproperly,withanendholecatheterin thePAandasecondoneintheRV,thepressuregradientsduringsystolecanbe recordedandmeasured. Intheoverwhelmingmajorityofcases,obstructionoftheRVoutflowtract,eitherin theinfundibulumoratthePAlevel,isduetocongenitaldisease.Whetherthisisat thevalvularlevelortheRVinfundibulummuscularlevelcanbedeterminedbyapull backfromthePAtotheRVoncebothcathetersarepositionedinthePA.Thisallows theoperatortoleaveonecatheterinthePAdistaltotheobstructionandpullbackthe secondcatheteracrossthevalvelevelandRVoutflowtractleveltonotewherethe pressuregradientexists.Certainly,therearecasesofobstructionatboththevalvular andinfundibularlevel.Estimatesofpulmonaryvalveareaarenotreportedclinically. Decisionmakingismadebasedonvalvegradientsandassociatedmeasurements ofRVfailure. TherearecongenitalcaseswherestenosisofthePAsisimportanttodocument hemodynamically.Inthesecases,simultaneouspressuremeasurementsarealso required.TheoperatorwillplacecathetersinthemainPA,withasimultaneous catheterintherightPAandthenintheleftPA.Fromthefemoralapproach,the catheterstendtobedirectedprimarilytotheleftPA.PlacingacatheterintherightPA canbeachievedtypicallyfromtheinternaljugularorsubclavianveinapproachwhen difficultiesareencounteredviathefemoralapproach.Analternativefromthefemoral veinistouseanangledpigtailcatheterplacedinthemainPA.Anglingthepigtailto facethepatient'srightsideandadvancingaguidewireinthiswaywilltypicallyallow theoperatortogainselectiveaccesstotherightPAforpressuremeasurements. Tricuspidvalvestenosis(TS)isseeninpatientswithprosthetictissuevalvesinthis location,priorTVrepairs,andinpatientswithcarcinoiddisease.Itisoccasionally seeninrheumaticheartdiseaseaswell.EvaluationoftheTVindiastolerequires theuseoftwosimultaneouscatheters,oneintheRAandoneintheRV.Pullback measurementsfromtheRVtotheRAareinaccurate.Thevalveareacalculationsfor theTVarenotusedclinicallyforguidingmanagementdecisions.

AorticValveGradients Figure5 Themean,peaktopeak,andpeakinstantaneousgradientsareshown. Ao=aortaLV=leftventricle.

MitralValveGradientMeasurementTechniques Figure6 Differencesinmitralgradientusingthepulmonarycapillarywedgepressureversustheleftventriclepressure(rightpanel)andusingtheleft atrialpressureversustheleftventriclepressure(leftpanel)inthesamepatient. LA=leftatriumLV=leftventriclePCWP=pulmonarycapillarywedgepressure.

HemodynamicMeasurements:MyocardialandPericardial Diseases
Oneofthemorecommonindicationsforcarefulhemodynamicstudyisforthe evaluationofpatientswithcongestiveheartfailure.Thisissometimeshelpfulasan initialdiagnostictool,andatothertimes,serialmeasurementsofhemodynamic values,aswellasCO,arehelpfultoevaluatetheeffectsofthevarioustherapies.For patientswithLVdysfunction,oneofthemorecommonclinicalentitiesencountered intheUnitedStates,theoperatorshouldconsiderthecardiacindexgeneratedatthe expenseofLVfillingpressure.PatientswithLVsystolicdysfunctionandpulmonary hypertension,alongwithanelevatedPVR,mayhavefurtherlimitationoftheirresting cardiacindexonthisbasis.Furthermore,documentationofthePVRatthetime hemodynamicevaluationinpatientswithleftheartfailureiscritical,asaPVR>5 Woodunitsisgenerallyacontraindicationtocardiactransplantation. Pulmonaryhypertensionitselfmaybesecondarytoleftsidedheartfailure,oritmay beduetointrinsiclungdiseaseoridiopathicelevationofpulmonaryresistance.This distinctioncanbereadilymadeinthecatheterizationlaboratory,basedonwhether theLVfillingpressure(thePCWP)iselevatedornormal.AnelevatedPCWPisa relativecontraindicationtotheuseofpulmonaryvasodilatordrugtherapy.In evaluatingpatientswithpulmonaryhypertension,itisalsoimportanttonotethe RVEDP.ElevationoftheRVEDPandreductionincardiacindexisanominoussign forpatientswithprimarypulmonaryhypertension. Patientswithhypertrophicmyocardialdiseasesandrestrictivemyocardialdiseases haveelevatedventricularfillingpressures,evenintheabsenceofsignificantsystolic dysfunction.Thehemodynamicevaluationofpatientswithhypertrophicobstructive cardiomyopathyshouldincludedocumentationoftheBrockenbroughresponse followingaprematureventricularcontraction(Figure7).Thosepatientswith hypertrophiccardiomyopathieswithoutobstruction,andthosewithrestrictive cardiomyopathies,canhavesignificantlyelevatedLVEDPandPCWPeveninthe absenceofsystolicdysfunction.ThesepatientshavenoncompliantLVs,andtheirLA compliancetendstobereducedaswell.TheymayhavelargeVwavesinthewedge tracingdespiteonlymodestamountsofMR.Theseindividualstypicallyhave elevatedPApressuresthatmaybeelevatedoutofproportiontothedegreeof PCWP.SuchpatientswillhaveelevatedPVRvaluesandmayalsohaveevidenceof RVfailure. WhenRVfailureispresentinpatientswithrestrictivecardiomyopathies,itmaybe,at times,difficulttodistinguishfrompatientswithelevatedfillingpressuresdueto constrictivepericarditisasbothmayhaveelevatedleftandrightsidedfilling pressures.Bothpatientsmayhaverapidearlydiastolicfillingpatternswith prominentYdescentsobserved.Thesubsequentrapidriseinfillingpressureafter theYdescentresultsinthesquarerootpatternonthewaveformtracing.Both groupsofpatientsmayalsohavealackoffalloranincreaseintheRApressurewith inspiration,knownasaKussmaul'ssign. Hemodynamicevaluationisimportantindistinguishingpericardialconstrictionfrom restrictivecardiomyopathy.Todistinguishthedifference,itisimportanttoevaluate simultaneousLVandRVpressures,andsimplerightheartcatheterizationmaynot suffice.Therearecertaincluesthatfavoronepathologicprocessovertheother. Patientswithrestrictivecardiomyopathiestendtohavethepersistenceofslightly higherLVfillingpressurescomparedtoRVfillingpressures.Thatis,thePCWP tendstobe?5mmHgtheRApressure.Likewise,theLVEDPtendstobe>5mmHg theRVEDPinpatientswithrestrictivecardiomyopathy.Inpatientswithpure pericardialconstriction,theretendstobeequalizationoftheLVEDPandRVEDPand equalizationoftheLAandRApressures. Moreover,inpatientswithpericardialconstriction,thePAsystolicpressuretendsto beonlymodestlyelevatedincomparisontothewedgepressure.Conversely,in patientswithrestrictivecardiomyopathies,themagnitudeofpulmonaryhypertension tendstobegreater.Theruleofthumbisthatthefindingfavorsarestrictive cardiomyopathyiftheRVsystolicpressureis>3timestheRVEDP. Recently,morespecifichemodynamicfindingshavebeendefinedthathelpedto

Figure7

Figure8

distinguishingpericardialconstrictionfromrestrictivecardiomyopathy.Thisinvolves measuringtheRVandLVsystolicpressuressimultaneouslyandanalyzinghowthey varyduringtherespiratorycycle.Inpatientswithpericardialconstriction,thereis discordanceofthesesystolicpressures.Thatis,inpatientswithpericardial constrictionduringinspiration,thereisariseintheRVsystolicpressureassociated withafallintheLVsystolicpressure.Conversely,withexpirationinpatientswith pericardialconstriction,thereverseoccurs.ThisdiscordancebetweentheRVand LVsystolicpressuresduringtherespiratorycycleishighlyspecificforpericardial constriction.14Inaddition,theratiosofthepressuretimeareasundertheRV+LV systolicpressuretracings(thesystolicareaindexes)varyinverselywithrespiration inpatientswithpericardialconstriction. Thus,withrestriction,theRV/LVpressuretimearearatioinexpiration,comparedto inspiration,willbeconcordant,andthevaluegenerallywillbe14Withconstriction, thevalueoftheRV/LVpressuretimearearatioinexpiration,comparedto inspiration,willbe>1.1,confirminganincreaseinRVfillingattheexpenseofLV filling(ventricularinteraction)(Figure8).14 Onecanalsogaininsightintothisdistinctionbysimultaneousmeasurementofthe PCWPcomparedtotheLVEDPsduringtherespiratorycycle.Withpericardial constriction,thepulmonaryvenousvascularbedisseparatefromtheintracardiac chambersduetothepericardialthickening.Withinspiration,thereisanormalfallin thepulmonaryvenouspressuresduetothenegativeintrathoracicpressure.In constrictivepericarditis,however,theLVEDPrisesduringinspirationduetotheshift oftheintraventricularseptum.Thisdecreasesthepressuredifferencebetweenthe PCWPandtheLVEDP.Withexpiration,theconverseoccurs.Inpatientswitha restrictivecardiomyopathy,thereisconcordanceofthePCWPandtheLVEDPs duringinspirationandexpiration.

TheBrockenbroughPhenomenon Figure7 Theintraventriculargradientbetweentheaortaandleftventriclepressuresareshowntoincreasewiththereductioninleftventriclevolume duringtheValsalva.Aprematureventricularcomplexisthenfollowedbyapostprematureventricularcontractionbeatthathasalowerpulse pressurethanthepreprematureventricularcontractionbeatandsomenotchingoftheaorticwaveform(bisferiens).

ConstrictivePericarditisVersusRestrictiveCardiomyopathy Figure8 Inthetoppanel(A)isapatientwithconstrictivepericarditisandthebottompanel(B)isfromapatientwitharestrictivecardiomyopathy.Both patientsexhibitrapidearlyfillingandequalizationoftherightventricle(RV)andleftventricle(LV)enddiastolicpressuresatendinspiration.In thetoppanel,theareaoftheRVpressuretimetracingincreaseswithinspirationwhiletheLVpressuretimetracingareadecreases.This confirmsRVLVdiscordance.Inthelowerpanel,theareasofboththeRVandLVpressuretimetracingsdecreasewithinspirationcomparedto expiration. LV=leftventricleRV=rightventricle. ReproducedwithpermissionfromTalrejaDR,NishimuraRA,OhJK,HolmesDR.Constrictivepericarditisinthemodernera:novelcriteriafor diagnosisinthecardiaccatheterizationlaboratory.JAmCollCardiol200851:3159.

MeasurementsofCardiacOutputandVascularResistance
ThemostcommontechniqueinthecatheterizationlaboratorytoestimateCOistheFickmethod.Thismethodinvolves measuringthearteriovenousoxygen(AVO2 )differenceandmeasuring,ormorecommonly,estimatingthepatient's oxygenconsumption.TheFickequationis: CO=oxygenconsumption/(thesystemicarterialoxygencontentthemixedvenousoxygencontent)orAVO2 difference Typically,theoxygenconsumptionismeasuredusingametaboliccart,oritisestimatedbasedonanequationwhich usesthepatient'sage,gender,andbodysurfacearea.Thesystemicarterialoxygencontentisequaltotheoxygen saturationofthearterialbloodmultipliedby(1.36mmofoxygenpergramofhemoglobin)multipliedbythepatient'sblood hemoglobinconcentration.Themixedvenousoxygencontent,intheabsenceofanintracardiacshunt,isbestmeasured atthePAlevelwherethemixedvenousbloodismostuniform.Themixedvenousoxygencontentis,therefore,most commonlymeasuredfromthePAsaturation.MostCOmeasurementsaretypicallyexpressedasliter/minutesothatthe denominatoroftheFickequationtypicallyhas10dl/lintheequationtoconverttheCOvaluetol/minratherthantodl/min. ThecardiacindexisderivedbytakingtheCOvalueanddividingitbythebodysurfacearea,whichisexpressedin l/min/M2 . AnalternativemethodforestimatingCOthatisreadilyavailableonacommercialbasisisthermodilution.Thermodilution involvesinjectingsalineataknowntemperaturebelowbodytemperatureandmeasuringthedownstreamtemperature. Thesecathetershaveaproximalinjectateportandathermistorlocatedatthedistaltipofthecatheter.Withthisdistaldip locatedinthePA,oneinjectssalineintheproximalport,andthethermistoratthedistalportmeasurestemperatureasa functionoftime.ThistemperaturecurveisusedtoderiveanestimateofCObasedonalgorithmswhichhavebeen computerized.ThecomputergeneratesadigitalreadoutasanestimateofCO. ItshouldbepointedoutthatnoestimateofCOisperfect.TheweakestlinkintheFickestimateofCOistheoxygen consumptionestimate.Thermodilutionvaluesaresubjecttoinaccuraciesinthealgorithms,whichderivetheoutput estimatesandcanbedisturbedbycommonpathophysiologicabnormalitiessuchasTRand/orlowCOstates. SinceCO"measurements"aremoreaccuratelydescribedasCOestimates,valveareaestimates,whichdirectlydepend ontheCOvaluesintheirnumerators,aredirectlysubjecttotheinherentinaccuracyinthesebloodflowestimates.Valve areaestimatesintheaorticandmitralpositionsareoftenreportedouttothehundredthdecimalplace.Whilecommon, suchreportinggivesthepretensethatthesevalveareaestimatesaremoreaccuratethantheytrulyare.Valvearea estimatestotheclosesttenthofacm2 aremorerealisticintermsoftheactualaccuracyofthesemeasurements. SystemicvascularresistanceandPVRmeasurementsarestraightforward.Systemicvascularresistanceisthemean systemicarterialpressureminusthemeanRApressuredividedbythesystemicbloodflow.Similarly,thePVRis obtainedbysubtractingthemeanLApressureormeanPCWPfromthemeanPApressure.Thisresultisdividedbythe pulmonarybloodflow.Intheabsenceofintracardiacshunting,thesystemicbloodflowandpulmonarybloodfloware identicalandequaltotheCO.

IntracardiacShunting
Thedetectionofanintracardiacshuntanditsquantitationreliesonoximetryevaluationfromthevariouschambersofthe heart.Ifonesuspectsanintracardiacshuntbasedonclinicalorprecatheterizationimagingdata,deliberateoximetryfrom varioussitesshouldbeobtainedasdescribedlater. Thereare,however,instanceswherepatientsareundergoingstandardrightandleftheartcatheterizationprocedures andhaveintracardiacshuntsdetectedwhichwerenotdisclosedpriortothecatheterization,whichpresentsmoreofa challenge.Inaddressingthissituation,whenFickCOisutilizedasthemethodforestimatingCO,oneshouldlookatthe AVO2 difference.Thisvalue,whichisthesystemicarterialoxygencontentminusthepulmonaryarterialoxygencontent, hasnormalvaluesbetween3.0and5.5volumepercent.Values>5.5volumepercentareindicativeoflowoutputstates. Values<3.0volumepercentareindicativeofhighoutputstatesorpatientsthathavesignificantintracardiacshunts.Thus, fromapracticalpointofview,anyindividualwhohasanAVO2 contentdifferenceof<3.0volumepercentshouldbe consideredtohaveanintracardiacshunt,untilprovenotherwise. TherearecertainlyotherconditionswhichwillcausetheAVO2 differencetobe<3.0volumepercent,includinghighoutput statesfromanemiaorsepsis.IfavaluefortheAVO2 differenceis<3.0volumepercent,thenadetailedoximetric evaluationisrequiredtodefinewhetherthelowAVO2 differenceisduetoanintracardiacshuntornot. Fromapracticalpointofview,oneneedstomakeoximetricmeasurementsawayfromtheheartsothatthedataobtained isproximalanddistaltothesiteofanyintracardiacshunt.Acommonalgorithmistoobtainoxygensaturationvaluesfrom thefollowinglocations: 1. Highsuperiorvenacava,definedasthesuperiorvenacavacephaladtothecrossingoftherightmainstem bronchus. 2. Lowsuperiorvenacava,thesuperiorvenacavacephaladtotheRAjunctionbutbelowthemainstembronchus. 3. Innominateveinsaturationattheleveloftheleftclavicle. 4. AsingleRAsaturation. 5. InferiorvenacavalsaturationbelowitsentranceintotheRAbutabovetheleveloftherenalveins. 6. RVsample. 7. PAsample. 8. Pulmonaryvenoussampleswhenfeasible. 9. Femoralarteryorradialarterysample. Usingthesevalues,thepulmonarybloodflow,thesystemicbloodflow,andtheeffectivepulmonarybloodflowcanbe readilycalculated.Thefollowingequationsdefinethesemeasurements: Pulmonarybloodflow=oxygenconsumption/(thepulmonaryvenousoxygencontentthepulmonaryarterial oxygencontent) Systemicbloodflow=oxygenconsumption/(systemicarterialcontentmixedvenousoxygencontent) Effectivepulmonarybloodflow(thefractionofmixedvenousbloodreachingthelungswithoutshunt contamination)=oxygenconsumption/(pulmonaryvenousoxygencontentmixedvenousoxygencontent) Themixedvenousoxygensaturationisestimatedas3timesthesuperiorvenacavalsaturationplustheinferiorvena cavalsaturationdividedby4.Lowsuperiorvenacavalsaturationisthebestmeasurementofthesuperiorvenacaval saturation,unlessananomalouspulmonaryveinisdrainingintothesuperiorvenacavaortheinnominatevein.Patients withanomalouspulmonaryveintotheinnominateveinorsuperiorvenacavacanbeidentifiedashavinghighvaluesin theleftinnominateveinsaturationorthelowsuperiorvenacavalsaturationcomparedtothehighsuperiorvenacaval saturation.Insuchuncommoncases,thehighsuperiorvenacavalsaturationshouldbeusedintheestimationofmixed venousoxygensaturation.Incasesoflefttorightintracardiacshunting,thePAsaturationwillbehigherthanthemixed venoussaturationcalculation.Incasesofrighttoleftintracardiacshunting,thepulmonaryvenoussaturationwillbe higherthanthesystemicarterialsaturation. Themagnitudeoftheshuntisdefinedbythesystemicbloodflow,pulmonarybloodflow,andeffectivepulmonaryblood flowvalues.Themagnitudeofanylefttorightshuntingisdeterminedbysubtractingtheeffectivepulmonarybloodflow fromthepulmonarybloodflowvalue.Themagnitudeofrighttoleftshuntingisderivedbysubtractingtheeffective pulmonarybloodflowvaluefromthesystemicbloodflowvalue.Pulmonarybloodflowdividedbysystemicbloodflow equalsthepulmonarybloodflowtosystemicbloodflowratio(Qp:Qs).Thisvaluecanbederivedsimplyatthetimeofthe procedurebydeterminingthenumeratorandthedenominatorusingthesaturationmeasurementsalone.Thus,ifone definesthenumeratorasthesystemicarterialsaturationminusthemixedvenoussaturation,andthedenominatoras thepulmonaryvenoussaturationminusthePAsaturation,thisyieldsthesameQp:Qsratio. Forpatientsonsupplementaloxygen,oneshouldsendabloodgasonthearterialsamplessothatthedissolvedoxygen

inplasmacanbeaddedintotheoxygencontent.Inadditiontothehemoglobinboundoxygenvalue,oneadds0.03xthe pO2 todeterminethetrueoxygencontentofthebloodsample.Thisoxygencontent,whichcontainsboththeplasma dissolvedoxygenandthehemoglobinboundoxygen,shouldbeusedtoderiveCOandsystemicandpulmonaryblood flowmeasurementsinsuchpatients. SystemicvascularresistanceandPVRarederivedinthesamesimplemannerinpatientswithintracardiacshunts,but onemustrememberthatthedenominatoroftheseequationsmustcontainaccuratevaluesofpulmonarybloodflowand systemicbloodflowforthesepatientswithintracardiacshunts.The"CO"cannotbeusedforsuchpatients.Forexample, forapatientwithanatrialseptaldefectanda2:1lefttorightshunt,thePVRwillbeestimatedtobetwiceitstruevalueif theCOorsystemicbloodflowmeasurementisputinthedenominatorofthePVRequationratherthanplacingthe accuratepulmonarybloodflowmeasurementintheequation.Likewise,forpatientswithashuntandstenoticvalve disease,theflowacrosstheaorticvalveandnotthe"CO"mustbeusedasthenumeratoroftheGorlinorHakkiformulas. Insummary,hemodynamicevaluationinthecatheterizationlaboratorycontinuestobeavitalcomponentofallcardiac catheterizationprocedures.Thesemeasurementssometimestakeabackseattocoronaryimaginginmanypatients undergoingcardiaccatheterization.Vitalinformation,however,canbeobtainedwiththesedata,whichcanbe instrumentalinimprovingthetreatmentofthesepatients.Catheterizationoperatorsshouldremainfamiliarwiththese measurementsandthemostaccuratewaystoobtainthemtoensurethatpatientsarediagnosedandtreatedaccurately anddiagnosesarenotmisinterpretedormissedaltogether.

KeyPoints
Invasivehemodynamicevaluationisindicatedtodeterminetheseverityofdiseaseiftherearediscrepantfindings betweentheclinicalhistory,physicalexamination,andimagingfindings,orifnoninvasiveimagingisnot conclusive. Meticulousattentiontotechnicaldetailisnecessaryinordertoobtainaccurateinvasivehemodynamicdata. Itiscriticalforcliniciansperforminginvasivehemodynamicstudiestohaveafirmunderstandingofnormaland pathologichemodynamicwaveformsandtorecognizepitfallsintheinterpretationofthisdata.Likewise,the operatorshouldunderstandthevariousmethodsforestimationofCOandhowthesedatamaybeusedto calculatestenoticvalveareaandintracardiacshuntmagnitude.

References
1. CournandAFLausonH,BloomfieldR,etal.Recordingofrightheartpressuresinman.ProcSocExpBiolMed 194455:346. 2. DeWoodMA,SporesJ,NotskeR,etal.Prevalenceoftotalcoronaryocclusionduringtheearlyhoursoftransmural myocardialinfarction.NEnglJMed1980303:897902. 3. HurrellDG,NishimuraRA,HiganoST,etal.Valueofdynamicrespiratorychangesinleftandrightventricular pressuresforthediagnosisofconstrictivepericarditis.Circulation199693:200713. 4. PijlsNH,DeBruyneB,PeelsK,etal.Measurementoffractionalflowreservetoassessthefunctionalseverityof coronaryarterystenoses.NEnglJMed1996334:17038. 5. ToninoPA,DeBruyneB,PijlsNH,etal.Fractionalflowreserveversusangiographyforguidingpercutaneous coronaryintervention.NEnglJMed2009360:21324. 6. ParhamW,ElShafeiA,RajjoubH,ZiaeeA,KernMJ.Retrogradeleftventricularhemodynamicassessment acrossbileafletprostheticaorticvalves:theuseofahighfidelitypressuresensorangioplastyguidewire.Catheter CardiovascInterv200359:50913. 7. OhJK,TaliercioCP,HolmesDR,Jr,etal.PredictionoftheseverityofaorticstenosisbyDoppleraorticvalvearea determination:prospectiveDopplercatheterizationcorrelationin100patients.JAmCollCardiol198811:1227 34. 8. GorlinR,GorlinSG.Hydraulicformulaforcalculationoftheareaofthestenoticmitralvalve,othercardiacvalves, andcentralcirculatoryshunts.I.AmHeartJ195141:129. 9. HakkiAH,IskandrianAS,BemisCE,etal.Asimplifiedvalveformulaforthecalculationofstenoticcardiacvalve areas.Circulation198163:10505. 10. BonowRO,CarabelloBA,ChatterjeeK,etal.2008focusedupdateincorporatedintotheACC/AHA2006 guidelinesforthemanagementofpatientswithvalvularheartdisease:areportoftheAmericanCollegeof Cardiology/AmericanHeartAssociationTaskForceonPracticeGuidelines(WritingCommitteetorevisethe1998 guidelinesforthemanagementofpatientswithvalvularheartdisease).EndorsedbytheSocietyofCardiovascular Anesthesiologists,SocietyforCardiovascularAngiographyandInterventions,andSocietyofThoracicSurgeons.J AmCollCardiol200852:e1142. 11. MeineTJ,HarrisonJK.Shouldwecrossthevalve:theriskofretrogradecatheterizationoftheleftventriclein patientswithaorticstenosis.AmHeartJ2004148:412. 12. HarrisonJK,DavidsonCJ,PhillipsHR,HardingMB,KissloKB,BashoreTM.Arapid,effectivetechniquefor retrogradecrossingofvalvularaorticstenosisusingstandardcoronarycatheters.CathetCardiovascDiagn 199021:514. 13. WippermannCF,SchranzD,StopfkuchenH,HuthR,FreundM,JungstBK.Evaluationofthevalvearea underestimationbythecontinuityequation.Cardiology199280:27682. 14. TalrejaDR,NishimuraRA,OhJK,HolmesDR.Constrictivepericarditisinthemodernera:novelcriteriafor diagnosisinthecardiaccatheterizationlaboratory.JAmCollCardiol200851:3159.

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3.8:CoronaryAngiography
Author(s): JamesBernardHermiller,Jr.,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Reviewtheindicationsandcontraindicationsforcoronaryarteriographyinpatientswithsuspectedcoronaryartery disease(CAD). 2. Reviewoptimalarterialaccesstechniqueforbothfemoralandradialaccess. 3. Detailnormalandvariantcoronaryanatomyandreviewappropriatecathetersandimagingtechniquesforoptimal angiographyandstenosisevaluation. 4. Discussthecomplicationsassociatedwithcoronaryangiography. 5. Developabasicworkingknowledgeofcoronaryanatomyanditsvariantsinpatientsundergoingcardiaccatheterization.

Introduction
DespitecontemporaryimprovementsinthenoninvasiveevaluationofCAD,selective coronaryarteriographyremainsessentialinconfirminganddefiningthepresence andextentofobstructivecoronarydiseaseandtherebydelineatingthemost appropriaterevascularizationstrategywhenoneisindicated.IntheUnitedStates alone,over1.5millioninpatientcardiaccatheterizationsandpercutaneouscoronary interventions(PCIs)areperformedperyear(Figure1). Notonlydoescoronaryarteriographyprovidereliableinformationaboutthe presenceorabsenceofcoronaryarteryobstructivedisease,itmaybeusedto identifytheinfrequentbutimportantetiologiesofnonatheroscleroticcasesofCAD, includingunderlyingvasculities(Figures2,3).

Figure1

Figure2

Figure3

InpatientInvasiveProceduresintheUnitedStates Figure1 PCI=percutaneouscoronaryintervention. ReproducedwithpermissionfromBashoreT,BalterS,BaracA,etal.2012AmericanCollegeofCardiologyFoundation/Societyfor CardiovascularAngiographyandInterventionsExpertConsensusDocumentonCardiacCatheterizationLaboratoryStandardsUpdate.JAmColl Cardiol2012publishedonline8May2012.

EtiologyofNonatheroscleroticCoronaryDisease Figure2

TableofVasculitides Figure3

IndicationsforCoronaryArteriography
TheClassIindicationsforcoronaryangiography,asprovidedbytheAmericanCollegeofCardiology(ACC)/American HeartAssociation(AHA)GuidelinesforCoronaryAngiography,aresummarizedasfollows1 : PatientswithknownorsuspectedCADwhohavesevereanginaonmedicaltreatment(CanadianCardiovascular SocietyclassIIIIV). Asymptomaticpatients,patientswithstableangina,orthosewithnonspecificchestpainwhohave"highrisk" criteriaonnoninvasivetesting.Highriskfeaturesinclude: Severerestingorexerciseinducedleftventricular(LV)dysfunction(LVejectionfraction[LVEF]<35%). Astandardexercisetreadmilltestdemonstratinghypotensionor>12mmSTsegmentdepression associatedwithdecreasedexercisecapacity. Stressimagingthatdemonstratesamoderateorlargeperfusiondefect(e.g.,particularlyintheanterior wall),multipledefects,alargefixedperfusiondefectwithLVdilatation,orincreasedlunguptake. Extensivestressordobutamineinducedwallmotion. Patientsresuscitatedfromsuddencardiacdeath,particularlythosewithresidualventriculararrhythmias. PatientswithanonSTsegmentelevationmyocardialinfarction(NSTEMI)orunstableanginawhodevelop recurrentsymptomsdespitemedicaltherapyorwhoareatintermediateorhighriskofsubsequentdeathor myocardialinfarction(MI).Highriskfeaturesinclude: Prolongedongoing(>20minutes)chestpain. Pulmonaryedema. Worseningmitralregurgitation. DynamicSTsegmentdepressionof1mmormore. Elevatedserumtroponinlevels. Hypotension. Intermediateriskfeaturesinclude: Anginaatrest(>20minutes)relievedwithrestorsublingualnitroglycerin. Anginaassociatedwithdynamicelectrocardiogram(ECG)changes,recentonsetanginawithahighlikelihoodof CAD,pathologicQwaves,STsegmentdepression<1mminmultipleleads,orageolderthan65years. PatientswithsuspectedPrinzmetal'svariantanginawhenthediagnosiscannotbemadebyothermeans. CoronaryangiographycoupledwiththeintenttoperformprimaryPCIasanalternativetofibrinolytictherapyin patientswithacuteSTsegmentelevationmyocardialinfarction(STEMI)orsuspectedMIinthosewithleftbundle branchblock. Patientswhoarewithin36hoursofaSTEMIwhodevelopcardiogenicshock,are<75yearsofage,and revascularizationcanbeperformedwithin18hoursoftheonsetofshock. PatientswithSTEMIorNSTEMI/unstableanginawhodevelopspontaneousischemiaorwithischemiaata minimalworkload(withorwithoutECGchanges)orwhohaveMIcomplicatedbyheartfailure(HF),hemodynamic instability,cardiacarrest,mitralregurgitation,orventricularseptalrupture. Thepresenceofshock,severepulmonarycongestion,orcontinuinghypotensionafteracuteorsuspectedMI. BeforedefinitivetherapyofamechanicalcomplicationofMI. PersistenthemodynamicinstabilityafterMI. Patientswhohaveundergonepriorrevascularizationifthereissuspicionofabruptvesselclosure. Recurrentanginaorhighriskcriteriaonnoninvasivetestingwithin9monthsofpercutaneousrevascularization. PatientswithknownorsuspectedCADscheduledtoundergohighrisknoncardiacsurgerywhohave: Significantleftmaincoronaryarterystenosis. Twovesseldiseasewithsignificantproximalleftanteriordescending(LAD)stenosisandeitherejection fraction<50%ordemonstrableischemiaonnoninvasivetesting. HighriskunstableanginaorNSTEMI. Beforecardiactransplantation. Annuallyinpatientsaftercardiactransplantationintheabsenceofclinicalsymptomsbecauseofthe characteristicallydiffuseandoftenasymptomaticnatureofgraftatherosclerosis. PotentialdonorsforcardiactransplantationwhoseageorcardiacriskprofileincreasesthelikelihoodofCAD. Patientswithintractablearrhythmiasbeforeelectrophysiologytestingorinpatientswhopresentwithadilated cardiomyopathyofunknownetiology. Beforevalvesurgeryorpercutaneousvalvuloplastyinanadultwithchestpain,myocardialischemiaby noninvasivetesting,orboth. Beforevalvesurgeryinanadultwithoutchestpain,butwithmultipleriskfactorsforCAD. Infectiveendocarditiswithevidenceofcoronaryembolization. Beforesurgicalcorrectionofcoronaryheartdisease(CHD)inadultswhenchestdiscomfortorassociated noninvasivetestingsuggestsunderlyingCAD. Beforesurgicalcorrectionofsuspectedcoronaryanomalies(e.g.,congenitalcoronaryarterystenosis,coronary arteriovenousfistula,orcertainanomalousoriginsofthecoronaryarteries). PriortosurgeryforCHDsthatarefrequentlyassociatedwithcoronaryarteryanomalies,whichcancomplicatethe

surgicalmanagement. InthepresenceofHFduetosystolicdysfunctionwithanginaorwithregionalwallmotionabnormalities,orwith evidenceofmyocardialischemiabynoninvasivetestingwhenrevascularizationisbeingconsidered. HFsecondarytopostinfarctionventricularaneurysmormechanicalcomplications. Inthesettingofaorticdiseases(e.g.,dissectionoraneurysm),whenknowledgeofthepresenceorextentofCAD isnecessaryformanagement. Hypertrophiccardiomyopathywithanginadespitemedicaltherapywhenknowledgeofthecoronaryanatomy mightaffecttherapy. Coronaryangiographyisnotindicated(ClassIII)inthefollowingsituations: Anginainpatientswhowishtoavoidrevascularizationeventhoughitmightbeappropriate. Anginainpatientswhoarenotcandidatesforrevascularizationorinwhomrevascularizationisnotlikelyto improvethequalityordurationoflife. AsascreeningtestforCADinasymptomaticpatients. Patientswithnonspecificchestpainwholackhighriskfeaturesorwhohavenotbeenhospitalizedmultipletimes withequivocalfindingsonnoninvasivetesting. Recurrentchestdiscomfortsuggestiveofunstableangina,butwithoutobjectivesignsofischemiaandwitha normalcoronaryangiogramduringthepast5years. Unstableanginainpatientswhoarenotcandidatesforcoronaryrevascularizationorinpatientsforwhom coronaryrevascularizationwillnotimprovethequalityordurationoflife. Symptomsinapostcoronaryarterybypassgraft(CABG)patientwhoisnotacandidateforrepeatsurgicalor percutaneousrevascularization. RoutineangiographyinasymptomaticpatientsafterPCIorothersurgery,unlesspartofanapprovedresearch protocol. Patientswhoare>12hoursfromtheonsetofacuteSTEMIandhavenosymptomsindicatingcontinuing ischemia. Lowrisknoncardiacsurgery,withknownCADandnohighriskresultsonnoninvasivetesting. Asymptomaticpatientsaftercoronaryrevascularizationwithexcellentexercisecapacityrequiringnoncardiac surgery. PatientswithmildstableanginawithgoodLVfunctionandnohighrisknoninvasivecriteriarequiringnoncardiac surgery. Patientswhorequirenoncardiacsurgerywhoarenotcandidatesforcoronaryrevascularizationduetocomorbid conditions. Candidatesforliver,lung,orrenaltransplantsurgery40yearsoldaspartofevaluationfortransplantationunless noninvasivetestingshowshighriskcriteria. BeforecardiacsurgeryforinfectiveendocarditiswhentherearenoriskfactorsforCADandnoevidenceof coronaryembolization. Asymptomaticpatientswithvalvediseasewhencardiacsurgeryisnotbeingconsidered. Beforecardiacsurgeryforvalvediseasewhenhemodynamicpreoperativeassessmentbycatheterizationis unnecessaryandthereisneitherpreexistingevidenceforCAD,norriskfactorsforCAD. RoutineevaluationofCHDinasymptomaticpatientsforwhomheartsurgeryisnotplanned. HFwithpreviouscoronaryangiogramshowingnormalcoronaryarterieswithnonewevidencetosuggest ischemicheartdisease. Thepresenceofcoronarycalcificationonfluoroscopyornotationofahighcalciumscorebyultrafastcomputed tomography(CT)scanningaloneisnotanindicationforcoronaryarteriography.

ContraindicationstoCoronaryArteriography
Contraindicationstocoronaryarteriographyinclude: Unexplainedfeveroruntreatedinfection. Severeanemiawithhemoglobin<8g/dl. Severeelectrolyteimbalance. Severeactivebleeding. Uncontrolledsystemichypertension. Digitalistoxicity. Previouscontrastreaction,butnopretreatmentwithcorticosteroids. Ongoingstroke. Otherdiseasestatesthatwarrantdeferralofcoronaryarteriographyinclude:1)acute renalfailure,2)decompensatedHF,3)severeintrinsicoriatrogeniccoagulopathy (internationalnormalizedratio[INR]>1.8),and4)activeendocarditis. Theseconditionsaregenerallyselflimited,and,intheabsenceofsignsor symptomsindicatingclinicalinstability,deferralofcoronaryarteriographyis generallyrecommended.Therareoccurrenceofpostprocedurallacticacidosisin diabeticpatientsreceivingmetformininvariablyoccursinpatientswithrenal insufficiency,andmetforminshouldnotbeusedinthisgroupanyway.Theriskof thissyndromeisminimizedifthedrugisdiscontinuedaftercoronaryarteriography, untiloneisassuredthatcontrastinducednephropathyhasnotoccurred(Figure4). Patientswithnormalrenalfunctiontakingmetforminareinstructedtonottakethe metforminthedayoftheprocedureandnottorestartitforatleast48hoursafterward anduntilanassuranceofnocontrastrelatednephropathyisdocumented.2
Figure4

GuidelinesforMetforminPriortoIodinatedContrast Figure4 ModifiedwithpermissionfromJohnWiley&Sons.HeuplerFAJr.Guidelinesforperformingangiographyinpatientstakingmetformin.Membersof theLaboratoryPerformanceStandardsCommitteeoftheSocietyforCardiacAngiographyandInterventions.CathetCardiovascDiagn 199843:1213.

ConsciousSedation
Conscioussedationismostcommonlyusedforthemajorityofprocedures performedinthecatheterizationlaboratory.Conscioussedationisdefinedbya minimallydepressedlevelofconsciousnessthatallowsapatienttorespond appropriatelytoverbalcommandsandtomaintainapatentairway.Appropriate sedationisimperativeandensurespatientcomfort.Preproceduralassessmentof thepatient'smentalstatusisanimportantfactor,andagradingsystemhasbeen developed(Figure5).3 Premedicationwithoraldiphenhydramineanddiazepamiscommon.Intravenous sedativehypnoticsandanalgesicregimensvary.Acombinationofmidazolamand fentanylcitrateisverypopularintravenous(IV)morphine,diphenhydramine,and hydromorphonehydrochloridearealsoused(Figure6).3 Conscioussedation protocolsmustbestrictlyadheredtoandexcessivesedationshouldbeavoided.All patientsshouldhavebaselinebloodpressure,oxygensaturation,andheartrateand rhythmdocumentedandhavecontinuoushemodynamic,ECG,andoximetry monitoringperformed,alongwithbeingmonitoredbyatrainedindividualwhoisnot directlyperformingtheprocedure. Accesstooxygen,suctionequipment,andaresuscitationcartisrequired.Reversal agentsshouldbereadilyaccessibleinthelaboratory(Figure7).3 General anesthesiaisoftenusediftransesophagealechocardiographyisrequiredfora procedure.Manypatientsundergoingvalvuloplasty,percutaneousaortic,ormitral valveproceduresatrialseptalpacingandpatentforamenovaleclosuresare managedwiththeassistanceofananesthesiologistundergeneralanesthesia. IssuesofAntithromboticTherapyDuringDiagnosticAngiography Aspirinisnotstoppedorheldpriortocardiaccatheterization,andifpatientshavenot beentakingaspirinitshouldbestartedpriortotheprocedure.Manypatientsare loadedwithorstartedonthienopyridinespriortocardiaccatheterizationifthereisa highlikelihoodofPCIandlowlikelihoodofCABG.Patientstakingwarfarinshouldbe instructedtostoptakingitatleast3dayspriortothecatheterization,andtheirINR shouldbecheckedpriortotheprocedure.AnacceptableINRtoperformfemoral arterycardiaccatheterizationprocedureis<1.8anINRof<2.2isacceptablefor radialaccess.4 Thesethresholdsareratherarbitraryandbasedonscantdata. Ofnote,arecentstudyoffullyanticoagulatedpatientsundergoingPCIfromeitherthe radialorfemoralaccesssitesuggestsamajoradvantageoftheuseoftheradial methodinthesepatientsinregardtoaccessbleedingfollowingtheprocedure.5 The overuseofvitaminKreversalofwarfarineffectsmaymakeitdifficulttoreestablisha warfarineffectfollowingtheprocedure,soallowingthepatient'sINRtodrift downwardafterstoppingthemedicationispreferred.Inhighriskgroups(e.g.,those withatrialfibrillation,mitralvalvedisease,certainprostheticheartvalves,oraprior historyofsystemicthromboembolism),abridgingprotocolisgenerallyfollowedwith IVunfractionatedheparin(UFH)orsubcutaneouslowmolecularweightheparin duringtheperiproceduralperiod.4 IVUFHisnotroutinelyusedduringcoronary arteriographyperformedfromthefemoralartery. Frequentflushingofallcatheterswithheparinizedsalinewillreducetheformationof microthrombiwithinthecathetertip.Patientsreceivingheparin,lowmolecular weightheparin,orglycoproteinIIb/IIIainhibitorswhoundergocardiaccatheterization safelywithonlyhaveaminimalincreasebleedingrisk,particularlyinthesettingof anacutecoronarysyndrome.Longertimetohemostasismayberequired postprocedure,andthecombinationofaspirin,heparin,andotherantiplatelet agentsincreasestheriskofbleeding.Newernonheparinanticoagulantsmay requireachangeinpracticeregardingthetimingofperformingcardiac catheterizationsandsubsequentangioplastyprocedures. Followingactivatedclottingtimes(ACTs)forpatientsonIVUFHhasbeenthe standardforyears.Withnewerlowmolecularweightheparins,factorXinhibitors, anddirectthrombininhibitors(e.g.,bivalirudin),ACTsarenotappropriate. Knowledgeofthetimewhenthelastdoseofthelowmolecularweightheparinor

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factorXinhibitorwilldictatefurtheranticoagulanttherapyduringPCIprocedures,risk ofbleeding,andthetimingofsheathremoval.Thehalflifeofbivalirudinisshort,25 minutesinpatientswithnormalrenalfunction. TheanticoagulanteffectofUFHcanbereversedwithprotamine,1mgforevery100 Uofheparin.Protaminecausesanaphylaxisorserioushypotensionin approximately2%ofpatients,andshouldnotbeadministeredtopatientswithprior exposuretoneutralprotamineHagedorninsulin,unstableanginaorhighrisk coronaryanatomy,orinthosewhohaveundergonecoronaryarteriographyby meansofthebrachialorradialarteries.

AmericanSocietyofAnesthesiologistsPhysicalStatusClassification Figure5

FirstLineParenteralDrugsforConsciousSedation Figure6

SpecificAntagonistsUsedinConsciousSedation Figure7

VascularAccess
Themostfrequentcomplicationofcoronaryangiographyandcoronaryinterventions occursatthevascularaccesssite.Carefulvascularentryisessentialinreducing suchcomplications,althoughvascularhemostasisobtainedaftertheprocedureis alsoacrucialcomponentoftheprocedure.Severalarterialaccesssitesare commonlyusedforcoronaryarteriography.Thespecificapproachwilldependon:1) operatorandpatientpreferences,2)anticoagulationstatus,and3)thepresenceof peripheralvasculardisease. FemoralArteryApproach Therightorleftfemoralarteriesarecommonlyusedaccesssitesforcoronary arteriography.Thecommonfemoralarterycoursesoverthemedialaspectofthe femoralhead,andthebifurcationofthecommonfemoralarteryintoitsbranchesis generallydistaltotheinferiormarginofthefemoralhead(Figures8,9,10).Tolimit thepotentialforcomplication,arterialaccessisbestachievedinthecommon femoralarteryoverthefemoralheadandbelowtheinguinalligament.Whilethe femoralskincreaseiscommonlyusedbyangiographersasalandmarkfor percutaneousentry,itisunreliable. Optimalfemoralaccessincludesfluoroscopicallyidentifyingtheinferiorborderofthe femoralheadwithahemostatclampplacedontheskin.Theoptimalpuncturehas beensuggestedtobe12cmbelowtheequatorbisectingthefemoralhead(Figure 11).Theanteriorwallofthecommonfemoralarteryshouldbepuncturedseveral centimetersbelowtheinguinalligament,butproximaltothebifurcationofthe superficialfemoralandprofundaarterialbranches(Figure12).Ifthepuncturesiteis proximaltotheinguinalligamentorbelowtheinferiorborderofthefemoralhead, hemostasisaftertheproceduremaybedifficultwithmanualcompression,the formerbeingassociatedwithretroperitonealbleeding,thelatterpseudoaneurysms andhematomaformation.Theinferiorborderoftheloopoftheinferiorepigastic arterycorrespondstothepositionoftheinguinalligament.Accesssuperiortothis pointisassociatedwithsignificantlyhigherratesofretroperitonealbleeding. BrachialandRadialArteryApproaches Inthepresenceofsevereperipheralvasculardiseaseofthelowerextremities, abdominalaorticaneurysm,particularlyinthepresenceofthrombus,ormorbid obesity,anonfemoralaccesssiteisrecommended.Bothradialandbrachialartery approachesarealternativeshowever,radialaccessisthepreferrednonfemoral route.Useoftheradialsiteisnowmorefrequentlyemployedincontemporary practiceelectivelyevenwhenthefemoralaccessisacceptable.Itsusemaylimit bleedingcomplicationscomparedwithfemoralaccessandenhancepatient comfort.68 Fortheradialapproach,anAllentestshouldbeperformedbeforearterial cannulationtoensurepatencyoftheulnararteryintheeventofradialartery occlusion(Figure13).Thebrachialarteryofanaveragesizedindividualwill accommodatean8Fr(French)(1Fr=0.33mmindiameter)sheath,whereasthe smallerradialarteryisgenerallylimitedto6oratmost7Frcatheters.Following radialsheathinsertion,UFH,nitroglycerin,andcalciumchannelblockerare administeredtolimitthromboticclosureandarterialspasm. Theradialapproachhasessentiallyreplacedthebrachialapproachexceptin circumstanceswhenupperextremityaccessisnecessaryandalargesheathsizeis required.Unliketheradialartery,thebrachialhasnodualcirculationandhematoma formationcanbecatastrophic,potentiallycausingabrachialneuropathy. Saphenousveingraftscanbecannulatedusingeitherthebrachialorradialartery. Theinternalmammaryarteryisbestapproachedfromtheipsilateralarm.
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TheAimofFemoralAccessIstoCannulatetheCommonFemoralArtery Figure8

FemoralArteryAnatomy Figure9 ReproducedwithpermissionfromMarkFreedandRobertSafian.

SchematicRepresentationoftheRelationshipBetweenInguinalLigamentandtheFemoralVascularAnatomy Figure10 ReproducedwithpermissionfromSafianRD,FreedMS.CoronaryIntervention:Preparation,EquipmentandTechnique.In:SafianRD,FreedMS. TheManualofInterventionalCardiology.3rded.Sudbury,MA:JonesandBartlettPublishers2001:8,Table1.2.Copyright2001. http://www.jbpub.com

LandmarkforFemoralArterialAccess Figure11 Tolimitthepotentialforcomplication,arterialaccessisbestachievedinthecommonfemoralartery.Whilethefemoralskincreaseiscommonly usedbyangiographersasalandmarkforpercutaneousentry,itisnotreliableinmanycases.Ithasbeensuggestedthattheinferiorborderof thefemoralheadbeidentifiedfluoroscopicallyanditslevelmarkedbyaclampplacedontheskin.Inthisfigure,theproperpositioningofthe clampisdemonstrated.Theskinpuncturewasmadeatthislevel,andthefemoralarteryenteredabout1cmaboveit.Contrastinjectedthrough thesheathrevealsitsinsertionsiteinthecommonfemoralartery.

LocalizationofthePunctureintheCommonFemoralArtery Figure12 Thearterialsheathentersthecommonfemoralarteryjustproximaltothebifurcationofthesuperficialfemoralarteryandtheprofunda.

AllenTestGradingUsingPulseOximetry Figure13 GradesAandBaresuitableforradialarterycatheterization.

VascularClosureDevices
ThemajorityofdiagnosticcoronaryangiogramsandPCIsareperformedusing femoralarteryaccess.Whenthearterialaccesssheathisremoved,hemostasisis achievedeitherbymanualcompressionofthearteryuntilahemostaticplugforms overthearterialentrysiteortheuseofanarterialclosuredeviceisutilized.Inthe settingofdiagnosticcoronaryangiography,hemostasisisusuallyobtained immediatelyaftertheprocedure.Ininterventionalcasesoffemoralpuncture,where avascularclosuredeviceisnotusedandUFHisutilizedastheanticoagulant,it shouldberoutinetoassesstheACTvaluebeforeaccesssitecompression followinginterventionalprocedureswheneverheparinhasbeenused. OncetheACThasreturnedtonearnormal(<180seconds),sheathscanbe removedandmanualpressureormechanicalpressureclampsapplied.For patientsreceivingbivalirudin,thesheathisremoved2hoursfollowing discontinuationofthethrombininhibitor.Iflyticagentshavebeenused,prolonged vascularcompressionmaybenecessary.Bedrestisaminimumof12hoursafter theprocedurefor45Frsheaths,while24hoursfor68Frsheathsiscommon practice.Theuseoftheradialorbrachialarteryapproachobviatestheneedfor prolongedbedrest,buthemostasismuststillbeachievedbymanualordevice pressure. Manualhemostasistimecanbeshortenedbytheuseofanexternalpatch containingpolyNacetylglucosamine(Syvekpatch).Thiscompoundactslocallyto causevasoconstriction,plateletactivation,redbloodcellagglutination,andfibringel formation,andhasnotbeenassociatedwithanyseriouscomplications.The boomerangdeviceisplacedintraarteriallyinatemporarymannertotamponadethe arteriotomyandfacilitatemanualcompression(Figure14). Overthelastdecade,avarietyofvascularclosuredeviceshavebeendeveloped. Localfemoralangiographyisgenerallyperformedtoproperlyplacethesedevicesin ordertoavoidsidebranchcompromise.Whileoveralltheydonotdecrease complicationscomparedwithmanualcompression,closuredeviceshavebecome thestandardofcareinmanycardiaccatheterizationlaboratoriesbecauseofthe convenience,includingareductioninbedresttimeandtimetohemostasis. Recently,anAHAScientificStatementontheuseofvascularocclusiondeviceshas beenpublished.9 Thekeyrecommendationsfromthisgroupcanbesummarizedas follows: ClassI. Afemoralarteriogramwithidentificationofthesheathinsertionsite andotherfeaturesofrelevanceshouldbedonetoensureanatomic suitability(LevelofEvidenceC). Manualcompressionregimensshouldachieveavascular complicationrateof<1%(LevelofEvidenceC). Dataoncomplicationsencounteredduringorafterdeploymentofthe arteriotomyclosuredevice(ACD)shouldbesystematicallycollected andreportedaspartoflocalcontinuousqualityimprovementand nationallytoaregistrysuchastheACCNCDR(National CardiovascularDataRegistry)andtotheFoodandDrug Administration(LevelofEvidenceC). ClassIIa UseofanACDisreasonableafterinvasivecardiovascular procedurestoachievehemostasis,shorterbedrest,andpatient comfort.Theuseshouldbeweighedagainsttheriskofincreased complicationsincertainpatientsubsetsandtakeintoaccountbody habitus,locationofthearteriotomy,sizeandconditionoftheparent vessel,sheathsize,andthepresenceofsystemicdisease(Levelof EvidenceB). ClassIIb ACDsshouldnotbeusedroutinelyforthespecificpurposeof reducingvascularcomplicationsinpatientsundergoinginvasive cardiovascularproceduresviathefemoralartery(LevelofEvidence B).

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Severaltypesofvascularclosuredevicesareapprovedforuse.Thesedevices reducebedresttimeandtherebyenhancelaboratoryefficiency,buthavenotbeen showntoreducetheoccurrenceofimportantvascularcomplications.10Someofthe complicationsoccurringaftertheuseofthesedevicesareextremelyrare,ifmanual compressionaloneisused.Thereareseveralcategoriesofthesedevices, including: Suturebaseddevices(e.g.,Perclose[Figure15]),whichremotelydeliver surgicalsuturethroughthemarginsofthepuncturesite,knottheendsofthe suturetogether,andslidetheresultingknotdowntothearterialsurfaceto duplicateasurgicalclosure.Initialtrialsshowedrapidhemostasisand ambulation,butwithsomeresidualcomplicationsdueto:1)incorrect placementofsutures,2)mechanicalbreakage,or3)infectionduetothe foreignbody.Subsequentgenerationsofthedevicehavereducedthesize andcomplexityofplacement.Meticulousattentiontoaseptictechniqueis necessaryand,insomesettings,prophylacticantibioticshavecontrolledthe infectionrisk. Collagenbaseddevicesapplyasmallpackofpurifiedbovinecollagentothe externalsurfaceoftheartery.Thiscanbedoneonlyexternallyorin conjunctionwithanintraarterialabsorbableanchorandsuture(i.e.,Angio Seal[Figure16]).Thesedevicesaregenerallyeasiertodeploythanthe sutureapproach,11althoughcorrecttechnicalplacementisessentialto avoidbleedingandminimizecomplications. Procoagulantbaseddevices(e.g.,Duett)temporarilyprovideinternal mechanicalhemostasiswithaminiatureballoontipcatheterwhilealiquid procoagulant(e.g.,thrombinandcollagen)isdepositedinthesofttissuejust outsidetheartery.Oncethismaterialisinplace,theballoonisdeflatedand removed,withrapidformationofthehemostaticplugfollowingcontactofthe bloodwiththeprocoagulant.Incorrectdepositionmightleadtopoor hemostasis,orprocoagulantdepositionwithinthearteriallumenwith productionofdistallimbischemiccomplications.Theriskofintravascular depositionofprothromboticmaterialshaslimitedtheuseofDuett.TheMynx device,usesanonthrombogenicmaterialpolyethyleneglycoldeposition abovethearteriotomytomechanicallytamponadebleeding,sealingthe arterialaccesssite(Figure17).TheExoSealdeviceisanotherextravascular closuredevicewithapainlessdeploymentmechanismthatdeliversapoly glycolicacid"feltlike"plugatopthefemoralarteryanchoredbythe neurovascularbundlesheath(Figure18). Clipbaseddevices(StarClose)canbeusedforvesselclosurewith deploymentofanitinolclipontothesurfaceofanartery.Whendeployed,the smallnitinolclipgraspsthetissueontopofthearteryaroundtheaccesssite inapursestringfashionandclosestheopeninginthefemoralarteryrapidly andsecurelywithminimaleffectonthelumendiameterorthebloodflow insidethevessel(Figure19). Vascularaccesssitecomplicationsoccurin13%ofpatients,andincludelocal bleedingandhematoma,femoralarterialpseudoaneurysm,retroperitoneal bleeding,femoralarteriovenousfistula,theneedforbloodtransfusionorrequired surgicalrepair,andprolongeddiscomfortandlengthofstay.Useofclosuredevices with"highsticks"abovetheinferiorborderoftheepigastricarteryloophavebeen associatedwithasubstantiallyhigherrateofretroperitonealbleeding(Figure20).

VascularClosureBoomerangDevice Figure14 TheBoomerangdeviceisappliedfor3045minutesassistingmanualcompression.

Perclose Figure15

AngioSealCollagenPlug Figure16

MynxVascularClosureDevice(VCD) Figure17

ExoSeal Figure18

StarClose Figure19

PunctureProximaltoInferiorBorderoftheLoopoftheInferiorEpigastricArtery Figure20

StenosisEvaluation
Animportant,althoughgenerallyignoredarea,isthatofthecompletenessandaccuracyofdiagnosticcatheterization procedures.Incomplete,oraborted,procedures,technicallyinadequateproceduresthatfailtoobtainthecritical informationfordiagnosticpurposesanderroneousinterpretationoftheacquiredinformation,aremarkersofqualityno lessimportantthantheaforementionedareas.Failuretoselectivelyengagenativecoronaryarteriesorcoronarybypass graftsoftenresultsininsufficientopacificationofthelumentoaccuratelyassesscoronaryanatomyorstenosispresence and/orseverity.Inabilitytorecognizethepresenceofanomalouscoronaryarteriescontributestothisproblem. Theimplicationsofinadequate,orincomplete,studiesaresignificantandrangefromtheneedtorepeatproceduresto theperformanceofunnecessaryandmoreinvasiveprocedures.Inadequateopacificationoftheventricleduetohand injectionsisinappropriate.Inthecoronaryinterventionalera,theneedforhighqualitydiagnosticangiographyisgreat, becauselifealteringdecisionsaregenerallymadeonthebasisofthisinformation.Thisincludesfailuretoopacify vesselsfullyduetoinappropriateinjection,incorrectcathetersizing,orfailuretoobtainadequateviewsthatbest characterizethelesion.Foralltheaboveissues,itisnotunreasonabletoexpectarateofinadequateorincomplete diagnosticproceduresofnogreaterthan1%.

CatheterSelection
Cathetersusedfordiagnosticcoronaryarteriographyaregenerallyconstructedof polyethyleneorpolyurethane,withsomecontainingabraidedwirewithinthewallto allowadvancementanddirectionalcontrol(i.e.,torqueability)andtopreventkinking. Overtime,thediametershavebeenreduced,andmostdiagnosticproceduresare nowtypicallyperformedwith56Frcatheters.Withtheuseofmechanicalinjection devices,4Frcathetersarealsoutilized.Thecathetershapesmostcommonlyused forcoronaryarteriographyinclude: TheleftJudkinscatheter(Figures21a,b).Preshapedtoallowentryintothe leftcoronaryostium,theleftJudkinsisthemostcommoncatheterfortheleft coronarysystem.Thepatient'sbodyhabitusandaorticrootsizedetermine thecurvesizeoftheleftJudkinscatheter,withadilatedascendingaorta requiringthelarger5.0or6.0curvecatheters.AleftJudkinscathetercanalso beusedwithleftbrachialorradialarteryaccess,butacathetercurve0.5cm smallerthanthatusedfromthefemoralapproachisoftennecessary. TherightJudkinscatheter(Figures22a,b,c).TheJudkinsrightcatheterhas agentleprimarycurveandrequiresclockwiserotationtocannulatetheright coronaryartery(RCA)whenadvancedfromafemoralarteryaccess.Ifused frombrachialorradialaccess,therightJudkinscatheterrequires counterclockwiserotationtoengagetheRCA.ArightJudkinscathetermay alsobeusedtocannulatesaphenousveingrafts(SVGs)andofteninternal mammarygraftsprovidinggoodvisualizationformanygraftstoleftcoronary branches,andalsosomegraftstotheRCA. LeftAmplatzcatheters(Figures23a,b).Amplatzleftcathetershavethree curvesizes(L1,L2,orL3),withthelargercurvesusedfordilatedaortas.An Amplatzleft0.75catheterisusefulforsomeRCAinterventions.Amplatz catheterscanbeusedfromthefemoral,brachial,orradialarteriestoengage boththeleftcoronaryarteries(LCAs)andRCAs,andareanalternativewhen aJudkinscatheterdoesnotengagethecoronaryostium.Theymayalsobe usedtoengagesomeSVGs,particularlyleftSVGsinthesettingofadilated aorticroot. RightAmplatzcatheter(Figures24a,b).AmodifiedrightAmplatzcatheter (AR1orAR2)canbeusedforengagementofahorizontalordownward takeoffoftheRCAorSVG.Itisalsosometimesusefulwhenastandardright Judkinscatheterpersistentlyengagesaconusartery.Itmayhelpfacilitate opacificationofanaberrantcircumflexarisingfromtheRCA. Internalmammaryartery(IMA)catheter(Figures25a,b).TheIMAcatheterhas anangulateddesignforengagementoftheIMAandisgenerallybetterthan therightJudkinscatheterforthispurpose.Itisalsousefulforanupward takeoffoftheRCAandsomeveingraftstotheLCA. Multipurposecatheter(Figure26).Themultipurposecatheterhasshallow primarycurveandishelpfulinengagingdowngoingRCASVGsandcanbe usedtoselectivelyengageanaberrantleftcircumflex(LCx)arisingfromthe RCA.Someoperatorsusethisasasinglecathetertocompletebothright andleftcoronaryangiography. Speciallydesignedcathetersfortheradialarteryapproachhavealsobeen developed(Figure27).Itisalsosometimesusefulwhenastandardright Judkinscatheterpersistentlyengagesaconusartery.Itmayhelpfacilitate opacificationofanaberrantcircumflexarisingfromtheRCA.

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JudkinsLeftCatheter(1of2) Figure21a

ReproducedwithpermissionfromMarkFreedandRobertSafian.

TipLengthoftheJudkinsLeftCatheter(2of2) Figure21b ReproducedwithpermissionfromMarkFreedandRobertSafian.

JudkinsRightCatheter(1of3) Figure22a ReproducedwithpermissionfromMarkFreedandRobertSafian.

TipLengthoftheJudkinsRightCatheter(2of3) Figure22b ReproducedwithpermissionfromMarkFreedandRobertSafian.

TechniquefortheEngagementoftheJudkinsRightCatheterintheRightCoronaryArtery(3of3) Figure22c ReproducedwithpermissionfromMarkFreedandRobertSafian.

AmplatzLeftCatheter(1of2) Figure23a ReproducedwithpermissionfromMarkFreedandRobertSafian.

TipLengthoftheAmplatzLeftCatheter(2of2) Figure23b P=primarycurveS=secondarycurveT=tertiarycurve. ReproducedwithpermissionfromMarkFreedandRobertSafian.

AmplatzRightCatheter(1of2) Figure24a ReproducedwithpermissionfromMarkFreedandRobertSafian.

TipLengthoftheAmplatzRightCatheter(2of2) Figure24b ReproducedwithpermissionfromMarkFreedandRobertSafian.

InternalMammaryArteryCatheter(1of2) Figure25a Eithertheleftcoronarybypasscatheter(LCB)orinternalmammaryartery(IMA)cathetercanbeusedtoengagetheleftIMAviatheleft subclavianartery. ReproducedwithpermissionfromMarkFreedandRobertSafian.

LeftCoronaryBypassandInternalMammaryArteryCatheters(2of2) Figure25b Eithertheleftcoronarybypasscatheter(LCB)orinternalmammaryartery(IMA)cathetercanbeusedtoengagetheleftIMAviatheleft subclavianartery. ReproducedwithpermissionfromMarkFreedandRobertSafian.

MultipurposeCatheter Figure26 Multipurposecanbeparticularlyusefulforengagingdowngoingrightcoronaryarterysaphenousveingraft. ReproducedwithpermissionfromMarkFreedandRobertSafian.

RadialArteryAccessGuideCathetersKimnyCatheters Figure27 Theshapesshownherearecommonlyusedfromtheradialartery. ReproducedwithpermissionfromMarkFreedandRobertSafian.

AnatomyandVariationsoftheCoronaryArteries
Majorepicardialbranches,plussecondandthirdorderbranches,canbeidentifiedusingcoronaryarteriography. Smaller"resistance"vesselsarenotvisualizedbyconventionalangiography,butcanbequalitativelyassessedusing framecountsandamyocardialblushscore.14Thesevesselsareresponsibleforautoregulationofcoronarybloodflow, whichoccursinresponsetoupstreamstenosesintheepicardialorconduitarteries.

NormalCoronaryAnatomy
Thefollowingnomenclatureisusedforthecoronaryartery: Leftmaincoronaryartery(LMCA).TheLMCAarisesfromthesuperiorportionoftheleftaorticsinus,justbelow thesinotubularridgeoftheaorta.TheLMCAbifurcatesintotheLADarteryandLCxbranches.Insomepatients, theLMCAtrifurcatesintotheLAD,LCx,andramusintermedius,whichtraversesbetweentheLADandLCx arteriesandhasadistributionsimilartoaproximaldiagonalorobtusemarginalbranch. LADartery.TheLADcoursesalongtheepicardialsurfaceoftheanteriorinterventriculargroovetowardthecardiac apex.ThemajorbranchesoftheLADaretheseptalanddiagonalbranches.Septalbranchesariseat90angles fromtheLADandpassintotheinterventricularseptumthebranchesrepeatedlydivideas"pitchforking"branches thatsupplyacascadeofvesselstotheseptum.ThediagonalbranchesoftheLADpassovertheanterolateral aspectoftheheart,butthereiswidevariabilityinthenumberandsizeofdiagonalbranches,withmost(90%)of thepatientshavingonetothreediagonalbranches.TheLADcoursesaroundtheLVapexandterminatesalong thediaphragmaticaspectoftheLV. LCxartery.TheLCxarteryoriginatesfromtheLMCAandcourseswithintheposterior(left)arteriovenous(AV) groovetowardtheinferiorinterventriculargroove.ThedistalLCxvariesinitssizeandlength,dependingonthe numberofposterolateralbranchessuppliedbythedistalRCA,andgivesoffonetothreelargeobtusemarginal branchesthatsupplytheposterolateralwall. RCA.TheRCAoriginatesfromtherightanterioraorticsinussomewhatinferiortotheoriginoftheLCA,and passesalongtherightAVgroovetowardthecrux(i.e.,apointonthediaphragmaticsurfaceoftheheartwherethe anteriorAV,theposteriorAVgroove,andtheinferiorinterventriculargroovecoalesce).ThefirstbranchoftheRCA isgenerallytheconusarteryandthesecondbranchoftheRCAusuallyisthesinoatrialnodeartery.Themid portionoftheRCAusuallygivesrisetooneorseveralmediumsizedacutemarginalbranches.Thesebranches supplytheanteriorwalloftherightventricle(RV)andmayprovidecollateralcirculationinpatientswithLAD occlusion.TheRCAterminatesinaposteriordescendingbranch(PDA)andoneormorerightposterolateral branches. Dominance.DominanceisdefinedbywhethertheLCAorRCAsuppliesthePDA.TheRCAisdominantin85%of patients,supplyingthePDAandatleastoneposterolateralbranch(e.g.,rightdominant).ARCAthatgivesriseto thePDAwiththeLCxarteryprovidingalltheposterolateralbranchesisdesignatedabalancedorcodominant circulation.WhentheLCxsuppliesthePDA,thecirculationisdesignatedasleftdominant.

AngiographicProjections
Duetotheobliqueorientationoftheheartwithinthechestcavity,thecoronary circulationisusuallybestvisualizedusingangulatedrightanterioroblique(RAO) andleftanterioroblique(LAO)projections(Figures2829a,b,c).Inadditiontoright orleftangulation,simultaneousrotationinto"cranial"(towardthehead)and"caudal" (towardthefoot)projectionsallowsvisualizationofcertaincoronaryarterysegments inunforeshortenedprojections(Figure29d,e).Althoughthe"optimal"angiographic projectiondependslargelyonbodyhabitus,variationinthecoronaryanatomy (Figures30a,b,c,d,e,f,g),andlocationoflesion,standardprojectionsfortheLCA include: Theanteroposterior(AP)projectionwithshallowcaudalangulationisoften performedfirsttoidentifylesionswithintheoriginoftheLMCA. LAOcaudalviewevaluatestheLMCA,theoriginoftheLAD,andproximal segmentoftheLCx(Figure31). LAOcranialviewdemonstratesthemidanddistalLAD,whichshouldhave sufficientleftwardpositioningoftheimageintensifiertoallowseparationof theLAD,diagonal,andseptalbranchesandnotsuperimposethespine (Figure32).Thisviewcanalsobehelpfulinevaluatingthedistalleftarising PDAandposterolateralbranchesinaleftdominantcoronarysystem. AshallowRAOorAPcranialviewevaluatesthemidanddistalportionofthe LADandoriginofthediagonalbranches(Figure33). TheRAOcaudalviewassessestheLCxanditsobtusemarginalbranches andcanbeusefulinevaluatingtheproximalLAD(Figure34). TheRCAshouldbevisualizedusingthefollowingviews: LAOcranialviewdemonstratestheRCAandoriginofthePDAand posterolateralbranches(Figure35). RAOviewshowsthemidRCAandproximal,mid,anddistalterminationof thePDA. APcranialprojectiondemonstratesthedistalterminationoftheRCA, includingthebifurcationoftheRCAandPDA(i.e.,the"crux")andtheright posterolateralbranches(Figure36). LeftlateralviewvisualizestheostiumoftheRCAandmidportionoftheRCA withseparationoftheRCAanditsRVbranches(Figure37).

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Figure36

Figure37

MinimizingOverlapandForeshortening Figure28 Whenviewingacineangiogram,itissometimesdifficulttovisualizethe3Dnatureofthecoronaryarterialsystem.Itisimportant,however,to keepinmindthenatureofthecoronarydistributionandthefactthata2Drepresentationinanyoneviewisinadequatetofullydelineate coronaryanatomy.Lesioneccentricity,foreshortening,andvesseloverlapmakeitnecessarythatthecoronaryarteriesareexaminedinmultiple views.Thisschematicshowstheright(RCA)andleft(LCA)coronaryarteriesdepictedintheleftanterioroblique(LAO)andrightanterior oblique(RAO)projections,respectively.Approximatefrontalandsagittalplaneprojectionsandangulationsforoptimalvisualizationofvarious portionsofthecoronaryarteriesareindicated.Thearterialbranchesarenotedas:SNA,sinusnodearteryRV,rightventricularAMacute marginalLC,leftcircumflexPDA,posteriordescendingarteryPLV,posteriorleftventricularOM,obtusemarginalS,septalD,diagonalLAD, leftanteriordescending. ReproducedwithpermissionfromLiipincott,WilliamsandWilkins.PepineCJ,HillJA,LambertCR,eds.DiagnosticandTherapeuticCardiac Catheterization,2nded.Baltimore:Lippincott,Williams&Wilkins,1994.www.lww.com

CoronaryImagingintheTransversePlane(1of3) Figure29a Coronaryimagingisperformedbyrotatingthecamerainthetransverseplane. RAO=rightanterioroblique. ReproducedwithpermissionfromMarkFreedandRobertSafian.

CoronaryImagingintheTransversePlane(2of3) Figure29b Inthe30rightanterioroblique(RAO)projection,aninterventricularplaneandAVplanesarevisualized.Therightcoronaryartery(RCA) transversestheanteriorAVplaneandgivesrisetothesinusnodebranch(SN),theconusbranch(CB),rightventricularbranches(RV),acute marginalbranches(AcM),aposteriordescendingbranch(PD),andaposterolateralbranch(PL).Theleftanteriordescending(LAD)artery transversestheanteriorinterventricularplaneandgivesrisetodiagonalbranches(D)andseptalbranches(S).Theleft(L)circumflex(CX) coursesintheposteriorAVplaneandgivesrisetoobtusemarginalbranches(OM). ReproducedwithpermissionfromMarkFreedandRobertSafian

CoronaryImagingintheTransversePlane(3of3) Figure29c TheserelationshipsdiscussedinFigure29barealsoshownhereintheLAOprojection. AcM=acutemarginalbranchCB=conusbranchCX=circumflexD=diagonalbranchL=leftLAD=leftanteriordescending LAO=leftanteriordescendingOM=obtusemarginalbranchPD=posteriordescendingbranchPL=posterolateralbranch RCA=rightcoronaryarteryRV=rightventricleS=septalbranchSN=sinusnodebranch. ReproducedwithpermissionfromMarkFreedandRobertSafian.

MovementofCameraTowardHead(1of2) Figure29d Movementofthecameratowardthehead(cranialangulation)permitsbetterdemonstrationofsomecoronaryarterysegmentsbyminimizingthe degreeofvesselforeshortening. ReproducedwithpermissionfromMarkFreedandRobertSafian.

MovementofCameraTowardFeet(2of2) Figure29e Movementofthecameratowardthefeetpermitsbetterdemonstrationofsomecoronaryarterysegmentsbyminimzingthedegreeofvessel foreshortening. ReproducedwithpermissionfromMarkFreedandRobertSafian.

LeftMainCoronaryArteryandRamusIntermedius:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(1of7) Figure30a AP=anteroposteriorBARI=bypassangioplastyrevascularizationinvestigationLAD=leftanteriordescendingLAO=leftanteriorobliqueLV= leftventricularRAO=rightanterioroblique.

LeftAnteriorDescendingArtery:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(2of7) Figure30b BARI=bypassangioplastyrevascularizationinvestigationLAO=leftanteriorobliqueRAO=rightanterioroblique.

LeftAnteriorDescendingArtery:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(3of7) Figure30c BARI=bypassangioplastyrevascularizationinvestigationLAD=leftanteriordescendingLAO=leftanteriorobliqueLV=leftventricularRAO =rightanterioroblique.

LeftCircumflexArtery:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(4of7) Figure30d BARI=bypassangioplastyrevascularizationinvestigationLAO=leftanteriorobliqueLV=leftventricularRAO=rightanterioroblique.

LeftCircumflexArtery:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(5of7) Figure30e BARI=bypassangioplastyrevascularizationinvestigationLAO=leftanteriorobliqueLV=leftventricularRAO=rightanterioroblique.

RightCoronaryArtery:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(6of7) Figure30f AP=anteroposteriorBARI=bypassangioplastyrevascularizationinvestigationLAD=leftanteriordescendingPDA=posteriordescending arteryRAO=rightanteriorobliqueRCA=rightcoronaryartery.

RightCoronaryArtery:Nomenclature,Definitions,Descriptions,andRecommendedAngiographicProjections(7of7) Figure30g AP=anteroposteriorBARI=bypassangioplastyrevascularizationinvestigationLAO=leftanteriorobliqueRA=rightatriumRAO=right anteriorobliqueRV=rightventricle.

LeftMainCoronaryArtery Figure31 Leftmaincoronaryarteryshownintheleftanteriorobliqueprojectionwithcaudalangulation.

LeftAnteriorDescendingArteryShowninLeftAnteriorObliqueProjection Figure32 Leftanteriordescendingarteryshownintheleftanterioroblique(LAO)projectionwithcranialangulation.

LeftAnteriorDescendingArteryShowninAnteriorProjection Figure33 Leftanderiordescendingarteryshownintheanteroposterior(AP)projectionwithcranialangulation.

LeftCircumflexCoronaryArteryShowninRightAnteriorObliqueProjection Figure34 LeftcircumflexcoronaryarteryshownintheRAOprojectionwithcaudalangulation. LAD=leftanteriordescendingRAO=rightanterioroblique.

RightCoronaryArteryShowninLeftAnteriorObliqueProjection Figure35 RightcoronaryarteryshownintheLAOprojectionwithcranialangulation. LAO=leftanteriorobliqueRV=rightventricular.

RightCoronaryArteryShowninAnteriorProjection Figure36 RightcoronaryarteryshownintheAPprojectionwithcranialangulation. AP=anteroposteriorRV=rightventricular.

RightCoronaryArteryShowninLeftLateralProjection Figure37 Rightcoronaryarteryshownintheleftlateralprojection. RV=rightventricular.

CongenitalAnomaliesoftheCoronaryCirculation
Congenitalcoronaryanomaliesareinfrequent(<1%)findingsoncoronary arteriography,butmaybeassociatedwithmyocardialischemiaincertainsettings (Table1).12ThemostcommonanomalyisaseparateoriginoftheLADandLCx coronaryarteries,followedbytheoriginoftheLCxfromtherightcoronarysinusand originoftheRCAfromtheleftcoronarysinus.Asinglecoronaryarteryisavery infrequentfinding.13,14Coronaryarteryanomaliesaredividedintothosethatcause anddonotcausemyocardialischemia.15Formoreinformation,seethemoduleon CoronaryAnomaliesandFistulaeinChapter17.

Table1

CoronaryAnomalies Table1 Thedatainthistablearebasedonanalysisof126,595angiograms.ThemostcommonanomaliesareseparateoriginsforLADandLCX,andLCX arisingfromtherightcoronarysinus. LAD=leftanteriordescendingLCX=leftcircumflexLMCA=leftmaincoronaryarteryLSV=leftsuperiorveinPSV=percutaneoussubclavian veinRCA=rightcoronaryarteryRSV=rightsuperiorvein. AdaptedwithpermissionfromYamanakaO,HobbsRE.Coronaryarteryanomaliesin126,595patientsundergoingcoronaryarteriography. CathetCardiovascDiagn199021:2840.

AnomaliesThatCauseMyocardialIschemia
Coronaryarteryfistulaearemicroormacrovascularconnectionsbetween thecoronaryarteryandacardiacchamber,vein,oranotherartery(Figure38). Aboutonehalfofthepatientswithacoronaryarteryfistulaareasymptomatic, buttheotherhalfdevelopsHF,infectiveendocarditis,mycocardialischemia, orruptureofananeurysm.16Fistulaecanarisefromanyofthecoronary arteries,anddrainintotheRV,RA,pulmonaryartery,LV,orsuperiorvena cava.6 Coronaryarteriographyisthebestmethodtoidentifythelefttoright shuntresultingfromthesefistulae. LCAoriginfromthepulmonaryartery.Thiscoronaryanomalyisgenerally manifestasHFandmyocardialischemiainthefirst4monthsoflife.17 However,about25%ofpatientssurvivetoadolescenceoradulthoodwhen theydevelopmitralregurgitation,angina,orHF.11Aortographydemonstrates alargeRCAwiththeabsenceofaleftcoronaryostiumintheleftaorticsinus. Duringthelatephaseofanaortogram,patulousLADandLCxbranchesare seenfillingbycollateralcirculationfromRCAbranches.Retrogradeflowfrom theLADandLCxopacifiestheLMCAanditsoriginfromthemainpulmonary artery.Theclinicalcourseofthepatienttendstobemorefavorableif extensivecollateralcirculationexists. Congenitalcoronarystenosisoratresiaofacoronaryarterycanoccurasan isolatedlesionorinassociationwithothercongenitaldiseases(e.g.,calcific coronarysclerosis,supravalvularaorticstenosis,homocystinuria, Friedreich'sataxia,Hurler'ssyndrome,progeria,andrubellasyndrome). Whenthisoccurs,theatreticvesselusuallyfillsbymeansofcollateral circulationfromthecontralateralside.18 Anomalousoriginofeithercoronaryarteryfromthecontralateralsinus (Figure39).AnoriginoftheLCAfromtheproximalRCAortherightaortic sinusthatpassesbetweentheaortaandtheRVoutflowtracthasbeen associatedwithsuddendeathduringexerciseinyoungpersons.1922The increasedriskofsuddendeathhasbeenattributedtomyocardialischemia andelectricalinstabilityduetoaslitlike,flowlimitingostiumwithacute takeoffanglesoftheaberrantcoronaryarteriesorbycompressionbetween thepulmonarytrunkandaorta.OriginoftheRCAfromtheLCAorleftaortic sinuswithpassagebetweentheaortaandtheRVoutflowtractissomewhat lessdangerous,buthasalsobeenassociatedwithsuddendeath. WheneithertheLCAor,morefrequently,theLCx,arisesanomalouslyfrom therightaorticsinus,thecourseoftheaberrantarterycanbe: Anteriortothepulmonaryartery. Posteriortotheaorta(Figures40,41,42). Betweentheaortaandpulmonaryartery. Throughtheproximalportionoftheintraventricularseptum. Determiningthecourseoftheanomalousarterycanbedifficult.Itis sometimeshelpfultoplaceapulmonaryarterycathetertoclearlyidentifythe locationofthemainpulmonaryarteryinmultipleangulatedviews.An arteriogramoftheaberrantcoronaryarteryinasteepAPcaudalprojection maybehelpfulindeterminingwhetherthecourseoftheaberrantcoronary arteryisbetweenthegreatvessels,althoughcoronaryCTangiographyis nowthepreferredapproachtoconfirmingtheaberrantarteriescourse. Singlecoronaryartery.Althoughtherearenumerousvariationsofthis anomaly,itassumeshemodynamicsignificancewhenamajorbranch passesbetweentheaortaandtheRVoutflowtract.

Figure38

Figure39

Figure40

Figure41

Figure42

FistulaFromProximalLeftAnteriorDescending Figure38 Leftcoronaryangiographyperformedintherightanteriorobliqueprojectionshowsanumberofsmallvessels(arrows)arisingfromtheproximal leftanteriordescending(LAD)andformingaplexusemptyingintotheproximalpulmonaryartery.Suchsmallcoronarytopulmonaryarterial fistulaearenotuncommonbutareinfrequentlycorrectlyidentified.Theyappeartohavenohemodynamicsignificance,andcanarisefrom proximalportionsofeithertheleftorrightcoronaryarterialsystems.

LeftMainCoronaryArteryArisingFromtheRightSinusofValsalva Figure39 RAO=rightanterioroblique. ReproducedwithpermissionfromPepineCJ,HillJA,LambertCR,eds.DiagnosticandTherapeuticCardiacCatheterization.3rded.Baltimore: LippincottWilliams&Wilkins1998:275.

LeftCircumflexFromRightCoronaryArtery Figure40 Intheleftpanel,injectionoftherightcoronaryartery(RCA)revealsfillingoftheleftcircumflex(LCX)artery.Thepathisdescribedbythe arrows.ItalwayscoursesposteriorlytotheaortatoreachtherightAVgroove.Intherightpanel,theleftanteriordescending(LAD)isshownas asinglevessel. ReproducedwithpermissionfromYamanakaO,HobbsRE.Coronaryarteryanomaliesin126,595patientsundergoingcoronaryarteriography. CathetCardiovascDiagn199021:2840.

AnomalousLeftCircumflexCoronaryArtery Figure41 Injectionoftherightcoronaryarteryintherightanteriorobliqueprojectiondemonstratesthattheleftcircumflexcoursesposteriortotheaorta. ReproducedwithpermissionfromBaimDS.GrossmansCardiacCatheterization,Angiography,andIntervention.7thed.CompanionCD. Philadelphia:LippincottWilliams&Wilkins2005.

AnomalousOriginofLeftCoronaryArteryFromRightSinusofValsalvainRightAnteriorObliqueProjection Figure42 Inthisinstance,thereisanextremeanteriorandsuperiorcourseoftheanomalousleftcircumflexartery.Thetopofthe"eye"isdisplayedand basedonthe"dotandeye"systemitsuggeststhattheleftcoronaryarterydoesnottravelbetweenthepulmonaryarteryandaorta.

AnomaliesNotCausingMyocardialIschemia
OriginoftheLCxarteryfromtherightaorticsinus.Aleftcircumflexarisingfromtherightaorticsinusgenerally coursesinferiorlyandposteriorlytotheaortatoentertheleftAVgroove. HighanteriororiginoftheRCAiscommonlyencounteredduringdiagnosticangiography,butisofno hemodynamicsignificance.Inadditiontoitsoriginmoredistallyintheaorta,thecoronaryostiumisalso commonlyanteriorandcanbeengagedwithanAmplatzleft1.0or2.0catheter.

CoronaryArterySpasm
Definedasadynamicandreversiblenarrowingorocclusionofanepicardial coronaryarteryduetofocalconstrictionofthesmoothmusclecellswithinthearterial wall,coronaryarteryspasmwasdescribedasaclinicalsyndromein1959by Prinzmetalandcolleagues.Thisvariantformofanginaor"Prinzmetal'sangina"is characterizedbytheonsetofsymptomsatrestorbothatrestandduringexertion, occurringinacyclicalpattern,oftenatthesametimeeveryday,andaccompaniedby STsegmentelevationintheECGleadsreflectingthedistributionoftheaffected coronaryartery. Coronaryarteryspasmcanbeinvokedby: Cigarettesmoking. Hyperventilation. Cocaineuse. Alcoholintake. Intracoronaryradiation. Administrationofcatecholaminesduringgeneralanesthesia. ThemarkedSTsegmentelevationmaybeaccompaniedbyAVblock,ventricular ectopicactivity,ventriculartachycardia,orventricularfibrillation.Dynamiccoronary arteryspasmrapidlyrevertstonormalasthepaindisappearsspontaneouslyoris terminatedbytheadministrationofnitroglycerin.MIanddeatharerare manifestationsofcoronaryarteryspasm.Coronaryarteryspasmcanbe superimposedonthepresenceofanintramyocardialbridge(Figure43). Coronaryarteriographymaybeusefulinpatientswithsuspectedcoronaryartery spasm,bothtoexcludethepresenceofconcomitantCADandtodocumentan episodeofcoronaryarteryspasmusingprovocativeIVmedications.MIinthe absenceofobviousepicardialcoronaryarterynarrowingisoftenattributedto coronaryarteryspasm,butotherconditions(e.g.,TakoTsubo,transientcoronary thrombosisfromarupturedintramuralcoronaryplaque,myocarditis,coronary embolism,hypercoagulablestates,coronarytrauma,andanemia)mustfirstbe excluded. Threeprovocativetestscanbeperformedtodetectthepresenceofcoronaryartery spasm: IVmethylergonovinemaleate.Althoughergonovinemaleateisnolonger available,methylergonovinemaleatecanbesubstitutedwithsimilarresults. Twotypesofangiographicresponsescanbeexpectedwithescalating dosage. Adiffusecoronaryvasoconstrictionmayoccurinalltheepicardial arteriesthatmaybeassociatedwithanginasymptoms.This physiologicresponsetoergonovineisnotdiagnosticofcoronary arteryspasms. Thesecondresponsetoergonovineisafocal,occlusivespasmofan epicardialarterythatisassociatedwithchestpainandSTsegment elevation.Nitroglycerinshouldbeadministereddirectlyintothe coronaryarterytorelievethecoronaryspasm.Thisresponsehas beenutilizedasadiagnosticresponseforcoronaryarteryspasm however,thespecificity,sensitivity,andsafetyhascalledintoquestion theuseofIVmethylergonovinemaleate. IVacetylcholinemayalsobeusedtodetectthepresenceofcoronaryartery spasm.Althoughitismoresensitive,itmaybelessspecificduetoits positiveresponseinpatientswithatheroscleroticCAD. Hyperventilationduringcoronaryarteriographyislesssensitive,buthighly specificforthepresenceofcoronaryarteryspasm. Intheabsenceofapositivestimulationtest,thediagnosisofcoronaryarteryspasm mustrelyonclinicalfeaturesandresponsetotreatmentwithnitratesandcalcium channelblockers.

Figure43

IntramyocardialBridge Figure43 Compressionofthemidsegmentoftheleftanteriordescendingarteryduringcardiacsystole.

CoronaryCollateralCirculation
Networksoftinyanastomoticbranchesinterconnectthemajorcoronaryarteries,butcannotbevisualizedinpatientswith normalormildlydiseasedcoronaryarteriesbecausetheycarryonlyminimalflowandareofsmall(<200mc)caliber.23In thepresenceofsignificant(>90%)coronaryobstruction,apressuregradientisgeneratedwithinanastomoticvessels, connectingthedistalhypoperfusedsegmentwiththeoriginofthecollateralchannel.Thispressuregradientfacilitates bloodflowthroughtheanastomoticvessels,resultinginprogressivedilatationandthedevelopmentofvisiblecollateral channels.Visiblecollateralchannelsariseeitherfromthecontralateralcoronaryarteryorfromtheipsilateralcoronary throughintracoronarycollateralchannelsorthrough"bridging"channelsthathaveaserpiginouscoursefromthe proximalcoronaryarterytothecoronaryarterydistaltotheocclusion. Kugel'sarteryisacollateralchannelcoursingthroughtheatrialseptumtoconnectthesinoatrialnodalarterytotheAV nodalartery.Thiscollateralchannelreconstitutesthedistalrightcoronarycirculationafterproximalocclusionofa dominantRCAorthedistalcircumflexcirculationafterproximalocclusionofadominantcircumflexartery.

QuantitativeAngiography
Quantitativeangiography,althoughinfrequentlyusedinclinicalpractice,isausefulresearchmethodtoreliablyassess thequantitativechangesinlumendimension,withsubstantiallylowerintraandinterobservervariabilitycomparedwith visual"eyeball"estimates,whicharenotoriouslypoorlyreproducible.24Absolutecoronarydimensionsaredetermined usingthecontrastagentfilleddiagnosticorguidingcatheterasthecalibrationdevice.Offlinequantitativeangiographic analysishasremainedthecornerstoneofevaluatingthevalueofdrugsanddevicesusedtopreventrestenosisafterPCI. Anumberofstandardmeasuresofchangesinlumendiameterovertimehavebeenintroduced.Theseindicesare typicallycalculatedforboththeentiretreatmentsegmentandalsojustwithinthestent. Acutegain,whichistheincreaseinlumengainafterPCI.Itisdeterminedbysubtractingthefinalminimallumen diameter(MLD)fromthebaselineMLD. Lateloss,whichisthelossinlumendiameterlateafterPCI.ItisdefinedbysubtractingthefollowupMLDfrom thefinalMLD. Netgain,whichistheincreaseinlumendiameterfromthebaselinetothefollowupangiogram.Itisdefinedas thebaselineMLDsubtractedfromthefollowupMLD. Latelossindex,whichisdefinedaslateloss/acutegainortheratiooflatelosstoacutegain. Binaryrestenosis,whichisdefinedas>50%followupdiameterstenosis.

ComplicationsofCoronaryAngiography
Thereisextensive,albeitdated,literatureonthemajorcomplicationsofdiagnostic cardiaccatheterization.Fortunately,the(composite)rateofmajoradversecardiac andcerebrovasculareventsis"acceptably"lowat<12%.25Asexpected,the likelihoodofmajorcomplicationsincreasessignificantlywiththeseverityofthe underlyingcardiacandnoncardiacdisease.Thepredominantfactorsaffectingrisk are:1)advancedcoronarydisease(e.g.,leftmain,triplevesseldisease),2) impairedventricularfunction,3)severevalvulardisorderssuchassevereaortic stenosis,4)lowcardiacoutput,5)pulmonaryhypertension,6)severeperipheral vasculardisease,and7)olderage.Majorandminorcomplicationsaftercoronary arteriographyinclude(Table2): Death(0.100.14%).Theincidenceofdeathduringcoronaryarteriographyis higherinthepresenceofleftmainCAD(0.55%),aLVEF<30%(0.30%),and NewYorkHeartAssociationfunctionalclassIVdisease(0.29%)(Table3). MI(0.060.07%).MImayoccurfromthrombosisofacriticalstenosisduring angiography,proximaldissectionofanarterybythecoronarycatheter,orwith embolizationofairorthrombusintothedistalcoronarybed. Cerebralischemiaorneurologiccomplications(0.070.14%).Strokemay occurfromembolizationofatheroscleroticdebrisintothecerebralcirculation orembolizationofaclotthatformedonthecoronarycatheters.26,27Embolic strokesduetoatheroscleroticdebrisorclotaregenerallyreversible.28,29 Severecontrastagentreactions(0.23%). Vascularaccesscomplications(0.51%)(Figure44).Theincidenceofthese complicationsisinfluencedbythepresenceofperipheralvasculardisease, thediameteroftheaccesssheath,andtheuseofanticoagulantand antiplateletagents(Figure45).30Accesssitecomplicationsinclude: Peripheralvascularthromboembolism.Thiscomplicationisgenerally notedbythepresenceofanischemialimb,withpain,paresthesias, coolness,andlossoffunction(Figure46).Immediateembolectomy isrequiredtoavoidtissuelossandthedevelopmentofcompartment syndrome. AVfistula.TheriskofAVfistulaisassociatedwiththepunctureofthe femoralveinaswellasthefemoralartery.Whenpunctureoccurs, thereistheopportunityforapersistentcommunicationtodevelop betweenthesetwovessels.SmallAVfistulaearewatched conservativelywithoutsurgicalrepair.Attemptstooccludethe communicationbyprolongedcompressionhavebeengenerally unsuccessful.Surgicalclosureisrecommendedforlargefistulas, althoughtheuseofacoveredstenthasbeenperformedatsome centers. Pseudoaneurysm.Pseudoaneurysmformationisassociatedwiththe punctureofthesuperficialordeepbranchesofthefemoralartery,as opposedtothecommonfemoralartery(Figures47a,b).Small(<2 cm)femoralpseudoaneurysmsclotspontaneouslyandusually requirenotreatment.Largerfemoralpseudoaneurysmsmayleadto complicationsincludingruptureandcompressionoftheadjacent femoralvein(withresultingvenousthrombosis)orofthefemoral nerve.Itisprudenttointervenewhentheyarelargerorwhenthey occurinpatientshavingacontinuedneedforanticoagulanttherapy. Vascularultrasoundcanbeusedtodetectthepresenceofa pseudoaneurysm(Figure47b),anddirectpercutaneousinjectionof thrombin(orfibrinadhesiveintothepseudoaneurysmtoaccelerate thrombosis),underultrasoundguidance,isassociatedwithahigh successrate.Alternatively,surgicalexplorationandrepairshouldbe reservedforfailuresoflessinvasiveprocedures.3133Predictorsof failurearemorelikelyifthepatientrequirescontinued anticoagulation,oriftheneckoftheaneurysmisverybroad. Retroperitonealhematoma.Accessingtheiliacarterymayresultin theinabilitytoachieveadequatecompressiontoachievehemostasis. Occultbleedingmayrequirevigorousfluidresuscitationandblood transfusions.Withthesemeasures,thebleedingusually

Table2

Table3

Figure44

Figure45

Figure46

Figure47a

Figure47b

Figure48a

Figure48b

tamponadesspontaneouslywithhemodynamicstabilization.Surgical interventionmaybenecessarytoligatethesiteofthearterial bleeding,butisundertakenonlyforongoinghemorrhagebecauseof theanatomicdistortioncausedbythediffusebleedingwithinthe retroperitonealspace.Thedevelopmentofhypotension,not attributabletoanothercause,shouldpromptconsiderationof bleeding.Earlydetectioncanbelifesaving.Onlyafterhemodynamic stabilizationandresuscitationshouldthepatientundergoevaluation byCTscan.34 Groinhematoma.Theexpansionofbloodintothethighcanproduce asignificantdegreeofswellingandpain.Althoughmostepisodes resolvespontaneously,surgicaltherapyisreservedforuncontrollable bloodlossorforthedevelopmentofacompartmentsyndrome. Peripheralneuropathy.Peripheralneuropathyfollowing catheterizationprocedureshasbeenrelatedtogroinhematoma, pseudoaneurysm,andretroperitonealbleeding,eachcapableof producingnervecompression.35Sensoryandmotordeficitsmaybe severeandpermanentlydisabling.Whilethereissomecontroversy astooptimaltherapy,earlyrecognitionwillmaximizethebenefitsof surgicaldecompression.Neuropathyfollowingproceduresusing brachialarteryaccessmayalsobeduetodirecttraumatothenerve. Cholesterolembolization.Themanipulationofacatheterthroughadiseased aortamaycauseembolizationofatheromatousdebrisand/oradherent thrombus.36,37Cholesterolembolizationcanbeassociatedwithsevere sequelae,includingrenalfailureanddeath.Livedoreticularisofthelower extremitiesisanimportantfinding(Figures48a,b).Thisdisordermay complicatetheadministrationofsystemicthrombolytictherapy,evenwithout concomitantintravascularcatheterization.Itiswisetoroutinelyadvanceand removecathetersoveraguidewire,especiallyinsituationsinwhichthe embolizationofclotoratheromatousmaterialmaybelikely(e.g.,apatient withaneurysmand/orsevereatheroscleroticdiseaseoftheaorta).Inthose withahistoryofpriorembolizationorknownaorticatheroscleroticdebris, radialaccessisrecommended. Coronarydissection.Theselectiveengagementofanyvesselwithacatheter maycausedissectionoftheproximalportionofthevessel.Catheterinduced dissectionaroundtheostiumofacoronaryarterymayextendintotherootof theaortaandprogressintoanextensivetype1aorticdissection,requiring surgery.Thesecomplicationsmayresultfromthecathetertraumatizinga plaqueorajetofcontrastproducedbyvigorousinjection. Airembolization.Theriskofclinicallysignificantcoronaryairembolusduring diagnosticcoronaryarteriographyislow,occurringin<0.1%ofcases,and preventablethroughmeticulouspreparationofthetubes,manifold,and syringesusedfordyeinjection.Airembolizationcancauseacutemyocardial ischemiawiththeclinicalsignificancedependingon:1)theamountofair embolized,2)itsvasculardistribution,and3)theunderlyingmyocardial function.Embolizationofsmallamountsofairisusuallynotclinicallyevident, butlargeramountsmayproduceprofoundsymptomsandsignsofischemia. Thisisusuallyshortlivedandistreatedwithsupportivemeasures.While infrequent,theinadvertentpowerinjectionoflargevolumesofairintotheLV mayoccur,resultinginCVcollapseandcerebralembolization.Whenusing flowdirectedcathetersinthesystemiccirculationorinsituationswherea righttoleftshuntexists,theballoonshouldbeinflatedwithcarbondioxide ratherthanairbecausetheformerismorerapidlyabsorbedfromthe vascularsystemshouldtheballoonrupture.Supportivemeasures(e.g., catheteraspirationofairandhyperbaricchambertherapy)maybehelpfulfor symptomaticairembolization.Ifanairembolusandairlockdoesoccur, 100%oxygenshouldbeadministered,whichallowsresorptionofsmaller amountsofairwithin24minutes.Morphinesulfatemaybegivenforpain relief.Ventriculararrhythmiasassociatedwithairemboluscanbetreated withlidocaineanddirectcurrentcardioversion.Theuseofanaspiration cathetertoremovethe"airlock"canfacilitatetreatment. Othercomplications.Perforationoftheheartoragreatvesselmayoccur duringcatheterization,especiallywhenstiffcathetersareadvancedwithout thebenefitofaleadingguidewire.Misalignmentofatransseptalneedlemay resultincardiacperforation,whichisusuallywelltoleratedwhenthepatient

isnotanticoagulatedandonlythetipoftheneedlehasexitedthe vasculature.Myocardiallacerationorintroductionofalargeborecatheter overtheneedlewillmorelikelyresultintamponade. Majorcomplicationrateshavenotappearedtochange,despiteincreasedpatient morbidityandlesioncomplexity.38,39Theskillandexperienceoftheoperatorand supportteamarefactorsinreducingrisk.Ingeneral,interventionscarryagreater riskofcomplicationthandiagnosticprocedureshowever,somediagnostic techniques(e.g.,transseptalcatheterizationanddirectpercutaneousLVpuncture) areassociatedwithuniquerisks,andshouldonlybeperformedbyappropriately trainedindividuals.

MajorComplicationRatesforDiagnosticCardiacCatheterization Table2 ACC=AmericanCollegeofCardiologyCABG=coronaryarterybypassgraftCHF=chronicheartfailureCVA=cerebrovascularaccidentMI= myocardialinfarctionSCA&I=SocietyforCardiacAngiographyandInterventions. *ACCNationalDatabaseReport1996.SomedefinitionsusedbytheACCaredifferentfromthoseusedintheSCA&IRegistry. Arrhythmia=bradycardiaonly. **Vascular=hematoma>10.16cm.

MortalityDataforCardiacCatheterization Table3 NYHA=NewYorkHeartAssociation. ReproducedwithpermissionfromPepineCJ,HillJA,LambertCR,eds.DiagnosticandTherapeuticCardiacCatheterization.3rded.Baltimore: LippincottWilliams&Wilkins1998:275.

VascularAccessComplications Figure44

FactorsThatIncreasetheRiskofFemoralBleedingComplications Figure45

SignsandSymptomsofAcuteExtremityIschemia(5Ps) Figure46

DiagnosisandTreatmentofPseudoaneurysm Figure47a Pseudoaneurysmformationasacomplicationofdiagnosticandtherapeuticangiographicproceduresisrelatedtotheactualsiteoffemoral access,thesizeoftheintravascularsheathused,andtheaggressivenessofanticoagulantandantiplatelettherapyatthetimeofsheath removal.Whilesmallpseudoaneurysmsmayspontaneouslythrombose,largeonesareunlikelytodosoandposeariskofrupture,whichmaybe catastrophic.Duplexultrasonographyhasbecometheprocedureofchoiceforestablishingthediagnosisofpseudoaneurysm.Inthisimagewe seeajetofflow(red)originatedinthearteryandenteringarelativelylargepseudoaneurysm. PSA=pseudoaneurysm.

DiagnosisandTreatmentofPseudoaneurysm Figure47b Whilethetraditionaltherapyforpseudoaneurysmissurgicalexplorationandrepair,mostcasescannowbeapproachedwithprolonged compressionguidedbyultrasoundimaging.Thisseemsmosteffectiveinthepatientsoffanticoagulantswhohavepseudoaneurysmswith discretenarrow"necks."Thisimagedemonstratesthatafter40minutesofultrasoundguidedcompression,thereisnolongerflowintothe pseudoaneurysm,whichisnowthrombosed. LT=leftPSA=pseudoaneurysmSFA=superficialfemoralartery.

LivedoReticularis Figure48a Thesephotographsdemonstratetwoofthefindingsofatheroembolisminapatientwiththeconditionsecondarytoanabdominalaneurysm.Note inthefullphoto,overtheknees,thereareareasofintense,serpiginouscyanosisduetoarteriolarocclusionbyatheromatousdebris.Inthe closeupoftherightlegandfoot,notethebluedigits,whichareduetoocclusionofthedigitalarteries,againbyatheromatousdebris. ReproducedwithpermissionfromSpittellJAJr.Vasospasticdisorders.CardiovascClin198313:7588.

CholesterolEmbolization Figure48b Peripheralmanifestationsofcholesterolembolization. ReproducedwithpermissionfromPettelotG,BraccoJ,BarrillonD,BaudouyM,MorandP.Imagesincardiovascularmedicine.Cholesterol embolization:unrecognizedcomplicationofthrombolysis.Circulation199897:1522.

KeyPoints
Coronaryarteriographyprovidesthemostspecificinformationaboutthepresenceorabsenceofcoronaryartery narrowing,andcontinuetoguidedecisionsregardingmedicaltherapyandrevascularizationpatientswithCAD. Themostfrequentcomplicationofcatheterizationisrelatedtothevascularaccesssiteandthesecomplications occurin13%ofpatients,andincludelocalbleedingandhematoma,femoralarterialpseudoaneurysm, retroperitonealbleeding,femoralarteriovenousfistula,theneedforbloodtransfusionorrequiredsurgicalrepair, andprolongeddiscomfortandlengthofstay. Majorcomplicationsareuncommon(<1%)aftercoronaryarteriography,butincludedeath(0.100.14%),MI(0.06 0.07%),andstroke(0.070.14%). Coronarydiagnosticcathetersareshapedtoselectivelyengagecoronaryandbypassgraftostiaandare designedtoallowadvancementanddirectionalcontrolwithoutkinking. Duetotheorientationoftheheartwithinthechestcavity,thecoronarycirculationisbestvisualizedusing angulatedRAOandLAOprojectionswithcranialorcaudalangulation. Acknowledgement:TheauthorswouldliketothankDebabrataMurkherjee,M.D.,F.A.C.C.,whoauthoredthismodulein ACCSAP7,whichformedthebasisforthismodule.

References
1. ScanlonP,FaxonD,AudetAM,etal.ACC/AHAguidelinesforcoronaryangiography.AreportoftheAmerican CollegeofCardiology/AmericanHeartAssociationTaskForceonpracticeguidelines(CommitteeonCoronary Angiography).DevelopedincollaborationwiththeSocietyforCardiacAngiographyandInterventions.JAmColl Cardiol199933:1756824. 2. HeuplerFAJr.Guidelinesforperformingangiographyinpatientstakingmetformin.MembersoftheLaboratory PerformanceStandardsCommitteeoftheSocietyforCardiacAngiographyandInterventions.CathetCardiovasc Diagn199843:1213. 3. ScheinmanM,CalkinsH,GilletteP,etal.NASPEpolicystatementoncatheterablation:personnel,policy, procedures,andtherapeuticrecommendations.PacingClinElectrophysiol200326:78999. 4. BashoreT,etal.2012AmericanCollegeofCardiologyFoundation/SocietyforCardiovascularAngiographyand InterventionsExpertConsensusDocumentonCardiacCatheterizationLaboratoryStandardsUpdate:AReportof theAmericanCollegeofCardiologyFoundationTaskForceonExpertConsensusDocuments.JAmCollCardiol 2012.InPress. 5. ZiakasAG,KoskinasKC,GavrilidisS,etal.Radialversusfemoralaccessfororallyanticoagulatedpatients. CatheterCardiovascInterv201076:4939. 6. CooperC,ElShiekhR,CohenD,BlaesingL,BurketM,BasuA.Effectoftransradialaccessonqualityoflifeand costofcardiaccatheterization:Arandomizedcomparison.AmHeartJ1999138:4306. 7. RaoSV,OuFS,WangTY,etal.Trendsintheprevalenceandoutcomesofradialandfemoralapproachesto percutaneouscoronaryintervention:areportfromtheNationalCardiovascularDataRegistry.JACCCardiovasc Interv20081:37986. 8. McNultyPH,EttingerSM,FieldJM,etal.Cardiaccatheterizationinmorbidlyobesepatients.CatheterCardiovasc Interv200256:1747. 9. PatelMR,JneidH,DerdeynCP,etal.,onbehalfoftheAmericanHeartAssociationDiagnosticandInterventional CardiacCatheterizationCommitteeoftheCouncilonClinicalCardiology,CouncilonCardiovascularRadiology andIntervention,CouncilonPeripheralVascularDisease,CouncilonCardiovascularSurgeryandAnesthesia, andStrokeCouncil.Arteriotomyclosuredevicesforcardiovascularprocedures:ascientificstatementfromthe AmericanHeartAssociation.Circulation2010122:188293. 10. DauermanHL,ApplegateRJ,CohenDJ.Vascularclosuredevices:theseconddecade.JAmCollCardiol 200750:161726. 11. DuffinDC,MuhlesteinJB,AllissonSB,etal.Femoralarterialpuncturemanagementafterpercutaneouscoronary procedures:acomparisonofclinicaloutcomesandpatientsatisfactionbetweenmanualcompressionandtwo differentvascularclosuredevices.JInvasiveCardiol200113:35462. 12. LevinDC,FellowsKE,AbramsHL.Hemodynamicallysignificantprimaryanomaliesofthecoronaryarteries: angiographicaspects.Circulation197858:2534. 13. HarikrishnanS,JacobSP,TharakanJ,etal.Congenitalcoronaryanomaliesoforiginanddistributioninadults:a coronaryarteriographicstudy.IndianHeartJ200254:2715. 14. AngeliniP.Coronaryarteryanomaliescurrentclinicalissues:definitions,classification,incidence,clinical relevance,andtreatmentguidelines.TexHeartInstJ200229:2718. 15. RappAH,HillisLD.Clinicalconsequencesofanomalouscoronaryarteries.CoronArteryDis200112:61720. 16. BurmaO,RahmanA,IlkayE.Coronaryarteriovenousfistulasfrombothcoronaryarteriestopulmonaryartery.Eur JCardiothoracSurg200221:86. 17. KandzariDE,HarrisonJK,BeharVS.Ananomalousleftcoronaryarteryoriginatingfromthepulmonaryarteryina 72yearoldwoman:diagnosisbycolorflowmyocardialblushandcoronaryarteriography.JInvasiveCardiol 200214:969. 18. McConnellSE,CollinsKA.Suddenunexpecteddeathresultingfromananomaloushypoplasticleftcoronary artery.JForensicSci199843:70811. 19. AltunA,ErdoganO.Stentimplantationtothestenosedrightcoronaryarteryinapatientwhoserightandleft coronaryarteriesoriginatefromasingleostiumintherightsinusofValsalva.CardiolRev200311:1013. 20. FineschiM,DelSM,LeoscoD,CasiniS,BraviA.Arareanatomicvariationoftheanomalousoriginofallthree majorcoronaryarteriesfromtherightsinusofValsalva.GItalCardiol199828:5646. 21. WongC,SchreiberT.Stentingofananomalousleftcircumflexcoronaryarteryarisingfromtherightsinusof Valsalva.TexMed199894:646. 22. TurkayC,GolbasiI,BayezidO.AsinglecoronaryarteryfromtherightsinusofValsalvaassociatedwith atherosclerosis.ActaCardiol200257:3779. 23. PohlT,SeilerC,BillingerM,etal.Frequencydistributionofcollateralflowandfactorsinfluencingcollateral channeldevelopment.Functionalcollateralchannelmeasurementin450patientswithcoronaryarterydisease.J AmCollCardiol200138:18728. 24. GarroneP.BiondiZoccaiG.SalvettiI,etal.Quantitativecoronaryangiographyinthecurrentera:principlesand applications.JIntervCardiol200922:52736. 25. AmmannP,BrunnerLaRoccaHP,AngehrnW,RoelliH,SagmeisterM,RickliH.Proceduralcomplications followingdiagnosticcoronaryangiographyarerelatedtotheoperator'sexperienceandthecathetersize.Catheter

CardiovascInterv200359:138. 26. KuruvillaA,KuruttukulamG,FrancisB.Femoralneuropathyfollowingcardiaccatheterizationforballoonmitral valvotomy.IntJCardiol199971:1978. 27. FukumotoY,TsutsuiH,TsuchihashiM,MasumotoA,TakeshitaA.Theincidenceandriskfactorsofcholesterol embolizationsyndrome,acomplicationofcardiaccatheterization:aprospectivestudy.JAmCollCardiol 200342:2116. 28. HincheyJ,SweeneyP.Transientcorticalblindnessaftercoronaryangiography.Lancet1998351:15134. 29. SegalAZ,AbernethyWB,PalaciosIF,BeLueR,RordorfG.Strokeasacomplicationofcardiaccatheterization:risk factorsandclinicalfeatures.Neurology200156:9757. 30. SamalAK,WhiteCJ.Percutaneousmanagementofaccesssitecomplications.CatheterCardiovascInterv 200257:1223. 31. KangSS,LabropoulosN,MansourMA,BakerWH.Percutaneousultrasoundguidedthrombininjection:anew methodfortreatingpostcatheterizationfemoralpseudoaneurysms.JVascSurg199827:10328. 32. KangS,LabropoulosN,MansourMA,etal.Expandedindicationsforultrasoundguidedthrombininjectionof pseudoaneurysms.JVascSurg200031:28998. 33. MatsonMB,MorganRA,BelliAM.Percutaneoustreatmentofpseudoaneurysmsusingfibrinadhesive.BrJRadiol 200174:6904. 34. WitzM,CohenY,LehmannJM.Retroperitonealhaematomaaseriousvascularcomplicationofcardiac catheterisation.EurJVascEndovascSurg199918:3645. 35. KuruvillaA,KuruttukulamG,FrancisB.Femoralneuropathyfollowingcardiaccatheterizationforballoonmitral valvotomy.IntJCardiol199971:1978. 36. FukumotoY,TsutsuiH,TsuchihashiM,MasumotoA,TakeshitaA.Theincidenceandriskfactorsofcholesterol embolizationsyndrome,acomplicationofcardiaccatheterization:aprospectivestudy.JAmCollCardiol 200342:2116. 37. BlancoVR,MorisC,BarrialesV,GonzalezC.Retinalcholesterolemboliduringdiagnosticcardiaccatheterization. CatheterCardiovascInterv200051:3235. 38. ChandrasekarB,DoucetS,BilodeauL,etal.Complicationsofcardiaccatheterizationinthecurrentera:asingle centerexperience.CatheterCardiovascInterv200152:28995. 39. JacksonJL,MeyerGJ,PettitT.Complicationsfromcardiaccatheterization:analysisofamilitarydatabase.MilMed 2000165:298301.

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3.9:IntravascularImagingTechniques
Author(s): JamesBernardHermiller,Jr.,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Reviewtechniquestoexamineintracoronaryanatomy. 2. Describeintravascularultrasound(IVUS)structureandimageinterpretation. 3. UtilizeIVUSinassessinglesionmorphology,determiningstenosisseverity,andoptimizingpercutaneouscoronary intervention(PCI)resultsandoutcomes. 4. Reviewnewerintravascularimagingtechnologies,includingopticalcoherencetomography(OCT).

CoronaryAngioscopy
Coronaryangioscopyusesvisiblelightconductedthroughfiberopticfilamentsto obtaindirectvisualinformationofthesurfacecharacteristicsandintraluminal morphologyofcoronariesinvivo.Theimagesaredisplayedonamonitorand providedetailaboutthesurfacemorphologyofthetargetlesionandassociated plaques.Thetechniquerequirestheinterruptionofcoronaryflow,sothefieldof inspectionmustbeclearedofbloodbyasalineinfusion(Figure1). Angioscopyallowsthecharacterizationofatheromatypeandruptureandintraplaque hemorrhage.Itcandistinguishplateletrich,redthrombusfromfibrinrich,white thrombus.Angioscopyhasprovidedimportantinformation,notobtainablebyother techniques,onthepathogenesisofacutecoronarysyndromes(Figure2).However, angioscopyisnotwidelyusedforthedailyclinicalevaluationofpatientsandis primarilyaresearchtechnique.1,2

Figure1

Figure2

IntracoronaryAngioscopy Figure1 Thisdemonstratesacaseinwhichtheculpritvesselofacutecoronarysyndromeeventhadbeenobservedbyangioscopyatbaseline.The patientwasa48yearoldman.(A)Initialclinicalpresentationwhenangioscopywasperformedwasinferioracutemyocardialinfarction.The culpritlesionwasinthedistalrightcoronaryartery.(B)Thesecondeventwasalsoinferioracutemyocardialinfarction,51monthslater.The culpritlesionwasintheproximalrightcoronaryarterywhereyellowplaquehadbeendetected. PCI=percutaneouscoronaryintervention. ReproducedwithpermissionfromKuboT,ImanishiT,TakaradaS,etal.Assessmentofculpritlesionmorphologyinacutemyocardialinfarction: abilityofopticalcoherencetomographycomparedwithintravascularultrasoundandcoronaryangioscopy.JAmCollCardiol200750:9339.

ComparisonofIntracoronaryAngioscopy,OCT,andIVUS Figure2 Intraluminalthrombiincorrespondingimages.(PanelA)ThrombuswithOCTsignalattenuation.(PanelB)Coronaryangioscopy:largewhite thrombusandsmallredthrombusadheringtoaroughsurfaceofyellowplaque.(PanelC)IVUS:thrombus(arrows)identifiedthemassimages protrudingintothevessellumenfromthesurfaceofthevesselwall. IVUS=intravascularultrasoundOCT=opticalcoherencetomographyRT=redthrombusT=signalattenuationWT=whitethrombus.

ReproducedwithpermissionfromKuboT,ImanishiT,TakaradaS,etal.Assessmentofculpritlesionmorphologyinacutemyocardialinfarction: abilityofopticalcoherencetomographycomparedwithintravascularultrasoundandcoronaryangioscopy.JAmCollCardiol200750:9339.

IntravascularUltrasound

Contrastarteriographyprovidesonlyasilhouetteofthelumenshape.Assuch,it cannotquantifytheextentofvesselwallatherosclerosisandislimitedinitsabilityto identifythemechanismsofarteriallumenchangeovertime(e.g.,plaqueorvessel wallremodeling).3 Alternatively,IVUSisabletodefinethemechanismofvesselwall changescontributingtolumenobstructionafterPCI,inparticularrestenosisand stentthrombosis.4 IVUSisasafeandaccuratemethodofcharacterizingvesselwallcomposition.IVUS hasevolvedsubstantiallyandiscurrentlyperformedwithrapidexchange.IVUSuses mechanicalarrayordynamicarrayimagingcathetersthathavealowprofile(i.e.,2.6 Fr),andarecompatiblewith5Frguidingcatheters.Imagefrequencyhasbeen increasedto40MHzforenhancedtissuecharacterization.5 VesselWallComposition IVUScandifferentiatethevesselwallintothreecomponents: Intima:Thisiscomposedofendothelialcells,subjacentsmoothmuscle cells,andextracellularmatrix.Itis150200mcindiameterandispartitioned fromthemediabytheinternalelasticlamina. Media:Thesearecomposedofsmoothmusclecells,elastin,andcollagen. Theseare100350mcindiameterandareencircledbytheexternalelastic membrane(EEM). Adventitia:Thiscontainsfibroustissue.Itis300500mcindiameterandis encasedbyperivascularstromaandepicardialfat.Thisisidentifiedonthe IVUSimagebylocalizationoftheecholucentEEM,whichdefinestheinner boundaryoftheadventitia.Itsidentificationisthekeytoimageinterpretation. Anormalvesselwallhasa"threelayer"appearance,duetodifferencesinacoustic impedancebetweenthecelllayers(Figure3).Thisisaconsequenceofdifferential collagencontentbetweenthethreearteriallayers.Vesselsizeisdeterminedbythe areawithintheEEMcrosssectionalarea(CSA).ThelumenCSAisidentifiedby tracingtheintimalborder.PlaqueareaisdefinedastheEEMCSAminustheluminal area.Dynamicchangesinthevesselwallsizehavebeencharacterizedaspositive (i.e.,Glagov)ornegative(i.e.,constrictive)remodeling.6 IVUShasbeenusedto assesschangesinplaquevolumeafterlipidloweringtherapy.79 TypesofPlaque ThreetypesofplaquearedescribedusingIVUS5,10,11: Fibrofattyorsoftplaquesarehypoechoiccomparedwiththeadventitia,and indicateahighlipidcontentpresentinapool(Figure4). Fibrousplaqueshavebrightnesssimilartotheadventitia,andareconsistent withahighercontentofcollagenandelastin(Figure5). Calcifiedplaquesareidentifiedbytheirbright,echogeniccomponentswith acousticshadowingoftheunderlyingvascularstructures.Acalcifiedplaque maybecharacterizedassuperficialordeep.Itmayalsobequantifiedbyits circumferentialextent(from0to360degrees)(Figure6). Thrombusisdistinguishedfromsoftplaquebyitsmobility,lobularedges,and movementawayfromthevesselwallduringthecardiaccycle(Figure7).10IVUShas demonstratedthediffusenatureofatheroscleroticdiseaseinpatientsundergoing PCI.Inthisgroup,>90%ofpatientshaveplaqueoutsidethetargetsite,ofteninwhat appeartobenormalsegmentsangiographically.11Thisconfirmstheearlier pathologicalfindingsofGlagovandcolleagues,6 showingthatthecoronaryartery undergoes"adaptive"remodeling(i.e.,vesselexpansion)inmostpatientsinthe earlystagesofatherosclerosis,beforeanyluminalnarrowingisapparent.Arterial constrictionalsooccursinsomepatients,particularlydiabetics,duetonegative arterialremodeling.12 ThincapsandthickcapsidentifiedbyIVUSmayidentifypatientssusceptibleto plaquerupture.IVUS,andspecificallytheIVUSderivedminimumlumenarea,has beenusedasasurrogatetoassessthefunctionalsignificanceofcoronarylesions.

Figure3

Figure4

Figure5

Figure6

Figure7

IVUSImaging Figure3 Intravascularultrasound(IVUS)imagingrevealsthatthevesselwallhasthreelayers.Thediagramtotherightillustrateslumenwithblood speckleneartheimagingcatheter,theplaque,theecholucentmedia,andadventitia.ThefundamentalelementsinIVUSinterpretationare identifyingthemediaandlumenborders.

FibrofattyPlaqueMorphology Figure4 Fibrofattyplaqueisrepresentedintheseimages.Thisplaqueisrelativelysonolucent(previouslyreferredtoassoft)andischaracterizedbynot beingasbrightastheadventitia.Itslowechogenicityisgenerallyduetohighlipidcontentinamostlyacellularintima.

FibrousPlaqueMorphology Figure5 Fibrousplaqueisrepresentedinthesetwoimages.Theplaqueischaracterizedasbeingasbright,orbrighterthan,theadventitia(hyperechoic). Themajorityofatheroscleroticlesionsarefibrotic.Verydense,fibrousplaquesmaycausesomuchacousticshadowing(notedintheleftward imagefromnoonto3oclock)thattheycouldbemisclassifiedascalcified.

CalcifiedPlaqueMorphology Figure6 Calcifiedplaqueisrepresentedintheseimages.Theplaqueischaracterizedasbeingbrighterthantheadventitia(i.e.,hyperechoic).Bright echoes,brighterthantheadventitia,obstructthepenetrationofultrasound(i.e.,acousticshadowing).Onlytheleadingedgeisdetectedand thicknesscannotbedetermined.Calcifiedplaquemayresultinreverberations,withtheoscillationofultrasoundbetweentransducerandcalcium causingrepeatingarcs.Thiscanbeseeninthesecondimagefromtheleft.

Thrombus Figure7 Thrombusisnotedintheseintravascularultrasound(IVUS)images.Itappearsasanintraluminalmass,oftenwithalayered,lobulated,or pedunculatedappearance.Itisrelativelyecholucentorvariablegrayscalewithspecklingorscintillation.Bloodflowinmicrochannelsmayalso beapparentwithinsomethrombi.Stagnantbloodflowcansimulateathrombus.Injectionofcontrastorsalinemaydispersethestagnantflow, clearthelumen(whichappearsblack),andallowdifferentiationofstasisfromthrombosis.Nosinglefeatureispathognomonicforthrombus,and thediagnosisofthrombusbyIVUSshouldbeconsideredpresumptive.

IntravascularUltrasoundUseDuringPercutaneousCoronary Intervention
IVUSmaybeusedforseveralpurposesduringPCI.13,14Theseinclude:
Figure8

Characterizingbaselineplaquecomposition,vesselsize,andlesion accessibilityandaidingindeviceselectionforPCI. Confirmingorrefutingangiographicestimatesofstenosisseverity, particularlyinregionsdifficulttovisualizeusingconventionalmethods(e.g. bifurcations,trifircuations,overlappingvessels,hazylesions). AssessinganatomicalresultsanddetectingcomplicationsafterPCI, includingdissectionsandresidualminimalCSA. Assessingstentsizing,expansion,andapposition. Assessingtheetiologyofstentrestenosisorstentthrombosis. Fractionalflowreserve(FFR),ratherthanIVUS,shouldbeusedtoassessthe functionalsignificanceofacoronarystenosis,andIVUSshouldbeusedtooptimize stentdeployment. VesselWallChangesAfterPercutaneousCoronaryIntervention IVUSprovidesuniqueinsightintothesequentialchangesthatoccurwithinthe vesselwallafterPCI.15SerialIVUSstudiesshowthatlumenrenarrowingafter balloonangioplastyandatherectomyrelatesbothtoarterialremodelingand,toa lesserextent,intimalhyperplasia.16Incontrasttothesefindings,IVUSstudieshave shownthatlumenrenarrowingafterstentimplantationisvirtuallyallduetointimal hyperplasiawithintheaxiallengthofthestentoritsborderthedegreeofintimal hyperplasiaissubstantiallyreducedwiththeuseofdrugelutingstents.17 ProceduralIVUSisalsousefultodetectthepresenceofincompletestentapposition andexpansion(Figure8).Itcanalsodetectedgedissectionsorhematomasnot notedangiographicallythatmaypredisposetostentthrombosis(Figure9).

Figure9

IncompleteStentApposition Figure8 Thestentisnotinfullcontactwiththeunderlyingvesselwall.Thestrutsarenotopposedtotheintima.Characteristically,theunopposedstruts reverberate,givingthemapillaredappearance,asnotedinthisimage.

IntramuralHematoma Figure9 Anintramuralhematomaisshownintheseimages.Occurringattheedgeofstentsmostcommonly,hematomacharacteristicallyhasan echolucentcrescentassociatedwithbloodstasis.Thehematomaisnotedtobeoutsidetheexternalelasticmembrane.

IntravascularUltrasoundVirtualHistology
ThestabilityandmorphologyofstandardIVUShasgivencluestothepotential plaquevulnerability.InFigure10,alarge,sonolucent(i.e.,lipidladen)plaquewitha thinfibrouscapisnotedintheimagetotheleft.Thisrepresentsanunstableplaque. Incontrast,therightpanelillustratesastableatheromacoveredbyathick,organized fibrouscapwiththenolipidpool. Analternativeimagingmodalityisvirtualhistology,anIVUSderivedcolorcoded plaquecharacterizationtechnique.Itisbasedontheanalysisoftheradiofrequency (RF)componentofthebackscatteredultrasoundsignal.Ascomparedwithstandard IVUS,thisimagingmodalityhasthepotentialforamoredetailedassessmentof differentplaquecomponents.Usinginvitrostudies,fourplaquetypes(fibrous tissue,fibrofatty,necroticcore,anddensecalcium)couldbecorrelatedwitha specificspectrumoftheRFsignal(Figures11,12).Thedifferentplaque componentsareassignedtocolorcodes.Fibroustissue,fibrofatty,necroticcore, anddensecalciumregionsarelabeledindarkgreen,lightgreen,red,andwhite, respectively.Thistechnique,givenitsabilitytoidentifylipidrichplaques,maybeof valueinidentifyingpotentiallyvulnerableplaque.18 ThisisprimarilyaresearchtoolatthistimeInthePROSPECT(ProvidingRegional ObservationstoStudyPredictorsofEventsintheCoronaryTree)trial,virtual histologywasusedtoassessplaquevulnerabilityoutsidetheculpritlesion.10 Althoughvirtualhistologywasabletoidentifythincappedfirbroatheromas,the percentageofpatientshavingeitheramyocardialinfarctionordeathrelated nonculpritlesionswasonly1%.19

Figure10

Figure11

Figure12

VulnerableVersusStableAtheroma Figure10 Alargesonolucent(i.e.,lipidladen)plaquewithathinfibrouscapisnotedintheimagetotheleft,whichrepresentsanunstableplaque.Inthe rightpanel,thestableatheromaiscoveredbyathick,organized,fibrouscapwiththenolipidpool.

ComponentTypesinAtheroscleroticPlaque Figure11 Thebackscatterultrasoundisusedtoidentifyfourcomponenttypesinatheroscleroticplaque,generatingacolorcodedvirtualhistology.

IVUSVirtualHistology Figure12 Thetoprowofthreeimagesdemonstratesatypicalvirtualhistologicviewoftheplaque,withthecorrespondingIVUSimagebelow.Threeplaque typesaredemonstrated:1)Thincappedfibroatheroma2)Fibrousplaqueand3)Fibrocalcificplaque.

OpticalCoherenceTomography
OCTisarecentlydevelopedandapprovedmethodofcatheterbased,high resolutionintravascularimagingthathasdemonstratedconsiderablepotentialasa methodforassessingunstableplaque,stentappositionandcoverage,andlumen dimension.20,21Itisanalogoustoultrasound,measuringthebackreflectionof infraredlight,ratherthansound.TheadvantagesofOCTincludeitsresolution, whichishigherthananycurrentlyavailableimagingtechnology.Table1presentsa comparisonofOCTversusIVUS.ResolutionsofOCTcatheterbasedsystemsare intherangeof10to20mc,approximatelytenfoldhigherthanIVUS. Thelightlabcathetersystem,StJude,hasbeenapproved.22Becausethesystem reliesonthereflectionoflight,bloodmustbeflushedfromthelumenoftheartery withcontrastinjection.Using1012ccofcontrast,injectedover5seconds,allows anautomaticcatheterpullbackandinterrogationovera50mmvascularsegment.

Table1

ComparisonofOpticalCoherenceTomographyandIntravascularUltrasound Table1 OCT=opticalcoherencetomographyIVUS=intravascularultrasound+=ok++=good+++=excellent. ReproducedwithpermissionfromJangIK.Opticalcoherencetomographyorintravascularultrasound?JACCCardiovascInterv20114:4924.

AdditionalImagingTechniques
Anumberofotherimagingtechniqueshavebeenproposedtocharacterizethevulnerabilityofplaquewithinthecoronary vessel.23Theseinclude: Infraredspectralimaging. ElastographyandPalpographytodetectplaquedeformability. Intracoronarymagneticresonanceimaging(MRI)withandwithoutspecificimagingligands.

KeyPoints
IVUSisasafeandaccuratemethodofcharacterizingvesselwallcomposition. IVUSisabletodefinethemechanismofvesselwallchangescontributingtolumenrenarrowingafterPCI. IVUSisusefulinoptimizingPCIresults,particularlyincomplexlesions. Otherfunctionalmodalities,ratherthanIVUS,shouldbeprimarilyutilizedtodeterminethephysiologicsignificance ofatheroscleroticlesions. OCTisanewintravascularimagingtechniquethathasatenfoldhigherresolutionthanIVUS. Acknowledgement:TheauthorswouldliketothankDebabrataMurkherjee,M.D.,F.A.C.C.,whoauthoredACCSAP7, whichformedthebasisforthismodule.

References
1. MizunoK,SatomuraK,MiyamotoA,etal.Angioscopicevaluationofcoronaryarterythrombiinacutecoronary syndromes.NEnglJMed1992326:28791. 2. KuboT,ImanishiT,TakaradaS,etal.Assessmentofculpritlesionmorphologyinacutemyocardialinfarction: abilityofopticalcoherencetomographycomparedwithintravascularultrasoundandcoronaryangioscopy.JAm CollCardiol200750:9339. 3. YockPG,FitzgeraldPJ.Intravascularultrasound:stateoftheartandfuturedirections.AmJCardiol199881:27E 32E. 4. MintzGS,PopmaJJ,PichardAD,etal.Arterialremodelingaftercoronaryangioplasty:aserialintravascular ultrasoundstudy.Circulation199694:3543. 5. MintzGS,NissenSE,AndersonWD,etal.AmericanCollegeofCardiologyClinicalExpertConsensusDocument onStandardsforAcquisition,MeasurementandReportingofIntravascularUltrasoundStudies(IVUS).Areportof theAmericanCollegeofCardiologyTaskForceonClinicalExpertConsensusDocuments.JAmCollCardiol 200137:147892. 6. GlagovS,WeisenbergE,ZarinsC,StankunaciciusK,KolettisG.Compensatoryenlargementofvarioushuman atheroscleroticarteries.NEnglJMed1987316:13715. 7. MatsuzakiM,HiramoriK,ImaizumiT,etal.Intravascularultrasoundevaluationofcoronaryplaqueregressionby lowdensitylipoproteinapheresisinfamilialhypercholesterolemia:theLowDensityLipoproteinApheresis CoronaryMorphologyandReserveTrial(LACMART).JAmCollCardiol200240:2207. 8. NissenS,TsunodaT,TuzcuE,etal.EffectofrecombinantApoAIMilanooncoronaryatherosclerosisinpatients withacutecoronarysyndromes:arandomizedcontrolledtrial.JAMA2003290:2292300. 9. NissenS,TuzcuE,SchoenhagenP,etal.Effectofintensivecomparedwithmoderatelipidloweringtherapyon progressionofcoronaryatherosclerosis:arandomizedcontrolledtrial.JAMA2004291:107180. 10. UrenN,YockP,FitzgeraldP.Intravascularultrasoundimageinterpretation:normalarteries,abnormalvessels, andatheromatypespreandpostintervention.In:SiegelRJ,ed.IntravascularUltrasoundImaginginCoronary ArteryDisease.NewYork:MarcelDekker,Inc.1998:1937. 11. MintzGS,PainterJA,PichardAD,etal.Atherosclerosisinangiographically"normal"coronaryarteryreference segments:anintravascularultrasoundstudywithclinicalcorrelations.JAmCollCardiol199525:147985. 12. KornowskiR,MintzGS,LanskyAJ,etal.Paradoxicdecreasesinatheroscleroticplaquemassininsulintreated diabeticpatients.AmJCardiol199881:1298304. 13. ParkSJ,AhnJM,KangSJ.Paradigmshifttofunctionalangioplasty:newinsightsforfractionalflowreserveand intravascularultrasoundguidedpercutaneouscoronaryintervention.Circulation2011124:9517. 14. MintzGS,WeissmanNJ.Intravascularultrasoundinthedrugelutingstentera.JAmCollCardiol200648:4219. 15. DangasG,AmbroseJ,RehmannD,etal.Balloonoptimizationversusstentstudy(BOSS):provisionalstenting andearlyrecoilafterballoonangioplasty.AmJCardiol200085:95761. 16. AhmedJ,MintzG,CastagnaM,etal.Intravascularultrasoundassessmentofthemechanismoflumen enlargementduringcuttingballoonangioplastytreatmentofinstentrestenosis.AmJCardiol200188:10324. 17. SerruysP,DegertekinM,TanabeK,etal.Intravascularultrasoundfindingsinthemulticenter,randomized,double blindRAVEL(RAndomizedstudywiththesirolimuselutingVElocityballoonexpandablestentinthetreatmentof patientswithdenovonativecoronaryarteryLesions)trial.Circulation2002106:798803. 18. StoneGW,MaeharaA,MintzGS.Therealityofvulnerableplaquedetection.JACCCardiovascImaging20114:902 4. 19. StoneGW,MaeharaA,LanskyAJ,etal.Aprospectivenaturalhistorystudyofcoronaryatherosclerosis.NEnglJ Med2011364:22635. 20. StamperD,WeissmanNJ,BrezinskiM.Plaquecharacterizationwithopticalcoherencetomography.JAmColl Cardiol200647:C6979. 21. IkenagaH,IshiharaM,DaiK,NakamaY,OhtaniT.Mechanismsofverylatestentthrombosisafterdrugeluting stentimplantation:findingsfromcoronaryangioscopyandopticalcoherencetomography.JACCCardiovasc Imaging20114:12179. 22. JangIK.Opticalcoherencetomographyorintravascularultrasound?JACCCardiovascInterv20114:4924. 23. VancraeynestD,PasquetA,RoelantsV,GerberBL,VanoverscheldeJL.Imagingthevulnerableplaque.JAmColl Cardiol201157:196179.

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3.10:PhysiologicAssessmentofCoronaryStenosis
Author(s): JamesBernardHermiller,Jr.,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Discussthevariousphysiologicindicesforassessingcoronarystenosisseverity,andcitetherelativeadvantagesand disadvantagesofthesetechniquesinpatientswithcoronaryarterydisease(CAD). 2. Reviewtheroleoffractionalflowreserve(FFR)inassessingphysiologicsignificanceofcoronaryobstructivediseaseand helpingdefineappropriaterevascularizationtherapy.

AssessmentoftheCoronaryCirculation
Thevisualappearanceofastenosisatcoronaryangiographycorrelatespoorlywith thefunctionalsignificanceofagivenlesion.Thisisespeciallytrueforintermediate stenoses(i.e.,4070%luminaldiameternarrowing)(Figure1).TheFFRderived fromthecoronarypressurewireisinvaluableinevaluatingthephysiological significanceofacoronarylesion.UnlikeDopplerderivedcoronaryflowreserve (CFR),FFRisameasureofepicardialstenosisseverityandnotalteredby resistanceinthemicrovascularbed.1 Consequently,FFRhasreplacedDopplerflow velocityasaclinicaltooltodeterminelesionfunctionalseverityinthecatheterization laboratory.2

Figure1

WhyDoestheAngiogramFailtoPredictPhysiology? Figure1 Theangiogramisatwodimensionalimageofthreedimensionalstructures.Mostintermediatelesionsareovalshapedwithtwodiameters:one narrowandonewidedimension.Theangiogramofaneccentriclesioncannotreliablyindicateflowadequacy.Otherlesions(lowerright)may appearhazybutwidelypatent,onlytoberesponsibleforanginaduetoplaquerupture,asdemonstratedbyintravascularultrasoundcross section(farrightcorner). ReproducedwithpermissionfromKernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.J AmCollCardiol201055:17385.

PhysiologyofCoronaryBloodFlow (1of2)
Undiseasedepicardialcoronaryarteriescontributelittleresistancetocoronaryblood flow,resistanceresidingprimarilyatthelevelofthearteriolesandcapillaries(the "microvasculature"),whichdilateorconstrictinresponsetoavarietyofphysiologic andpharmacologicstimuli.3 Inresponsetophysiologicstimuli(e.g.,exercise),the microvasculatureinthedistributionofanormalcoronarydilates,resultinginatwo tosixfoldincreaseincoronarybloodflow. Themaximumvasodilatorycapacityofthecoronaryvasculatureisexpressedbythe term"coronaryflowreserve(CFR),"whichistheratioofmaximumhyperemicblood flowtobasalflow.Astheseverityofanepicardialcoronarystenosisincreases, perfusionpressuredistaltothestenosisdecreases,leadingtoprogressive vasodilationofthemicrovasculaturetocompensatefortheflowlimitationcreatedby thestenosis.Thisautoregulationmaintainsdistalmyocardialperfusionuntilthe epicardialstenosisbecomessosevere(>90%diameterreduction)thatthe vasodilatorycapacityofthemicrovasculatureisexhausted.Beyondthispoint, evidenceofmyocardialischemiawillusuallydevelop.Lessseverestenoses(40 90%diameterstenosis)havelittleeffectonrestingflow,butcanlimittheincreasein bloodflowinresponsetodemand,therebyresultinginareductioninCFR.4 DopplerCoronaryFlowVelocityMeasurements ThemeasurementofDopplerflowvelocitywithinacoronaryarteryprovidesan objective,physiologicmeasurementthatisrelatedtotheactualvolumetriccoronary bloodflow.ThemagnitudeoftheDopplerfrequencyshiftisproportionaltothe velocityoftheredbloodcellsmovingpastthetransducer,thusallowing determinationofthecoronarybloodflowvelocity.Assumingthatthearterydoesnot changeincaliber,flowvelocityisdirectlyproportionaltothevolumetricflow. Therefore,theratioofcoronaryflowvelocitiesisequivalenttotheratioofcoronary flows,andCFRiscomputedastheratioofthemaximumtobasalcoronaryflow velocity(Figure2).5 NormalRangeforCoronaryFlowVelocityReserve Coronaryflowvelocityreserve(CFVR)measuresthecombinedresponseofthe epicardialarteryandthemicrocirculationtohyperemicstimuli.Therefore,apatient withoutepicardialdisease,butwithabnormalmicrovascularfunctioncanhavean abnormalCFVR.ThislimitstheuseofCFVRfortheevaluationofintermediate coronarylesionsinpatientswithmicrovascularalterations(e.g.,thoseinducedby leftventricular[LV]hypertrophy,priormyocardialinfarction[MI],diabetes,orother conditionsknowntoincreasebasalcoronaryflow[e.g.,anemia,hyperthyroidism]).6 Althoughcoronarybloodflowcanincreasefourtosixfoldundermaximalstimulation innormalarteries,valuesofCFVR>2.0areconsiderednormal.79Anabnormal CFRV(2.0)correspondedtoreversiblemyocardialperfusionimagingdefectswith highsensitivity(8692%),specificity(89100%),predictiveaccuracy(8996%),and positiveandnegativepredictivevalues(84100%and7795%,respectively).1012 TheuncertaintyofthemicrocirculatorycontributiontoanabnormalCFVRmakes CFVRalonelessusefulforepicardiallesionassessment,andisnolongerusedfor stenosisassessmentinclinicalpractice. IntracoronaryPressureMeasurements FractionalFlowReserve Intracoronarypressuremeasurementsduringdruginducedhyperemiaprovide anothermeanstodeterminethefunctionalimportanceofacoronarystenosis.Ina normalepicardialartery,thedistalcoronaryarterypressureremainsconstantwithin theartery.Inthepresenceofastenosis,however,thereisadecrementinthedistal pressurethatisproportionaltotheseverityofthestenosis.Tomaintainresting myocardialperfusion,arteriolarresistancedecreasestocompensateforthe pressuredropcausedbytheepicardialstenosis(Figure3).13

Figure2

Figure3

Pijlsandcolleaguesdevelopedandvalidatedanindexfordeterminingthe physiologicimpactofacoronarystenosis,calledthe"myocardialfractionalflow reserve(FFR)."14FFRisdefinedasthemeandistalcoronarypressuredividedby themeanproximalcoronaryoraorticpressuremeasuredduringmaximal hyperemia.FFRisdefinedastheratioof(i.e.,percentofnormal)flowinthestenotic arterytotheflowinthesamearteryinthetheoreticabsenceofthestenosis.2 Becauseflowisproportionaltopressure,ifresistanceisminimalandconstant (Ohm'sLaw),pressurecanbeusedasasurrogateofflowduringmaximal hyperemia,whichminimizesresistance. Pressureinanormalcoronaryarteryisequaltoaorticpressure(Pa).Thus,FFRis simplycalculatedastheratioofmeanpressuredistal(Pd)toastenosistoPa duringmaximalhyperemia(Figure3).IncontrasttoCFR(theratioofhyperemicto basalbloodflow),FFRhasaclearnormalvalueof1.Thisisbecausenormal epicardialresistanceistrivial,andPaistransmittedcompletelytothedistalartery, makingboththenumeratoranddenominatorthesamevalue.AnFFRof0.75means thatthestenoticvesselonlyprovides75%ofthenormalexpectedflowinthe theoreticalabsenceofthestenosis. Inthecatheterizationlaboratory,coronaryarterypressureismeasuredbya pressuresensorwire,andtheproximalpressureismeasuredviathecoronary catheter.Thismeasurementmustbeperformedundermaximalhyperemicflow, eliminatingtheresistanceofthemicrocirculation.Inthiscircumstance,flowis limitedsolelybytheresistanceoftheepicardialstenosis,whichmakesFFRa specificindexforevaluatingtheseverityoftheepicardialstenosis.15FFRisequalto 1.0foranormalvesselanddecreasesprogressivelybelow1.0asthestenosis severityincreases.UnlikeDopplermethods,theFFRisunaffectedbychangesin arterialpressure,inotropicstate,orheartrate,andisunaffectedinsituationswhere basalflowisaltered(e.g.,LVhypertrophy).16

MeasurementofCoronaryBloodFlowReserve Figure2 TheDopplerflowmaybeusedtodeterminecoronarybloodflowreserve(CFR)bytheintracoronaryinjectionofthepotentvasodilator adenosine.Undernormalconditions,coronarybloodflowshouldincreasebyapproximately250%orgreater.Whilethisdevicemeasuresflow velocity,thelatter(flowvelocity)isconsideredasurrogateforbloodflow.Thetechniquemaybehelpfulindeterminingthehemodynamic significanceofcoronarylesions,especiallythoseconsidered"borderline"byangiography.

FactorsProducingResistancetoCoronaryBloodFlow Figure3 Theangiographictwodimensionalimagescannotaccountforthemultiplefactorsthatproduceresistancetocoronarybloodflowandlossof pressureacrossastenosis.Theeccentricandirregularstenosis(upperpanel)showsarrowsdesignatingentranceeffects,friction,andzones ofturbulenceaccountingforseparationenergyloss.Thecalculationofpressureloss(deltaP)acrossastenosis(lowerrightpanel) incorporateslength(l),areasofstenosis(As ),referencearea(An),flow(Q),andcoefficientsofviscousfrictionandlaminarseparation(f1and f 2)ascontributorstoresistanceandhencepressureloss. ReproducedwithpermissionfromKernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.J AmCollCardiol201055:17385.

PhysiologyofCoronaryBloodFlow (2of2)
Technique Twocommercialsystems(RadiWire,RadiMedical,St.JudeMedicalandthe PrimeWire,VolcanoTherapeutics,Houston,TX)havebeendeveloped,whichusea 0.014inchmicromanometertippedguidewiretomeasurepressureacrossa stenosis.Amaximumhyperemicstimulusisperformedwithintracoronaryor intravenous(IV)orintracoronaryadenosine.Theintracoronarydoseofadenosineis 1848mcgfortheleftcoronaryarteryand1220mcgfortherightcoronaryarteryto reducetheriskofsinusnodeoratrioventricular(AV)nodedepression.Theearly (<15seconds)onsetofmaximumdilationandtheduration(<15seconds)ofthe hyperemicresponseafterintracoronaryadenosinehaveledtotheuseofa continuousIVinfusionofadenosine(180mcg/kg/min)asanalternative.The infusioniscontinuedfor12minutesduringcontinuouspressuregradient recording. Althoughbecauseofitssimplicityandlowercost,intracoronarybolusinjectionof adenosineismostoftenused,IVadenosinemaybesuperior,asaclinicallyrelevant overestimationofFFR(andthusunderestimationoflesionseverity)occursin8%of lesionswhenintracoronaryadenosineisusedcomparedwithasustainedinfusion ofIVadenosine.17Furthermore,IVadenosineprovidesamoreconsistentand sustainedresponse,andcanbeusedfora"pullback"methodthatallows identificationoftheexactlocationofthetransstenoticpressuredrop. AssessmentofIntermediateLesions FFRvalues0.75areassociatedwithischemicstresstestinginnumerous comparativestudies,withhighsensitivity(88%),specificity(100%),positive predictivevalue(100%),andoverallaccuracy(93%).FFRvalues0.80are associatedwithnegativeischemicresults,withapredictiveaccuracyof95%. Reportsfromsinglestresstestingcomparisonsandvariationsintestingand patientshaveproducedasmallzoneofFFRuncertainty(0.750.80),theuseofwhich requiresclinicaljudgment(Figures3,4,5).1 TheDEFER(FFRtoDetermineAppropriatenessofAngioplastyinModerate CoronaryStenoses)studyrandomized325patientsscheduledforpercutaneous coronaryintervention(PCI)intothreegroupsandreportedthe5yearoutcomes (Figure6).18IfFFRwas>0.75,patientswererandomlyassignedtothedeferral group(n=91,medicaltherapyforCAD)orthePCIperformancegroup(n=90,PCI withstents).IfFFRwas0.75,PCIwasperformedasplanned,andpatientswere enteredintothereferencegroup(n=144).Completefollowupwasobtainedin98% ofpatients. Overall,theeventfreesurvivalwasnotdifferentbetweenthedeferredandperformed groups(80%and73%,respectively,p=0.52),andbothweresignificantlybetterthan inthereferencegroup(63%,p=0.03).Thecompositerateofcardiacdeathand acuteMIinthedeferred,performed,andreferencegroupswas3.3%,7.9%,and 15.7%,respectively(p=0.21fordeferredvs.performedandp0.003forreference vs.bothofthedeferredandperformedgroups).TheDEFERstudyandothersmall studiesusingtheFFRtoguidedecisionmakinghaveindicatedthatstentingofa lesionwithanFFR0.75to0.80cansafelybedeferredforupto5years(Table1). GuidingMultivesselPercutaneousCoronaryIntervention
Figure9 Figure3

Figure4

Figure5

Figure6

Table1

Figure7

Figure8

Coronaryangiographyisoftenperformedinclinicalsituationsinwhich preproceduralfunctionaltestinghasnotbeenobtained.Additionally,inthesettingof multivesseldisease,theneedtotreatindividualstenosisisoftendifficultto determine.Althoughrevascularizationofischemiaproducinglesionsimproves patientoutcomes,theclinicalbenefitsofrevascularizationofstenoticbutnon ischemiaproducinglesionsarelessclear.Intraproceduralassessmentofthe functionalsignificanceofindividualstenosismayhelpdefinetheoptimal revascularizationstrategy.

TheobjectiveoftheFAME(FractionalFlowReserveVersusAngiographyin MultivesselEvaluation)trialwastocompareclinicaloutcomesafterPCIonthebasis ofconventionalangiographicdeterminationoflesionseverityversusFFRcombined withangiographyinpatientswithmultivesseldisease(Figure7).19Thisprospective, randomized,multicentertrialincluded1,005patients,whowererandomizedtoeither angiographyguidedorFFRguided(forlesionswithFFR0.80)PCI.Patients assignedtoangiographyguidedPCIhadallidentifiedlesionstreatedwithadrug elutingstent(DES),whereasthoseassignedtoFFRguidedPCIhadonlyidentified lesionswithanFFRof0.80treatedwithDES.IntheFFRgroup,37%oflesionshad anFFR>0.80.Evaluationofischemia,asdefinedbyanFFR<0.80,resultedinfewer lesionsreceivingstents(2.71vs.1.91,p=0.001).At1year,thecompositeeventrate was18.3%intheangiographyguidedgroupcomparedwith13.2%intheFFR guidedgroup(p=0.02). TheresultsoftheFAMEtrialsuggestthatidentificationofischemiaproducing lesionsbyuseofsystematicassessmentofFFRinpatientsundergoingmultivessel PCIisassociatedwithimprovedclinicaloutcomescomparedwithangiographic assessmentalone.Asubsequentanalysisexaminingtherelationshipbetween investigatorderivedangiographicpercentdiameterstenosiswasrevealing.20In stenoseswithanangiographicseverityof5070%,65%werefunctionally nonsignificantand35%werefunctionallysignificantbytheFFR.Eveninmore severestenoses(between71%and90%angiographicstenosisseverity),20%ofall lesionsdidnotinducereversiblemyocardialischemia,asestablishedbyanFFR valueabovetheischemicthreshold. AssessmentofLeftMainDisease FFRappearshelpfulinidentifyingpatientswithintermediateleftmaindisease suitableforsurgicalrevascularizationorcontinuedmedicaltherapy,withexcellent survivalandloweventrates.21,22Figure8showsexamplesofpatientswithleftmain diseaseevaluatedphysiologically.Figure9demonstratesthepoorrelationship betweenleftmainpercentdiameterstenosisandFFR. AssessmentofCoronaryInterventionResults MeasuringFFRafterPCItoassesstheadequacyoftheinterventionhasbeen assessedinmultiplestudies.Afterballoonangioplastyalone,acombinationofan FFR>0.90andaresidualdiameterstenosisof<35%predictedahighereventfree survivalafter2yearscomparedwiththoseinwhomtheFFRwas<0.90.23Afterstent placement,anFFR0.94hasbeenassociatedwithsatisfactorystentexpansion andlowfollowupmajoradversecardiaceventrates.However,despitethesedata, inthecaseofpoststentassessment,intravascularultrasoundisrecommendedfor stentappositionbecauseFFRcanbenormalizedwithunappreciatedsuboptimal stentdeployment. FFRcanbeaparticularlyhelpfulapplicationfortheevaluationofostialnarrowings, especiallyinsidebrancheswithinstents(called"jailed"branches).Theyare particularlydifficulttoassessbyangiographybecauseoftheoverlaporientation relativetotheparentbranch,stentstrutsacrossthebranch,andimage foreshortening.Kooetal.24comparedFFRwithquantitativecoronaryangiographyin 97"jailed"sidebranchlesions(vesselsize2.0mm,percentstenosis>50%by visualestimation)afterstentimplantation.Nolesionwith<75%stenosishadFFR 0.75.Among73lesionswith75%stenosis,only20lesions(27%)were functionallysignificant.Kooetal.25alsoreportedthe9monthoutcomeofFFR guidedsidebranchPCIstrategyforbifurcationlesions.Branchinterventionwas performedin26of28patientswithFFR0.75.Inthissubgroup,FFRincreasedto >0.75. Althoughmostsurgicalrecommendationsforpatientswithmultivesseldiseaseare tobypassalllesionswith>50%diameternarrowing,thepatencyrateofsaphenous veingraftsonvesselswithhemodynamicallynonsignificantlesionshasbeen questioned.Botmanetal.26foundthattherewasa2025%incidenceofgraft closurein450coronaryarterybypassgrafts(CABGs)whenplacedon nonhemodynamicallysignificantlystenosedarteries(preoperativeFFR>0.80)at1 yearoffollowup.InpatientsrequiringCABGformultivesselrevascularization, angiographiclesionsofuncertainsignificancewouldbenefitfromFFR,providing

prognosticinformationregardingpotentialoffuturebypassgraftpatency.FFRhas seriousimplicationsforbestlongtermCABGpatency. GuidelineRecommendations: Thefollowingarerecommendationsfromthe2011ACC/AHA/SCAIGuidelinefor PCI27: ClassIIa:FFRisreasonabletoassessangiographicintermediatecoronary lesions(5070%diameterstenosis),andcanbeusefulforguiding revascularizationdecisionsinpatientswithstableischemicheartdisease (LevelofEvidenceA).

FactorsProducingResistancetoCoronaryBloodFlow Figure3 Theangiographictwodimensionalimagescannotaccountforthemultiplefactorsthatproduceresistancetocoronarybloodflowandlossof pressureacrossastenosis.Theeccentricandirregularstenosis(upperpanel)showsarrowsdesignatingentranceeffects,friction,andzones ofturbulenceaccountingforseparationenergyloss.Thecalculationofpressureloss(deltaP)acrossastenosis(lowerrightpanel) incorporateslength(l),areasofstenosis(As ),referencearea(An),flow(Q),andcoefficientsofviscousfrictionandlaminarseparation(f1and f 2)ascontributorstoresistanceandhencepressureloss. ReproducedwithpermissionfromKernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.J AmCollCardiol201055:17385.

PressureSignalsCalculatedtoUseFFR Figure4 Phasicandmeanpressuresignalsusedtomeasurefractionalflowreserve(FFR),calculatedastheratioofdistalcoronarypressure(Pd)to aorticpressure(Pa)atmaximalhyperemia,whichisequalto0.78inthisexample.Forreferencetocoronaryflow,avelocitysignalisshadedand shownatthebottomtoidentifythetimeofmaximalhyperemia.Thevelocitysignalisonlyavailableincombinedsensorwirestudies. CVR=coronaryvasodilatoryreserve. ReproducedwithpermissionfromKernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.J AmCollCardiol201055:17385.

CineAngiographicFrameofIntermediateLeftAnteriorDescendingCoronaryArteryStenosis Figure5 Pressurewiretransducerlocatedatarrow.Lowerpanelshowsphasicandmeanaorticanddistalcoronarypressurewithsignificantpressure lossduringhyperemia.Fractionalflowreserve(FFR)is75/110=0.68. ReproducedwithpermissionfromKernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.J AmCollCardiol201055:17385.

DataFromtheDEFERStudy:5YearFollowUpStudy Figure6 (Left)EventfreesurvivalcurvesfortheDefer,Perform,andReferencegroups.(Right)Incidenceofcardiacdeath/myocardialinfarction(MI)for thethreegroups. ReproducedwithpermissionfromPijlsNH,vanSchaardenburghP,ManoharanG,etal.Percutaneouscoronaryinterventionoffunctionally nonsignificantstenosis:5yearfollowupoftheDEFERstudy.JAmCollCardiol200749:210511.

OutcomesAfterFFRBasedDeferralofCoronaryInterventioninIntermediateCoronaryLesions Table1 *Leftmainstenosis. Unstableanginapectoris. Multivesseldisease. MACE=majoradversecardiacevents(principallyratesofpercutaneouscoronaryinterventionnosignificantratesofdeath/myocardial infarction).CFR=coronaryflowreserveFFR=fractionalflowreserve. ModifiedwithpermissionfromKernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.JAm CollCardiol201055:17385.

DataFromtheFAMEStudy:KaplanMeierSurvivalCurvesfor1YearFollowUpoftheFAMEPatients Figure7 (PanelA):Eventfreesurvivalformajoradversecardiaceventswassignificantat1year.Nodifferencesineventfreesurvivalfordeath(Panel B),myocardialinfarction(PanelC),orcoronaryarterybypassgrafting/percutaneouscoronaryintervention(PCI)(PanelD). FAME=FractionalFlowReserveVersusAngiographyinMultivesselEvaluationFFR=fractionalflowreserve. ReproducedwithpermissionfromToninoPA,DeBruyneB,PijlsNH,etal.Fractionalflowreserveversusangiographyforguidingpercutaneous coronaryintervention.NEnglJMed2009360:21324.

AssessmentofLeftMainDiseaseUsingFFR Figure8 Examplesofdiscordancebetweentheangiographicappearanceandthefractionalflowreserve(FFR)valuesofleftmainlesions.(PanelA)An angiographicallytightleftmainstenosiswithanFFRvalueof0.89.(PanelB,.C,AnangiographicallymildleftmainstenosiswithanFFRvalueof 0.68(PanelD). ReproducedwithpermissionfromHamilosM,MullerO,CuissetT,etal.Longtermclinicaloutcomeafterfractionalflowreserveguidedtreatment inpatientswithangiographicallyequivocalleftmaincoronaryarterystenosis.Circulation2009120:150512.

PoorCorrelationBetweenAngiographic%DiameterStenosisandFFR Figure9 Scatterplotsshowingthedistributionofpercentdiameterstenosisandthecorrespondingfractionalflowreserve(FFR)values.Thesoliddots representpatientswithisolatedleftmaincoronaryarterystenosis.However,alargescatterofthedatawasobserved.Thesensitivity, specificity,anddiagnosticaccuracyofpercentdiameterstenosisbyquantitativecoronaryangiographyanalysis>0%topredictanFFR<0.80 were33%,91%,and71%,respectively. ReproducedwithpermissionfromHamilosM,MullerO,CuissetT,etal.Longtermclinicaloutcomeafterfractionalflowreserveguidedtreatment inpatientswithangiographicallyequivocalleftmaincoronaryarterystenosis.Circulation2009120:150512.

KeyPoints
Thereisapoorcorrelationbetweenaphysiologicallysignificantstenosisandangiographicpercentdiameter stenosis. IntracoronarypressuremeasurementsandmeasurementofFFRduringdruginducedhyperemiaprovidea meanstodeterminethefunctional/hemodynamicsignificanceofacoronarystenosis. StentingofcoronarylesionsthatarenotsignificantbyFFR(>0.8)canbesafelydeferredandtreatedwithmaximal medicaltherapy. AstrategyofmultivesselstentingthatincorporatesFFRresultsinsuperioroutcomes,fewerstentsperpatient, andlesscostcomparedtoangiographicallydrivenPCI.

References

1. KernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterizationlaboratory.JAmColl Cardiol201055:17385. 2. GibsonCM,PintoD.Fractionalflowreserve:anewsetoflensesfortheocculostenoticreflex?JACCCardiovasc Interv20103:12823. 3. GouldK,LipscombK,HamiltonGW.Physiologicbasisforassessingcriticalcoronarystenosis.Instantaneous flowresponseandregionaldistributionduringcoronaryhyperemiaasmeasuresofcoronaryflowreserve.AmJ Cardiol197433:8794. 4. SeilerC,KirkeeideR,GouldKL.Basicstructurefunctionrelationsoftheepicardialcoronaryvasculartree.Basis ofquantitativecoronaryarteriographyfordiffusecoronaryarterydisease.Circulation199285:19872003. 5. OfiliE,LabovitzAJ,KernMJ.Coronaryflowvelocitydynamicsinnormalanddiseasedarteries.AmJCardiol 199371:3D9D. 6. SkalidisEI,KochiadakisGE,KoukourakiSI,ParthenakisFI,KarkavitsasNS,VardasPE.Phasiccoronaryflow patternandflowreserveinpatientswithleftbundlebranchblockandnormalcoronaryarteries.JAmCollCardiol 199933:133846. 7. KernMJ,BachRG,MechemCJ,etal.Variationsinnormalcoronaryvasodilatoryreservestratifiedbyartery, gender,hearttransplantationandcoronaryarterydisease.JAmCollCardiol199628:115460. 8. AndersonHV,StokesMJ,LeonM,AbuHalawaSA,StuartY,KirkeeideRL.Coronaryarteryflowvelocityisrelatedto lumenareaandregionalleftventricularmass.Circulation2000102:4854. 9. HamasakiS,AlSuwaidiJ,HiganoST,MiyauchiK,HolmesDRJr,LermanA.Attenuatedcoronaryflowreserveand vascularremodelinginpatientswithhypertensionandleftventricularhypertrophy.JAmCollCardiol 200035:165460. 10. DonohueTJ,MillerDD,BachRG,etal.Correlationofpoststenotichyperemiccoronaryflowvelocityandpressure withabnormalstressmyocardialperfusionimagingincoronaryarterydisease.AmJCardiol199677:94854. 11. MillerDD,DonohueTJ,YounisLT,etal.Correlationofpharmacological99mTcsestamibimyocardialperfusion imagingwithpoststenoticcoronaryflowreserveinpatientswithangiographicallyintermediatecoronaryartery stenoses.Circulation199489:215060. 12. JoyeJD,SchulmanDS,LasordaD,FarahT,DonohueBC,ReichekN.IntracoronaryDopplerguidewireversus stresssinglephotonemissioncomputedtomographicthallium201imaginginassessmentofintermediate coronarystenoses.JAmCollCardiol199424:9407. 13. DeBruyneB,PijlsNH,PaulusWJ,VantrimpontPJ,SysSU,HeyndrickxGR.Transstenoticcoronarypressure gradientmeasurementinhumans:invitroandinvivoevaluationofanewpressuremonitoringangioplastyguide wire.JAmCollCardiol199322:11926. 14. PijlsNH,VanGelderB,VanderVoortP,etal.Fractionalflowreserve.Ausefulindextoevaluatetheinfluenceofan epicardialcoronarystenosisonmyocardialbloodflow.Circulation199592:318393. 15. SegersP,FostierG,NeckebroeckJ,VerdonckP.Assessingcoronaryarterystenosisseverity:invitrovalidationof theconceptoffractionalflowreserve.CatheterCardiovascInterv199946:3759. 16. deBruyneB,BartunekJ,SysSU,PijlsNH,HeyndrickxGR,WijnsW.Simultaneouscoronarypressureandflow velocitymeasurementsinhumans.Feasibility,reproducibility,andhemodynamicdependenceofcoronaryflow velocityreserve,hyperemicflowversuspressureslopeindex,andfractionalflowreserve.Circulation 199694:18429. 17. JeremiasA,WhitbournRJ,FilardoSD,etal.Adequacyofintracoronaryversusintravenousadenosineinduced maximalcoronaryhyperemiaforfractionalflowreservemeasurements.AmHeartJ2000140:6517. 18. PijlsNH,vanSchaardenburghP,ManoharanG,etal.Percutaneouscoronaryinterventionoffunctionally nonsignificantstenosis:5yearfollowupoftheDEFERstudy.JAmCollCardiol200749:210511. 19. ToninoPA,DeBruyneB,PijlsNH,etal.Fractionalflowreserveversusangiographyforguidingpercutaneous coronaryintervention.NEnglJMed2009360:21324. 20. ToninoPAL,FearonWF,DeBruyneB,etal.Angiographicversusfunctionalseverityofcoronaryarterystenosesin theFAMEstudy:FractionalFlowReserveVersusAngiographyinMultivesselEvaluation.JAmCollCardiol 201055:281621. 21. JastiV,IvanE,YalamanchiliV,WongpraparutN,LeesarMA.Correlationsbetweenfractionalflowreserveand intravascularultrasoundinpatientswithanambiguousleftmaincoronaryarterystenosis.Circulation 2004110:28316. 22. HamilosM,MullerO,CuissetT,etal.Longtermclinicaloutcomeafterfractionalflowreserveguidedtreatmentin patientswithangiographicallyequivocalleftmaincoronaryarterystenosis.Circulation2009120:150512. 23. PijlsNH,KlaussV,SiebertU,etal.Coronarypressuremeasurementafterstentingpredictsadverseeventsat followup:amulticenterregistry.Circulation2002105:29504. 24. KooBK,KangHJ,YounTJ,etal.Physiologicassessmentofjailedsidebranchlesionsusingfractionalflow reserve.JAmCollCardiol200546:6337. 25. KooBK,ParkKW,KangHJ,etal.Physiologicalevaluationoftheprovisionalsidebranchinterventionstrategyfor bifurcationlesionsusingfractionalflowreserve.EurHeartJ200829:72632. 26. BotmanCJ,SchonbergerJ,KoolenS,etal.Doesstenosisseverityofnativevesselsinfluencebypassgraft patency?Aprospectivefractionalflowreserveguidedstudy.AnnThoracSurg200783:20937. 27. LevineGN,BatesER,BlankenshipJC,etal.2011ACCF/AHA/SCAIGuidelineforPercutaneousCoronary Intervention.AreportoftheAmericanCollegeofCardiologyFoundation/AmericanHeartAssociationTaskForce onPracticeGuidelinesandtheSocietyforCardiovascularAngiographyandInterventions.JAmCollCardiol 201158:e44122.

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3.11:AorticandPulmonaryComputedTomographyandMRAngiography
Author(s): AnnaLisaCrowley,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Identifytheadvantagesanddisadvantagesforcomputedtomographyangiography(CTA)andmagneticresonance angiography(MRA)imagingoftheaortaandpulmonaryvasculature. 2. Identifywhichpatientsareatriskfordevelopingnephrogenicsystemicfibrosis. 3. InterpretMRAandCTAimagestoidentifythenormalanatomyandanatomicvariantsoftheaortaaswellasthefollowing aorticpathologies:aorticdissection,penetratingaorticulcer(PAU),thrombus,aneurysm,coarctation,patentductus arteriosus,andvasculitis. 4. InterpretMRAandCTAimagestoidentifythenormalanatomyofthepulmonaryarteryandthefollowingpulmonaryartery pathologies:pulmonaryarterydilatation,pulmonaryarterystenosis,pulmonaryembolus,andpulmonaryarteriovenous malformations(AVMs). 5. InterpretMRAandCTAimagestoidentifynormalanatomyandanatomicvariantsofthepulmonaryveins,aswellas pulmonaryveinstenosis. 6. IdentifytheetiologyandappearanceofcommonartifactsonMRAandCTAimages.

Introduction
Background Diseasesoftheaorta,pulmonaryarteries,andveinscausesignificantmorbidityand mortality.1 Bothmultidetectorcomputedtomography(MDCT)andmagnetic resonance(MR)havebeenusedtoassesstheaortaandpulmonaryvasculature (Figure1).Unenhancedandcontrastenhancedstudieseachhaveavaluablerole fordiagnosingvascularpathology.Noncontrastenhancedstudiesareusefulfor assessingthevesselwall,stents,andstentgraftintegrity.Contrastenhanced studiesaremostusefulforassessingthevessellumen. MDCTgeneratesathreedimensionaldatasetbyacquiringmultipletwo dimensionaldatasetsinrapidsuccessionwithhighspatialresolutionand subcentimetersizedvoxels.Twoandthreedimensionalreconstructionscanbe obtainedinmultipleorientationsthatcanmorereadilybeinterpretedbyreferring physicians.Electrocardiographicgatingisvaluabletodecreasemotionartifact, whichcanoccasionallymimicadissection.MDCTexaminationsincluderadiation exposure,whichcanrangeupto1420mSv.2 Usingbismuthbreastshields, loweringpeakkilovoltageandtubecurrent(mA)throughautomatictubecurrent modulationhavebeenshowntodecreaseradiationdosewhilemaintainingimage quality.2 MRAcanalsoassesstheaortaandpulmonaryvasculaturewithouttheuseof radiation.Techniquestoassessthevesselwallincludecineimages(e.g.,steady statefreeprecession),aswellasdarkandbrightbloodmorphologicimages(e.g., halffourieracquisitionturbospinechoandlowresolutionsteadystatefree precession,respectively).ContrastenhancedMRAtechniquesincludetemporally resolvedsubsecondcontrastenhancedMRAandconventional3DMRA(both typicallyagradientechoacquisition). TemporallyresolvedsubsecondcontrastenhancedMRA(timeresolvedMRA)is helpfulinidentifyingabnormalbloodflow/connectionssuchasshuntflowthrougha patentductusarteriosusorananomalouspulmonaryvenousconnection.This techniqueinvolvesasmalleramountofcontrast(typically5ml)andworsespatial resolutionincomparisonwithconventional3DMRA.Whileelectrocardiographic (ECG)gatingispreferredduring3DMRAinordertoreducemotionartifact,itcanbe performedwithoutECGgatinginordertoreducethesequencescantimeinthose patientswithdifficultbreathholding.RoutinecontraindicationsforMRAinclude thosepatientswithimplantedferromagneticmetal.MRsafetydataforvarious devicesandimplantshavebeenpublished.3 ContrastMedia IodinatedcontrastisusedforvesselopacificationonCTA.Potentiallylifethreatening reactionstoiodinatedcontrastarerare(<1%ofcases)howevernonlifethreatening adversereactionsaremorecommon.4 Nonioniccontrastagentshavefewer adversereactionsincomparisonwithioniccontrastagents.Premedicationwith antihistaminesandcorticosteroidsinpatientswithiodineallergiespriortocontrast administrationhasbeenshowntodecreasetheincidenceofanaphylactoid reactions.4 Arecentsystematicreviewshowedthatantihistaminesgivenimmediatelypriorto theadministrationofcontrastmaybeusefulinpreventinganaphylactoidreactions andaresuggestiveofaprotectiveeffectofcorticosteroidswhengivenintwodoses atleast6hourspriorandagain2hourspriortotheadministrationofcontrast.4 Renalinsufficiencycanbeexacerbatedwithiodinatedcontrastandisarelative contraindication. Paramagneticcontrastisusedtoenhanceimagequalitybyincreasingthesignalto noiseratio,reducingmotionartifactsandscantimes,andeliminatingflowartifacts thatareseeninotherMRAtechniquessuchastimeofflightorphasecontrastMRA. Gadoliniumisthemostwidelyusedcontrastagentduetoitshighrelaxivityand favorablesafetyprofilewhenboundtoachelator.Gadoliniumchelatesshortenthe
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T1relaxationtimeofbloodinproportiontotheirconcentrationinblood.5 Sideeffectssuchasnausea,rash,andanaphylaxisarerare(<1%ofcases).While gadoliniumisnotnephrotoxicwhenadministeredintravenously,ithasbeen associatedwithnephrogenicsystemicfibrosis.Nephrogenicsystemicfibrosisisa rare,butpotentiallydebilitating,systemicdiseasethatischaracterizedbythe thickeningoftheskinandsubcutaneoustissues.Ithasbeendescribedexclusively inpatientswithrenalimpairment(typicallyestimatedglomerularfiltrationrate<30 ml/min/1.73m2 onrenalreplacementtherapyorinacutekidneyinjury)andlinkedto gadoliniumexposure.6,7 Thediagnosisofnephrogenicsystemicfibrosisisbasedonbothclinicaland histopathologicfindings.In2010,theFoodandDrugAdministration(FDA)required changesindruglabelingforgadoliniumbasedcontrastagentstominimizetherisk ofnephrogenicsystemicfibrosis.8 NewerMethods Methodstodecreasethegadoliniumassociatedrisksinthosewithrenal impairmentarebeinginvestigated.First,administeringthelowestpossible gadoliniumdose,whileachievingadequatespatialresolution,isdesirable.Withthe increasedavailabilityanduseofMRat3.0T,theamountofcontrastneededto achievesimilarimagequalitycanbereducedincomparisonwithimagingat1.5T duetoincreasedspatialresolutionandenhancedvesseltobackgroundcontrast.9 Second,newerintravenouscontrastagents,suchasultrasmall,superparamagnetic ironoxidenanoparticles,arebeingexploredaspotentialalternativesto gadolinium.10 Oneoftheseagents,ferumoxytol,hasbeenapprovedbytheFDAforuseasaniron replacementforanemiainpatientswithchronickidneydisease.11Ferumoxytol's favorablesafetyprofileinpatientswithchronickidneydiseaseisappealingforMRA, andfurtherstudiesareongoingtoinvestigateitsrole.Finally,improvementsinMR hardwareandsoftwarehaveledtorenewedinterestinnoncontrastenhancedMRA techniques.Oneofthemostpromisingappearstobe3Dsteadystatefree precessionMRA.Thistechniqueallowsforbrightbloodimages(imagecontrast determinedbyT2:T1ratio)withbotharteriesandveinsappearingbright(although venousinflowsuppressionispossible)(Figure2). Studieshaveshownthat3DsteadystatefreeprecessionMRAmeasurementsof aorticandpulmonaryveindiametersareessentiallyequalincomparisonwith contrastenhancedMRA(CEMRA).12,13NoncontrastenhancedMRA(NCEMRA)is appealingbecauseitobviatestheneedforintravenousaccess,andconsequently reducestherisksandcostsassociatedwithcontrast.However,theseexaminations stillrequirelongerscantimescomparedwithCEMRA. ModuleScopeandAppropriatePatientTestSelection Theremainderofthismodulewillfocusonthenormalanatomyanddescribethe identificationandimagingapproachtoabnormalitiesoftheaorta,pulmonaryartery, andveins.Whiletheimagingapproachtoaorticandpulmonaryvasculatureapplies tobothCTAandMRA,itisimportanttorecognizethatseveralfactorsmustbe consideredwhenselectingthemostappropriateimagingtestforagivenpatient. Thesefactorsincludepatientage,gender,andrenalfunction,abilitytoobtain vascularaccess,breathhold,acuityoftheneedfordiagnosis,andtheneedfor serialimaging.

NormalAnatomy Figure1 3Dvolumerenderedmagneticresonanceangiographyimagedemonstratingthenormalrelationshipbetweentheheart,aorta,pulmonaryartery, andpulmonaryveinsinanterior(panelA)andposterior(panelB)orientations. A=anteriorP=posterior.

Noncontrast3DSteadyStateFreePrecessionThoracicMagneticResonanceAngiographyImagesintheAxialOrientationattheLevelofthe RightPulmonaryArtery(panelA)andLeftCoronaryArteryOrigin(panelB) Figure2 AA=ascendingaortaDA=descendingaortaRPA=rightpulmonaryarterySVC=superiorvenacava.

ImagingtheAorta (1of2)
ImagingtheNativeAorta NormalAnatomy Thenormalaortaconsistsofaleftsidedthoracicaorta(ascending,arch,and descendingsegments),whichcontinuesastheabdominalaorta(suprarenaland infrarenalsegments)aftertraversingthediaphragmthroughtheaortichiatus(Figure 1).Innormalanatomy,theascendingaortaonlyhastwobranches:therightandleft coronaryarteries.Thearchhasthreebranches:thebrachiocephalictrunk(which dividesintotherightsubclavianandrightcommoncarotidarteries),theleftcommon carotidartery,andtheleftsubclavianartery.Thedescendingthoracicandabdominal aortahavemultiplebranches. Thereareseveralnormalvariantarchvesselanatomies(Figure3)includingtheleft commoncarotidarteryoriginatingfromthebrachiocephalictrunk(bovinearch) (Figure3,panelA),theleftvertebralarteryoriginatingdirectlyfromtheaorticarch (Figure3,panelB),andanaberrantoriginoftherightsubclavianarterydistaltothe originoftheleftsubclavianartery(Figure3,panelC). Anothernormalvariantispseudocoarctation,whichresultsinahighproximalarch andpseudokinkingoftheredundantaortawhereitistetheredtothepulmonary arterybytheligamentumarteriosum.However,nohemodynamicallysignificant lumenalnarrowingispresentinpseudocoarctation.Normalanatomicvariants shouldbedescribedbecausetheirpresencemayimpacttheabilitytoperform catheterbasedorsurgicalinterventionsifindicated. AorticDissection Promptimagingevaluationisrequiredinthosesuspectedofhavinganacuteaortic dissectionortraumaduetoanincreasedmortality.Whilelargedissectionsmaybe apparentonnoncontrastimaging,contrastisoftenemployedtodelineatetheentry site.Identifyingtheentrysiteoftheaorticintimaltear,dissectionextent,termination site,andbranchesinvolvedarecrucialcomponentsoftheimagingevaluation.Most commonly,aorticdissectionsoriginateintheascendingaorta,14ineithernormalor enlargedaortas. TheDeBakeyandStanfordclassificationsystemsarecommonlyusedtodescribe dissectionlocationandextent.14Acutedissectionsthatinvolvetheascendingaorta (DeBakeytypeI[ascendinganddescendingaortainvolvedFigure4,panelA],typeII [onlyascendingaortainvolved],andStanfordtypeA[ascendingaortainvolvedwithor withoutdescendingaortainvolvementFigure4,panelA])aresurgicalemergencies andcarryaworseprognosisincomparisonwithdissectionsthatonlyinvolvethe descendingaorta(DeBakeytypeIII,StanfordtypeB).14Inaddition,imagingshould includeassessmentforassociatedcomplicationsofdissectionsuchasaortic rupture,coronaryarterydissection,andhemopericardiumincludingtamponade, intramuralhematoma(IMH),PAU,andbranchocclusions. Furthermore,distinguishingthetrueandfalselumensisimportant,especiallywhen branchesareinvolvedandsurgicalorendovascularrepairisconsidered.Typically, thetruelumenissmallerthanthefalselumenandcanbedistinguishedby identifyingthetruelumenintheundissectedportionoftheaortaandtrackingits coursedistally.Determiningthepresenceorabsenceofflowinthefalselumenand anyinvolvedbranchescanbeaccomplishedwitheithercontrastenhancement (Figure4,panelB)orflowvelocityimaging(Figure4,panelC)onnoncontrastMRA. Themostimportantstepispromptlycommunicatingfindingstothereferring physician,becausemortalityisdirectlyrelatedtodurationfromsymptomonset. PenetratingAorticUlcer/IntramuralHematoma PAUsandIMHsaresimilartoaorticdissectionsintermsofprognosis.APAUis thoughttorepresentfocalintimaldissectionsfromulceratedaorticatheromas.15 ImagingviaCTAorMRAdemonstrateafocaloutpouching/disruptioninthenormal
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aorticcontour(Figure5).Penetratingulcerscanbesingleormultipleandcanoccur intheascendingordescendingaorta(morecommon).APAUcandevelopintoa pseudoaneurysm,moreextensivedissection,orIMH(Figure6).AnIMHrepresentsa focalhemorrhageoftheaorticmediawithoutavisibleintimaltear.Noncontrast computedtomography(CT),MRA,orcineMRimagingishelpfulinidentifyingthe hematomaintheaorticwall,becauselumenographicimagingalonewithoutwall visualizationmaymissIMH. ItisworthnotingthatIMHmayprogresstodissection,especiallyinenlarged aortas.16Thrombusisalsowellvisualizedonpostcontrastimagesusinga"longTI" delayedenhancementsequence(Figure6,panelD).ByprescribingaTItime equivalenttothenullpointoftissuewithnogadoliniumuptake(typically600650 ms),thrombusappearsblack,whereasallothertissuesappeargrayorbright.17 Aneurysm Atrueaorticaneurysmisdefinedasanenlargedaortainvolvingtheintimal,medial, andadventitiallayers(Figure7).Incontrast,apseudoaneurysmisacontained ruptureoftheintimaandmedia,typicallywithanarrowneck(Figure6).Thoracic aneurysmscanbedescribedasfusiform(symmetricdilatationoftheentireaortic circumference)orsaccular(localizedaorticoutpouching).TheCrawford classificationsystemcanbeusedtocharacterizethoracoabdominalaneurysmsby locationandextent.14 TypeIaneurysmsextendfromtheleftsubclavianarterytotherenalartery.TypeII aneurysmsextendfromtheleftsubclavianarterytotheaorticbifurcation.TypeIII aneurysmsextendfromthemidthoraxtotheaorticbifurcation.TypeIVaneurysms extendfromthediaphragmtotheaorticbifurcation.Thelocationandsizearerelated tothelikelihoodofdissection/ruptureandguidekeymanagementdecisionsin asymptomaticpatients.Therefore,everyimagingevaluationshouldlistthelocation, extent,andsizeoftheenlargedaorta. Determininganaccurateaorticsizeisimportant.However,measurement discrepanciesoccurandareproblematicbecausedecisionsaboutmanagement oftenrelyonanaccurateaorticsize.Thereareseveralreasonsthatdifferentsize measurementsmaybeobtainedonthesamestudyandalsowhenevaluatingserial studies. First,measurementdifferencesmaybeintroducedbycomparingaorticsizesusing multipletechniques,withdifferentspatialresolutions,differentdatasets,and differentimagingplanes.Thethoracicaortagrowsslowlyatapproximately1mma year.SuchasubtledifferencecannotbedetectedbyCTAorMRA.Infact,ithasbeen reportedthatvariationsinsizeofupto4mmmaysimplybeduetothelimitationsin resolutionforbothCTAandMRA.18Inaddition,aorticmeasurementsshouldalways beperformedonthesourceimagesratherthanonpostprocessedimages(which aresubjecttopotentialsizealterationsduetocropping).Also,aorticmeasurements areoftenobliquewhenperformedonaxialimagesincomparisonwithbiorthogonal measurements. Second,measurementdiscrepanciesmaybeintroducedbyobtaining measurementsthateitherincludeorexcludedtheaorticwall.Ofnote,walltowall measurements(fromnoncontrastimages)aregenerallylargerthanlumenographic measurements(fromcontrastenhancedimages).Asaresult,itisimportantto measuretheaortainthesameanatomiclocationsusingthesametechnique, sequence/image,andplane,ifpossible,whenassessingserialstudiesforinterval change.Similarly,itisimportanttocompareafollowupCTAorMRAtoboththe originalaswellasthemostrecentstudy.Smallincrementalchangesinaorticsize maynotbeapparentontwoconsecutivestudies.However,absolutechangesmay bemoreapparentincomparisonwithanoriginalstudyoveralongertimeperiod, distinguishingtruedifferencesfrominterstudyvariability.Notingthesepotential sourcesofsizediscrepancyassisttheimagerinaccuratelydistinguishingtrue differencesinaorticsizefromintraandinterstudyvariability. Despitetheselimitationsinobtaininganaccurateaorticsize,diametersabove whichtheincidenceofaorticrupture/dissectionincreasessharplyhavebeen identifiedas6cmintheascendingaortaand7cminthedescendingaorta,oran

aorticsizeindexof2.75cm/m2 .19Whileaorticaneurysmsizeandlocationare importantimagingfindingstoidentify,otherfeaturessuchasshape,lossofthe normalsinotubularindentation,concomitantvalvularorcoronaryarterydisease,and presenceofaporcelainaortaareadditionalinformationthatcanbeobtainedbyCT and/orMRthatcanimpactmanagementdecisions.

NormalAnatomy Figure1 3Dvolumerenderedmagneticresonanceangiographyimagedemonstratingthenormalrelationshipbetweentheheart,aorta,pulmonaryartery, andpulmonaryveinsinanterior(panelA)andposterior(panelB)orientations. A=anteriorP=posterior.

VariantAnatomyoftheOriginsoftheAorticArchSidednessandGreatArchVesselsin3DVolumeRenderedMagneticResonance AngiographyImages Figure3 (PanelA)Commonoriginofthebrachiocephalicandleftcommoncarotidarteries(bovinearch). (PanelB)Aberrantrightsubclavianarteryoriginatingaftertherightcarotidartery,leftcarotidartery,andleftsubclavianartery.Notethatthe aberrantrightsubclavianarterycoursesposteriorlytoresumeitsnormalcourse. (PanelC)Separateoriginoftheleftvertebralarterydirectlyfromtheaorticarch. (PanelD)Rightsidedaorticarchwithmirrorimagebranchingofthegreatarchvessels.Notethatthebrachiocephalicarteryisthefirstvesselto originatefromthearchhowever,itdividesintotheleftcarotidandleftsubclavianarteriesratherthantherightcarotidandrightsubclavian arteriesinthenormal,leftsidedaorticarch.Next,therightcommoncarotidarteryoriginatesfromthearch,followedbytherightsubclavian artery.

StanfordTypeAorDeBakeyTypeIAorticDissectionOriginatingintheAscendingAortaandTerminatingintheAbdominalAorta Figure4 ThedashedlineinpanelAdepictstheimagingplaneforpanelsBandC. (PanelA)3Dvolumerenderedmagneticresonanceangiographyimagedemonstratingthedissectionflap. (PanelB)Contrastenhancedmagneticresonanceangiographyintheaxialorientationatthelevelofthepulmonaryarterybifurcation, demonstratingthedissectionflapinboththeascendingaorta(arrowhead)anddescendingaorta(arrow). (PanelC)Velocityencodedimagedemonstratingflowinboththetrueandfalselumensofthedissectionintheascendinganddescending thoracicaortainanaxialorientationatthelevelofthepulmonaryarterybifurcation(sameimagingplaneasinpanelB).

PenetratingAorticUlcerina3DVolumeRenderedMagneticResonanceAngiographyImage(arrowinpanelA),CineMagneticResonanceImage (arrowinpanelB),andContrastEnhancedMagneticResonanceAngiographyImageinanAxialObliqueOrientation(arrowinpanelC) Figure5 ThedashedlineinpanelAdepictstheimagingplaneforpanelC.

AorticPseudoaneurysm Figure6 (PanelA)Aorticpseudoaneurysmina3Dvolumerenderedmagneticresonanceangiographyimage(arrows).ThedashedlineinpanelA depictstheimagingplaneforpanelsB,C,andD. (PanelB)Cinemagneticresonanceimagedemonstratingthepseudoaneurysm.Thewhitearrowsoutlinetheborderofthepseudoaneurysmwith theblackdottedarrowdepictingtheflowcommunicationbetweenthetrueaorticlumenandpseudoaneurysm.Ofnote,thrombusisseenlining thewallofthepseudoaneurysm(whitearrows). (PanelC)Contrastenhancedmagneticresonanceangiographyimageinanaxialobliqueorientationdemonstratingthepseudoaneurysm (arrows). (PanelD)LongTIimagedemonstratingthedarksignalofthethrombusliningthewallofthepseudoaneurysm(whitearrows).Notealsothe dissectioninthedescendingaorta(panelsA,B,C,andD).

ThoracicAorticAneurysmina3DVolumeRenderedMagneticResonanceAngiographyImage(panelA)andInfrarenalAorticAneurysmina3D VolumeRenderedMagneticResonanceAngiographyImage(panelB) Figure7

ImagingtheAorta (2of2)
CongenitalAbnormalities CongenitalabnormalitiesoftheaortacanalsobedeterminedbyCTAorMRA.A doubleaorticarchorarightsidedaorticarch(Figure3,panelD)canbeidentified withorwithoutmirrorbranchingofthegreatarchvessels.Thepresenceofaright sidedaorticarchmaybeassociatedwithothercongenitalabnormalities,suchas situsinversusandaberrantarchvesselanatomy,resultinginavascularring surroundingthetrachea.Aorticcoarctationcanbeidentifiedjustdistaltotheoriginof theleftsubclavianartery(Figure8). Onceacoarctationisidentified,imagingshouldincludeevaluationoftheaortic valve,becausethereisanincreasedriskofbicuspidaorticvalveinthosepatients withaorticcoarctation,aswellasevaluationofthepresenceandextentofcollateral vessels.Inaddition,velocityencodedcardiacmagneticresonance(CMR)imaging canmeasurevelocityatthelevelofobstruction,aswellasflowproximalanddistalto thecoarctation.Increasedflowdistaltotheaorticcoarctationsignifiesthepresence ofsignificantcollateralflow. TimeresolvedMRAisespeciallyusefulfordetectingabnormalshuntlocations. Velocityencodedimagingcanquantifytheshuntflow(e.g.,throughapatentductus arteriosusFigure9),whichimpactsmanagementdecisions.Anothercongenital abnormalityisasinusofValsalvaaneurysm.CTAorMRAisusefulinidentifying whichsinusisaneurismal,aswellasidentifyingifruptureintoanintracardiac chamberispresent.Mostcommonly,therightsinusofValsalvaisaffected.Similar toothercongenitalvascularabnormalities,sinusofValsalvaaneurysmsare associatedwithothercongenitalabnormalitiesthatcanbedetectedonCTorMR, includingventricularseptaldefect,bicuspidaorticvalve,aorticregurgitation,and coarctation. Vasculitis Imagingoflargevesselvasculitis(e.g.,Takayasuandgiantcellarthritis)consistsof bothnoncontrastandcontrastCTAorMRA.Imagingbeforecontrastadministration allowsformeasurementofwallthicknessandpossiblythedetectionofmural thrombus.Contrastadministrationallowsfordetectionofarterialaneurysmsor stenosis,aswellasdeterminesifathickenedaorticwallenhanceswithcontrast, suggestiveofaninflammatoryorvasculitisprocess(Figure10). ImagingthePostoperativeAorta Imagingofthepostoperativeaortashouldbeginwithanunderstandingofthe underlyingpathologythatnecessitatedtheinterventionwithreviewofpreoperative images,ifavailable.Next,acarefulreviewofthespecificprocedureperformed shouldbedone,becauseaorticrepairscouldbesurgicalorendovascular.Both thesestepsassistindeterminingwhichfindingsarenewandabnormalversus thosewhicharechronicandexpectedpostoperativechanges.Forexample,the identificationofadissectionmaybemanageddifferentlyifitisanewfindingafteran operationorifitwasknownandpresentpriortotheoperation. Mostsurgicalaorticrepairsinvolveaninclusionorinterpositiongrafttechnique.The inclusiontechniqueinvolvesaortotomyandplacementofasyntheticgraftinthe diseasedportion,andthenativeaortaisleftandwrappedaroundthegraft.The interpositiontechniqueinvolvesresectionofthediseasedportionandplacementof agraftintheplaceofthediseasedportion.Identifyingthegraftiseasieston noncontrastCTasahighdensitymaterial.Thegraftisoftenobscuredoncontrast enhancedMRorCT.However,itspresencecanstillbediscernedasanabrupt changeincontourbetweenthegraftandnativeaorta,orbyvisualizinghigh attenuationfeltringsusedtoreinforceanastomoticsites(Figure11,panelA). Occasionally,graftshaveanangulation,whichmaymimicadissectionflaponaxial images.(Figure11,panelsA,B).Anothernormalfindinginthepostsurgicalaortais thepresenceofaspacebetweenthegraftandnativeaorta.Itmaybethrombosed
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Figure15

and,ingeneral,doesnotenhancewithcontrast.Incontradistinction,contrast extravasationafterinterpositiongraftplacementcouldrepresentfistulaformation, and/orinfection,andmaybeassociatedwithapseudoaneurysm.Additional complicationsincludeperigraftfluid,softtissue,orgascollections.Thesefindings mayrepresentedemaororganizedhematomafollowingrepairanddonotenhance withcontrast.Thelattercanbeseenasanormalearlypostoperativefinding. However,perigraftgasthatisneworpersists>6weeksaftersurgeryissuspicious forinfectionorfistula. Moreendovascularaorticrepairsarebeingperformed.Stentprosthesescontainan innermetallicskeletoncoveredbyanouterpolyestergraftmembrane.Whilemost endovascularstentsaremadeofnonferromagneticmaterial,specificmanufacturer informationshouldbereviewedpriortoconsiderationofperforminganMRA.Most currentversionsofthestentgrafts(e.g.,nitinol)produceminimalifanyartifact.20,21 Itshouldbenoted,however,thatstainlesssteelstentmaterialresultsinasignal voidonMRA,renderinglumenalvisualizationimpossible.Incontrast,themetallic skeletoniswellvisualizedonunenhancedCT,regardlessofmetaltype.The coveringlayerisnotseenwellonCT.However,itisborderedbycircumferential metalringsatbothends,whichcanbevisualized.Thenormalpostoperativestent graftedaortamaycontainlowdensityperigraftfluidoraorticwallthickening,which usuallyresolveinthefirst8weeksafterplacement.Complicationswellvisualizedby noncontraststudiesincludestentcollapseandmigration(Figure12). Insomecases,astentmayintentionallyorinadvertentlyocclude(partiallyor completely)theoriginoftheleftsubclavianarteryandcarefulimagingshouldbe performedtoassessforretrogradeflowinthevertebralartery(flowvelocityimaging onCMRishelpfulinthiscase).Endoleaksaredefinedaspersistentflowintothe excludedportionoftheaortaandarebestvisualizedaftercontrastadministration (Figure13).TheyareclassifiedintotypesIV.22 TypeIendoleaksarethemostcommonandresultfromanincompletesealofthe endsofthestenttotheaorticwall.TypeIIarecausedbyretrogradeflowintothe excludedaorticlumenfrompatentbranchvessels(typeIIa:singlebranchvessel withretrogradeflowIIb:multiplebranchvesselswithretrogradeflow).TypeIII endoleaksarecausedbyjunctionaldehiscenceordevicedegeneration.TypeIV endoleaksresultfromporosityofthestentusedforthoracicendovascularrepair, andTypeVendoleaksaredefinedasincreasingsizeoftheexcludedaorticlumen withoutenhancementoftheexcludedlumen.Othercomplicationsthathavebeen describedincludenewdissectionorpseudaoaneurysmformationduetodirect traumatotheintimabythestent. ArtifactsandPitfallsinImagingtheAorta ArtifactscanbeseeninbothCTAandMRAimaging.Notincluding/acquiringthe entireareaofinterest,insufficientcontrastdose,andpoortimingforcontrast triggeringmayresultininadequatevesselopacification,whichcaneithermissor mimicpertinentfindingssuchasadissection(Figure14).Similarly,patientmotion andpoorECGgatingmayalsomimicadissectionduetotruevesselposition imageacquisitionmismatch. Inadditiontothepitfallsinserialaorticmeasurementsdescribedearlier,pitfallsin imagingthepostoperativeaortaincludenotrecognizing/understandingthe preoperativeanatomyandnormalpostoperativeaortaappearance,bothearlyand late,afterrepair.Cautionisadvisedtonotmistakenormalpostoperativefindingsfor pathology.Inparticular,artifactsshouldalwaysbeinthedifferentialdiagnosisofa suspectedangiographicabnormality.Forexample,recognitionofthepresenceof stainlesssteelstentmaterialduringanMRAisimportanttonotmisinterpretthe normalexpectedsignalvoidforashortsegmentvesselocclusion(Figure15). Evenintheabsenceofpriorstentdocumentation,anastutereadershouldsuspect astentartifactiftherearesharplydemarcatedbordersofashortsegmentocclusion, absentcollateralvessels.Inaddition,anyimplantedmetallicprosthesis,suchasa jointprosthesis,mayproducesignallossinthesurroundingareaandmustbe noted.

VariantAnatomyoftheOriginsoftheAorticArchSidednessandGreatArchVesselsin3DVolumeRenderedMagneticResonance AngiographyImages Figure3 (PanelA)Commonoriginofthebrachiocephalicandleftcommoncarotidarteries(bovinearch). (PanelB)Aberrantrightsubclavianarteryoriginatingaftertherightcarotidartery,leftcarotidartery,andleftsubclavianartery.Notethatthe aberrantrightsubclavianarterycoursesposteriorlytoresumeitsnormalcourse. (PanelC)Separateoriginoftheleftvertebralarterydirectlyfromtheaorticarch. (PanelD)Rightsidedaorticarchwithmirrorimagebranchingofthegreatarchvessels.Notethatthebrachiocephalicarteryisthefirstvesselto originatefromthearchhowever,itdividesintotheleftcarotidandleftsubclavianarteriesratherthantherightcarotidandrightsubclavian arteriesinthenormal,leftsidedaorticarch.Next,therightcommoncarotidarteryoriginatesfromthearch,followedbytherightsubclavian artery.

TrueAorticCoarctationina3DVolumeRenderedMagneticResonanceAngiography Figure8 (PanelA)Trueaorticcoarctationina3Dvolumerenderedmagneticresonanceangiographyimage(solidwhitearrow).Notealsoa pseudocoarctationrepresentedbythedottedarrowinpanelA.ThedashedlineinpanelAdepictstheimagingplaneforpanelB. (PanelB)Contrastenhancedmagneticresonanceangiographyimageintheaxialorientationdemonstratingthetruecoarctation(solidwhite arrow).

PatentDuctusArteriosusina3DVolumeRenderedComputedTomographyAngiographyImage Figure9 Arch=aorticarchDA=descendingthoracicaortaPA=pulmonaryarteryPDA=patentductusarteriosus.

GiantCellArteritis Figure10 Darkbloodprecontrastmagneticresonanceangiographyimagedemonstratesbothascendingaortic(AA)anddescendingaortic(DA)wall thickening(whitearrowsinpanelA).Darkbloodpostcontrastmagneticresonanceangiographyimagedemonstratescontrastenhancementin thethickenedaorticwall(whitearrowsinpanelB). RPA=rightpulmonaryartery.

NormalPostoperativeAppearanceofAscendingAorticGraftAfterAscendingAortaandHemiarchRepairforChronicTypeAAorticDissection Figure11 (PanelA)Axialcomputedtomographyangiographyimageshowsthethinfocalflap(arrow)alongtheleftlateralaspectoftheascendingaorta suspiciousfordissection. (PanelB)SagittalobliquecomputedtomographyangiographyimageshowsthattheflapseeninpanelAcorrespondstokinkatjunctionoftwo graftcomponents(arrow).Also,notethethickhighdensityfeltpledgets(arrowheads)atthesiteofcannulationfromcardiopulmonarybypass. AA=ascendingaortaDA=descendingthoracicaorta. AdaptedwithpermissionfromHoangJK,MartinezS,HurwitzLM.MDCTangiographyofthoracicaortaendovascularstentgrafts:pearlsand pitfalls.AJRAmJRoentgenol2009192:51524.

65YearOldManWithStentGraftBirdBeakingandBucklingDuetoAorticArchCurvature Figure12 (PanelA)SagittalobliqueCTAimageobtained3monthsafterthoracicendovascularaorticrepairforpenetratingulcerindescendingthoracic aortashowsnewpenetratingulcer(arrow)andintramuralhematoma(arrowheads). (PanelB)SagittalobliquemaximumintensityprojectionCTAimageobtainedafteradditionalstentgraftingshowstherearethreeoverlapping stentgrafts:SG1,SG2,andSG3.Theoriginalstent,SG1,isinthedistaldescendingthoracicaorta(whitearrows).SG1isoverlappedbylonger SG2(blackarrows),whichextendsfromthedistalaorticarchtothedescendingthoracicaorta.Attheaorticarch,SG3(whitearrowheads) overlapsSG2andcoverstheleftsubclavianartery.Dissectiondevelopedduringtheprocedurerequiringcoilingoffalselumen(black arrowheads)andLSA. (PanelC)AxialCTAimageshowsacomponentofthestentgraftprojectedinlumenofthedistalaorticarch(arrow)thatisconcerningforstent collapse. (PanelD)SagittalobliqueCTAimageshowsthatSG3isbuckledandprotrudesintoaorticlumen(arrow)atitsjunctionwithSG2.Inaddition,SG3 doesnotdirectlyapposelessercurveofaorticarch(arrowhead),resultinginbirdbeaking.Bothfindingsareduetocurvatureoftheaortic archlimitingcloseappositionofthestentgrafttotheaorticwall. CTA=computedtomographyangiographyLSA=leftsubclavianartery. AdaptedwithpermissionfromHoangJK,MartinezS,HurwitzLM.MDCTangiographyofthoracicaortaendovascularstentgrafts:pearlsand pitfalls.AJRAmJRoentgenol2009192:51524.

EndoleakAfterThoracicEndovascularAorticRepairforTypeBAorticDissection Figure13 (PanelA)AxialCTAimageobtained3daysafterthoracicendovascularaorticrepairshowspersistentlyenhancingfalselumenexternaltostent graft(asterisk). (PanelB)AxialCTAimageobtained4weeksafterthoracicendovascularaorticrepairshowsenlargingandpersistentlyenhancingfalselumen (asterisk).Sourceofendoleakwasleftsubclavianartery(notshown). AA=ascendingaortaCTA=computedtomographyangiographyDA=descendingthoracicaorta. AdaptedwithpermissionfromHoangJK,MartinezS,HurwitzLM.MDCTangiographyofthoracicaortaendovascularstentgrafts:pearlsand pitfalls.AJRAmJRoentgenol2009192:51524.

ArtifactMimickingDissection Figure14 Contrastenhancedmagneticresonanceangiographyimageinanaxialorientationattheleveloftherightpulmonaryartery(RPA).Anartifact (arrows)isseeninboththeascendingthoracicaorta(AA)anddescendingthoracicaorta(DA)thatmimicsadissection.Notethatthe pseudodissectionextendsbeyondthelateralborderofthedescendingthoracicaortaconsistentwithartifact.Comparisonwithotherimages confirmsthepresenceofartifact(notshown).

SignalVoidFromaRightRenalArteryStent(arrow)MimickingaFocalRenalArteryStenosisinaCoronal,ContrastEnhancedMagnetic ResonanceAngiographyImage Figure15

ImagingthePulmonaryArteryandItsBranches

ImagingtheNativePulmonaryArtery NormalAnatomy Thenormalpulmonaryarteryarisesfromtherightventricleandbifurcatesintotwo mainbranches,therightandtheleft.Eachrightandleftpulmonaryarterybranches intosegmentalandthensubsegmentalarteries.Pulmonaryarterymeasurements arevariable,similartoaorticsizemeasurements,dependingonthetechniqueand methodusedtoacquirethemeasurement.OnunenhancedaxialCTimages,the normalpulmonaryarterywalltowalldiameterswasbeenreportedtobe2.720.3 cm.23A3.32cmcutoffforpulmonaryarterysizehasbeenshowntobespecificfor pulmonaryhypertension,althoughlesssensitive.23 PulmonaryArteryDilatation Pulmonaryarterydilatationismostcommonlyassociatedwithpulmonary hypertension(Figure16).Examinationofthesurroundinglungparenchyma,right heartsize,andfunctionmaygiveadditionalcluestowhetherornottheetiologyis primaryorsecondary. PulmonaryArteryStenosis Branchpulmonaryarterystenosisismostcommonlyseeninadultsafterrepairof congenitalheartdisease.Itcanbefocalordiffuse(Figure17).Identificationofboth minimallumenalsizeandhemodynamicsignificanceviaflowdifferentialobtained fromvelocityencodedMRimagingorlungperfusionhelpguidemanagement. PulmonaryEmbolism MDCTwithcontrastcombinedwithvenousphaseimaginghasbeenshowntobe highlysensitiveandspecificfortheidentificationofacutepulmonaryembolism(PE) incomparisonwithacompositereferencetestthatincludestheWellsscoreand digitalsubtractionangiography(90%and95%,respectively)(ifneeded).24 GadoliniumenhancedMRAhasalsobeenusedforthediagnosisofPE(Figure18). IthasbeenfoundtobesensitiveandspecificforPEinthecentralandsegmental arteries,butnotforthesubsegmentalarteries.25 InthePIOPEDIII(ProspectiveInvestigationofPulmonaryEmbolismDiagnosisIII) study,thesensitivityandspecificityforPEusingMRAandMRvenographyin technicallyadequatestudieswas92%and96%,respectively.26However,itwas notedthat25%ofstudiesweredeemeduninterpretable,mostlyduetorespiratory motionartifactandlackofvesselopacification.27Thecurrentrecommendationsare thatmultidetectorCTAispreferabletoMRAforthediagnosisofpulmonaryembolus. However,MRAcanbeconsideredonlyinthosepatientsforwhomstandardPE diagnostictestsarecontraindicated,andonlyatcentersthatroutinelyperformit well.26 PulmonaryArteriovenousMalformations AVMscanalsobeidentifiedbyCTAorMRA(Figure19).Ifclosureisindicated, definingtheanatomiclocationofAVMsfacilitiesproceduralplanning,includingcoil sizing.Stenosesofthepulmonaryarterialtreeareoftenassociatedwithadditional congenitalanomalies. ImagingthePulmonaryArteryPostinterventionIncludingArtifacts/Pitfalls Similartotheaorta,interventionstothepulmonaryarterytreeincludecoils,grafts, and/orstents.Graftreconstructionsareoftenundertakeninthosepatientswith congenitalheartdisease.Understandingtheunderlyinganatomyandsurgical procedure(s)performedallowtheimagertoappropriatelyselectanadequatefieldof view.Forexample,itisimportanttonotewhetheraninternalorexternalFontan variantispresentandtoidentifyifapulmonarystumpisorisnotpresent,becauseit maybeanidusforthrombus.Anotherexamplethatrequiresawidefieldofview (largecoronalangiogram)isidentificationofbothsuperiorandinferiorlimbsofthe systemicvenous,aswellasthepulmonaryvenousconduitsinaMustardor Senningrepair.Imagingofstentsinthepulmonaryarterialtreeissubjecttothe samelimitationsdescribedearlierforaorticstents.
Figure16

Figure17

Figure18

Figure19

PrimaryPulmonaryHypertension Figure16 Severelyenlargedmain(MPAs),right(RPAs),andleftpulmonaryarteries(LPAs)ina3Dvolumerenderedmagneticresonanceangiography image.

PulmonaryArteryStenosis Figure17 3Dvolumerenderedmagneticresonanceangiographyimagedemonstratingafocalstenosis(arrow)attheoriginoftherightpulmonaryartery (RPA).BoththeRPAandleftpulmonaryartery(LPA)arediffuselysmall,whilethemainpulmonaryartery(MPA)isofnormalsize.

BilateralPulmonaryEmboli Figure18 Contrastenhancedmagneticresonanceangiographyimageintheaxialorientationatthelevelofthepulmonaryarterybifurcationdemonstratinga largerightpulmonaryartery(RPA)embolus(asterisk)andasmallerleftpulmonaryartery(LPA)embolus(asterisk). MPA=mainpulmonaryartery.

PulmonaryArteriovenousMalformation(arrow)inaCoronal,ContrastEnhancedMagneticResonanceAngiographyImage Figure19 LA=leftatriumLLPV=leftlowerpulmonaryveinLPA=leftpulmonaryarteryLUPV=leftupperpulmonaryveinRLPV=rightlowerpulmonary veinRMPV=rightmiddlepulmonaryveinRPA=rightpulmonaryarteryRUPV=rightupperpulmonaryvein.

ImagingthePulmonaryVeins
ImagingtheNativePulmonaryVeins NormalAnatomy Normally,fourpulmonaryveinsentertheleftatriumthroughseparateostia(two rightsidedandtwoleftsided)(Figure20).Commonnormalvariantanatomy includesbothupperandlowerpulmonaryvenousbranchesjoiningtoforma commontrunkpriortoenteringtheleftatrium,aswellasanadditionalrightmiddle pulmonaryveinostiaintotheleftatria(Figure21).28CTAandMRA3Ddatasetsare importedtogenerateelectroanatomicmapsusedduringelectrophysiologicablation procedures.Identifyingandreportingnormalvariantanatomyassistswithplanning forablationprocedures.Abnormalpulmonaryvenousconnectionsareimportantto identifyandarecoveredelsewhereinthesedidactics. PulmonaryVeinStenosis Pulmonaryveinstenosisisarareconditionthatcanbeprimaryorsecondary,and involvesingleormultiplepulmonaryveins.Pulmonaryveinstenosisinchildrenor adultswithoutaprecedingorconcomitantcauseisdesignated"primary"pulmonary veinstenosis(Figure22),whereas,pulmonaryveinstenosisfollowingsurgicalor cathetermanipulation(e.g.,anomalouspulmonaryveinrepairorablation procedurestotreatatrialfibrillation)orresultingfromextrinsiccompressionor involvement(e.g.,neoplasmgrowth,sarcoid,orfibrosingmediastinitis)is designated"secondary"pulmonaryveinstenosis. CTAandMRAarekeyindiagnosinganddefiningtheextentofstenosis.Ofnote, velocityencodedMRimagingcanprovideadditionalpeakvelocitydata,whichmay helpdeterminethehemodynamicseverityofastenosis.Oncethelocation,extent, andseverityofpulmonaryveinstenosisareidentified,bothCTandMRcanprovide additionalinformationregardingthepresenceofextrinsicinvolvementfrom neoplasm,sarcoid,orfibrosingmediastinitis. ImagingthePulmonaryVeinsPostinterventionIncludingPitfalls Similartoimagingtheaortapostintervention,understandingthedetailsandnormal appearanceofthepulmonaryveinspostinterventiongreatlyenhancesthe recognitionofanyabnormalfindings.Asanexample,stentsareoftenplacedinthe pulmonaryveinstotreatsymptomaticpulmonaryveinstenosis(Figure23).Asignal voidistobeexpectedforsomestentmaterialsonMRA.Itisimportanttodistinguish thisnormalfindingfrominstentrestenosisorstentmigration(Figure24).
Figure20

Figure21

Figure22

Figure23

Figure24

NormalPulmonaryVenousAnatomyinAnterior(panelA)andPosterior(panelB)3DVolumeRenderedMagneticResonanceAngiography Images Figure20 Notefourpulmonaryveinsareseenenteringtheleftatriumthroughseparateostia(tworightsidedandtwoleftsided).

NormalVariantPulmonaryVenousAnatomy Figure21 (PanelA)3Dvolumerenderedmagneticresonanceangiographyimageofaleftcommonpulmonaryvein(solidarrow).Notethattheleftupper andleftlowerpulmonaryveinsjointogethertoformacommontrunkpriortoenteringtheleftatrium. (PanelB)3Dvolumerenderedmagneticresonanceangiographyimageofarightmiddlepulmonaryveinwithaseparateostiumintheleftatrium (dottedarrow).

PulmonaryVeinStenosis(arrow)attheOstiumoftheRightUpperPulmonaryVeininAnterior(panelA)andPosterior(panelB)Orientationsof3 DVolumeRenderedMagneticResonanceAngiographyImages Figure22

PulmonaryVenousStentsintheRightUpperandRightLowerPulmonaryVeins(arrows)inanObliqueCoronalComputedTomography AngiographyImage Figure23

MigrationoftheLeftLowerPulmonaryVenousStent(Arrows)IntotheLeftAtriumonanObliqueCoronalContrastEnhanced3DMagnetic ResonanceAngiographyImage Figure24 Notealsothesignalvoidfromthestent(arrows)intheLUPVobscuringtheabilitytodetermineifstenosisispresent. LA=leftatriumLLPV=leftlowerpulmonaryveinLUPV=leftupperpulmonaryveinRLPV=rightlowerpulmonaryveinRUPV=rightupper pulmonaryvein.

Summary/KeyPoints
BothCTAandMRAhavebeenusedtoassesstheaorticandpulmonaryvasculature.Imaginganditsinterpretation requiresunderstandingofthenormalappearanceofthesestructuresbothinnativeandrepairedstates.Inaddition, promptidentificationandcommunicationofabnormalitiestothereferringphysicianiscriticaltooptimizingpatient management.Decisionsaboutwhichspecifictesttouseisdependentonseveralfactors,includingtestaccessibility,test indication,patientage,gender,renalfunction,othercomorbidities,orpresenceofimplantedferromagneticmetal.

SuggestedReading
1. ChungJH,GhoshhajraBB,RojasCA,DaveBR,AbbaraS.CTangiographyofthethoracicaorta.RadiolClinNorth Am201048:24964. 2. GrosseC,GrosseA.CTfindingsindiseasesassociatedwithpulmonaryhypertension:acurrentreview. Radiographics201030:175377. 3. HartungMP,GristTM,FranoisCJ.Magneticresonanceangiography:currentstatusandfuturedirections.J CardiovascMagnReson201113:19. 4. SteinPD,ChenevertTL,FowlerSE,etal.,onbehalfofthePIOPEDIII(ProspectiveInvestigationofPulmonary EmbolismDiagnosisIII)Investigators.Gadoliniumenhancedmagneticresonanceangiographyforpulmonary embolism:amulticenterprospectivestudy(PIOPEDIII).AnnInternMed2010152:43443,W1423.

References

1. CentersforDiseaseControlandPrevention.WISQARSleadingcausesofdeathreports19992007.Availableat: http://webappa.cdc.gov/sasweb/ncipc/leadcaus10.html.Accessed5/20/2011. 2. HurwitzLM,YoshizumiTT,GoodmanPC,etal.Radiationdosesavingsforadultpulmonaryembolus64MDCT usingbismuthbreastshields,lowerpeakkilovoltage,andautomatictubecurrentmodulation.AJRAmJ Roentgenol2009192:24453. 3. MRIsafety.com.Availableat:http://www.mrisafety.com/.Accessed2/29/12. 4. DelaneyA,CarterA,FisherM.Thepreventionofanaphylactoidreactionstoiodinatedradiologicalcontrastmedia: asystematicreview.BMCMedImaging20066:2. 5. PrinceMR,GristTM,DebatinJF.3DContrastMRAngiography.3rded.NewYork:Springer2002. 6. DeoA,FogelM,CowperSE.Nephrogenicsystemicfibrosis:apopulationstudyexaminingtherelationshipof diseasedevelopmenttogadoliniumexposure.ClinJAmSocNephrol20072:2647. 7. HighWA,AyersRA,CowperSE.Gadoliniumisquantifiablewithinthetissueofpatientswithnephrogenic systemicfibrosis.JAmAcadDermatol200756:7102. 8. U.S.FoodandDrugAdministration.FDAdrugsafetycommunication:newwarningsforusinggadoliniumbased contrastagentsinpatientswithkidneydysfunction.Availableat http://www.fda.gov/Drugs/DrugSafety/ucm223966.htm.Accessed5/2/2011. 9. HartungMP,GristTM,FranoisCJ.Magneticresonanceangiography:currentstatusandfuturedirections.J CardiovascMagnReson201113:19. 10. NeuweltEA,HamiltonBE,VarallyayCG,etal.Ultrasmallsuperparamagneticironoxides(USPIOs):afuture alternativemagneticresonance(MR)contrastagentforpatientsatriskfornephrogenicsystemicfibrosis(NSF)? KidneyInt200975:46574. 11. U.S.FoodandDrugAdministration. http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm170316.htm. Accessed3/1/12. 12. FranoisCJ,TuiteD,DeshpandeV,JerecicR,WealeP,CarrJC.UnenhancedMRangiographyofthethoracic aorta:initialclinicalevaluation.AJRAmJRoentgenol2008190:9026. 13. KrishnamMS,TomasianA,MalikS,DesphandeV,LaubG,RuehmSG.Imagequalityanddiagnosticaccuracyof unenhancedSSFPMRangiographycomparedwithconventionalcontrastenhancedMRangiographyforthe assessmentofthoracicaorticdiseases.EurRadiol201020:131120. 14. ChungJH,GhoshhajraBB,RojasCA,DaveBR,AbbaraS.CTangiographyofthethoracicaorta.RadiolClinNorth Am201048:24964,vii. 15. QuintLE,WilliamsDM,FrancisIR,etal.Ulcerlikelesionsoftheaorta:imagingfeaturesandnaturalhistory. Radiology2001218:71923. 16. KazerooniEA,BreeRL,WilliamsDM.Penetratingatheroscleroticulcersofthedescendingthoracicaorta: evaluationwithCTanddistinctionfromaorticdissection.Radiology1992183:75965. 17. WhiteJA,PatelMR.TheroleofcardiovascularMRIinheartfailureandthecardiomyopathies.MagnReson ImagingClinNAm200715:54164,vi. 18. ElefteriadesJA,FarkasEA.Thoracicaorticaneurysmclinicallypertinentcontroversiesanduncertainties.JAm CollCardiol201055:84157. 19. DaviesRR,GalloA,CoadyMA,etal.Novelmeasurementofrelativeaorticsizepredictsruptureofthoracicaortic aneurysms.AnnThoracSurg200681:16977. 20. LtourneauGuillonL,SoulezG,BeaudoinG,etal.CTandMRimagingofnitinolstentswithradiopaquedistal markers.JVascIntervRadiol200415:61524. 21. AyusoJR,deCaraltTM,PagesM,etal.MRAisusefulasafollowuptechniqueafterendovascularrepairofaortic aneurysmswithnitinolendoprostheses.JMagnResonImaging200420:80310. 22. HoangJK,MartinezS,HurwitzLM.MDCTangiographyofthoracicaortaendovascularstentgrafts:pearlsand pitfalls.AJRAmJRoentgenol2009192:51524. 23. EdwardsPD,BullRK,CouldenR.CTmeasurementofmainpulmonaryarterydiameter.BrJRadiol 199871:101820. 24. SteinPD,FowlerSE,GoodmanLR,etal.,onbehalfofPIOPEDIIInvestigators.Multidetectorcomputed tomographyforacutepulmonaryembolism.NEnglJMed2006354:231727. 25. OudkerkM,vanBeekEJ,WielopolskiP,etal.Comparisonofcontrastenhancedmagneticresonance angiographyandconventionalpulmonaryangiographyforthediagnosisofpulmonaryembolism:aprospective study.Lancet2002359:16437. 26. SteinPD,ChenevertTL,FowlerSE,etal.,onbehalfofthePIOPEDIII(ProspectiveInvestigationofPulmonary EmbolismDiagnosisIII)Investigators.Gadoliniumenhancedmagneticresonanceangiographyforpulmonary embolism:amulticenterprospectivestudy(PIOPEDIII).AnnInternMed2010152:43443,W1423. 27. DirkSostmanH,JablonskiKA,WoodardPK,etal.Factorsinthetechnicalqualityofgadoliniumenhanced magneticresonanceangiographyforpulmonaryembolisminPIOPEDIII.IntJCardiovascImaging201228:303 12. 28. MaromEM,HerndonJE,KimYH,McAdamsHP.Variationsinpulmonaryvenousdrainagetotheleftatrium: implicationsforradiofrequencyablation.Radiology2004230:8249.

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3.12:RadiationSafetyDuringCardiacImagingProcedures
Author(s): MahadevappaMahesh,MS,PhD,FAAPM,FACR,FSCCT

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. 2. 3. 4. Describethebasicconceptbehindradiationeffects. Citethedifferencebetweenstochasticanddeterministiceffects. Discussthebasicprinciplesofradiationsafety. Identifythedifferencesintheradiationdosesexpectedfromvariouscardiovascularproceduresthatuseionizing radiation. 5. Listthewaysthatradiationdosefromdiagnosticcardiologystudiesmaybeminimized.

Introduction
Radiationhasbeenafactoflifeonthisplanetsinceitsbeginning.Thebackgroundsourcesforionizingradiationinclude cosmicrays,terrestrialradiation,andinternallydepositedradioisotopes.IntheUS,accordingtoNCRPreport160 publishedin2009,approximately50%oftheannualradiationdosecomesfromnaturalsources(3.1mSv),andthe remaindercomesfromhumanactivities,includingconsumerproducts(0.1mSv)andmedicalsources(3.0mSv).

BiologicalEffectsofRadiation
Radiationfromxraysorgammaraysinteractsattheatomicleveltoexciteorbitalelectronsortodepositenergyinto tissue.Asmorethan80%ofthebodyiswater,radiationexposureprincipallyinteractswithwater.Thismaycreatefree radicalsthat,althoughtheyonlylastforafewmilliseconds,caninteractwithothercellsandcreateinjury.IftheDNAis attacked,itcanbedisruptedandittheneitherrepairsitselforispermanentlydamaged.DirectinjurytotheDNAmayalso occurfromthexrayorgammaray.Thebiologicaleffectsofthisradiationcanbebroadlyclassifiedintotwocategories:1) stochastic(probabilistic)effects,and2)deterministiceffects. StochasticEffects A"stochasticeffect"isoneinwhichtheprobabilityoftheeffectofradiationontheDNA,ratherthanitsseverity,increases withradiationdose.Radiationinducedcancerandgeneticeffectsarestochasticinnature.Stochasticeffectsarebelieved nottohaveathresholddosebecauseinjurytoafewcellsorevenasinglecellcouldtheoreticallyresultintheproduction ofthedisease,asthecellmaynotdie,butreproduceinamutatedmanner. DeterministicEffects Deterministiceffectsareeffectswhere,intheprobabilityofcausingbiologicalharm,willbezeroatsmallradiationdoses however,abovesomelevelofdose,calledthe"thresholddose,"theprobabilitywillincreaserapidlywiththedose.Such effectsarecalled"deterministiceffects"or"acuteeffects."Theseeffectshaveathresholdofdose,andtheseverityofthe effectincreaseswithincreaseddose.Thisresultswhenenoughinjuryhasoccurredtoanorganthatmanycellsdieand theorganbecomesdysfunctional.Cataracts,erythema,epilation,andevendeatharesomeofthedeterministiceffects. Radiationdoses>2Gy(absorbeddose)aretypicallyconsideredathresholddosethatcanyielddeterministiceffects relatedtotheskininparticular. Stochasticeffectsareregardedastheprincipalhealthriskfrommedicalradiation,andthus,fromradiationexposures duringcardiacimagingprocedures.Inadditiontostochasticeffects,deterministiceffectsarealsoofconcernwith prolongedfluoroscopicinterventionalproceduresandwithcardiacCTPerfusion.

RadiationInteractionWithMatter
Xraysandgammarayshaveveryshortwavelengthsandcaninteractwithmatterinanumberofways.Themost importantarethe"Comptoneffect"andthe"photoelectriceffect."Radiationinteractionwithmatterresultsinscatteringof theradiation,resultinginpoorerimagedefinitionandincreasedexposuretoboththepatientandtheoperator.

RadiationTerminology
Severaltermsareusedtoquantitatetheradiationexposureandtheseareofteninterchangeableandleadtoconfusion. Forsimplisticpurposes,theradiationdosecanbedefinedintermsofgray(Gy)units.Thebiologicaleffectivenessofthe radiationabsorbeddosecanbeexpressedastheeffectivedoseusingsieverts(Sv).Effectivedoseconceptallow comparisonofradiationrisksamongdifferentxrayimagingprocedures.Typically,effectivedosevaluesformostimaging proceduresrangeintheorderof120millisieverts. Theeffectivedosereflectsstochasticriskandisderivedfromtheweightedsumoftheestimatesofrisktoindividual organs.Itisbestusedtocomparedifferentprocedures.Inthecardiaccatheterizationlaboratory,theeffectivedoseis estimatedfromthe"doseareaproduct,"ameasureobtainedfromatransmissionchamberfittedtotheoutputofthexray tube.ThedoseareaproductrepresentsthetotalradiationdosedeliveredtothepatientandisexpressedinGy/cm2 .It canbeconvertedtotheeffectivedosebyuseofaconversionfactor,andtheresultsaredefinedinSv.ForthecardiacCT procedures,theeffectivedoseisestimatedfromthe"doselengthproduct",aproductofcomputedtomographydose indexmeasuredusingstandardphantomsandthescanlengthandisexpressedinmGycm.Itcanbeconvertedtothe effectivedosebyusingconversionfactor(0.017mSv/mGycm)andtheresultsareexpressedinmSv. Toquantifydeterministicinjuryisoftendifficultandcumbersome.However,sincedeterministiceffectsrequiresacertain thresholddose,especiallyduringprolongedfluoroscopyprocedures,thecumulativedosereadingasdisplayedonall newersystems(manufacturedafter2006)canbeusedasanindicatortoestimateskindose.Oneoptioninthecardiac catheterizationlaboratoryistheuseofthedoseatinterventionalreferencepoint.Thisisanestimateddosethatis determinedbyassumingthepatientisattheisocenterofthexraysystemandselectingapoint15cmbacktowardthex raytube.Itisthenpresumedthatthisisthelocationoftheskin.

BasicRadiationSafetyPrinciples
TheconceptofALARA(AsLowAsReasonablyAcceptable)isabasicradiologicprinciplefortheuseofmedicalradiation. Thethreepillarsofradiationsafetyare:1)time,2)distance,and3)shielding. Time Minimizingthetimeofexposureduringanytypeofimagingprocedurethatutilizesradiationhasadualadvantageofnot onlyminimizingradiationdosetothepatient,butalsoscatterradiationdosetopersonnelworkingwiththepatient.Thisis especiallyimportantininterventionalfluoroscopyprocedures,wherethescatterradiationdosesareofgreatconcern. Distance Theradiationdosedecreasesasinversesquareofthedistancefromaradiationsource.Thismeans,ifonemeasuresa doseof100Uat1mfromaradiationsource,thedosemeasuredat2mis25Ubecauseoftheinversesquarelaw. Therefore,distanceisconsideredasasecondpillarofradiationsafetybecauseincreasingdistancefromtheradiation sourcealwaysdecreasesradiationdose. Shielding Thethirdpillarofradiationprotectionisshielding.Shieldingimpliesprotectingallthosewhoareworkingaroundpatients utilizingradiationtoguidetheprocedure(suchasininterventionalfluoroscopy).Wearinganapronof0.5mmlead equivalentissufficienttoblockanyscatterradiationbynearly20times.Lightweightapronsmadeofsyntheticmaterials arealsoavailable,whicharedeemedsafeaslongasthespecificationindicatesthattheapronsareof0.5mmlead equivalent.Duringthecardiacinterventionalprocedures,alongwithaprons,oneshouldalsoutilizeothershielding devicessuchastablemountedleadskirtsandceilingmountedleadshields.

RadiationDosesinTypicalCardiacImagingProcedures
ComputedTomography CardiacCTimagingbecamemorefeasiblewiththemultidetectorCT(MDCT) technologythatcanyield>16slicesperrotation.Infact,mostcardiacCTimaging proceduresareperformedwitha64sliceMDCTscannerandhigher.Variousscan parametersthatconstituteaCTprotocolaffectbothradiationdoseandimage quality. Amongtheprimaryscanparametersincludetubecurrent,tubevoltage,pitch,and scantime.Understandinghowscanparametersaffectbothradiationdoseand imagequalityiskeytooptimizinganyCTprotocol.Table1liststypicalradiation dosesforvariouscardiacimagingproceduresexpressedintermsoftheeffective dose. InterventionalFluoroscopy Estimatingradiationdoseduringinterventionalfluoroscopyproceduresis challengingsinceradiationexposureduringeachprocedurevariesmarkedly becauseofvariousfactorsincludingpatientsize,complexityoftheprocedures, experienceoftheoperator,andfluoroscopysystemsandhowthesystemsareset forperformingsuchprocedures.Thekeyradiationdosedescriptorsincludethe doseareaproductandtheestimatedskindosesdescribedearlier.Table1lists typicalradiationdosesforvariousinterventionalfluoroscopyprocedures. Fluoroscopicdosesrangefrom1015timeslessthancineangiographydoses, dependingonframerates,amountofmagnification,etc.Inaddition,mostcardiac proceduresincludenotonlyfluoroscopyguidancebutalsoincludecineimaging. Theradiationdoseforcineimagingissignificantlyhigherthanfluoroscopydoses.In fact,incertaincardiacinterventionalprocedures,thecontributionsfromfluoroscopy dosesaresmallercomparedtocineimaging. NuclearCardiacProcedures TypicalradiationdosesforvariousnuclearcardiacproceduresarelistedinTable1. Withnuclearprocedures,theradiationdosedependsonthetypeandamountof radioactiveisotopeusedintheprotocol.Theotherkeyaspectwithnuclearmedicine proceduresisthatitisnotonlykeytoexpressthedoseintermsoftotalbody effectivedose(milliSievert),butalsotheestimatedcriticalorgandoses.Becauseof thelonghalflifeofthallium201,itresultsinconsiderablymoreradiationexposure thantheotherradionuclides.
Table1

ValuesandRangesofEffectiveDoseEstimatesReportedintheLiteratureforSelectedCardiovascularImagingStudies Table1 Datacombineprospectivelytriggeredandretrospectivelygatedprotocols.Therepresentativeeffectivedoseisapproximately1mSvfor prospectivelytriggeredcoronarycalciumCTscansand3mSvforretrospectivelygatedscans. F18FDG=F18deoxyglucoseorfluorodeoxyglucose.

CardiacComputedTomographyPerfusion
PotentialforRadiationInjuriesandHowtoAvoidThem ThenatureoftheCTperfusionprocedureitselfhasapotentialtoyieldradiationskininjuriesifpropercareisnottakenin termsofsettingCTscanparameters.IftheCTdoseindexforaCTperfusionscanis25mGy(attubevoltageof80kVp) andmultipleimagesareacquiredatthesamelocation,thereisapotentialforthecumulativedosetoexceedthenominal thresholddose,resultinginskininjuries.Forexample,iftheCTperfusionscanissettoacquiremorethan100scansat thesamelocation,thenthecumulativeskindosecanbeasmuchas25mGyx100=2500mGyor2.5Gy. Typicalthresholddoseforcausingradiationskininjuriesisapproximately2.0Gy,andtherefore,thecumulativedose fromCTperfusionscancanfallinthisrange.Ifthescantechniqueisincorrectlysettoahighertubevoltage(from80kVp to120kVp),withallotherfactorsbeingsame,thecumulativedosecanbeashighas6Gy.Hence,oneshouldreview suchCTprotocolstomakesurethatthescantechniquesminimizeradiationexposureinordertoreducethechanceof radiationinjury.

RadiationDoseReductionStrategies
ComputedTomographyProcedures VariousdosereductionstrategiesarerecommendedintheSocietyforCardiovascularComputedTomography(SCCT) guidelinesonradiationdoseanddoseoptimizationstrategiesincardiovascularCT.1 Thefollowingareonlyafew strategies,listedinabridgedform: Tubecurrent(mA):Electrocardiogram(ECG)basedtubecurrentmodulationshouldbeusedonpatientsto reducedose,exceptinpatientswithhighlyirregularheartrhythm.ThereisadirectrelationshipbetweenthemA andthenumberofxraysproduced.ThehigherthemA,themorexraysandthemoreradiationdelivered. Tubepotential(kVp):Typically,mostCTprotocolsaresetat120kVp.Lowertubepotentialof100kVpcouldbe consideredforpatientswithabodymassindex<30kg/m2 andhighertubepotentialmaybeneededforseverely obesepatients.However,foranyCTperfusionscans,lowertubepotentialof80kVpshouldbeconsideredfor reasonsdiscussedearlier.NotethekVprepresentsthemaximalvoltageacrossthexraytube.Thegreaterthe kVp,thegreatertheenergyofthexraysproduced.IfthekVpistoohigh,however,thereislossofimagecontrast, asthexraysoverpenetratetheiodinevascularcontrasttheimagethusappears"washedout." Scanlength:Thescanlengthshouldbesetattheminimumlengthclinicallynecessary.Scanlengthrelatestothe lengthofthexrayexposureperframe.Thelongerthescanlength,themorelikelymotionartifactmayoccurand thegreatertheradiationdose. InterventionalFluoroscopyProcedures Variousstepstominimizeradiationrisksduringinterventionalfluoroscopyproceduresinclude: Minimizetimeofexposure. Usemagnificationmodeonlywhenneeded. Keepthepatientasclosetotheimagereceptorsandasfarawayfromthexraytubeaspractical. Usepulsedfluoroscopywheneverpossiblewithframerates<15frames/second. Minimizetheuseof"highdose"fluoroscopy. Keepthenumberofacquisitionrunstoaminimum. Usecopperandotherfiltersatthexrayoutput. Keepthesourcetoimagedistance(S.I.D.)asnarrowaspossible. Limitthenumberofcineangiographicimagesandsavefluoroimagingwhenpossible. MoredetailsonthetopicsdiscussedinthismodulecanbefoundintheReferences/SuggestedReadingsection.Even thoughthebenefitsofcardiovascularimagingfaroutweightheassociatedradiationrisk,itisimperativeforoperatorsto minimizetheriskassociatedwithcardiovascularimagingwhileprovidinghighqualityimagesfordiagnosisand intervention.

KeyPoints
Weliveinaradioactiveenvironmentwithbackgroundexposurefromcosmicrays,terrestrialsources,and radioactivesubstancesweingest.Medicalradiationcontributes. Radiationresultsinionizationofwatertofreeradicals,withDNAinjuryordirectinjurytoDNA.Theeffectsare enhancedasaresultofscatteringwithinthetissue. Stochasticinjuryresultsincellviability,butgeneticdefectsandcancers.Ithasnothresholddose.Deterministic injuryresultsinenoughcellsofanorgandying,andtheinjuredorganthenbecomingdysfunctional.Itrequiresa thresholddose.Theskinismostofteninvolvedwithxrays. ALARA(AsLowAsReasonablyAchievable)remainsthemantraforreducingradiationinjury. Time,distance,andshieldingarethekeystoreducingoperatorandpatientexposure. Radiationdosevariesconsiderablyamongthevariouscardiovascularprocedures.Usingthelatesttechniques, theexposurefromCTangiography,diagnosticcardiaccatheterization,andtechnetium99mstudiesareallabout thesame(approximately79mSv).Percutaneouscoronaryinterventionstudiesapproximatelydoublethedosein general.Thalliumhasthehighestexposureduetoitsmodeofexcretionandlonghalflife. Properuseoftheequipmentandprotectivedevicescansubstantiallyreducebothoperatorandpatientexposure toionizingradiation. InCTangiography,reducingthexraytubevoltage(kVp)from120to100or80helpsincreaseimagecontrastand helpsreducetheoverallradiationdose.

References/SuggestedReading
Reference 1. HalliburtonSS,AbbaraS,ChenMY,etal.,onbehalfoftheSocietyofCardiovascularComputedTomography. SCCTguidelinesonradiationdoseanddoseoptimizationstrategiesincardiovascularCT.JCardiovascComput Tomogr20115:198224. SuggestedReading 1. GerberTC,CarrJJ,AraiAE,etal.Ionizingradiationincardiacimaging:ascienceadvisoryfromtheAmerican HeartAssociationCommitteeonCardiacImagingoftheCouncilonClinicalCardiologyandCommitteeon CardiovascularImagingandInterventionoftheCouncilonCardiovascularRadiologyandIntervention.Circulation 2009119:105665. 2. MettlerFAJr,HudaW,YoshizumiTT,MaheshM.Effectivedosesinradiologyandnuclearmedicine:acatalog. Radiology2008248:25463. 3. JakobsTF,BeckerCR,OhnesorgeB,etal.MultislicehelicalCToftheheartwithretrospectiveECGgating: reductionofradiationexposurebyECGcontrolledtubecurrentmodulation.EurRadiol200212:10816. 4. EarlsJP,BermanEL,UrbanBA,etal.ProspectivelygatedtransversecoronaryCTangiographyversus retrospectivelygatedhelicaltechnique:improvedimagequalityandreducedradiationdose.Radiology 2008246:74253. 5. MaheshM.MDCTPhysics.TheBasics:Technology,ImageQualityandRadiationDose.Philadelphia:Lippincott Williams&Wilkins2009. 6. NationalCouncilonRadiationProtectionandMeasurements.NCRPReportNo.160:IonizingRadiationExposure ofthePopulationoftheUnitedStates.Bethesda,MD:NCRP2009. 7. MaheshM.Fluoroscopy:patientradiationexposureissues.Radiographics200121:103345.

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3.13:ContrastMediaComplications
Author(s): PeterA.McCullough,MD,MPH,FACC,FACP,FAHA,FCCP

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Reviewthephysiochemicalpropertiesofiodinatedcontrastandtheireffectinthebody. 2. Recognizephysiologicalandpathophysiologicalchangesquicklyinapatientwhoisreceivingiodinatedcontrast. 3. Diagnoseandmanageformsofacuteallergicreactionsduetocontrast,aswellassubsequentchangesinrenal functionasaresultofcontrastinducedacutekidneyinjury(CIAKI). 4. Provideamoreinformedconsentandoptimallymanagepatientswithcontrastassociatedcomplications.

HistoryofIntravascularContrastImaging
In1928,MosesSwickwascreditedfordevelopingthefirstwatersolubleiodinatedcontrastforurologicalimagingwith intravenousinjection.Monoanddiiodinatedcontrastagentscausedconsiderableamountsofnauseaandvomitingat thattime.Diatrizoate(Hypaque,Renografin)wasintroducedin1956asahighosmolarcontrastagentwithafully substitutedtriiodinatedbenzeneringthatwaswelltoleratedandquicklybecamethemainstay,alongwithsimilaragents (iothalamate,Conray)forintravenousandintraarteriolarimaging. In1968,TorstenAlmnadvancedthefieldwiththedevelopmentofnonionic,lowosmolarcompoundsforusewith myelography.Bythe1980sintheUnitedStates,ioxaglate(Hexabrix)wasavailableasanionic,lowosmolarmedia,and iohexol(Omnipaque)andiopamidol(Isovue)wereintroducedasnonionic,lowosmolaragents.Foralloftheseagents, approximately36%ofthecompoundwascomposedofiodine.1 By1993,publishedtrialshadsupportedyetanewnonionic,isoosmolaragent,iodixanol(Visipaque)withfewer symptomaticadverseevents.Later,therewouldbeconsiderableinterestintherenalsafetyofthisnewestagent comparedtolowosmolaragents.2 Andthus,today,thechoiceshavebeenlargelyreducedtononionicloworiso osmolarcontrastinthecardiaccatheterizationlaboratory.

ContrastMediaPrimer
IodinatedContrast PhysiochemicalpropertiesofvariousiodinatedcontrastagentsaregiveninFigure 1. HighOsmolar Diatrizoate(RenografinorHypaque)isamonomerwith300mgI/mlandan osmolality(particleconcentrationinsolution)of1550mOsm.Metrizoateisalsoa monomerwith370mgI/mlandanosmolalityof2100mOsm.Thesetwomonomers arestillusedinsomecatheterizationlaboratoriesaroundtheworld. LowOsmolar Ioxaglate(Hexabrix)isanionicdimerwith320mgI/mland580mOsm,andwasthe firstlowosmolaragent.Othersinthiscategoryincludethenonionicmonomers, suchasiohexol(Omnipaque)andiopamidol(Isovue)notedearlier. IsoOsmolar Iodixanol(Visipaque)isanonionicdimerwith320mgI/mland290mOsm,whichis similartothatofwholeblood(280303mOsm/kg),whichrepresentsthe concentrationofsubstancessuchassodium,chloride,potassium,urea,glucose, andotherionsintheblood. IonicVersusNonionic Thepresenceofachargedentityonthecontrastmoleculehasbeenassociatedwith ahigherdegreeofadverseeventsincludingnauseaandwarmthsensation,hence, thedevelopmentofnonionicagents. Gadolinium Gadoliniumisarareearthmetal,whichisparamagneticatroomtemperatureand thushasdetectablemotioninmagneticresonanceimaging(MRI).Solutionsof organicgadoliniumcomplexesandgadoliniumcompoundsareusedas intravenousMRIcontrastagenttoenhanceimagesinmedicalMRIandMR angiography(MRA)procedures.Normally,thesecompoundsareexcretedintothe urineasintactchelates. Inpatientswithimpairedrenalfunction,theagentsgadodiamide,gadoversetamide, andgadopentetatedimegluminehavebeenshowntohavemuchlongerhalflives anddissociateandresultingadoliniumdepositionintheskinandinternalorgans, whichcanleadtothedevelopmentyearslaterofnephrogenicsystemicfibrosis.3 Forthisreason,whentheestimatedglomerularfiltrationrate(GFR)is<30ml/min, gadoliniumshouldbeavoided.
Figure1

OsmolalityofVariousIodinatedContrastgents Figure1 HOCM,highosmolarCMIOCM,isosmolarCMLOCM,lowosmolarCM ReproducedwithpermissionfromMcCulloughPA.Renalsafetyofiodixanol.ExpertRevCardiovascTher20064:65561.

AllergicReactions
AnaphylactoidReactions Iodinatedcontrastcausesthereleaseofmediatorsfrommastcellsandbasophils,whicharenotdependenton immunoglobulinE(IgE).Mastcellsecretorygranulescontainpreformedmediatorsthatarerapidly(withinsecondsto minutes)releasedintotheextracellularenvironmentuponcellstimulation.Thesemediatorsincludehistamine,neutral proteases,proteoglycans,andsomecytokines,suchastumornecrosisfactor(TNF)alpha.Theyareresponsiblefor manyoftheacutesignsandsymptomsofmastcellmediatedallergicreactions,includingedema,bronchoconstriction, andincreasedvascularpermeability. Higherosmolarandioniccompoundscausegreaterreleasethanothers.Insomeindividuals,asanidiosyncratic response,thereissufficientreleasetoresultinanaphylactoidreactionscharacterizedbyurticaria,facialswelling, vomiting,lifethreateningarrhythmias(i.e.,ventriculartachycardia),hypotension,overtbronchospasm,laryngealedema, pulmonaryedema,seizures,syncope,anddeath.Histamineandtryptasereleasecorrelatewiththeseverityofthe reaction.ThereisnoassociationbetweenIgEmediatedanaphylaxiswithbeestings,nuts,orshellfishandcontrast relatedanaphylactoidreactions. Clinicaltrialssupporttheuseofprophylaxisinpatientswithaknowncontrastallergy,withacomprehensiveapproach beingprednisone40mgp.o.bid,diphenhydramine50mgp.o.tid,andranitidine150mgp.o.bid,thedaybeforeandthe morningoftheprocedure.4 Inurgentcases,methylprednisolone250mg,diphenhydramine25mg,andranitidine50mg orfamotidine10mg,canbegivenpriortotheprocedure.Whilebreakthroughreactionsarecommon,themanifestations areusuallynotsevere. TCellMediatedLateContrastReactions Latecontrastreactionsmostcommonlytononionic,dimeric,iodinatedcontrastmedia(iodixanol)thatoccur1hourto1 weekafterexposureareduetoTcellactivationandmanifestasnausea,vomiting,headache,fever,itching,anda maculopapularexanthema.5 Thesepatientswillskintestpositivetoiodixanolandthisformofcontrastshouldbe avoidedinthefuturehowever,crossreactivitytoothercontrastagentshasbeenreported.Itisnotanallergytoiodine however,50%ofthesepatientswillreportanallergytoatleastoneothermedication.LateTcellreactionsareselflimited andrequireonlysupportive,symptomaticcareofnauseaandpruritus.

HemodynamicEffects
HeartRate Ingeneral,theinjectionofiodinatedcontrastresultsinatransientbradycardiaascontrastreplacesbloodtothesinoatrial andatrioventricularnodes,followedbyaslightincreaseinbasalheartrate.Theseeffectsaremorepronouncedwith highratherthanlowosmolaragents. HeartRateVariability Heartratevariabilityincreasesslightlywithintracoronaryinjectionofiodinatedcontrastandthisisoflittlesignificance. However,changesinheartratevariabilitywithintravenousinjectionscouldtheoreticallyimpacttheacquisitionandquality ofimageswithcomputedtomographicangiography. LeftVentricularEndDiastolicPressure Becausecontrastisbothavolumeandosmoticload,leftventricular(LV)pressurerisesduringleftventriculography.In patientswithreducedLVejectionfraction,thesharpriseinLVenddiastolicpressurecanprecipitateheartfailure.Forthis reason,leftventriculography,ifperformed,shouldbedoneaftercoronaryangiographyandintervention.

ChangesinThrombosisandPlateletAggregation
ThrombinTime Ionicmorethannonioniccontrastmediahaveslightanticoagulantpropertiesandareknowntoprolongthethrombintime bytransientlycomplexingwiththrombin.Thiseffectisinsignificantinthesettingofsystemicanticoagulationwithheparin ordirectthrombininhibitors. PlateletAggregability Becausecontrastmediacausecrenulationofcellmembranes,theyinduceplateletmembranesandthecomplexbiology ofproandantiaggregatorysubstances.Ingeneral,iodinatedcontrastmaterialreduceplateletaggregability.However,in thesettingofmorepowerfulantiplateletagentsincludingaspirin,thienopyridine,andglycoproteinIIb/IIIareceptor antagonists,thiseffectisnotclinicallysignificant. SummaryofClinicalTrialsWithThromboticOutcomes TheCOURT(COntrastmediaUtilizationinhighRiskPTCAPercutaneousTransluminalCoronaryAngioplasty)trial evaluatedtheeffectofioxaglate(ionic,lowosmolar)versusiodixanol(nonionic,isoosmolar)ontherateofinhospital majoradversecardiacevents(MACE)followingpercutaneouscoronaryintervention(PCI).6 In856highriskpatients, MACEwasreducedby45%withiodixanol. TheVICCtrial(Visipaque[iodixanol]vs.Isovue[iopamidol]inCardiacComplications)comparedtheeffectsofiodixanol withthoseofiopamidol(nonionic,lowosmolar)intermsofinhospitaland30dayMACE.7 Theresultsofthisstudy foundlowerratesofMACEwithiodixanol(iopamidol,9.4%vs.iodixanol,5.3%p=0.005)andsupportedtheobservations oftheCOURTtrial.

ContrastInducedAcuteKidneyInjury (1of2)

Epidemiology Contrastinducedacutekidneyinjury(CIAKI),formerlyknownascontrastinduced nephropathy,isoneofthemostcommoncausesofiatrogenicrenalinjury.CIAKI hasbeenvariouslydefinedasariseinserumcreatinine(Cr)>25%or>0.5mg/dl, 0.3mg/dl,ordoublinginthe24to96hourperiodaftercontrastexposure.It occursinapproximately15%ofpatientswhohaveatleastoneriskfactorforthis complicationincludingreducedbaselinerenalfunction(Crclearanceorestimated GFR[eGFR]<60ml/min),diabetes,age>75years,heartfailure,orLVejection fraction<45%.Ifhypotensiondevelopsinthecatheterizationlaboratoryorifintra aorticballoonpump(IABP)isused,thenCIAKIisalsoexpected. ApproximatelytwothirdsofCIAKIismanifestbyatransientriseandfallinserumCr andhasnoclinicalconsequences.Theremainingthirdresultsinadetectableloss inkidneyfunctionmeasured36monthslater.AmongthosewithaneGFRafter angiography<90ml/min,thesubsequentadjustedmeanrateofdeclineineGFR duringlongtermfollowupwas0.2ml/mininpatientswithoutCIAKI,0.8ml/min followingmild(0.3mg/dlCrrise)injury,and2.8ml/minfollowingmoderateto severe(acutedoublingofCr)CIAKI.8 Fortunately,ratesofCIAKIresultinginthe needfordialysisorthedevelopmentofpermanentendstagerenaldiseasearerare (<1%). Ithasbeenconsistentlyobserved,thatallformsofCIAKIcomparedtothe85%of catheterizationlaboratorypatientswhodonotdevelopthecondition,areassociated withincreasedratesofmyocardialinfarction,stroke,heartfailure,rehospitalization, dialysis,anddeath.9 Thus,attemptstopreventCIAKIappeartobejustified. RiskPrediction TheriskfactorsforCIAKIlistedearlierareindependent,butsomewhatlessthan additiveintheriskpredictionforthiscomplication.Thus,an80yearoldmalewith diabetesandheartfailureundergoingPCIwithIABPsupportwouldbeexpectedto havea>50%rateofCIAKIanda~13%chanceofrequiringtemporaryorpermanent dialysisaftertheprocedure(Figure2).10Thus,postoperativemonitoringofserum Crandurineoutputaremandatoryinsuchhighriskcases. Pathophysiology Iodinatedcontrastisacomplex,vasoactivesubstance.Byitseffectoncell membranes,thereisatransientreleaseofnitricoxidebyendothelialcellsas contrastmovesthroughthevasculature.Sinceallcontrastmediaareverywater soluble,penetrationintothevascularmedia(fromtheendoluminalandvase vasorum)resultsintransientvasoconstrictioninproportiontotheosmolalityofthe agent.Allformsofiodinatedcontrastmediacauseanapproximate50%restrictionin flowofthevasarecta,whichsupplytheoutermedullaofthekidneywithblood.11 Thiszoneofthekidneyhasalowoxygentensionnormally(pO2 ~10mmHg)and withasustainedreduction(~2hours)inflow,isvulnerabletoischemicinjury.Asthis formofinjuryisoccurringtoproximalanddistaltubularcells,thereisstasisof contrastintheurinaryspace,uptakeintoproximaltubularcells,andleakageof contrastintotheperitubularspacewhereitcanresideforupto8daysafterthe procedure.Suchcasescanbereadilyidentifiedashavingapersistentnephrogram (Figure3). Iodinatedcontrastistoxictorenaltubularcellsandinduceslossofthenormalbrush border,oxidativestress,injury,anddeath.Theperpetuationofoxidativestress reactionsmaybeduetothereleaseoftinyamountsoflabileironfromtubularcells. ThisformofunligandedironconvertsreadilyfromtheFe2+toFe3+stateservingas acatalystfortheHaberWeissandFentonequations,whichgeneratehydrogen peroxideandthehydroxylradical,bothofwhichinducecelltocelldeath.Thusasa commonresponsetoinjury,renaltubularcellsupregulatetheirproductionand secretionofneutrophilgelatinaseassociatedlipocalin(NGAL,siderocalin2),which attemptstomopuplabileironandremoveitfromtherenalparenchymaintothe urine.Figure4summarizesthepathophysiologyofCIAKI.
Figure2

Figure3

Figure4

ValidatedRiskPredictionofContrastInducedAcuteKidneyInjury Figure2 Anemia=baselinehematocritvalue<39%formenand<36%forwomenCHF=congestiveheartfailureclassIII/IVbyNewYorkHeart Associationclassificationand/orhistoryofpulmonaryedemaCIN=contrastinducednephropathyeGFR=estimatedglomerularfiltrationrate hypotension=systolicbloodpressure<80mmHgforatleast1hourrequiringinotropicsupportwithmedicationsorintraaorticballoonpump (IABP)within24hoursperiprocedurallySCr=serumcreatinine. AdaptedwithpermissionfromMehranR,AymongED,NikolskyE,etal.Asimpleriskscoreforpredictionofcontrastinducednephropathyafter percutaneouscoronaryintervention:developmentandinitialvalidation.JAmCollCardiol200444:1393.

ExampleofaPersistentNephrograminaPatientWithReducedRenalFunctionUndergoingComputedTomographyEnhancedWithIntravenous IodinatedContrast Figure3 AdaptedwithpermissionfromKonethI,WeishauptD,BachliEB.Persistentnephrogramafteradministrationofanisoosmolarcontrastmedium. NephrolDialTransplant200419:16545.

PathogenesisofContrastInducedAcuteKidneyInjury Figure4 ReproducedwithpermissionfromBrownJR,McCulloughPA.ContrastNephropathyandKidneyInjury,TextbookofCardiovascularIntervention. NewYork:SpringerPublishingCompany2012.

ContrastInducedAcuteKidneyInjury (2of2)
PreventiveStrategies TherearenoprovenpreventivestrategiesforCIAKIhowever,giventhe developmentoftheliteratureinthisareaandrecognitionofreversibleriskfactors, therehasbeenadeclineinratesofCIAKIobservedinseveralpopulationbased studies.UltimateavoidanceoftheriskofCIAKIisachievedbyforegoingthe procedure.TheremaybesomecasesinwhichtheriskofCIAKIissufficientlyhigh, thatitoutweighsthebenefitoftheprocedure. Prudentmeasuresforallpatientsatriskincludecessationofmetformin,whichcan contributetometabolicacidosisifrenalfailuredevelops.Metformincanbere initiatedoncerenalfunctionisdeterminedtobeatbaselineaftertheprocedure. Avoidanceofnephrotoxinsforseveraldaysbeforetheprocedureincluding nonsteroidalantiinflammatorydrugs(NSAIDs),aminoglycosides,vancomycin, amphotericin,andcalcineurininhibitors(cyclosporin,tacrolimus),allasfeasible,is suggested.Volumedepletion,whichcanoccurwhenpatientsareheldwithnothing bymouth,shouldbeavoidedwiththeuseofpreprocedureintravenouscrystalloid. Ingeneral,whentheeGFRis<15ml/min,ifacontrastprocedureisgoingtobe undertaken,thenpreparationsshouldbemadeforeitherhemofiltrationbeforeand duringtheprocedureorpostproceduredialysis,andthepatientshouldbeinformed andagreeabletothisapproach.FundamentalsofCIAKIpreventioninclude:1) avoidingdehydrationandbaselinereductionsinrenalbloodflowwithintravenous volumeexpansionusingisotonicsolution,2)minimizationofthevolumeofcontrast, 3)useofiodixanolinveryhighriskcases,and4)carefulsupportivecareafterthe procedure.12 TheAmericanCollegeofCardiology/AmericanHeartAssociation2009focused updateguidelinesforthemanagementofpatientswithSTelevationmyocardial infarctionandPCIgiveaClassI,LevelofEvidenceAforiodixanol,andaClassI, LevelofEvidenceBforlowosmolaragentssuchasiopamidol,basedonclinical trialswithCIAKIasoutcomes.13Approximately300ccofintravenousisotonic crystalloidcanbegiven13hoursbeforetheprocedure,andthensetatarateof1.5 ml/kg/htoensureaurineoutputof150ml/hinthefirstfewhoursafterthe procedure.14 Therehavebeenaconsiderablenumberofclinicaltrialsoftestingsodium bicarbonatesolutions,shorttermNacetylcysteine,ascorbicacid,theophylline, prostaglandins,dopamine,andotheragentsunfortunately,noneofthese approacheshaveconsistentlyreducedtheratesofCIAKI,andnoneofthemhave reducedendstagerenaldiseaseorhardendpoints,whichareroutinelyobservedin communitybasedstudies(Figure5).
Figure5

OutcomesAfterCoronaryAngiographyandInterventionStratifiedbyRenalOutcome Figure5 Contrastinducedacutekidneyinjury(CIAKI)isdefinedasriseincreatinine(Cr)0.3mg/dl(Stage1)anddoublingCr(Stage2/3). AdaptedwithpermissionfromJamesMT,GhaliWA,TonelliM,etal.Acutekidneyinjuryfollowingcoronaryangiographyisassociatedwitha longtermdeclineinkidneyfunction.KidneyInt201078:8039.

Summary
Thediscoveryanduseofintravasculariodinatedcontrastagentsclearlyhasaidedthedevelopmentofinvasiveand interventionalcardiologyaswellasotherdisciplinessuchasradiology,gastroenterology,urology,andgynecology. Iodinatedcontrastisacomplex,vasoactivesubstance,whichtriggersthereleaseofavarietyofmediatorsfrom endothelialcells,smoothmusclecells,mastcells,andbasophils.Thisexplainstheconstellationofcomplications cardiologistscanexpecttoexperienceincludinganaphylactoidreactions,lateTcellreactions,andcontrastinduced acutekidneyinjury. Futurerefinementoftheseagentsandthedevelopmentofprotectivedrugsorstrategiesholdthepromiseofreducingor eliminatingthesecomplications,andpossiblytranslateintoreductionsinhardoutcomesofrehospitalization, progressionofchronickidneydisease,endstagerenaldisease,anddeath.15

KeyPoints
Acutehypotension,rash,andgastrointestinalsymptomsafterintravasculariodinatedcontrastadministration shouldberecognizedasanaphylactoidreactions,andareduetothereleaseofhistaminefrommastcellsand basophils.LateTcellmediatedreactionscanoccurin~1.5%ofpatientswhoreceivenonionicdimersandare manifestedbyaselflimitedpruriticrash,nausea,andvomiting. Allformsofiodinatedcontrastareverywatersolubleandareavidlytakenupbyproximaltubularcells,wherethey causecellularinjury. TheriskofCIAKIcanbeanticipatedbasedonage,estimatedrenalfiltrationfunction,andpresenceofother baselineriskfactors. Therearenoprovenprophylacticstrategiestoreducetherenalriskofcontrastagents. PrudentmeasuresforapatientathighriskofCIAKIinclude:1)cessationofmetformin2)avoidanceof nephrotoxinssuchasNSAIDs,aminoglycosides,etc.3)intravenouscrystalloidbeforetheproceduretominimize volumecontractionand4)limitingthevolumeofcontrastusedduringtheprocedure.

References
1. McClennanBL.PrestonM.Hickeymemoriallecture.Ionicandnonioniciodinatedcontrastmedia:evolutionand strategiesforuse.AJRAmJRoentgenol1990155:22533. 2. McCulloughPA.Renalsafetyofiodixanol.ExpertRevCardiovascTher20064:65561. 3. AimeS,CaravanP.Biodistributionofgadoliniumbasedcontrastagents,includinggadoliniumdeposition.JMagn ResonImaging200930:125967. 4. TramrMR,vonElmE,LoubeyreP,HauserC.Pharmacologicalpreventionofseriousanaphylacticreactionsdue toiodinatedcontrastmedia:systematicreview.BMJ2006333:675. 5. WebbJA,StaculF,ThomsenHS,MorcosSK,onbehalfofthemembersoftheContrastMediaSafetyCommittee oftheEuropeanSocietyofUrogenitalRadiology.Lateadversereactionstointravasculariodinatedcontrastmedia. EurRadiol200313:1814. 6. DavidsonCJ,LaskeyWK,HermillerJB,etal.RandomizedtrialofcontrastmediautilizationinhighriskPTCA:The COURTtrial.Circulation2000101:21727. 7. Harrison,KJ,HermillerJB,VetrovecGW,etal.Arandomizedstudyof1276patientsundergoingPCIusing iodixanol(Visipaque)vs.iopamidol(Isovue):Comparisonofinhospitaland30daymajoradversecardiacevents. TheresultsoftheVICCtrial.Circulation2003108(SupplIV):IV3545. 8. JamesMT,GhaliWA,TonelliM,etal.Acutekidneyinjuryfollowingcoronaryangiographyisassociatedwithalong termdeclineinkidneyfunction.KidneyInt201078:8039. 9. JamesMT,GhaliWA,KnudtsonML,etal.,onbehalfoftheAlbertaProvincialProjectforOutcomeAssessmentin CoronaryHeartDisease(APPROACH)Investigators.Associationsbetweenacutekidneyinjuryandcardiovascular andrenaloutcomesaftercoronaryangiography.Circulation2011123:40916. 10. McCulloughPA,AdamA,BeckerCR,etal.,onbehalfoftheCINConsensusWorkingPanel.Riskpredictionof contrastinducednephropathy.AmJCardiol200698:27K36K. 11. SendeskiM,PatzakA,PerssonPB.Constrictionofthevasarecta,thevesselssupplyingtheareaatriskforacute kidneyinjury,byfourdifferentiodinatedcontrastmedia,evaluatingionic,nonionic,monomericanddimericagents. InvestRadiol201045:4537. 12. McCulloughPA.Multimodalitypreventionofcontrastinducedacutekidneyinjury.AmJKidneyDis200851:16972. 13. KushnerFG,HandM,SmithSCJr.,etal.2009focusedupdates:ACC/AHAguidelinesforthemanagementof patientswithSTelevationmyocardialinfarction(updatingthe2004guidelineand2007focusedupdate)and ACC/AHA/SCAIguidelinesonpercutaneouscoronaryintervention(updatingthe2005guidelineand2007focused update):areportoftheAmericanCollegeofCardiologyFoundation/AmericanHeartAssociationTaskForceon PracticeGuidelines.JAmCollCardiol200954:220541. 14. StaculF,AdamA,BeckerCR,etal.,onbehalfoftheCINConsensusWorkingPanel.StrategiestoReducethe RiskofContrastInducedNephropathy.AmJCardiol200698:59K77K. 15. McCulloughPA.Contrastinducedacutekidneyinjury.JAmCollCardiol200851:141928.

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3.14:NoninvasiveVascularEvaluation(UltrasoundArterial/Venous)
Author(s): ManeshR.Patel,MD,FACC

LearnerObjectives
Uponcompletionofthismodule,thereaderwillbeableto: 1. Evaluatearterialwaveformsinpatientswithsuspectedperipheralarterialdisease(PAD)tocorrectlyidentifythedisease andincreaseappropriateriskreductioninpatientswiththedisease. 2. Identifytheappropriateclinicalindicationsforcarotidultrasoundsothatpatientswillbetreatedinaccordancewith guidelinerecommendedtherapy. 3. SummarizetheguidelinerecommendedcriteriafornoninvasivetestingforPADsothatavailabletechnologyisused efficiently.

Introduction
Theprimarygoalsofnoninvasivevasculartestingaretoconfirmthediagnosisandtoestablishtheextentandthe locationofthedisease.1 Thisrequiresknowledgeofthearterialandvenousconditionsbeinginvestigated.Evaluationof venousdiseaseoftenrangesfromthrombosistovenousinsufficiency.ThemostcommonarterialconditionisPAD causedbyatherosclerosis.Traditionally,PADisusedtorefertoarterialobstructivediseaseofthelowerextremities involvingthedistalaortatothetoes.However,atherosclerosisinthemesentericsystem,renalarteries,andcarotid arteriesisoftenalsoconsidered.PADofthelowerextremitiescanbepresentasaspectrumfromasymptomatic atherosclerosistointermittentclaudicationandfinallycriticallimbischemia.TheclinicalspectrumofPADisoften categorizedbytheRutherfordClassificationortheFontaineClassification,asfollows: RutherfordClassification: Stage0:Asymptomatic Stage1:Mildclaudication Stage2:Moderateclaudication Stage3:Severeclaudication Stage4:Restpain Stage5:Ischemiculcerationnotexceedingulcerofthedigitsofthefoot Stage6:Severeischemiculcersorfrankgangrene FontaineClassification: StageI:Asymptomatic StageII:Intermittentclaudication.Thisstagetakesintoaccountthefactthatpatientsusuallyhaveaveryconstant distanceatwhichtheyhavepain: StageIIa:Intermittentclaudicationafter>200metersofpainfreewalking StageIIb:Intermittentclaudicationafter>200metersofwalking StageIII:Restpain StaveIV:Ischemiculcersorgangrene NoninvasivevascularevaluationforPADisaimedathelpingtoclassifythepatient'sriskandtoprovidetreatmentsaimed atsymptomreductionandriskreduction.Ofnote,PADisassociatedwithsignificantmorbidityandmortality.2 Patients withPAD,evenintheabsenceofahistoryofmyocardialinfarctionorischemicstroke,haveapproximatelythesame relativeriskofdeathfromcardiovascularcauses,asdopatientswithahistoryofknowncoronaryorcerebrovascular disease.2 Inaddition,theallcausemortalityisapproximatelyequalinmenandwomenandiselevatedevenin asymptomaticpatientswithobjectivelydocumentedarterialinsufficiency. DespitethehighprevalenceofPADandthestrongassociationwithcardiovascularmorbidityandmortality,patientswith PADarelesslikelytobediagnosedandlesslikelytoreceivestandardpreventivetreatmentfortheirunderlying atheroscleroticriskfactorscomparedwiththoseindividualswithcoronaryarterydisease.3,4 Itshouldbenotedthatathoroughhistoryandphysicalexaminationwithfocusedvascularreviewofsystemsisrequired toappropriatelyemploynoninvasivevasculartechnologies.

AnkleBrachialIndex
Theanklebrachialindex(ABI)servesastheprimarytoolforestablishingthe diagnosisofPAD,providingprognosticinformation,andmonitoringtherapyor revascularization.TheABIisobtainedbymeasuringthesystolicbloodpressure frombothbrachialarteriesandfromboththedorsalispedisandposteriortibial arteriesinasupinerestingpatient.Ideally,thisisaccomplishedwithappropriately sizedbloodpressurecuffsinthearmsandlegsabovetheankleswithahandheld (5mHzor10mHz)Dopplerprobe.5 CarehastobetakentoensuretheDoppler probestaysonthearteryduringmeasurement.Byconvention,thehighestsystolic pressureinthearmsisused,andthehighestsystolicpressureinthedorsalis pedalis(DP)orposteriortibialis(PT)foreachleg(Figure1). Patientswithoutdiseaseandnormalpulsewavereflectionshouldhaveapressure inthelowerextremitythatis10mmHggreaterthantheupperextremity.Therefore,a normalABIshouldbe>1.00.However,inordertoincreasethespecificityoftheABI, thecutoffof0.90isusedtoidentifydisease.Additionally,patientswithperipheral vasculardiseasemayhaveaxillaryorsubclavianstenosis,andmeasurementof pressuresinbotharmswithidentifypatientswithupperextremitydisease(>20mm Hgsystolicbloodpressuredifference). TheABIhasbeenvalidatedagainstcontrastangiography6 withaspecificityof0.96 forobstructions>50%atacutoffABIof0.91.FowkesshowedthatanABIcutoffof 0.90hadasensitivityof95%andaspecificityof100%comparedwithinvasive angiography.7 SeveralstudieshavelookedatthereproducibilityoftheABIandfound thereproducibilitytobe0.10.Therefore,theABIisthefirstlineinofficetestfor patientswithsuspectedPAD. Inpatientswithlongstandingdiabetes,renaldysfunction,orheavilycalcifiedarteries, theABIcanbenoncompressible(ABI>1.30)andnondiagnostic.Forthesepatients, toebrachialindexesand/orvascularultrasoundmaybeofuse. Additionally,forpatientswithclassicclaudicationsymptomsorhighpretest probability,restandpostexercise(5minutewalkat2%grade)ABIsareusedto confirmthediagnosis.

Figure1

AnkleBrachialIndexMeasurement Figure1 ABI=anklebrachialindexDP=dorsalispedalisPT=posteriortibialis. ReproducedwithpermissionfromHirschAT,HaskalZJ,HertzerNR,etal.ACC/AHA2005guidelinesforthemanagementofpatientswith peripheralarterialdisease(lowerextremity,renal,mesenteric,andabdominalaortic):executivesummaryacollaborativereportfromthe AmericanAssociationforVascularSurgery/SocietyforVascularSurgery,SocietyforCardiovascularAngiographyandInterventions,Society forVascularMedicineandBiology,SocietyofInterventionalRadiology,andtheACC/AHATaskForceonPracticeGuidelines(WritingCommittee toDevelopGuidelinesfortheManagementofPatientsWithPeripheralArterialDisease)endorsedbytheAmericanAssociationofCardiovascular andPulmonaryRehabilitationNationalHeart,Lung,andBloodInstituteSocietyforVascularNursingTransAtlanticInterSocietyConsensusand VascularDiseaseFoundation.JAmCollCardiol200647:1239312.

SegmentalDopplerPressuresandPulseVolumeRecordings
OncethediagnosisofPADhasbeenestablished,thelocationanddegreeof obstructionisoftenofclinicalimportance.Noninvasiveanatomictechniques,such ascomputedtomographyangiographyormagneticresonanceangiography,are oftenperformed/recommended.AssessmentofsegmentalDopplerpressures (SDP)andpulsevolumerecordings(PVR)allowsinclinicrealtimeevaluationof obstructivePAD.Arterialpressuresandwaveformscanbemeasuredwith plethysmographiccuffsplacedsequentiallyalongthelimbatvariouslevels:atthe upperthigh,lowerthing,uppercalf,andlowercalfinmostlaboratories. InamanneranalogoustotheABI,thesystolicbloodpressuremeasuredatvarious levelscanbeindexedtothebrachialarterypressuretoprovideanindicationatthe levelofobstruction.Forexample,areductioninpressurebetweentheupperand lowerthighwouldindicateanobstructionatthesuperficialfemoralartery.By convention,agradient>20mmHgbetweenlevelsisconsideredtorepresent significantstenosis.5,8 PVRsareusuallyperformedbyinjectingastandardvolumeofairintopneumatic cuffsthatareplacedonthelimbs.Thevolumeofairinjectedisenoughtoocclude thevenouscirculation,butnotthearterialcirculation,resultinginmeasurementof arterialvolumechangesbelowthecuffbythetransducerdisplayedasapressure pulsecontour.Thisisanalogoustothearterialwaveformmeasurementbycatheters inthearterialsystem. AnormalPVRissimilartoanarterialwaveformandiscomposedofsystolic upstroke,sharpsystolicpeak,andasharpdownstrokewithadichroticnotch.Infact, triphasicwaveformscanbecapturedinnormalpatientswithreductiontoblunted monophasicwaveformsinpatientswithobstructivedisease.Astandardapproach forevaluationofPVRsisusedforanalysisofseverity(Figure2).Takentogether, boththeSDPandPVRanalysescanprovidedetailedinformationregardingthe presence,location,andseverityofdiseaseinpatientswithsuspectedPAD.

Figure2

PulseVolumeRecordingsWithIncreasingSeverityofDisease Figure2 ReproducedwithpermissionfromGerhardHermanM,GardinJM,JaffM,MohlerE,RomanM,NaqviTZ.Guidelinesfornoninvasivevascular laboratorytesting:areportfromtheAmericanSocietyofEchocardiographyandtheSocietyforVascularMedicineandBiology.VascMed2006 11:183200.

IndicationsforAnkleBrachialIndexTesting
Ingeneral,giventheeaseofperformanceandhighdiagnosticaccuracy,theABIis oftenconsideredastandardfirstlinetestforpatientswithsuspectedPAD.The PARTNERS(PADAwareness,Risk,andTreatment:NewResourcesforSurvival) programstudyevaluatednearly7,000patients>50yearsoldwithdiabetesor>70 yearsoldforthepresenceofPADwithinofficeABIs.4 Nearly30%ofthepatients werefoundtohavePAD,andthisstudyandothershaveformedthebasisforthe AmericanDiabetesAssociationrecommendationforscreeningdiabeticpatients >50yearsold. However,itshouldbenotedthattheUnitedStatesPreventiveHealthServiceshave notendorsedroutineABIscreeninginasymptomatichighriskpatients.Therefore, thecurrentagreeduponindicationsforABItestingandnoninvasiveSDP/PVR includepatientswithexertionallegsymptomsconcerningforPAD,patientswithrest legpain,absenceofdistalpulses,and/orpatientswithconcernsaboutulcerationor tissuelossinthelowerextremity.ABIsandvascularimaging(Table1)isalso performedfollowingvascularrevascularizationtoevaluateandtofollowphysiologic bloodflowtothelimb.

Table1

VascularImagingTests/Indications Table1 AAA=abdominalaorticaneurysmABI=anklebrachialindexCTA=computedtomographicangiographyMRA=magneticresonance angiographyPAD=peripheralarterialdiseasePVR=pulsevolumerecording. ReproducedwithpermissionfromGerhardHermanM,GardinJM,JaffM,MohlerE,RomanM,NaqviTZ.Guidelinesfornoninvasivevascular laboratorytesting:areportfromtheAmericanSocietyofEchocardiographyandtheSocietyforVascularMedicineandBiology.VascMed

200611:183200.

BasicPrinciplesofVascularUltrasound
Duplexvascularultrasoundreferstotheperformanceofultrasoundimagingthat capturesbothgrayscaleimagingandDopplerultrasoundinformation.5 This providesinformationontwodimensionalstructureandfunctioninformation,along withbothDopplerspectrumanalysisandcolorflowanalysis.Inherentintheabilityto getdiagnosticimagesistheimportanceofappropriateprobepositiontovesselfor imageacquisition.Perpendicularimagingisimportantfordirectultrasound reflectionandthebrightestandhighestqualitystructuraldetail. ForDopplerimaging,ideallya60degreeangle(angleofincidence)isrequired betweentheprobeandthevesselwalltoensureappropriatedeterminationofpeak velocities.Imagingdoneathigherorloweranglescanoverestimateor underestimatethetruepeakvelocity(Figure3).Thisrepresentsoneofthemost commonwaysvascularultrasoundcanbemisleading. ColorDopplerisessentialfortheidentificationofstenosiswithinvascular structures.Theobstructionleadstoahighvelocityjetofthebloodflow,whichis identifiedwitheitheranabruptchangeincolororaliasing/whiteningofthecolor signal.Additionally,poststenoticmosaicflowrepresentingturbulencefillsthe diastolicwindoworspectralbroadening.Althougheachofthesefeaturesareused withvascularimagingtoidentifystenosis,itisimportanttoensurethatthecorrect anatomicstructureandanglearebeingusedtoidentifythestenosis.Inthecarotid system,thisincludesensuringthatthevascularultrasoundisidentifyingstenosisof theinternalcarotidarteryratherthantheexternalcarotidartery.Forwaysof separatingthecarotidarteries,seethesectiononCarotidArteryUltrasound Imaginginthismodule.

Figure3

ImportanceofAngleofIncidenceforDopplerUltrasound Figure3 ReproducedwithpermissionfromGerhardHermanM,GardinJM,JaffM,MohlerE,RomanM,NaqviTZ.Guidelinesfornoninvasivevascular laboratorytesting:areportfromtheAmericanSocietyofEchocardiographyandtheSocietyforVascularMedicineandBiology.VascMed 200611:183200.

HighResistanceandLowResistanceVascularBeds
Certainvascularbedsarecharacterizedbylowerresistanceandsomediastolicsignalonvascularultrasoundimaging thathelpswithdiagnosticassessment.Theseincludetheinternalcarotidartery,coronarycirculation,renalcirculation, and,sometimes,thepostprandialceliacaxis.Theaortaandthelowerextremityvesselsarenotableforhighresistance andlittlediastolicflowinthenormalstate. Themajorlimitationsforhighqualityvascularultrasoundimagesrevolvearoundtheinabilitytoaccuratelycaptureorget ultrasoundwavestotheintendedanatomicstructures.Therefore,significantbowelgas,edema,orobesityrepresent significantlimitationsforvascularimaging.

CarotidArteryUltrasoundImaging
Ingeneral,apatient'sindicationforcarotidvascularevaluationincludethosewith recenthemisphericstrokeorfocaltransientischemicattacksymptoms,suchas amaurosisfugax,rarelysyncopeduetobilateralcarotiddisease,orcervicalbruits. Managementofpatientswithconcernsforcarotidarterydiseaseinvolvesthe evaluationtodetermineifthereisdiseaseinthecommon,internal,andexternal carotidarteriesandtoevaluatethevertebralarteries.Akeyerrorthatmustbe avoidedisconfusionbetweensignificantdiseaseintheexternalandinternalcarotid arteries,asthemanagementofeachisdistinctlydifferent.Theexternalcarotidartery canbedistinguishedfromtheinternalcarotidarterybythepresenceofhigh resistanceatrest,eightextracranialbranchesthatmaybeseen,andvisible oscillationsduringatemporaltapduringultrasoundimaging.Allofthesefindings maybeneededtodistinguishthevessels. Thisvascularevaluationrequiresevaluationofpeaksystolicvelocities,enddiastolic velocity,andspectralbroadening.Additionally,directplaquecharacterizationand visualizationisalsodone.Criteriaforsignificantinternalcarotidarterystenosishave beendevelopedandvalidatedagainstangiographywithanaccuracyof93%for stenosisbetween5099%.9 Thesecriteriashouldbereviewedandusedto determineifanatomicimagingisrequiredfordeterminationofcarotidtherapy(Table 2). Carotidvascularimagingcanbemisleadinginpatientswithlongtubularstenosis wherethevelocityisnotfocallyelevated,inlowcardiacoutputstatessuchassevere heartfailureorsevereaorticstenosis,orinpatientswithcontralateralocclusion wherethevelocitymaybefalselyelevatedinacompensatorystate.

Table2

CriteriaforCarotidStenosis Table2 CCA=CommoncarotidarteryEDV=enddiastolicvelocityICA=internalcarotidarteryPSV=peaksystolicvelocity ReproducedwithpermissionfromGerhardHermanM,GardinJM,JaffM,MohlerE,RomanM,NaqviTZ.Guidelinesfornoninvasivevascular laboratorytesting:areportfromtheAmericanSocietyofEchocardiographyandtheSocietyforVascularMedicineandBiology.VascMed 200611:183200.

AbdominalUltrasoundImaging
Abdominalultrasoundimagingisindicatedforevaluationofabdominalaorticaneurysms(AAAs)inpatientswithafamily historyofAAAs,enlargedpulsatileaortaonexam,acuteabdominalpain,andhighriskindividualssuchasmales>50 yearswithasmokinghistoryandaneurysminotherterritories.10 Thenormalsizefortheabdominalaortais2.0cm.AnAAAisdefinedbyasizeof3.0cm.TypicalgrowthratesforAAAs between3.0and5.0cmis0.30.4cmperyear,oftenleadingtoyearlyfollowup. Renalarteryevaluationisoftendoneatthesametimeasabdominalultrasound.Astherapeuticoptionsforrenalartery diseasehavediminished,sohaveclinicalindicationsforrenalvascularultrasound.Thecurrentindicationsinclude concernforfibromusculardysplasia,flashpulmonaryedemathoughttobesecondarytohypertensiveurgency,and severeresistanthypertension.Thecurrentcriteriaforsignificantrenalarterystenosisincluderenalarterytoaortapeak systolicvelocityratio>3.5,peaksystolicvelocity>200cm/sec,andenddiastolicvelocity>150cm/sec.

VenousUltrasoundEvaluation
Commonindicationsforvenousultrasoundincludeconcernfordeepvenous thrombosis,evaluationofvenousconduitsforbypasssurgery,andevaluationof arteriovenousfistulafollowinginvasiveprocedures.Diagnosticcriteriaforvenous thrombosisincludevisualizationofanintramuralthrombusinthedeepvein,lackof compressibilityofthevenouslumen,fillingofthelumenwithechos,diminished Dopplerwaveforms,andlackofaugmentationofvenousflowwithcompressionof calfmuscles. Evaluationofacquiredarteriovenousfistulaversuspseudoaneurysmsfollowing invasiveproceduresisacommonindicationforvascularultrasound.Arteriovenous fistulacanbecharacterizedbytheinterfaceoflowresistanceandhighresistance flowintheadjacentartery,highvelocityarterializedflowinaportionoftheadjacent vein,ahighvelocityflowatthejunctionofthearteryandvein,andfinally,avisualized connectionbetweenthearteryandvein.Thecharacteristicfindingofa pseudoaneurysmisidentificationoftheneckconnectingthevesselwiththe adjacenthematoma,andthetoandfroflowfindingwithspectralDoppler(Figure4). Thesecriteriashouldbeusedtoevaluateaccesssiteconcerns.

Figure4

Pseudoaneurysm:ToandFroSpectralDopplerWaveform Figure4

KeyPoints
ABIiscalculatedbyusingthehighestbloodpressureperlimboverthehighestarmpressure. ABI<0.9isdiagnosticofPAD. TheangleofincidenceforDopplerimagingis60degrees. AAAsarediagnosedwhen>3cmandtreatedwhen5cm. Internalcarotidarterystenosisisconsideredseverewhensystolicvelocitiesare>230cm/secanddiastolic velocitiesare>100cm/sec. Routinecarotidscreeningisnotindicatedinasymptomaticpatients.

References
1. HirschAT,HaskalZJ,HertzerNR,etal.ACC/AHA2005guidelinesforthemanagementofpatientswithperipheral arterialdisease(lowerextremity,renal,mesenteric,andabdominalaortic):executivesummaryacollaborative reportfromtheAmericanAssociationforVascularSurgery/SocietyforVascularSurgery,SocietyforCardiovascular AngiographyandInterventions,SocietyforVascularMedicineandBiology,SocietyofInterventionalRadiology,and theACC/AHATaskForceonPracticeGuidelines(WritingCommitteetoDevelopGuidelinesfortheManagementof PatientsWithPeripheralArterialDisease)endorsedbytheAmericanAssociationofCardiovascularand PulmonaryRehabilitationNationalHeart,Lung,andBloodInstituteSocietyforVascularNursingTransAtlantic InterSocietyConsensusandVascularDiseaseFoundation.JAmCollCardiol200647:1239312. 2. NewmanAB,ShemanskiL,ManolioTA,etal.,onbehalfoftheCardiovascularHealthStudyGroup.Anklearm indexasapredictorofcardiovasculardiseaseandmortalityintheCardiovascularHealthStudy.ArteriosclThromb VascBiol199919:53845. 3. McDermottMM,MehtaS,AhnH,GreenlandP.Atheroscleroticriskfactorsarelessintensivelytreatedinpatients withperipheralarterialdiseasethaninpatientswithcoronaryarterydisease.JGenInternMed199712:20915. 4. HirschAT,CriquiMH,TreatJacobsonD,etal.Peripheralarterialdiseasedetection,awareness,andtreatmentin primarycare.JAMA2001286:131724. 5. GerhardHermanM,GardinJM,JaffM,MohlerE,RomanM,NaqviTZ.Guidelinesfornoninvasivevascular laboratorytesting:areportfromtheAmericanSocietyofEchocardiographyandtheSocietyofVascularMedicine andBiology.JAmSocEchocardiogr200619:95572. 6. LijmerJG,HuninkMG,vandenDungenJJ,LoonstraJ,SmitAJ.ROCanalysisofnoninvasivetestsforperipheral arterialdisease.UltrasoundMedBiol199622:3918. 7. FowkesFG.Themeasurementofatheroscleroticperipheralarterialdiseaseinepidemiologicalsurveys.IntJ Epidemiol198817:24854. 8. GerhardHermanM,GardinJM,JaffM,MohlerE,RomanM,NaqviTZ.Guidelinesfornoninvasivevascular laboratorytesting:areportfromtheAmericanSocietyofEchocardiographyandtheSocietyforVascularMedicine andBiology.VascMed200611:183200. 9. GrantEG,BensonCB,MonetaGL,etal.Carotidarterystenosis:grayscaleandDopplerUSdiagnosisSocietyof RadiologistsinUltrasoundConsensusConference.Radiology2003229:3406. 10. ScottRA,AshtonHA,KayDN.Abdominalaorticaneurysmin4237screenedpatients:prevalence,development andmanagementover6years.BrJSurg199178:11225.

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Chapter3Exam
Visittheonlineversionoftheproducttoseethecorrectanswerandcommentary.

1.Youareevaluatingapatientpriortocoronaryangiographyandherevealsahistory ofallergytoshellfish(IgEmediated)andwondersifhewillbeallergictocontrast. Yourresponseshouldbewhichofthefollowing? A. Thereisnorelationshiptoiodinatedcontrastallergy. B. Therecanbecrossreactivitybetweentheiodineinshellfish,andiodinated contrastandprophylaxisisindicated. C. Iodinatedcontrastiscontraindicated. D. Desensitizationiswarranted.

2.A68yearoldmalepresentswithanacuteSTsegmentelevationmyocardial infarction.Intheelevator,onthewaytothecatheterizationlaboratory,thepatient statesheisallergictocontrastandhadtobeintubatedforadayafterthishappened ayearago. Whichofthefollowingshouldbethenextmanagementsteps? A. Proceedwithangiographyitistoolateforanyprophylaxis. B. Methylprednisolone250mg,diphenhydramine25mg,andfamotidine10 mg,allintravenouslyassoonasthepatiententersthelaboratory. C. Placeaballoonpumpandprepareforhypotension. D. Diphenhydramine50mgintravenouslyassoonasthepatiententersthe laboratory.

3.An85yearoldmalepatientisundergoingprecatheterizationevaluationandis foundtohaveaCrof2.8mg/dl,heartfailure,anemia,anddiabetes.Youplantouse approximately100ccofiodinatedcontrast.Heishemodynamicallystable. YouestimatehispercentageriskofsignificantCIAKIrequiringdialysistobewhich ofthefollowing? A. <1%. B. 5%. C. 10%. D. 13%. E. 19%.

4.

TheXdescentintheRApressuretracingoccursatwhichtime? A. Duringatrialsystole. B. Duringventriculardiastole. C. Duringatrialdiastole. D. Duringinspiration. E. DuringTVopening.

5. A24yearoldwomanwithshortnessofbreathisexaminedanddiscoveredtohave anapicalmidsystolicclickandmurmur.WhensheperformsaValsalva,theclick andmurmuroccurearlierinsystole,butdonotchangeinintensity.Whichofthe followingishermostlikelydiagnosis? A. Bicuspidaorticvalve. B. Hypertrophicobstructivecardiomyopathy. C. Mitralstenosis. D. Mitralvalveprolapse.

6. A69yearoldpatientwithlongstandingdilatedcardiomyopathynowcomplainsof markeddyspneaonexertionandorthopnea.Hisexamshowsbloodpressure90/70 mmHg,pulsusalternans,normalJVP,clearlungs,noabdominojugularrefluxor peripheraledema,andcoolextremities.Youwouldclassifyhimaswhichofthe following? A. Dryandwarm. B. Dryandcool. C. Wetandwarm. D. Wetandcool.

7.A63yearoldmanwithnopriormedicalhistorypresentstotheemergency departmentwiththesuddenonsetofdyspneaandchestpain.Hetraveledona10 hourflightonthedaypriortopresentation.Youareconcernedthathemighthavea pulmonaryembolus. WhichofthefollowingisthebestdiagnostictestforthedetectionofPE? A. Ddimer. B. Lowerextremityultrasound. C. ThoracicMRangiogram.

D. MDCTangiogram. E. Transthoracicechocardiogram.

8.A73yearoldwomanunderwentaorticgraftrepairforanascendingaortic aneurysm1yearpriortopresentation.Youareseeingherintheclinicforroutine followup.Sheisasymptomatic.YouorderaMRangiogramtoassessforany complicationsafterheroperativerepair. Basedontheimage(Figure1),whichofthefollowingisyourinterpretationofthe MRAfindingsandplanformanagementofthesefindings? A. Normalpostoperativeaorta,returntoclinicin1year. B. Newaorticdissection,immediatesurgicalrepair. C. Newaorticdissection,medicaltherapy. D. Pseudoaneurysm,immediatesurgicalrepair. E. Penetratingaorticulcerattheaorticgraftanastomosissite,immediate surgicalrepair.
Figure1

9.A74yearoldfemalewithahistoryofbreastcancerisseenforincreasedswelling inherleftleg.Thepatientstatesthatshenoticedincreasedswellingoverthelast week,withmildimprovementovernight.Examinationrevealssomewoodyedemain theleftlowerextremitywithpittingattheankle.Thereisnoclearpainondorsiflexion. Avascularultrasoundisorderedtoruleoutdeepvenousthrombosis. WhichofthefollowingfindingsshowninVideo1isdiagnosticfordeepvenous thrombosis? A. Toandfroflowinthevein. B. Evidenceofvenouscongestion. C. Lackofcompressibilityofvein. D. Evidenceoflowresistanceinthevenoussystem. E. Augmentationofvenousflowwithcalfmusclecompression.

10.A63yearoldmalewithahistoryoftobaccouseandhyperlipidemiawasbrought emergentlytothecathlabaftercomplainingofchestpainandarresting.Emergency MedicalServiceswasactivatedand,onarrival,thepatientwasinventricular tachycardiarequiringdefibrillation.PostdefibrillationandECGinthefield,thepatient demonstratedacuteanteriorSTsegmentelevationmyocardialinfarction.The patientwasmildlyresponsivewithbloodpressureof90/50mmHgandheartrateof 105bpm. Inthecatheterizationlaboratory,thepatienthadanintraaorticballoonpumpplaced andpercutaneousinterventionof100%occludedproximalleftanteriordescending

Figure1

arterywithabaremetalstent.Thepatientwassupportedwithintraaorticballoon pumpinthecriticalcareunitfor24hoursandeventuallyrecoveredtodischarge home7daysafteradmission.Heisnowseenintheclinic7dayspostdischargefor routinepostacutemyocardialinfarctioncare.Duringthevisit,heisnotedtohavea softresolvinghematomaandbruitinhisrightgroin.Avascularultrasoundis performed. Somerepresentativeultrasoundimagesareshown(Figure1). Whichofthefollowingisthecorrectinterpretationandmanagementplan? A. Largepseudoaneurysmcompressiontreatment. B. Largehematoma,otherwisenormalwaveformsconservativemanagement. C. Largepseudoaneurysmthrombininjection. D. Atrioventricularfistulaconservativemanagementwithreevaluationin1 month. E. Atrioventricularfistulathrombininjection.

11. Correctstatementsregardingcongenitalcoronaryarteryanomaliesincludewhichof thefollowing? A. MostcoronaryAVfistulaareclinicallysignificant,causingischemiaasa resultofcoronarysteal. B. TheLMCAarisingfromtherightsinusofValsalvaisclinicallysignificant whencoursingposteriortothepulmonaryartery,anditscourseisbest confirmedbycoronaryangiography. C. ThemostcommoncongenitalcoronaryanomalyistheLCxarisingfromthe rightcoronarysinus. D. Themostcommoncongenitalcoronaryanomalyisseparateostiaforthe LAD.

12.A55yearoldnondiabeticmanpresentswithprogressiveanginadespitebeta blocker,statin,aspirin,andnitrates.Heundergoescatheterization,which demonstratesafocal95%stenosisinthemidleftanteriordescendingartery(LAD), afocal80%stenosisinthenondominantmidcircumflex,andlong70%inthelarge dominantproximalrightcoronaryartery(RCA).Heelectstoundergopercutaneous therapy.TheLADwasstentedwithasingleDESstent,andFFRwasperformedon theLAD,RCA,andleftcircumflexarteryusingintravenousadenosine.TheLADFFR is0.62,theRCAFFRis0.72,andtheleftcircumflexFFRis0.90. WhichofthefollowingstatementsisFALSE? A. FFRisdefinedastheratioof(i.e.,percentofnormal)flowinthestenotic arterytotheflowinthesamearteryinthetheoreticabsenceofthestenosis. B. FFRisdefinedasthemeandistalcoronarypressuredividedbythemean proximalcoronaryoraorticpressuremeasuredduringmaximalhyperemia. C. IVadenosineisamoreconsistentandsensitivemethodofobtaining maximumcoronaryvasodilatationthanintracoronaryadenosine.

D. TheFAMEtrialresultswouldsuggestthatthispatientwouldbebesttreated bystentingtheLADandRCA,asopposedtothreevesselstenting. E. Althoughtheleftcircumflexlesionappearedtobeangiographicallymore severethantheRCAstenosis,functionalseverity(FFR)isnotsolelydependent onpercentdiameterstenosis,butalsolesionlengthandtheamountof myocardiumsubtendedbytheepicardialartery.

13. WhichofthefollowingstatementsisTRUEregardingradiationmeasures? A. Thedoseareaproductisameasurementoftheamountofskininjurya patientreceivesduringacardiaccatheterization. B. Thedoseareaproductcorrelateswiththeriskofstochasticinjury. C. Theeffectivedoseisameasureoftheamountofskininjuryapatient receivesduringacardiaccatheterization. D. Theeffectivedoseisameasureoftheriskofdeterministicinjury.

14. WhichofthefollowingeffortsresultsinanINCREASEintheradiationdoseapatient receivesinthecardiaccatheterizationlaboratory? A. Keepingthesourcetoimagedistancenarrow. B. Usingfluoroscopicratherthancinedoses. C. Usingmagnifiedviews. D. Decreasingtheframingrate. E. Focusingononeareaofthepatientandnotmovingthegantry.

15. Oneeffectivemethodofreducingthedoseofxrayrequiredfortheperformanceof cardiacCTistoalterthexraytubekVp.Topreserveimagequality,yetkeepthe radiationdosetoaminimum,atwhichofthefollowingkVpshouldthesystemideally besetformostpatients? A. 140kVp. B. 135kVp. C. 120kVp. D. 100kVporlower.

16. Inacutechestpain,acardiacCTisconsideredappropriateinwhichoneofthe followingscenarios? A. AnECGisnormalandcardiacenzymesarenegative. B. AnECGisuninterpretableandpretestprobabilityishigh. C. Cardiacenzymesindicateamyocardialinfarctionispresent. D. Apulmonaryembolismoraorticdissectionispossible.

17. Thehighestlevelofevidencesupportingrecommendationsoncalciumscoring includeswhichofthefollowing? A. Observationaldatafromselfreferredcohorts. B. Observationaldatafrompopulationscreeningstudies. C. Randomizedcontrolledtrialsshowingimprovedpatientmanagement. D. Randomizedcontrolledtrialsshowingimprovedpatientoutcomes.

18. Thenumberofdetectorrowsonascanner(e.g.,64,256,or320)determineswhich ofthefollowing? A. Spatialresolutiontheabilitytoseesmallerstructures. B. Temporalresolutiontheabilitytoavoidmotionartifacts. C. Accuracyfordetectionofacoronarystenosis. D. Volumecoverageduringdataacquisition.

19. WhichcardiacCTscanmodeenablesthedeterminationofventricularejection fraction? A. Axial. B. Helical. C. Ungated. D. Prospectivelytriggered.

20. UnderestimationofLVEFbySPECTisacommontechnicallimitation.Themajor reasonforthisiswhichofthefollowing? A. 8framegating. B. 16framegating. C. 32framegating. D. 64framegating.

21. WhichofthefollowingisthemajordifferencebetweenpharmacologicgatedSPECT andPETMPIwithregardtoLVfunctionassessment? A. OnlyrestimagescanbegatedwithPET. B. PETstressEFisgeneratedatpeakpharmacologichyperemicstress. C. SPECTstressEFisgeneratedatpeakhyperemicstress. D. OnlystressimagescanbegatedwithSPECT.

22.A70yearoldmanpresentedtotheclinicwithrecurrentnonexertionalmid precordialchestpainradiatingtotherightarmof1monthduration.Pastmedical historyincludesdiabetesmellitusfor15yearsandsevererightkneeosteoarthritis. HisbaselineECGwasnormal,withnoischemiaorpreviousinfarction.Physical examisunremarkable.Heisalreadyonoptimalmedicaltherapyincludingan aspirin,statin,andACEinhibitor.HeunderwentpharmacologicstressTc99m sestamibitestingusingasamedayrest/stressprotocol.Duringtheadenosine infusion,chestpainsimilartopresentationwasnotedandresolvedspontaneously. ThepeakadenosineECGandSPECTmyocardialperfusionimagesareshown (Figures1,2). Basedonthefindings,whichofthefollowingisthemostappropriate recommendation? A. Dischargethepatientwithanoutpatientworkupfornoncardiacetiologyof atypicalchestpain. B. Dischargethepatientonaspirinandabetablocker. C. Coronaryangiography. D. Performmaximum,symptomlimitedtreadmilltestingin2weeks.

Figure1

Figure2

23.A72yearoldladywithacardiachistorypresentedwithprogressiveshortnessof breathoverafewweeksduration.Shehasahistoryofhypertension,whichhasnot beenwellcontrolled.Onexamination,herbloodpressureis150/86mmHgandher heartrateis75bpm.Shehasregularrhythm,aprominentS4 ,andherLVapical impulseislaterallydisplacedwithasustainedpointofmaximalintensity.Her jugularvenouspressureiselevatedandshehas1+pedaledema.Heronly

Figure1

medicationisatenolol50mgdaily.Herbaseline12leadECGshowsnormalsinus rhythmleftatrialenlargementandLVhypertrophywithsecondarySTTwave repolarizationchanges.SheundergoesapharmacologicalSPECTMPI.Thestress ECGportionofthetestiswithinnormallimits.GatedSPECTshowsmildglobal hypokinesis,withanEFof42%.Perfusionimagesareshown(Figure1). Basedonthefindingsofthisstudy,whichofthefollowingshouldbethenextstepin themanagementofthispatient? A. Coronaryangiography. B. Stressechocardiography. C. Reassurance. D. Aggressiveriskfactormodification.

24. WhichofthefollowingisthebasisfordetectionofischemicviablemyocardiumbyTl 201? A. Ischemicmemorydetection. B. Propertyofredistribution. C. Mitochondrialfunctionassessment. D. Glucosemetabolismevaluation. E. Collateralflowenhancement.

25. WhichofthefollowingstatementsisTRUE? A. Themagneticfieldstrength(1.5T)thatisoftenusedforcardiovascularMRI is3,000timesstrongerthantheearthsmagneticfield. B. Whenapatientisplacedintheboreofthescanner,alltheprotonsalign paralleltothefield. C. GadoliniumbasedcontrastmediaprimarilyshortentheT1inthetissues whereitisdistributed. D. ThetimeconstantT2describestheexponentialregrowthoflongitudinal magnetization.

26. Whichofthefollowingliststhecorrecttimelineincludingallthecomponentsofa multitechniqueCMRexamination? A. Morphology,cine,restperfusion,additionalimaging,stressperfusion, delayedenhancement.

B. Cine,morphology,restperfusion,delayedenhancement,stressperfusion, additionalimaging. C. Cine,morphology,stressperfusion,delayedenhancement,restperfusion, additionalimaging. D. Cine,morphology,stressperfusion,additionalimaging,restperfusion, delayedenhancement. E. Morphology,cine,stressperfusion,additionalimaging,restperfusion, delayedenhancement.

PleasevisittheonlineversiontoengageinthisExam. 1.ThecorrectanswerisA.Iodineisnotanallergen.Anaphylactoidreactionstocontrastare duetoreleaseofhistaminefrommastcellsandbasophils,andarenotduetocirculatingIgE. References


1. SchabelmanE,WittingM.Therelationshipofradiocontrast,iodine,andseafoodallergies:amedical mythexposed.JEmergMed201039:7017.

2.ThecorrectanswerisB.Becausethedestabilizationofmastcellandbasophilmembranes containinghistamineisthepreventivetarget,corticosteroidsgivenimmediatelyplayarole.Once histamineisreleased,itseffectsonthevasculatureandgastrointestinalsystemcanbe attenuatedbyblockadeofH1 andH2 receptorswithdiphenhydramineandfamotidine, respectively. References


1. TramrMR,vonElmE,LoubeyreP,HauserC.Pharmacologicalpreventionofseriousanaphylactic reactionsduetoiodinatedcontrastmedia:systematicreview.BMJ2006333:675.

3.ThecorrectanswerisD.Avarietyofmultivariateriskpredictionschemessuggestthatthe expectedriskofseriousrenalfailureaftercontrastrequiringtemporaryorpermanentdialysis markedlyincreasesinthelowrenalfiltrationfunctionpopulation.Thesefactorscanbeintegrated insuchascoringscheme,whichhasbeenvalidatedbyMehranandcolleagues. References


1. MehranR,AymongED,NikolskyE,etal.Asimpleriskscoreforpredictionofcontrastinduced nephropathyafterpercutaneouscoronaryintervention:developmentandinitialvalidation.JAmColl Cardiol200444:13939.

4.ThecorrectanswerisC.TheXdescentisanegativedefectionintheatrialpressure waveform.Itoccursduringatrialrelaxation(diastole).Atrialsystolecausesapositivedefection calledtheAwaveinthepressuretracing.TheXdescentintheRAtracingoccursduringearly ventricularsystole,duringTVclosure.TheXdescentoccursregardlessofthephaseofthe respiratorycycle,althoughitsmagnitudemayvarysomewhatduringrespiration. 5.ThecorrectanswerisD.Mitralvalveprolapseisassociatedwithamidsystolicclickand murmurthatoccursearlierinsystole(i.e.,closertoS1 )whentheventricularvolumeissmaller, asoccurswithaValsalvamaneuver.Anearlysystolicejectionclickcanbeappreciatedin patientswithabicuspidaorticvalve,butitstimingisnotalteredwithaValsalvamaneuver. Hypertrophicobstructivecardiomyopathymaybeassociatedwithasystolicmurmur,butnoclick isaudible.Anopeningsnapmayoccurwithmitralstenosis,butitislocatedinearlydiastole. 6.ThecorrectanswerisB.Hehasnosignsofcongestion(i.e.,JVD,abdominojugularreflex,or peripheraledema),sohewouldbeclassifiedas"dry."Becausehehasevidenceofdecreased perfusion(hypotension,narrowpulsepressure,pulsusalternans,andcoolextremities),heis alsoclassifiedas"cool."

7.ThecorrectanswerisD.ThebestdiagnostictestforthedetectionofPEismultidetectorCTA basedonthePIOPEDIIandIIIstudydata.Allotheroptionsareincorrect. 8.ThecorrectanswerisA.Thisisanormalpostoperativeaorta.Theangiogramdemonstrates anormal,nonobstructivekinkattheanastomoticsitesooptionsB,C,D,andEareincorrect. 9.ThecorrectanswerisC.Diagnosticcriteriaforvenousthrombosisincludevisualizationofan intramuralthrombusinthedeepvein,lackofcompressibilityofthevenouslumen,fillingofthe lumenwithechos,diminishedDopplerwaveforms,andlackofaugmentationofvenousflowwith compressionofcalfmuscles.The"toandfro"flowintheveinischaracteristicofan pseudoaneurysmandnotdeepvenousthrombosis.Evidenceofvenouscongestionisnot diagnosticfordeepvenousthrombosis.Theimage(Video1)showsattemptedcompressionofa deepveinwithafillingdefectconsistentwithdeepvenousthrombosis.Thevenoussystemis lowresistance,whichisnotanabnormalfinding.Finally,asstated,thelackofaugmentationof venousflowwithcalfmusclecompressionindicatesdeepvenousthrombosis. 10.ThecorrectanswerisD.Thepatientclinicalscenarioisonethatisnotuncommonandit highlightstheriskforgroincomplications.Theserisksincludeemergentprocedures,multiple siteaccesswithlargesheathforintraaorticballoonpump,andanticoagulationforSTsegment elevationmyocardialinfarction.Thefindingsonultrasoundconsistentwithatrioventricularfistula includedirectvisualizationofconnectionbetweenarteryandveinintheleftpanel,interfaceoflow resistanceandhighresistanceflowintheadjacentartery,andahighvelocityflowatthejunction ofthearteryandthevein.Thetreatmentforanatrioventricularfistulaseen1weekpostcath withoutevidenceofsignificantgroinhematomaisconservativemanagementandreevaluation, asasignificantportionisspontaneouslyclose. Ina3yearprospectiveobservationalstudyof>10,000patientsundergoingcardiac catheterization,atrioventricularfistulaformationoccurredin1%ofpatients,withaclosurerate overthefollowingyearin4050%ofpatients.1 Thefindingsofpseudoaneurysmonvascular ultrasoundrequirevisualizationofaneckwith"toandfro"flowonspectralDoppler.Thetreatment fortheseisdependentonthesizeoftheneckandthelocation. References
1. KelmM,PeringsSM,JaxT,etal.Incidenceandclinicaloutcomeofiatrogenicfemoralarteriovenous fistulas:implicationsforriskstratificationandtreatment.JAmCollCardiol200240:2917.

11.ThecorrectanswerisD.Mostcoronaryfistulaareanincidentalfindingatcoronary angiographyandareofnoclinicalsignificance(optionA).TheLMCAarisingfromtheright coronarysinusisnotnecessarilysignificantparticularly,sincemanyoftheseleftmainscourse posteriortotheaortaandthereforearenotassociatedwithischemiaorsuddendeath,unlike thosethatcrossbetweenthepulmonaryarteryandaorta(optionB). Althoughcoronaryangiographycanbehelpful,butnotdiagnosticindeterminingthecourseofan anomalousleftmain(orrightcoronaryarisingfromtheleftcoronarysinus),thebestapproachis coronaryCTangiography.Thesecondmostcommoncongenitalcoronaryanomolyistheleft circumflexarisingfromtheRCAorrightsinusofValsalva(incidence0.4%)(optionC).Themost commoncongenitalanomalyisseparateostiafortheLADandLCx(incidenceof1%)(optionD). References
1. LevinDC,FellowsKE,AbramsHL.Hemodynamicallysignificantprimaryanomaliesofthecoronary arteries.Angiographicaspects.Circulation197858:2534. 2. HarikrishnanS,JacobSP,TharakanJ,etal.Congenitalcoronaryanomaliesoforiginanddistribution inadults:acoronaryarteriographicstudy.IndianHeartJ200254:2715.

12.ThecorrectanswerisD.FFRisdefinedastheratioof(i.e.,percentofnormal)flowinthe stenoticarterytotheflowinthesamearteryinthetheoreticabsenceofthestenosis,andis definedasthemeandistalcoronarypressuredividedbythemeanproximalcoronaryoraortic pressuremeasuredduringmaximalhyperemia,whichisgenerallydoneusingeither intracoronaryorIVadenosine,thelatterbeingmoreconsistent(optionsAC). TheFAMEtrial,whichrandomizedpatientswithmultivesseldiseasetoFFRdirectedPCIversus angiographicallydirectedstenting,demonstratedthatthosetreatedwithFFRguidedPCIhad superioroutcomes,fewerstentsutilized,fewervesselsstented,andatalowercost(optionD).

FFRisinfluencednotonlybythepercentstenosis,butalsobythelesionlengthandtheamount ofviablemusclesubtended.Assuch,afocal80%stenosisofthesmallcircumflexwas associatedwithanormalFFR(>0.80),whereastheRCA,havingadiffusefocal70%stenosis andsupplyingalargeamountofmyocardium,hadamarkedlyabnormalFFR(optionE). References


1. KernMJ,SamadyH.Currentconceptsofintegratedcoronaryphysiologyinthecatheterization laboratory.JAmCollCardiol201055:17385. 2. GibsonCM,PintoD.Fractionalflowreserve:anewsetoflensesfortheocculostenoticreflex?JACC CardiovascInterv20103:12823.

13.ThecorrectanswerisB.Thedoseareaproductisderivedfromanionizingchamber attachedtotheoutputofthexraytubeinthecardiaccatheterizationlaboratory.Itrepresentsthe totaldosegiventothepatientanddoesnotspecificallycorrelatewithdosetoanindividualorgan (suchastheskin).Itdoescorrelatewiththeoverallstochastic(geneticorcancer)risktothe patient.Theeffectivedosecanbederivedfromthedoseareaproductbyuseofaconversion factor.Itisderivedfromaweightedsumoftheestimateofvariousorgandosesandisametric usedinradiationsafety.Italsocorrelateswithstochasticinjury.Deterministicinjuryisthreshold dependent,withtheskinbeingthemostcommonorganinjuredinthismanner. 14.ThecorrectanswerisC.Anythingthatresultsinmagnificationinthecatheterization laboratorywillresultintheneedforanincreaseddose.Sincexraysdivergewhentheyleavethe xraytube,thegreaterthesourcetoimagedistance,themoretheimageismagnified.The imagecanalsobemagnifiedbyeitheranalogordigitalmethodsand,inbothcases,tosatisfy theexposureequationandtokeepagoodsignaltonoiseratio,anincreaseindoseisrequired. Fluoroscopicimageshavelessresolutionandcontrastbecauseoflowerdoses.Focusingona singleareaofthepatientwithoutmovingthegantryresultsinagreaterchanceofskininjury,and doesnotofitselfincreaseordecreasethedosecomparedtomovingthegantrytoimagea differentarea 15.ThecorrectanswerisD.Theimagequalityinxrayssystems,suchasCT,requiresthatan exposureequationbemet.ThisequationiskVpxmAxpulsewidth.ThekVpisthemaximal voltageacrossthexraytube(thehigherthevoltage,thegreaterthexraystrength),themA representsthenumberofelectronssenttomakexraysinthexraytube(andthusthenumberof xraysproduced),andthepulsewidthishowlongthesexraysareappliedforeachframe.Avery highkVpcanresultinanoverlypenetratedimagewithreducedimagecontrast.Thelowerthe kVp,thebettertokeepcontrasthighandtoreducetheamountofradiationexposure.ManyCTs aresetroutinelyat120orhigherthan120kVp.ReducingthekVpto100orlowerhelpsreduce theradiationexposureandatthesametimeimprovesimagecontrast. 16.ThecorrectanswerisA.AmongappropriateindicationsforcardiacCTinacutechestpain, testingisappropriatewhenthereisaloworintermediatepretestprobabilityandnegativeinitial evaluation.Whenpretestprobabilityishigh,amyocardialinfarctionisdiagnosed,oratriplerule outisrequested,cardiacCTiseitherofuncertainappropriatenessorinappropriate. 17.ThecorrectanswerisB.Highqualityevidencefrommultiplepopulationscreeningstudies supportstheimpactoncalciumscanningonCHDriskpredictionoverthatachievedthroughrisk factorscreeningalone.Althoughdatafromsuchstudiessuggestthatcalciumscoredataleadto differentpatternsofmedicationuse,therearenodefinitiverandomizedcontrolledtrialsshowing thatpatientmanagementandoutcomesareimproved. 18.ThecorrectanswerisD.Anumberoftechnicaldescriptorsareusedforscanners,oneof whichisthenumberofdetectorrows.Thisdeterminesthevolumecoverageduringdata acquisitionmoredetectorrowsmeansmoresimultaneousdataacquiredduringscanning.A detectorrowistypicallyabout0.625mmwide,suchthata64rowscannerprovidesabout4cm ofsimultaneouscoverage.Spatialresolutionisdeterminedbythedetectorwidth(0.625mm), andtemporalresolutionisdeterminedbythespeedatwhichthegantryrotatesaroundthe patient.Accuracyforstenosisdetectionisgenerallycomparableamongscannerswith comparabletemporalandspatialresolution. 19.ThecorrectanswerisB.Helicalscanninginvolvescontinuousradiationexposurethrough thecardiaccycle,thusthescanacquiresbothsystolicanddiastolicdata.However,continuous deliveryofradiationleadstohighradiationexposure.Axial(alsoknownasprospectively

triggered)scanningisanonoffscanmodethatacquiresscandataonlyduringaprespecified portionoftheECGcycle(typicallydiastole),andthuscannotdetermineejectionfraction,butdoes leadtolowerradiationexposure.ACTperformedusinganungatedtechnique,whichisthemost commonmodeforgeneralCT,doesnotregisterCTdatawiththeECG,andthereforecannot determineejectionfraction. 20.ThecorrectanswerisA.Eightframegatingisassociatedwithapproximatelya5pointEF underestimationcomparedto16framegatingSPECT.Thisisduetoinadequatesamplingofthe ventricularvolumecurve(aliasing).Thus,thelowerlimitsofnormalEFforan8framegated SPECTstudyis45%.SixteenframegatingEFimprovesthesamplingrateandcorrelateswithan echolowernormalEFof50%. 21.ThecorrectanswerisB.BothSPECTandPETEFmeasurementandvolumeassessment canbedoneatrestandstress.TheadvantagewithPETisthat,giventheshorthalflifeofPET perfusiontracers,thegatedstudyacquisitionbeginsimmediatelyafterisotopeinjection.This canoccurafterpeakvasodilatorstress,andtheEFobtainedismorerepresentativeoftheactual peakstressEFcomparedtoSPECT,wherethegatedacquisitionisdone3045minutespost stress. 22.ThecorrectanswerisC.ThepeakadenosineECGshowsSTsegmentdepressionwith vasodilatorstress.TheSPECTimagesdonotshowdefiniteperfusionabnormalities.This findingissuspiciousforbalancedischemiaandthreevesseldiseaseinthisdiabeticpatient. Multiplestudieshaveshownthatinthispatientpopulation,theprevalenceofthreevessel diseaseismorethan50%andisassociatedwithworseoutcomes.Thus,thispatientrequires furtherevaluationwithcoronaryangiography(Figure3).
Figure3

23.ThecorrectanswerisD.Thenuclearscanshowsasmalldilatedventriclewithaminimal areaofreversibleperfusionabnormalityinthemiddistalinferiorwall.Theextentofperfusion abnormalityappearsoutofproportiontotheLVdilationanddysfunction,andfavorsaprimary diagnosisofnonischemicetiologysuchashypertensiveheartdisease.Itiswellknownthatthe extentofstressinducedischemiaisapowerfulpredictorforadversecardiovasculareventsin patients.Furthermore,ithasbeendemonstratedinpatientswithminimalornoischemiathat medicaltherapyissuperiortorevascularization(seetext). Thispatientsscandoesnotreveallargeareasofscarorischemia,andhence,aninitialstrategy ofaggressivemedicaltherapyandriskfactormodificationwouldbethemostreasonablefirst step.Thereisnoindicationforcoronaryangiographyorfurthertesting. 24.ThecorrectanswerisB.Tl201isapotassiumanalogueandutilizestheNa+/K+ATPase pumptocrossthecellmembrane.Onceinside,thecellthalliumredistributesovertimeandthe relativechangebetweeninitialand4to24houruptakebetweenischemicandnonischemic myocardiumgetslesswithredistribution,enablingtheassessmentofviability. 25.ThecorrectanswerisC. 26.ThecorrectanswerisD.

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