Andersons pediatric cardiology 1694
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MostchemotherapyprotocolsincludeserialassessmentoftheECG,with
particularemphasisonthecorrectedQTinterval.AvoidanceofQT-prolonging
medicationsandmonitoringofelectrolytesisessentialwithcertaintherapiesto
reducelikelihoodofthedevelopmentofpotentiallyfatalventriculararrhythmia
suchastorsadesdepointes,especiallyinpatientsatriskfortherapy-related
diarrheaandemesis.16
Echocardiography
Traditionally,studiesofCTCinpediatricpopulationshavebeenbasedon
shorteningfraction,andmanychemotherapyprotocolscontinuetoincludethis
asthesolemarkertoidentifychangesofconcern.Morerecently,EFhasbeen
incorporatedbutisnotuniversallyused.Thereisnospecifiedechocardiographic
protocolincludedinCOGguidelines,onlythatan“echocardiogramor
comparableimagingshouldbeperformedtoevaluatecardiacanatomyand
function.”Guidelinesareavailableforthemultimodalityimagingassessmentof
adultpatientsthroughoutcancertherapy,andthecardio-oncology
echocardiogramprotocolincludedcanbeusedasaguideforpediatricpatients.25
Includedaretwo-dimensional(2D)andthree-dimensional(3D)assessmentsof
function,strainimaging,andmeasuresofrightventricularfunction.Both3DEF
andparametersoftissuedeformation(strainandtissueDoppler)have
demonstratedtheabilitytodetectsubclinicaldysfunctioninadultandpediatric
studies.26–28Despitethis,themajorityofcurrentscreeningeffortsinpediatric
patientsfocusonstandardechocardiographicmeasuresandonlyinlong-term
survivors.29Onerecentstudydiddetailabnormalmyocardialstrainina
heterogeneousgroupof25pediatricpatientsimmediatelyaftertheirfinal
treatmentbutdidnotincludetimepointsduringtreatment.30Unfortunately,as
opposedtostudiesinadults,thoseinchildrenandadolescentshaveyetnot
proventheabilityofchangesinmyocardialstraintopredictlaterchangesin
symptomaticheartfailureorevenEF.26
CardiacMagneticResonance
Cardiacmagneticresonance(CMR)hasincreasingutilityindetectingcancer
treatment–relatedcardiotoxicity,particularlyinpatientswithlimitedimaging
windowsandforassessmentoftherightventricle.Onestudyoflong-term
survivorsofpediatriccancersfoundabnormalleftandrightventricularfunction
(EF<55%)inapproximately80%ofthecohortatalmost8yearsposttherapy,
includingdysfunctionthatwouldmeetmosttreatmentcriteria(leftventricular
EF<45%)innearly20%.31Thisproportionofdysfunctionwassimilarto
anotherstudyofadultsurvivorsshowingnearly15%hadleftventricularEFless
than50%byCMR,with75%ofthisgroupmisclassifiedasleftventricularEF
greaterthan50%by2Dechocardiography.27Inanothergroupofasymptomatic
survivorsatleast2yearsaftertherapy,increasedextracellularvolume,
suggestingfibrosis,wasdemonstratedeveninthesettingofnormalleft
ventricularEF.Thisincreaseinextracellularvolumecorrelatedwithdecreased
VO2,suggestingamuchgreaterpotentialburdenofcancertreatment–related
cardiotoxicitythanpreviouslyrealized.32
SerumBiomarkers
Serumbiomarkersserveasmeasurablesurrogatesfordiseasepresence,
progression,orseverity.33Althoughrecommendedintheroutineassessmentof
adultpatients,cardiacbiomarkershavenotyetbeenincorporatedtosurveillance
forpediatricandadolescentpatients.Troponins,brainnatriureticpeptide(BNP),
andN-terminalpro-BNPhavebeenshownabnormallyelevatedbeforeinitiation
oftherapy,indicatingabaselinestateofcardiacstressorinjuryrelatedtoillness,
withfurtherincreasesduringandafteranthracyclinetreatment.34–37Inonestudy,
childrendiagnosedwithacutelymphoblasticleukemiahadelevatedtroponins
afteranthracycline,butnotnonanthracycline,therapy.38Inanotherstudyof
childrenundergoingcancertherapy,plasmaBNPwassignificantlygreaterwhen
shorteningfractionwasdecreased,39andN-terminalpro-BNPvalueswere
elevatedinpatientsreceivinganthracyclinewhencomparedwithcontrolsor
nonanthracyclinechemotherapy.40Patientsinlong-termfollow-upmaycontinue
toshowelevationsinthesebiomarkersasevidenceforongoingorsubclinical
cardiotoxicity.41,42Asearchfornewserumbiomarkersisongoing,43including
earlydatasuggestingpromiseforcirculatingmicroRNAsasmonitoringtoolsin
pediatricpatients.44Therearealsogenepolymorphismsdescribedthatmay
identifysusceptibilitytoCTCforindividualswithagivengenotype.45–48
Ultimately,acombinationofimaging,serumbiomarkers,andgeneticprofileis
likelytoyieldthemostsensitivemethodtoeitherpredictordetectCTCduring
andaftertherapy.25,49
OtherModalities
ExerciseTestingandStressEchocardiography
Cardiopulmonaryexercisetesting(CPET)allowsinsighttoapatient'scardiac
function,cardiovascularsymptoms,andaerobicfitnessunderthestressof
exercise.StudieshavedemonstrateddecreaseinexercisecapacitybyCPET,and
subclinicalmyocardialsystolicanddiastolicdysfunctionbyexercise
echocardiography,whencomparingsurvivorsofchildhoodcancerstohealthy
controls.50–54TestingwithCPETalsohaspotentialtoidentifyischemicdisease
anddysrhythmias.
MultigatedRadionuclideAngiography
Useofmultigatedradionuclideangiography(MUGA)hasbeenincorporatedinto
adultmonitoring,generallyforitsreproducibilityandaccuracyatmeasuringEF
whencomparedwith2Dechocadriography.16,25However,withitslimitedability
togivestructuralinformation,poorcharacterizationoftherightheart,useof
radiation,andtheemergenceof3DechocardiographyandCMR,MUGAisused
lessfrequentlyoverallandrarelyinchildren.
AmbulatoryRhythmMonitoring
Theneedforextendedrhythmmonitoring(Holtermonitor,eventmonitor,loop
recorder)isnotspecificallyaddressedinfollow-upguidelinesforpediatric
patients.Inclusionisatthediscretionofthespecialistbasedonhistory,exam,or
ECGfindings.
