Andersons pediatric cardiology 657
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Allat-riskpatientsrequirerepetitiveassessmentofthemodifiableand
nonmodifiableCVRFssummarizedabove.Additionally,thepresenceoftwoor
moreadditionalCVRFsshouldresultinthepatientbeingtreatedasiftheyarein
ahigherriskcategory(e.g.,a“moderaterisk”patientbeingtreatedas“high
risk”).Tier-specificcut-offsforintensificationoftherapyandtreatmentgoals
havebeenestablishedforeachriskcategory.19
Certaincongenitalheartlesionsplaceindividualsatincreasedriskfor
atheroscleroticCAD,specificallythosewithcoronaryarterystructural
abnormalities,lesionsinwhichcoronaryarteryinterventionsoccurred,and
obstructivelesionsoftheleftventricleandaorta.19Surgerieswhere
manipulationofthecoronaryarteriesoccurredincludearterialswitchoperation
fortranspositionofthegreatarteries,repairofanomalousoriginoftheleft
coronaryarteryfromthepulmonaryartery,andpatientsundergoingtheRoss
procedureforleftventricularoutflowtractobstruction.Followingthese
procedures,individualsareatincreasedriskforostialstenosisandmayalsobeat
increasedriskforthedevelopmentofatherosclerosis.19PatientswithWilliams
syndromeareatriskofdevelopinghypertensionsecondarytorenalartery
stenosisandischemicinjurysecondarytocoronaryarteryandsupravalvaraortic
stenosis.19Leftventricularandaorticobstructivelesions,includingaortic
stenosisandcoarctationoftheaorta,areassociatedwithanincreasedriskof
cardiovasculardiseaseinadulthood.Aorticstenosisresultsinleftventricular
hypertrophy,whichitselfisaknownriskfactorforcardiovasculardisease
morbidityandmortalityinadults.211Inaddition,despitenormalcoronaryartery
patencyandanatomy,coronaryflowmaybelimitedbythepresenceofaortic
stenosis.Thisresultsinreductionsinmyocardialbloodflowandreductionsin
coronaryflowreserves.Further,thepresenceofleftventricularhypertrophy
predisposespatientstoreducedperfusiontothesubendocardium.19In
coarctationoftheaorta,theassociationwithfutureacquiredcardiovascular
diseaseriskislikelyrelatedtoincreasedarterialstiffness211predisposingto
systemichypertension.19Inadditiontohypertension,thesepatientsdemonstrate
abnormalitiesofvascularreactivityandbaroreceptorfunction.213,214
Coronaryarteryvasculopathy(CAV)isthemostcommoncauseofmortality
inpediatricorthotopichearttransplantrecipientsbeyond1year
posttransplantation.215ThehistopathologyofCAVdiffersgreatlyfrom
atheroscleroticCAD.TheintimalhyperplasiaseenwithCAVistypically
comprisedofmonocyteandT-cellaccumulationalongwithsmoothmuscle
proliferation.216Whilecatheterizationandsurgicalinterventionsmayprove
immediatelysuccessfulinalleviatingstenoticareas,therestenosisrateishigh
andlong-termoutcomesarepoorandretransplantationmaybetheonly
option.217WhileCAVandatheroscleroticCADarepathologicallyverydifferent,
theysharecommonriskfactorsandcomorbidities.Forexample,duetothe
intensityanddurationofsteroidtreatment,obesityposttransplantisacommon
occurrence.218,219ThishasbeenshowntobeassociatedwithCAV.217In
addition,asaresultofimmunosuppressivetherapy,obesity,andgenetic
predispositions,childrenposttransplantareatincreasedriskforcombined
dyslipidemia,whichinturnisalsoassociatedwithanincreasedincidenceand
severityofCAV.19Statintherapyhasbeenshowntolowerposttransplant
dyslipidemiaandtheincidenceofCAVinchildrenandadults.220,221Moreover,
childrenposttransplantareatincreasedriskforhypertensionandrenal
dysfunction,particularlyinthosetreatedwithcyclosporine.19Bothhypertension
andrenaldysfunctionareassociatedwithanincreasedincidenceofCAV.222
Insulinresistanceanddeconditioningareadditionalriskfactorsthatshouldbe
monitoredinthepediatrictransplantrecipient.19
Kawasakidiseaseisasystemicvasculitisthatcanresultinacutecoronary
arteryaneurysms.19Theriskforcoronaryarteryaneurysmsishigherinyounger
(<6months)orolder(>8yearsold)children,males,inthosewhodidnotreceive
timelytreatmentwithintravenousimmunoglobulin,inthosewhoremainfebrile
despitetreatmentwithintravenousimmunoglobulin,andinthosewithlaboratory
testsindicativeofsevereandpersistentinflammation.19Followingtheacute
illness,affectedcoronaryarteriesundergoremodelingthatmayresultin
progressivestenosisduetointimalproliferation.LikeCAV,thepathogenesisof
coronaryarterystenosisinKawasakidiseaseismarkedlydifferentfromthatof
atheroscleroticCAD.19Theriskforstenosisispositivelycorrelatedwiththesize
ofthecoronaryarteryaneurysms,withsignificantlyincreasedriskinthosewith
giantaneurysms(≥8mmindiameter).223Thestenosisishypothesizedtooccur
duetoasmoothmusclecell–derivedmyofibroblasticprocessinthepresenceof
subacuteorchronicinflammatorycells.224Ofnote,whilethesecoronarylesions
mayappearto“resolve,”theymaygoontodemonstrateintimalproliferation
andcoronarystenosis.225The2017AHAScientificStatementonKawasaki
Diseaseprovidesacomprehensiveguideregardingthediagnosis,subsequent
surveillance,andtreatmentstrategyforchildrenwithKawasakidisease–induced
coronaryarterylesions.225
Childrenwithhigh-riskconditionsareatthesameorgreaterriskforthe
developmentoftheknownmodifiableCVRFsdiscussedaboveandmaybeeven
morepotenttowardsthedevelopmentofprematurecardiovasculardisease.19In
addition,thesechildrenmaybelessphysicallyactive,whichitselfmay
independentlypredisposetowardsprematurecardiovasculardisease.Cardiac
rehabilitationprograms,whenappropriate,mayimproveexercisecapacity,as
hasbeendemonstratedattimesinthecongenitalheartdiseasepopulation.226,227
InvasiveandNoninvasiveAssessmentsof
Atherosclerosis
GiventheincreasingtrendsinCVRFsinyouthandtheirknownassociationwith
atherosclerosis,detectingearlyatherosclerosishasbecomeincreasingly
importantinhigh-riskyouth.Invasiveassessmentsincludecatheter-based
angiographicassessmentsofthecoronaries,intravascularultrasound(IVUS),
andopticalcoherencetomography(OCT).InKawasakidiseasewithcoronary
arteryaneurysms,IVUShasbeenusedtodemonstratesymmetricaland
asymmetricalwallthickeningandhasbeenparticularlyusefulinsegmentsthat
havenarrowedtowards“normal”luminaldimensions,asdiscussedabove.228,229
Morerecently,OCThasbeenusedtocharacterizekeyluminalchangesincluding
fibrosis,stenosis,fibroticintimalthickening,andfocalcalcifications.230While
invasiveangiography,IVUS,andOCTmayallprovidekeyinformation,their
routineuseislimitedbytheirinvasivenatureandonlypatientswithperfusion
defectsshouldbefollowedwithcoronaryangiography.225Further,invasive
imagingassessmentsarenotcurrentlyrecommendedforFH.141
Noninvasivemodalitiestoassessmarkersofatheroscleroticburdenand
arterialstiffnesshaveshowngreatpromise.However,todatethereisinsufficient
normativedatatorecommendroutinescreening.Asaresult,theuseofthese
modalitiesarecurrentlyforresearchpurposesonly.231,232
Coronarycalcificationassessedbyelectron-beamcomputedtomographyisan
establishedmarkerforCADinadultsandispredictiveoffutureCVD
events.233,234Moststudiesinadultshavedemonstratedagreaterprevalenceof
coronaryarterycalcificationwithincreasingage.231Thereforewhilesome
studieshaveidentifiedincreasedcoronarycalciuminhigh-riskchildrenand
youngadults(FH,renaldisease,type1diabetes),235–238itsutilityinpediatricsis
limitedduetoexposuretoradiationandlowprevalenceofsignificant
