Andersons pediatric cardiology 1921

WithhalfofallpatientswithlateFontanfailurehavingpreservedsystolic
ventricularfunction,271,272theutilityofthistypeofroutinesurveillancemaybe
limited.Moresensitivemarkersofcardiacfunctionwouldbeuseful.In
particular,anincreasedend-diastolicvolume(EDV)index,mostreliably
measuredwithcardiacMRI,maybeabettermarkerforcardiacstatusand
appearstohavebetterprognosticvalueintheFontanpopulation.264,273,274EDV
reflectsthepreloadofthesystemicventricleandisinfluencedbyacombination
offactorsincludingvenouscapacitanceanddegreeofventriculardilatation.Itis
elevatedimmediatelyafterFontancompletionbutreducestonormallevelsafter
thefirstyear.275TheetiologybehindtheprogressiveincreaseinEDVinthelater
yearsisnotunderstood.Itmaybetheresultofchronicvolumeoverload,
secondarytofluidretention,aortopulmonarycollaterals,atrioventricularvalve
regurgitation,andventriculardyssynchronysecondarytoarrhythmia.274
Theelectrocardiogramprovidesinsightintolossofsinusnodefunction,heart
block,andotherarrhythmias,whichareparticularlyprevalentinthosewith
originalatriopulmonarytypeFontanconnections.276,277Holtermonitoringand
eventandimplantablelooprecordermonitoringaddlayersofadditional
surveillancewherearrhythmiaissuspected.
SymptomsmaybeunderreportedintheFontanpopulationduetoalifetime
adjustmenttoadifferentfunctionalnormality,andself-assessmentoffunctional
statusispoorlycorrelatedwithquantitativeassessment.278Henceserial
assessmentwithcardiopulmonaryexercisetestingisusefulforongoing
surveillance.Exercisecapacitydeclinesovertime,andtherateofdeclinemay
betterpredictfutureadverseeventsthantheabsoluteexercisecapacityata
particularpointintime.37,38,45,278–280Thefrequencyandageatwhichtostartis
notclearlyestablished,especiallyinthoseinNewYorkHeartAssociationclass
1or2.
Theliverandkidneyaredetrimentallyimpactedbyelevatedsystemicvenous
pressureandrestrictedcardiacoutput.Consequently,abnormalitiesofthese
organsareoftenapparentintheFontanpopulationandcanbefoundevenin
thosewithlittleinthewayoffunctionallimitation.153,161,163,166,281Current

recommendationsareforintermittentscreeningwithliverandrenalfunction
serumtestingandultrasoundscanswithoutclearlyspecifiedintervals.248,251,253
Thesensitivityandspecificityofthesetestsasearlyscreeningtoolsinthis
populationarenotconclusive.11,153,166,168,282,283Newbiomarkersandimaging
modalitiesareemerging,281,283,284but,aswithexistingrenalandliverfunction


testing,theirpredictivevalueneedstobeestablishedpriortotheirbeing
incorporatedintosurveillanceprograms.Recentreportsofhepatocellular
carcinomainolderFontanpatientswithcirrhosishighlighttheimportanceof
screeningforbothoftheseconditions.181
RoutinesurveillanceandtestingintheFontanpopulationareanevolving
process.Asinformationfromlargerpopulation-basedstudiesemerges,more
robustguidelinescanbedevelopedforthelifetimecareoftheFontanpatient.

MedicalTreatment
Anticoagulation
GiventhepropensityforthrombosisintheFontancirculation,139,140,143,285–289
theneedforantithromboticprophylaxisisgenerallyaccepted,withthehighest
ratesofthrombosisdescribedinretrospectivestudieswhereprophylaxiswasnot
universal.129,287,290,291Thetwomostwidelyusedprophylacticmedicationsare
aspirinandwarfarin.Evenwiththeseagents,thereremainsasubstantialrateof
thrombosis(7%to19%ofcases).129,131,287,290–294Themortalityriskassociated
withclinicallyevidentthrombosisissignificant,rangingfrom12%to
28%.287,290,291,294,295Moreover,therecurrenceriskissubstantial,withfurther
thrombosesoccurringinmorethanaquarterofpatients.131,290Twotimeperiods
ofgreatestriskforthrombosishavebeenidentified,withinthefirstyearof
Fontanoperationandlate(≥10yearspostFontan).129,290,291,296
Thereisadiversityofopinionastowhetherwarfarinoraspirinshouldbe
usedasprimaryantithromboticprophylaxisinFontanpatients.Thisisreflected

inmarkedpracticevariationasdetailedinrecentsurveys.248,249Dosageregimes
andINRtargetsarepoorlydefined,andcurrentguidelinesareunabletoprovide
conclusiveevidencefortheirrecommendations.297Theonlyprospective
randomizedcontroltrialtodatecomparingaspirinandwarfarin131didnot
demonstrateacleardifferenceinthromboticeventsbetweenthetworegimes
overa2-yearperiod,despiteintensivethrombosissurveillance.Nevertheless,
subanalysissuggeststhatthosereceivingwarfarinwhohaveconsistently
subtherapeuticINRmeasurementsareathigherriskofthromboticevents.296
Thisfindingissupportedbyseveralretrospectiveanalyses.291–294
Anticoagulationwithwarfarincarriesasignificantriskofserioushemorrhagic
events.Ofinterestintheaforementionedstudy,thistypeofcomplication


occurredin1.75%inthewarfaringroupover2yearscomparedwithnoneinthe
aspiringroup.131Othershavereportedsignificantbleedingeventson
prophylacticanticoagulationwitheventsprimarilyoccurringinpatients
anticoagulatedwithwarfarin,especiallywhentakenformanyyears.290–292Inthe
adultFontanpopulation,theidealantithromboticregimeisaconundrumbecause
theremaybeanincreasedriskofhemorrhagerelatedtogastricvaricesandother
comorbidities,inadditiontotheriskofthrombosis.Tofurthercomplicate
matters,thereisahighriskofasecondthromboticeventifapatientcommenced
onwarfarinfollowingathromboticeventhashisorherwarfarindiscontinued
becauseofableedingevent.290
Inadditiontotheelevatedriskprofile,long-termwarfarintherapycarriesa
higherfinancialcostandhasgreaterimpactonQOLcomparedwithaspirin.The
needforregularbloodtests,thedifficultyinmaintainingaconsistenttherapeutic
window,andtheneedtoavoidat-riskactivitieshassignificanteconomicsocial
andpsychologicalcost.298
Giventheaforementioned,manycenterslimitwarfarinprophylaxistothe
high-riskearlypostoperativeFontanperiod,usingaspirinafterthefirst

postoperativeyearinallbutthoseathigherthannormalriskofthrombotic
episodes.Thereislittleexperiencewiththeuseofnewerantithromboticagents
intheFontancirculation,butthismaychange.Perhapsofgreaterinterestisthe
potentialrolepharmacogeneticsmayhaveinindividualizingtheprophylaxis
regimen.Geneticvariantsareknowntoinfluencewarfarindoserequirements
andtheriskofbleedingeventsearlyafterstartingtreatment.298,299Inaddition,
aspirinresistanceiswellrecognized.300–302Routinetestingforgenetic
susceptibilitytothrombosis,propensityforbleeding,andresistanceto
antithromboticmedicationmayformpartoftheassessmentandtreatment
individualizationinthefuture.However,withthepossibleexceptionofaspirin
resistance,thereiscurrentlyinsufficientevidencetosupportarecommendation
inthisarea.303

RoleofAngiotensin-ConvertingEnzyme
Inhibition,AldosteroneAntagonists,andβBlockade
InthewellFontanpatient,theuseofangiotensin-convertingenzyme(ACE)
inhibitors,knowntobeefficaciousinadultpatientswithstructurallynormal