Andersons pediatric cardiology 1927

significantcyanosis.Thelackofpulsatilitywithinthepulmonaryarteriesfurther
compromisespulmonaryvascularresistancecalculations.60,376Embolizationof
venovenouscollateralshasbeenthetraditionalmainstayoftreatmenttoimprove
oxygensaturationsandsymptoms.However,recentdata,albeitretrospective,
suggestworsenedsurvivalinpatientswhohaveembolizationcomparedwith
thosewhoaretreatedmedically.355
Inadditiontopulmonaryvascularremodeling,patientswithtypeIIIFontan
failuretypicallyhavemultiorgansysteminvolvement,includingcirrhosisand/or
portalhypertension,andtheinterrelationshipoftheheartandliverisof
particularimportanceinthissubtypeofFontanfailure.ElevatedCVPcauses
livercongestionandalterationsinliverperfusion,whichleadtofibrosisand
cirrhosisovertime.Morerecentlyrecognizedisthephenomenonofliverdisease
causingheartdiseaseandtheconstellationofabnormalitiesthathavebeen
describedasthecirrhoticcardiomyopathy.Approximately50%ormoreof
cirrhoticpatientsmayhavefeaturesofcardiacdysfunctionthataretheresultof
liverdisease.Theseincludediastolicdysfunction,chamberdilation,systolic
dysfunction,QTprolongation,arrhythmias,conductionabnormalities,and
bluntedheartrateresponsewithchronotropicincompetence.The
pathophysiologyiscomplexandmultifactorialbutappearstoberelatedtothe
neurohormonalchangesofcirrhosis.Inaddition,increasedplasmavolumeand
fluidretention,aswellasthesystemicvasodilationandreducedsystemic
vascularresistance,necessitateanincreaseincardiacoutputandplacean
increasedburdenontheheart.ThisisespeciallyanissuefortheFontan
circulation.Pulmonaryarteriovenousmalformationsduetothelackofhepatic
effluentcanalsooccur,377resultingincyanosisandfurthervolumeload.
Additionalfactorsattributabletoliverdiseaseincludeabnormalitiesincardiac
cellmembranecompositionthatincludealterationsincholesteroland
phospholipidmetabolism.β-Receptordownregulation,changesinpotassium
channels,muscarinicreceptoralterations,andabnormalcalciumhandlingmay
allplayarole.378
Treatmentofthisphenotypecanbeparticularlydifficult.Inadditiontorelief

ofcongestionwithloopdiureticsandaldosteroneinhibitors,itisoftennecessary
todiscontinuemedicationsthatlowerthesystemicvascularresistance,suchas
ACEinhibitorsandARBs.Thesemedicationsshouldbegenerallyavoidedin
thissubgroupbecauseoftheriskofhypotensionandkidneyinjury,including
hepatorenalsyndrome.379Vasoconstrictors,suchasmidodrine,cansometimesbe
usefultoincreasesystemicvascularresistanceandpreserveorgan


perfusion.380,381
Ifpulmonaryvascularresistanceiselevatedoriftherearesignificant
venovenouscollaterals,somehaveadvocatedtheuseofpulmonaryvasodilator
therapy,althoughcurrentlydataareinsufficienttomakeabroad
recommendation.Thesemedicationsareexpensiveandnotwithoutrisks.For
example,theeffectsofsildenafilmaynotbelimitedtopulmonaryvascular
dilationbutcanalsocauseperipheralvasodilation.Bosentanshouldbeusedwith
cautioninpatientswithliverdisease.ThereisasubsetofFontanfailurepatients
whobenefitfrompulmonaryvasodilatortherapy,butadditionalstudiesare
neededtobetteridentifythissubset.

TypeIV:FontanFailureWithAbnormal
Lymphatics
LymphaticabnormalitiesarenotinfrequentinpatientswithaFontancirculation
andcanpresentasPLEorplasticbronchitis,withthelatteroccurringmore
frequentlyinthepediatricpopulation.Theprolongedlossofserumproteinsthat
includealbuminandimmunoglobulinscanleadtoanasarca,malnutrition,and
recurrentbacterialinfections.Athoroughhemodynamicevaluationtoensure
thereisnoanatomicobstructionwithintheFontancircuitorpulmonaryarteries
iscriticalinallpatientswithFontanfailurebutevenmoresointhisphenotype.
Lymphangiographyormagneticresonancelymphaticimagingcanbe
particularlyhelpfulintheevaluationofplasticbronchitis382andcanguide

thoracicductligationorpercutaneouslymphaticinterventions.383Inhaledtissue
plasminogenactivatorandvesttherapyhavealsobeenused.384,385
ThereisexperiencetreatingPLEwithoralbudesonide,andtheremaybea
roleforpulmonaryvasodilatortherapy,althoughdataarelimited.203,386Cardiac
transplantationisthedefinitivetreatment.387Asinplasticbronchitis,thereis
growinginterestinpercutaneousembolizationofabnormallymphaticchannels
thatformbetweenliverandsmallbowelandspillalbumin-richlymphintothe
intestinallumen.Indeed,arecentreportdemonstratedimprovedsymptomsand
albuminlevelsafterpercutaneousembolizationofhepatoduodenalchannels
identifiedbyhepaticlymphangiographyandcontrast-guidedduodenoscopy.188
Furtherstudiesareneededtodeterminethelong-termeffectsofthisstrategy.

Exercise


Pulmonarybloodflowisdependentonadequatesystemicvenousreturn,which
isaugmentedduringexertionbytheventilatorypumpandbythemusclepump.
Theventilatorypumpincreasesvenousreturntothechestwithinspirationand
thenegativepressuregeneratedbythediaphragmandrespiratorymuscles.The
ventilatorypumpmaycontributelesstoaugmentationofvenousreturnwhen
comparedwiththemusclepump,whereexercisingmusclespumpbloodand
improvepulmonarybloodflowandcardiacoutput.334Resistancetraininghas
beentraditionallydiscouragedinpatientswithsevereheartdisease.However,a
smallAustralianstudydemonstratedimprovedexercisecapacityandobjective
measuresofcardiacoutputwithmoderatetohighintensityresistancetraining.
Thesubjectsinthisstudyunderwentsupervisedhigh-intensitytotalbody
resistancetraining3daysfor20weekswithafocusoncalfmuscles.Resistance
trainingmachineswereused,andthesubjectswereinstructedtoavoidValsalva
maneuverbyexhalingduringthestrainportionoftheexercise.Valsalva
maneuvercanleadtoadropinvenousreturnandcardiacoutput.Participants

performedthreesetsofeightrepetitionsoneachmachine,whichincludedchest
press,lateralpulldown,seatedrow,legpress,kneeextension,kneeflexion,and
calfraisesthatwerebothseatedandstanding.Theparticipantsofthestudywere
relativelyhealthywithoutsignificanthypoxia,heartfailure,orcardiac
arrhythmia.336Aerobicexercisewasnotaddedtoresistancetraininginthis
study.Resistancetraininglikelyprovidesmorebenefitthanaerobictrainingfor
thepurposesofimprovingexercisecapacityintheFontanpopulation.388
Althoughexerciseingeneralandresistancetraininginparticularappeartohave
therapeuticmeritinhealthierFontanpatients,additionalstudiesareneededto
determinethetherapeuticroleofresistancetraininginthosewithFontanfailure.

Anticoagulation
Althoughpracticesvary,ourexperienceisthatmostFontanfailurepatients
requireanticoagulation.Thromboemboliceventsarecommoninpatientswith
Fontancirculationandareinneedofthromboembolicprophylaxis.However,
thereisnoclearconsensusaboutwhentouseaspirin,vitaminKantagonists,or
otheranticoagulants.PracticeguidelinesfromtheAmericanCollegeof
CardiologyandtheAmericanHeartAssociationrecommendvitaminK
antagonistsforFontanpatientswithatrialshunt,atrialthrombus,atrial
arrhythmias,orthromboembolicevent.Mostexpertswouldalsoanticoagulate
patientswithclassicatriopulmonaryFontan,particularlywithadilatedright