TetralogyofFallot

Epidemiology:
Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease in all age groups,
constitutingapproximately8%ofcongenitalheartdiseaseoverall.TOFoccursinapproximately0.19
0.26/1,000livebirths.IntheUnitedStates,theprevalenceofTOFisapproximately3.9per10,000live
births.

Definition:TetralogyofFallotischaracterizedbythepresenceoffouranatomicalfindings:
1. Ventricularseptaldefect
2. Pulmonarystenosis(rightventricularoutflowobstruction)
3. Dextropositionoftheaorta(overridingaorta)
4. Rightventricularhypertrophy

Pathophysiology:
The figure below compares the normal anatomy and blood flow of the heart to that found in
TetralogyofFallot.TheinitialdefectinTOFisanarrowingoftherightventricularoutflowtractinto
the pulmonary artery. This prevents deoxygenated blood from entering the pulmonary circuit. In
responsetothisoutflowobstruction,themyocardiumoftherightventriclehypertrophiesinorderto
contract forcefully enough to push blood past the stenosis. Additionally, patients have a large
ventricularseptaldefectwhichallowsshuntingofbloodbetweentheventricles.Inapatientwithan
isolated VSD, the blood flow is shunted initially from lefttoright. However, in TOF, the right
ventricularoutflowobstructionmayimpedethenormalbloodflowsosignificantlythattheleftside
oftheheartbecomesthepathofleastresistance.Bloodfromtherightventricleisthenforcedinto
theleftventricle,creatingarighttoleftshuntandsubsequentcyanosis.Finally,theaortaoverrides
theventricularseptaldefect,straddlingtheVSD.Thisallowsdeoxygenatedbloodshuntedfromthe
rightventricletoimmediatelyexittheheartmixedwithbloodfromtheleftventricle.

The most important determinant of the severity and clinical consequences of TOF is the degree of
rightventricularoutflowobstruction.Withalesserobstruction,bloodisshuntedfromlefttoright
and permitted to preferentially enter the pulmonary circulation, allowing for oxygenation. With a
greater degree of obstruction, however, blood is forced in the opposite direction, away from the
pulmonary circulation, leftward across the VSD and ultimately blood exits the heart before being
oxygenated. Patients will present with differing degrees of outflow obstruction, and this may
fluctuatethroughoutthecourseoftheillness.


OtherAssociatedAbnormalities:
Of note, approximately 40% of patients with TOF have additional congenital heart defects. This
includesfrankpulmonicstenosis,rightaorticarch,abnormalitiesofthecoronaryarteries,collateral
vesselssupplyingthepulmonaryarteries,patentductusarteriosusorotherdefects.Itisimportantto
evaluatethepatientforallassociatedheartdefectsasthismayaffectsurgicalinterventionormedical
therapy.

Additionally,cliniciansshouldrecallthatTOFisassociatedwithanumberofgeneticsyndromes.This
includesTrisomy21(DownSyndrome)aswellasDiGeorgeSyndromeandvelocardiofacialsyndromes.

PresentingSignsandSymptoms:
The timing and features of presentation depend on the degree of right ventricular outflow
obstruction.Patientswithmoresevereobstructionwillpresentearlierduetocyanosis.Thismaybe
asearlyastheimmediatenewbornperiod.Forpatientswithmoremoderatedisease,thepresenting
signmaybeaheartmurmur(seebelow).Finally,forpatientswithmilddisease,withsocalledpink
tetralogy due to the lack of cyanosis, their presentation may consist of signs and symptoms of
congestiveheartfailureduetothelefttorightshuntingacrosstheVSDandsubsequentpulmonary
overcirculation. Ultimately, most patients with mild disease will become cyanotic as the degree of
outflowobstructionincreasesovertime.

ClinicalFeatures:
PatientswithTOFhaveanumberofdistinguishingsignsandsymptomsthatcanbefoundonphysical
examandelucidatedwithadetailedhistory.
Cardiacexam:Mostimportantly,theheartmurmurheartinTOFisnotduetotheVSD!Itisin
fact due to the right ventricular outflow obstruction. The murmur is typically crescendo
decrescendowithaharshsystolicejectionquality;itisappreciatedbestalongtheleftmidto
upper sternal border with radiation posteriorly. (Remember, an isolated VSD murmur is a
holosystolicmurmur,bestheardinthetricuspidarea.Itmayradiatetotherightlowersternal
border.) Patients will have a normal S1 and possibly a single S2 due to diminished P2
component.
Cyanosis:Ifpatientsarecyanotic,thisismostcommonlyseenonthelipsornailbeds.
Tetspells:Tetspellsarehypercyanoticepisodesprecipitatedbyasuddenincreaseinrightto
leftshuntingofblood.Theycanbeelicitedbyactivity(e.g.feeding,crying),ortheymayoccur
without warning. The classic description is of a patient who becomes cyanotic and then
assumesasquattingpositiontorelievethecyanosisandhypoxia.Squattingservestoincrease
peripheral vascular resistance, thereby increasing the pressure in the left heart, and
subsequentlyforcingbloodbackintothepulmonarycirculation.

ChestXRay:Asseenonthechestxraybelow,patientswithTOFhaverightventricularhypertrophy,
abootshapedheartanddecreasedpulmonaryvascularmarkings.

Electrocardiogram: On EKG, patients with TOF will show increased right ventricular forces as
evidencedbytallRwavesinV1.Additionally,rightatrialenlargementismanifestedbyprominentP
wavesinV1(*).Rightventricularhypertrophyisdemonstratedbyarightwarddeviatedaxis.

Echocardiogram:FindingsonechocardiogramarethemainstayofdiagnosisinTOF.Echocardiogram
will demonstrate a ventricular septal defect with an overriding of the aorta, pulmonic stenosis and
rightventricularhypertrophy.ThisconstellationoffindingsservestoclinchthediagnosisofTOF. In
about25%ofcases,patientswillalsohavearightaorticarch.Asseenintheechocardiogrambelow,
theblood(blue)fromboththerightventricleandleftventricleenterstheoverridingaortaacrossthe
VSD.

Treatment:
OnceTOFisdiagnosed,almostallpatientsundergocorrectivesurgicalrepairwithinthefirstyearof
life.Intheinterimperiod,prostaglandintreatmentmaybenecessarytomaintainthepatencyofthe
ductusarteriosus.Additionally,somepatientsmayrequiredigoxinordiureticsifsignsofheartfailure
arepresent.

Treatment of hypercyanotic spells is directed towards improving pulmonary blood flow. These
include oxygen, knee/chest position, morphine, intravenous fluids, sodium bicarbonate, beta
blockersorpharmacologicallyincreasingsystemicvascularresistancebyadministrationofdrugs,such
asphenylephrine.

Onceaninfanthasdevelopedprogressivecyanosisorhasevidenceofhypercyanoticspells,surgical
correctionisindicated.Therearetwocommonsurgicalprocedures:

BlalockTaussig shunt creates a shunt between the aorta and the pulmonary artery using the
subclavian artery. This is used as a palliative procedure in infants who are not acceptable
candidatesforintracardiacrepairduetoprematurity,hypoplasticpulmonaryarteries,orcoronary
arteryanatomy.Patientswillrequireadditionalsurgeryasthisisnotacurativesurgery.

IntracardiacrepairisthedefinitiverepairforpatientswithTOFandisthepreferableprocedure.
Thisconsistsofpatchclosureoftheventricularseptaldefect,andenlargementoftheRVOTwith
reliefofallsourcesofobstruction.Insomecases,thepulmonaryvalvemayneedtoberemoved
toeliminatetheobstruction.

Intracardiac repair for TOF. The

ventricularseptaldefectisclosedwitha
patch.Therightventricularoutflowtract
is enlarged by opening the RVOT and
pulmonary valve, resecting the
subinfundibular muscle bundles, and
patchingtheareaopen.Insomecases,a
conduitmaybeinsertedtofurtheropen
theRVOT.

OutcomeandComplications:
Overall, patients undergoing surgical repair for TOF have an excellent prognosis with a 20year
survival rate of over 90%. Complications of surgical repair of TOF include arrhythmias particularly
ventricular tachycardia (VT), and atrial arrhythmias. Furthermore, patients may experience right
ventricularhypertrophyorenlargementduetoresidualpulmonarystenosisandbackwardbloodflow
into the right ventricle. Longterm complications include the need for additional surgeries,
neurodevelopmentaldelayandmyocardialfibrosis.Patientsshouldbefollowedcloselybyapediatric
cardiologisttomonitorfortheseshorttermandlongtermcomplications.


References:
1. Uptodate:Pathophysiology,clinicalfeaturesanddiagnosisofTetralogyofFallot
2. SCGreenwayetal.DeNovoCopyNumberVariantsIdentifyNewGenesandLociinIsolated,
SporadicTetralogyofFallot.NatureGenetics41,931935(2009).
3. MSilberbach,DHannon.PresentationofCongenitalHeartDiseaseintheNeonateandYoung
Infant.PediatricsinReview.Vol28,No.4.(2007).
4. Uptodate:OverviewoftheManagementofTetralogyofFallot
5. TetralogyofFallotRepair,ChildrensHospitalofPennsylvannia,
http://www.chop.edu/img/cardiaccenter/tetralogyoffallotrepair.
6. DVReddy.CaseBasedPediatricsforMedicalStudentsandResidents:CyanoticCongenital
HeartDisease.http://www.hawaii.edu/medicine/pediatrics/pedtext/s07c03.html,Dec2002.
7. TetralogyofFallot.NationwideChildrensHospita,Columbus,OH.
http://www.nationwidechildrens.org/tetralogyfallot.