Ventricular arrhythmias and sudden death in tetralogy of Fallot

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REVIEW

Ventricular arrhythmias and sudden death in tetralogy of Fallot

Arythmies ventriculaires et mort subite dans la tétralogie de Fallot

Philippe Maury

^a^,^b^,∗

, Frederic Sacher

^c

, Anne Rollin

^a

, Pierre Mondoly

^a

, Alexandre Duparc

^a

,

Katja Zeppenfeld

^d

, Sebastien Hascoet

^e^,^f

, on behalf of the Réseau francophone de rythmologie pédiatrique et congénitale

aUniversityHospitalRangueil,31059Toulousecedex09,France

bUnitéInsermU1048,Toulouse,France

cInserm1045,LIRYCInstitute,BordeauxUniversityHospital,Bordeaux,France

dDepartmentofCardiology,C5-P,LeidenUniversityMedicalCentre,Leiden,TheNetherlands

eUniversityChildrenHospital,Toulouse,France

fMarie-LannelongueHospital,DepartmentofCongenitalHeartDiseases,LePlessis-Robinson, France

Received25October2016;receivedinrevisedform3December2016;accepted5December 2016

Availableonline17February2017

KEYWORDS TetralogyofFallot;

GUCH;

Ventricular tachycardia;

Suddendeath;

Ablation

Summary Malignantventriculararrhythmiasandsuddencardiacdeathmaylate happenin repairedtetralogyofFallot,althoughprobablylessfrequentlythanpreviouslythought,espe- ciallywiththeadventofnewsurgicaltechniques/management.Ventriculartachycardiasare causedbyreentryaroundthesurgicalscars/patchesandvalves.Manypredictivefactorshave beenproposed,whichsufferfrompooraccuracy.Thereiscurrentlynorecommendedindication forprophylacticimplantablecardioverterdeﬁbrillatorimplantation—exceptmaybeinthecase ofmultipleriskfactors—whileradiofrequncyablationmaybeproposedinsecondarypreven- tionwithorevenwithoutaback-upimplantablecardioverterdeﬁbrillatorinselectedcases.

Abbreviations: ACHD,adultcongenitalheartdisease;GUCH,grown-upcongenitalheartdisease;ICD,implantablecardioverterdeﬁbril- lator;RVOT,rightventricularoutﬂowtract;SCD,suddencardiacdeath;TOF,tetralogyofFallot;VT,ventriculartachycardia.

∗Correspondingauthor.DepartmentofCardiology,UniversityHospitalRangueil,31059Toulousecedex09,France.

E-mailaddress:mauryjphil@hotmail.com(P.Maury).

http://dx.doi.org/10.1016/j.acvd.2016.12.006

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Repeated cardiologicalinvestigationsandmonitoringshouldbeproposedforevery operated patient.

MOTSCLÉS

TétralogiedeFallot; Mortsubite;

Arythmies ventriculaires; Cardiopathie congénitalede l’adulte; Ablation

Résumé Desarythmiesventriculairesmalignesouunemortsubitepeuventsurvenirtardi- vement aprèscorrection chirurgicale de tétralogie de Fallot, quoique probablement moins fréquemmentqueprécédemmentsupposé,surtoutavecl’avènementdenouvellestechniques chirurgicalesoudepriseencharge.Lestachycardiesventriculairessontduesàdesréentrées autour/entrelescicatricesdeventriculotomieoupatchsetlesanneauxvalvulaires.Uncertain nombredefacteursfavorisantsontétéproposésquisouffrentcependantdevaleursprédictives insuffisantespourêtreutilisésseulsenpratiqueclinique.Iln’yaactuellementpasderecom- mandationpourl’implantationprophylactiquededéfibrillateurenpréventionprimaire—sauf peut-êtreencasd’associationdefacteursprédictifsmultiples—alorsquel’ablationpercutanée parradiofréquencepeutêtreproposéeenpréventionsecondaireavecoumêmesansdéfibrilla- teurdanscertainscassélectionnés.Desinvestigationscardiaquesrépétéesetunesurveillance aulongcoursdoiventêtreeffectuéschezchaquepatientopéré.

Background

Congenitalheartdiseaseispresentin0.9%oflivingbirths;

currently, 90% of those affected will reach adulthood becauseofrecentprogressmadeinpaediatrics,cardiology, surgeryandresuscitation[1,2].Amongwhatarecommonly called ‘‘grown-up congenital heart diseases’’ (GUCHs) or, morerecently,‘‘adultcongenitalheartdiseases’’(ACHDs), tetralogyofFallot(TOF)hasapreponderantplace,because of its relatively high prevalence (7—10% of all congenital heart diseases;1/3500 to1/4300 inthe adultpopulation) [3,4],andbecauseitispossibletohavecorrectivesurgery, leadingtoalmostnormalanatomyandphysiologyinadult- hood. Indeed,verylong-term follow-up hasdemonstrated thathealthstatusisexcellent,withamortalityratethatis consideredtobelow(14%mortalityforhospitalsurvivorsat 40-year follow-up, aftersurgery performed inthe 1970s), even if it is still higher than in the general population, mainlybecauseofheartfailureandventriculararrhythmias [5].Thus,thethirdreasonformakingTOFoneofthemain GUCHsof concernis thelateriskof malignantventricular arrhythmiasandsuddencardiacdeath(SCD).

The aim of this review is tohighlight the mechanisms of ventricular arrhythmias in TOF,and to present current knowledgeof secondary andprimarypreventionofSCDin thissetting.

SCD in GUCH patients

The occurrence of SCD in patients with previous surgical repairofcongenitalheartdefectsisatragicevent,asmany areusually considered to be‘‘cured’’ of their congenital heart disease (even if this terminology may be a bit too optimistic), with rather low mortality rates and usually

excellent quality of survival. Some of these SCDs are probablylinkedtoparoxysmalhigh-degreeatrioventricular block(e.g. in repaired TOF withrelevant intraventricular conduction disturbances, but also in ventricular septal defect, cushion defect or congenitally corrected transpositionof the greatarteries). Someother SCDs arecaused byventricularﬁbrillation inducedbyfastventricularrates duringsupraventriculartachycardia(e.g.atrialtachycardia with 1/1 atrioventricular conduction after atrial switch for transposition of the great arteries, or after Fontan procedures for single ventricle). Other causes probably includehaemodynamiccompromise,embolism,myocardial infarction or aneurism rupture, but it is now clear that mostSCDs(a proportionestimatedat around75%[6]) are secondary to arrhythmias, and among these, malignant ventricular arrhythmiashave been documented in 85% of casesatthetimeofthecardiacarrest[6].

EveniftheculpritGUCHforSCDhaschangedinrecent decades, TOF remains one of the main GUCHs carrying the risk of late SCD. In 1974, congenital aortic stenosis, Eisenmenger’ssyndrome,TOFandhypertrophicobstructive cardiomyopathywereresponsibleformorethanhalfofSCDs inchildren(non-operateddefectsinmost)[2];whereasTOF, systemic topulmonary anastomosis, pulmonary hyperten- sioncausedbylefttorightshuntanddilatedcardiomyopathy were present in half of the SCDs in a report published 10years later (postoperative in a signiﬁcant number of cases)[7].In1998,Silkaetal.foundthatin3600patients withGUCH,mostlateSCDswerelinkedtoaorticstenosis, aorticcoarctation, transpositionof the greatarteriesand TOF,leadingtoayearlySCDrateof0.22%(50to200times higherthaninthegeneralpopulation);mostweresuspected tohaveanarrhythmiccause[6].SimilarcausesofSCDhave beenfoundinmorerecentstudies[8].However,evenifitis alwaysaclinicallyrelevantissue,SCDisnotthemajorcause

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ofdeathinGUCH,representingonlyone-quarterofall-cause mortalitiesinadultswithGUCHinmanyseries[6,9,10],or evenfewer,accordingtomorerecentdata[11],whileitis knowntoaccountfor half of cardiac deathsamong those withacquiredheartdisease.

ProspectivetrialsregardingSCDinGUCHarelackingfor manyreasons:

• ﬁrst,theseareveryheterogeneousdefects;

• second, the number of cases needed to reach statisti- calpowermakesanytrialalmostunachievable(e.g.TOF wouldrequire1700patientstobefollowedfor10years) [12];

• third,earlier conclusionsmay notberelevanttonewer generations of patients with GUCH (complete repairs duringthe neonatalperiod,improved physiologicalout- comes,extendedsurvivalofpatientswithmorecomplex forms)[13].

SCD and ventricular arrhythmias in TOF

Themodern managementofTOF beganbeforethe 1960s, after the ﬁrst surgical complete repair performed by Dr D. C. Lillehei in 1954. As early as 1975 — around 15 to 20yearslater—theﬁrstcasesofunexpectedcardiacarrest inrepairedTOFwerenoticed,andwerealreadysuspected tobecausedbymalignantventriculararrhythmias[14—16].

Since then, SCD has been identified repeatedly asthe major cause of mortality in repaired TOF, representing, however,only one-third tohalf ofall-cause mortalitiesin differentseries[14,17—19]. Over thepast 30years,many studieshaveevaluatedtheriskofSCDinTOFtobebetween 0and0.8%yearly[6,14,16—23].Inameta-analysisinclud- ing39 studies and 4583 patients, the laterate of SCD in TOF was evaluatedto be 1.8% over more than 8years of follow-up,i.e.anannualSCDrateofonly0.15%[21],which is, of course, higher than in the general population, but does not constitute an objectively ‘‘high’’ risk sufficient towarrantsystematicprevention.Forcomparison,ayearly risk ofSCD of upto0.8% in hypertrophic cardiomyopathy does not constitute an indicationfor an implantable car- dioverterdefibrillator (ICD)[24]. Interestingly,the risk of lateSCDinTOFisnotlinearbutincreasesovertime,espe- cially20—25yearsafter the surgery[6,19]. However,it is stillunclearifthisincreaseissimplycausedbyageingoris dependentonongoingprogressinsurgicaltechniques.

Fortheoccurrenceofsustainedventriculartachycardia (VT),theriskhasbeenevaluatedas4%at21-yearfollow-up (i.e.0.2%yearly)[17],andas14%in556adultsoperatedon forTOFafterafollow-upofaround30years[25].Therisk alsochangeswithage,withanincreaseataround40years ofage[25].Thus,itistemptingandlogical tomainlylink SCDinTOFtotheoccurrenceofsustainedVT.

Mechanisms of VT and SCD in TOF

DataonunrepairedTOF arescarce,asthese usuallyhave a very poor prognosis [26]; what we know comes from ancientstudies,where ventriculararrhythmiaswerecom- monlyfoundinolderTOFpatientsbeforerepair[27,28].

ForrepairedTOF,conduction disturbancesareprobably not a common cause of SCD becauselong-term evolution from right bundle branch block to bi-/tri-fascicular block isuncommon[22],andbecausepostoperativebi-fascicular block(withouttransienthigh-degreeatrioventricularblock) hasneverbeenshowntoleadtolateSCD[18,22,29,30].Only transient complete heart block that persisted beyondthe thirdpostoperativedayhasbeencorrelatedwiththeriskof lateSCD[31].EvenifprolongedQRSdurationhasbeencor- relatedwith SCD[17,32],QRS prolongation relatesrather toright ventricular size,and predictsmalignantventricu- lar arrhythmias[32]. Moreover,autopsies inpatients with TOFwhodiedfromSCDrevealedthattheconductiontissues wereundamaged,butfoundextensive fibrosisoftheright ventricularmyocardiumatboththeventriculotomysiteand the septum [33]. Ventricular arrhythmias such as premature beats[22,30]anddocumentedventricular fibrillation [30]weresoonsuspectedtobeinvolvedinSCDmechanisms and,finally,repeateddocumentationofsustainedVTduring abortedSCDinrepairedTOFpatients[32]sealedthecausal relationshipbetweenventriculararrhythmiasandSCD.

Afterthefirstcasesofsurgicalorintracardiacmapping andablation,reentrycircuitsaroundthesurgicalventricu- lotomyscars,usingfibroticareasofslowconduction,have beenshowntobethecauseofsustainedVTinrepairedTOF [34—37].Itisnotknown,however,ifventricularfibrillation is always caused by degenerating monomorphic sustained VT.

Factors associated with SCD in TOF

Manyfactorshavebeenproposedtotrytobetterdefinethe riskofSCDinrepairedTOF(Table1).Thesefactorsarebased onhistory, clinical features, surface electrocardiogramor signal-averaged electrocardiogram, and the presence of spontaneous or inducible arrhythmias or surgical characteristics, but alsoonechocardiographic or haemodynamic variables thought tobe associated with a poorer prognosis.Areviewofallthesevariablescanbefoundelsewhere [12].However,iftheholygrailofTOFriskstratificationlies inanyofthesevariables,itwouldsurelyhavebeenfound already. Apart fromthe combination of QRS prolongation andincreasedJTdispersion,whichhasbeenassociatedwith goodpositiveandnegativepredictive values[38],none of thesefactorshassufficientaccuracy,atleastindividually,to allowtheir usealoneforriskstratification inprimaryprevention.Moreover,mostofthesevariablesareprobablynot independentofeachother[12]andwouldbebetterusedin combination(seelater).

When trying to explore risk stratiﬁcation further, it seemedtomakesensetoﬁrstconsiderthepresenceofcom- plex asymptomatic ventricular arrhythmias as one of the majorvariableslinkedtoSCD;thesewerefoundin 13%of patientswhenlookingatroutineelectrocardiograms,andin aroundhalfofpatientswhenlookingat ambulatoryrecor- dings [15,20]. The dramatically lower rate of premature beatsonroutineelectrocardiogramsinuneventfulcompared with sudden-deathpatients, together with thelower SCD rateinpatientswithfrequentventricularprematurebeats successfullyversus unsuccessfully/nottreated withantiar- rhythmic drugs [15], supported this hypothesis. However,

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Table1 Factors proposed to be related to the risk of suddencardiac deathin repairedtetralogyof Fallot (modiﬁedfrom[12]).

Atrioventricularconductionblock

Rightbundlebranchblockwithleftaxisdeviation Atrialarrhythmias

Sustainedventriculartachycardia

Non-sustainedventriculararrhythmiason24-hour ambulatorymonitoring

Ventriculararrhythmiasonexercisetesting Rightventricularhypertension

Residualventricularseptaldefect Rightventriculardilation

Residualrightventricularoutﬂowtractobstruction Ventricularhypertrophy

Sizeofventriculotomyscar

Diminishedrightventricularmyocardialbloodﬂow reserve

Restrictiverightventricularphysiology Sizeofventriculotomyscar

Diminishedrightventricularmyocardialbloodﬂow reserve

Leftventricularend-diastolicpressure Leftventricularinvolvement

Abnormalsignal-averagedelectrocardiogram Complexormultipleoperations

Transventricularasopposedtotransatrialapproachto repair

QRSdurationonelectrocardiogram Olderageatoperation

Earlysurgicalera Coronaryarterydisease

conﬂictingdataexistonthatpoint[17],whilesymptomatic non-sustainedVThasbeenassociatedwithapooreroutcome [39].

Thelogicalnextstepwastoconsidertheroleofinducible ventriculararrhythmiasinselectingpatientspronetoSCD, despite the fact that inducible patients may have excel- lentoutcome[20]andthatSCDmayoccurinnon-inducible patientswithTOF[40].Khairyetal.reportedtheprognos- ticvalueofprogrammed ventricularstimulationafterTOF repair,asdeterminedinamulticentrecohortstudyinclud- ing252patientsinvestigatedfrom1985to2002(meanage 16±12years) [41]. Of note, two-thirds of these patients hadalreadypresentedwithsyncope,palpitations,sustained VTorevencardiacarrest.SustainedmonomorphicVTwas inducibleduringstandardprogrammedventricularstimula- tion in 30% of cases, and polymorphic VT in 5% of cases (underisoproterenolinaquarterofcases).Aftermultivari- ableanalysis,induciblepatientswereolder,andpresented withpalpitations, high-gradeventricularprematurebeats, previouspalliativesurgeryandalargecardiothoracicratio.

AquarterofinduciblepatientswereimplantedwithanICD (andonlyaveryfewnon-induciblepatients).Overall,17%

ofpatientsexperienced SCDor sustainedVTduring the6- yearfollow-up.InducibilityofanyVTwassigniﬁcantlylinked toarrhythmia-freesurvivalinamultivariableanalysis[41].

Analyses performed in patients without ICDs or in asymptomatic patients yielded similarresults; however, even if

negativeandpositivepredictivevaluesofinducibilityofany VTwereconsideredinteresting(98%and25%respectively), witha relativerisk of 10.4in asymptomatic patients,the 95%confidenceintervalswereverylarge,andthestatistical analysiscouldbeconsideredtobeofborderlinesignificance (P=0.0425).Moreover,asubsequentpublicationbythesame groupdidnotconfirmtheseresultsinpatientswithICD[42]

(seelater).

According to the 2014 guidelines for management of arrhythmiasinGUCH[1]andthe2015Europeanguidelines for SCD [24], programmed ventricular stimulation can be usefulinriskstratiﬁcationinadultswithrepairedTOFwho havemorethanoneriskfactorforSCD(includingleftven- tricularsystolicordiastolicdysfunction,non-sustained VT, QRS duration>180ms or extensive right ventricular scar- ring;classIIaindication).Accordingtothesameguidelines, anICDmaybeproposedforprimarypreventioninselected patientswithTOFincaseofmultipleriskfactors(i.e.those mentionedabove,inducible sustainedVT; classIIaindica- tion).Inouropinionandexperience,however,prophylactic ICD implantation is rare, and should be reserved mainly for leftventricular alteration and/or very broad QRS and impairedrightventricularfunction.

Medications for ventricular arrhythmias in TOF

Therehasbeennodedicatedstudyofantiarrhythmicdrugs inTOF or, moregenerally, in GUCH.Drugmanagement in GUCHisadaptedfromwhathasbeenlargelydemonstrated inacquiredheartdisease.Beta-blockersareprobablyuse- ful,while sotalol andamiodaroneshould beavoided— at leastasﬁrst-intentiontreatment— becauseoftherisk of proarrhythmia and relevant non-cardiological side effects duringlong-term therapy[1]. ClassIantiarrhythmic drugs may be harmful in case of diseased ventricle [1], as is presentinTOF.

ICDs in TOF

GUCH and children represent fewer than 1% of all ICD implantations.Seriesarefew,andareusuallylimitedtotens ofpatients,and,ofcourse,therehavebeennorandomized trials.ICDsinGUCHarehamperedbyanimportantrateof inappropriatetherapy,latetechnicalorpsychologicalissues orcomplicationswithresidualsigniﬁcantmortalityratesand evenrelevantSCDrates[43].

Patients with TOF form by far the largest subgroup of ICD recipients with congenital heart disease [44—46].

In secondary prevention, an older report on 25 operated patientswithTOFrevealed45%oversensing,20%appropri- ateantitachycardiapacing,5%appropriateICDshock,20%

inappropriateantitachycardiapacing,20%inappropriateICD shockand5%mortalityover2years[47].

In2008,Khairyetal.reportedtheirexperienceofICDs in 121 implanted patients with TOF, half of whom were implantedforprimaryprevention(althoughalargenumber hadsymptomscompatiblewithventriculararrhythmia)[42].

Thirtypercentofpatientsexperiencedappropriatetherapy over3.5years(81%VT,19%ventricularﬁbrillation).Theonly

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independent predictor was previous ventriculotomy inci- sion.One-quarterofpatientspresentedwithinappropriate therapy—eitherinprimaryorsecondaryprevention—and ICD-relatedcomplicationsoccurredin30%.Interestingly,the all-causemortalityratewashigh(2% yearly,ratherhigher than for unselected TOF), and half of the deaths were sudden, despite theICD [42]. Inthe subgroup of patients implantedforprimaryprevention,appropriateshockshap- penedin23%,andindependentpredictorswereelevatedleft ventricularend-diastolicpressureandthepresenceofnon- sustainedVT.Interestingly,inducibilitywasnotsigniﬁcantly linkedtotheoccurrenceofappropriateshock.Theauthors builtariskscoreforpredictingappropriateICDshockinpri- maryprevention,butotherauthorsfailedtovalidateitin asubsequentseriesof36patientswithTOFalsoimplanted forprimaryprevention[39].Inthiswork,onlysymptomatic non-sustained VT was associated with future appropriate therapyinaunivariateanalysis(which,infact,challenges thenotionthatthesewerereally‘‘primaryprevention’’TOF patients).Inthisreport,therewas19%appropriatetherapy, 42%inappropriatetherapyand5%mortalityoverthe5-year follow-up[39].However,itisnotcleariffastVTprompting ICDtherapy wasnon-sustainedwhendifferentICDsettings wereprogrammed.

InarecentFrenchretrospectiveregistryof62implanted patientswithTOF(18%inprimaryprevention),9%received appropriatetherapy inprimaryprevention comparedwith 50%insecondaryprevention,while34%experiencedmajor ICD-relatedcomplications, and 10% died over a follow-up of3.5years(Bouzeman,unpublisheddata).Thus,inappro- priatetherapies equal or exceed appropriatetherapies in patientswithTOFimplantedinprimaryprevention.

No relevant data are available today on the use of subcutaneous ICDs in GUCH and hence in TOF. What is knownfromverylimitedearlyexperienceisahighrateof inappropriate shocks (issues in tachycardia discrimination becauseof intraventricular conduction disturbances or T- waveabnormalities)andthedrawbackoftheimpossibility

ofanti-brady/tachy pacing,whichmayberelevantin TOF [48,49].Anincreasedriskofdeviceexteriorizationandthe use of right parasternalscreening have also been evoked in GUCH or children implanted with a subcutaneous ICD [48,50].

Finally,recentnewmodalitiesofsurgicalepicardialICD implantation in congenital heart disease have been proposed,butwithlimitedexperiencetodate[51].

VT ablation in TOF

Successful catheter ablation using conventional mapping techniques, with or without drugs, has been reported in short series of patients with TOF [52,53], although only limitedsuccessrateshavebeenreportedinotherseries[54]

becauseof complexanatomy, hypertrophied myocardium, dense ﬁbrosis, broad isthmuses,haemodynamic instability ornon-inducibility.

Zeppenfeldetal.weretheﬁrsttoinvestigate indepth the details of various VT reentry circuits in repaired TOF using three-dimensional mapping [55]. Four poten- tial slow-conducting VT isthmuses were present in most patients with TOF referred for sustained VT, and were also found in autopsied hearts from patients with TOF who died shortly after surgery: two isthmuses were bor- deredbytheanterior/lateralrightventricularoutﬂowtract (RVOT)scar/patchandthetricuspid(themainone)orpul- monary annulus (absent if transannularpatch); while the othertwoweredelineatedbytheventricularseptaldefect scar/patch andthe tricuspid(absentafter closureof per- imembranousseptaldefect)or pulmonaryannulus(Fig.1) [55]. Transecting anatomic isthmuses by linear radiofrequency lesions during sinus rhythm (Fig. 2) abolished all inducible VT, and led to a lack of VT recurrence in 90%

of cases at 30-month follow-up [55]. Of note, only half of the patientswere ﬁnallyimplanted withan ICD during follow-up.

Figure1. Anterior(left)andposterior(right)viewsofrepairedtetralogyofFallotrightventricularvoltagemap,showingscarsatthe sitesoftheventriculotomy/patchattheoutﬂowtract(left)andtheventricularseptaldefect(VSD)patch(right),togetherwiththefour potentialisthmusesdescribedbyZeppenfeldetal.[55](seetext).RVOT:rightventricularoutﬂowtract.

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Figure2. Activationduringsinusrhythmbefore(above)andafter(below)radiofrequency-inducedblockoftheisthmuslocatedbetween tricuspidandpulmonaryannulus,withtherespectiveelectrogramsfrombothsidesoftheisthmus.Activationiscodedbyrainbowcolours (fromredtopurple),showingprogressiveactivationfromlefttorightthroughtheisthmus(above)andinversionoftheactivationoncethe blockisachieved(below).

AlloperatedpatientswithTOFhaveatleastonepoten- tial anatomicalVTisthmus, butisthmuseswere narrower, longerandhadslowerconductioninpatientswithinducible VT, according to recent work from the same group [56].

Patientswithoutaslow-conductingisthmusdidnotpresent with VT during follow-up [56]. This factor may be proposed in the future for stratifying the risk of late SCD.

Thesamegroupalsodemonstratedthatright-sidedablation mayfailbecauseofseptalhypertrophy,overlyingpulmonary homograft oroverlying ventricularseptaldefectpatch. In these cases, representing 15% of the patients, VT had to beablatedfromtheleftventricle(septumor aortic root) [57].

Currentguidelinesrecommendaroleforablationonlyas analternativetoICDtherapyincarefullyselectedpatients withTOF(classIindication)[1].Otherwise,ablationisindi- catedasadjunctivetherapy toICDinadultswithTOFand recurrentmonomorphicVT,withorwithoutfaileddrugther- apy[1].

Towards better prevention of ventricular arrhythmia

SomesurgicalproceduresmaydecreaselateVToccurrence.

Forexample,bettercardioprotectionduringextracorporeal circulation, shorter transannularincisions or lack of tran- sectionoftheannulus,lessaggressivemuscleresectionand less generous RVOT patching [58,59] should be preferred when possible. Earlier correction is probably worthwhile becauseof lessprolongedcyanosis,lesspressureoverload of the right ventricle, and avoidance of aortopulmonary bypassand subsequent less left ventricular volume over- load [17]. Earlier correction of pulmonary valve stenosis orregurgitationbysurgicalorevenpercutaneousinterven- tion[60]isprobablyalsobeneﬁcial,evenifstillunproved.

Subpulmonaryresectionandventricularseptaldefectclo- sure can be accomplished transatrially, while pulmonary valve/arterysurgerycanbeachievedthroughapulmonary arteriotomy (‘‘RV infundibulum sparing repair’’) [61,62],

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whichwillprobablycarryareducedarrhythmiariskinthe longterm[63],despiteexperiencestillbeinglacking.

Finally,surgical ablation guidedby electrophysiological mappingperformed during or beforesurgerymay becon- sidered in TOF with inducible sustained monomorphic VT withanidentiﬁedcriticalisthmus(classIIbindication)[24].

Studiesarestillpending,however,fortheevaluationofthe clinical role of this dual strategy in decreasing late SCD occurrence.

Conclusions

Malignantventricular arrhythmiasandSCDprobablyoccur lessfrequentlythanpreviouslythoughtinrepairedTOF,and will possibly become even less common with the advent of new surgical techniques/management. There are currently no recommended indications for prophylactic ICDs (exceptperhaps in very selectedcases based onmultiple riskfactors),whileradiofrequencyablationmaybeproposed in secondary prevention, with or even without a back-up ICD in selected cases. Repeated cardiological investiga- tionsandmonitoringshouldbeproposedforeveryoperated patient.

Funding

None.

Disclosure of interest

Theauthorsdeclarethattheyhavenocompetinginterest.

References

[1]Khairy P, Van Hare GF, Balaji S, et al. PACES/HRS Expert ConsensusStatementontheRecognitionandManagementof ArrhythmiasinAdultCongenitalHeartDisease:developedin partnershipbetweenthePediatricandCongenitalElectrophys- iologySociety(PACES) and theHeartRhythmSociety(HRS).

EndorsedbythegoverningbodiesofPACES,HRS,theAmerican CollegeofCardiology (ACC),theAmerican HeartAssociation (AHA), the EuropeanHeart Rhythm Association(EHRA), the CanadianHeartRhythmSociety(CHRS),andtheInternational Society for Adult Congenital Heart Disease (ISACHD).Heart Rhythm2014;11:e102—65.

[2]LambertEC,MenonVA,WagnerHR,VladP.Suddenunexpected deathfromcardiovasculardiseaseinchildren.Acooperative internationalstudy.AmJCardiol1974;34:89—96.

[3]Marelli AJ, Ionescu-Ittu R, Mackie AS, Guo L, Dendukuri N, Kaouache M. Lifetime prevalence of congenital heart dis- easeinthegeneralpopulationfrom2000to2010.Circulation 2014;130:749—56.

[4]Villafane J, Feinstein JA, Jenkins KJ, et al. Hot topics in tetralogyofFallot.JAmCollCardiol2013;62:2155—66.

[5]CuypersJA,MentingME,KoningsEE,etal.Unnaturalhistory oftetralogyofFallot:prospectivefollow-upof40yearsafter surgicalcorrection.Circulation2014;130:1944—53.

[6]SilkaMJ,HardyBG,MenasheVD,MorrisCD.Apopulation-based prospectiveevaluationofriskofsuddencardiacdeathafter operationforcommoncongenitalheartdefects.JAmCollCar- diol1998;32:245—51.

[7]GarsonJrA,McNamaraDG.Suddendeathinapediatriccardi- ologypopulation,1958to1983:relationtopriorarrhythmias.

JAmCollCardiol1985;5:134B—7B.

[8]KoyakZ,HarrisL,deGrootJR,etal.Suddencardiacdeathin adultcongenitalheartdisease.Circulation2012;126:1944—54.

[9]HarrisonDA,ConnellyM,HarrisL,LukC,WebbGD,McLaughlin PR.Suddencardiacdeathintheadultwithcongenitalheart disease.CanJCardiol1996;12:1161—3.

[10]OechslinEN,HarrisonDA,ConnellyMS,WebbGD,SiuSC.Mode ofdeathinadultswithcongenitalheartdisease.AmJCardiol 2000;86:1111—6.

[11]Diller GP, Kempny A, Alonso-Gonzalez R, et al. Survival prospectsandcircumstancesofdeathincontemporaryadult congenitalheartdiseasepatientsunderfollow-upatalarge tertiarycentre.Circulation2015;132:2118—25.

[12]BrickerJT.SuddendeathandtetralogyofFallot.Risks,mark- ers,andcauses.Circulation1995;92:158—9.

[13]SilkaMJ,Bar-CohenY.Acontemporaryassessmentoftherisk forsuddencardiacdeathinpatientswithcongenitalheartdis- ease.PediatrCardiol2012;33:452—60.

[14]GarsonJr A,Nihill MR,McNamaraDG,Cooley DA.Statusof theadultand adolescentafterrepairoftetralogyofFallot.

Circulation1979;59:1232—40.

[15]GarsonJrA,RandallDC,GillettePC,etal.Preventionofsud- dendeath afterrepair of tetralogy ofFallot: treatment of ventriculararrhythmias.JAmCollCardiol1985;6:221—7.

[16]JamesFW,KaplanS,ChouTC. Unexpectedcardiacarrestin patientsaftersurgicalcorrectionoftetralogyofFallot.Circu- lation1975;52:691—5.

[17]Gatzoulis MA, Balaji S, Webber SA, et al. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet 2000;356:975—81.

[18]MurphyJG, GershBJ,MairDD,etal.Long-termoutcome in patientsundergoing surgicalrepair oftetralogyof Fallot.N EnglJMed1993;329:593—9.

[19]Nollert G, Fischlein T, Bouterwek S, Bohmer C, Klinner W, Reichart B. Long-term survival in patients with repair of tetralogy of Fallot: 36-year follow-up of 490 survivors of the ﬁrst year after surgical repair. J Am Coll Cardiol 1997;30:1374—83.

[20]ChandarJS,WolffGS,GarsonJrA,etal.Ventriculararrhyth- mias in postoperative tetralogy of Fallot. Am J Cardiol 1990;65:655—61.

[21]Garson Jr A. Ventricular arrhythmias after repair of congenital heart disease: who needs treatment? Cardiol Young 1991;1:177—81.

[22]QuattlebaumTG, VargheseJ, NeillCA,DonahooJS.Sudden deathamongpostoperativepatientswithtetralogyofFallot:a follow-upstudyof243patientsforanaverageoftwelveyears.

Circulation1976;54:289—93.

[23]WaienSA,LiuPP,RossBL,WilliamsWG,WebbGD,McLaughlin PR.Serialfollow-upofadultswithrepairedtetralogyofFallot.

JAmCollCardiol1992;20:295—300.

[24]PrioriSG,Blomstrom-LundqvistC,MazzantiA,etal.2015ESC Guidelinesfor themanagement ofpatientswithventricular arrhythmiasandthepreventionofsuddencardiacdeath:The TaskForcefor theManagementofPatients withVentricular ArrhythmiasandthePreventionofSuddenCardiacDeathofthe EuropeanSocietyofCardiology(ESC).Endorsedby:Association forEuropeanPaediatricandCongenitalCardiology(AEPC).Eur HeartJ2015;36:2793—867.

[25]KhairyP,AboulhosnJ,GurvitzMZ,etal. Arrhythmiaburden inadultswithsurgicallyrepairedtetralogyofFallot:amulti- institutionalstudy.Circulation2010;122:868—75.

[26]BertranouEG,BlackstoneEH,HazelrigJB,TurnerME,Kirklin JW.LifeexpectancywithoutsurgeryintetralogyofFallot.Am JCardiol1978;42:458—66.

(8)

[27] DeanﬁeldJE,McKennaWJ, PresbiteroP,EnglandD,Graham GR,Hallidie-SmithK.Ventriculararrhythmiainunrepairedand repairedtetralogyofFallot.Relationtoage,timingofrepair, andhaemodynamicstatus.BrHeartJ1984;52:77—81.

[28] SullivanID,PresbiteroP,GoochVM,ArutaE,DeanﬁeldJE.Is ventriculararrhythmiainrepairedtetralogyofFallotaneffect ofoperationoraconsequenceofthecourseofthedisease?A prospectivestudy.BrHeartJ1987;58:40—4.

[29] CairnsJA,DobellAR,GibbonsJE,TesslerI.Prognosisofright bundlebranchblockandleftanteriorhemiblockafterintracar- diacrepairoftetralogyofFallot.AmHeartJ1975;90:549—54.

[30] GillettePC, Yeoman MA,MullinsCE, McNamara DG.Sudden death after repair of tetralogy of Fallot. Electrocardio- graphic and electrophysiologic abnormalities. Circulation 1977;56:566—71.

[31] HokansonJS,MollerJH.Signiﬁcanceofearlytransientcom- pleteheartblockasa predictorofsuddendeath lateafter operative correction of tetralogy of Fallot. Am J Cardiol 2001;87:1271—7.

[32] Gatzoulis MA, Till JA, Somerville J, Redington AN. Mecha- noelectrical interaction in tetralogy of Fallot. QRS prolongation relates to right ventricular size and predicts malignantventriculararrhythmiasandsuddendeath.Circula- tion1995;92:231—7.

[33] Deanﬁeld JE, Ho SY, Anderson RH, McKenna WJ, Allwork SP, Hallidie-Smith KA. Late sudden death after repair of tetralogy of Fallot: a clinicopathologic study. Circulation 1983;67:626—31.

[34] Chinushi M, Aizawa Y, Kitazawa H, Kusano Y, Washizuka T, Shibata A. Successful radiofrequency catheter ablation for macroreentrant ventricular tachycardias in a patient with tetralogyofFallotaftercorrectivesurgery.PacingClinElec- trophysiol1995;18:1713—6.

[35] HortonRP,CanbyRC,KesslerDJ,etal.Ablationofventricular tachycardia associated with tetralogy of Fallot: demon- stration of bidirectional block. J Cardiovasc Electrophysiol 1997;8:432—5.

[36] MisakiT,TsubotaM,WatanabeG,etal.Surgicaltreatmentof ventriculartachycardiaaftersurgicalrepairoftetralogyofFal- lot.Relationbetweenintraoperativemappingandhistological ﬁndings.Circulation1994;90:264—71.

[37] StevensonWG,DelacretazE,FriedmanPL,EllisonKE.Identiﬁ- cationandablationofmacroreentrantventriculartachycardia withtheCARTOelectroanatomicalmappingsystem.PacingClin Electrophysiol1998;21:1448—56.

[38] BerulCI,HillSL,GeggelRL,etal.Electrocardiographicmarkers oflatesuddendeathriskinpostoperativetetralogyofFallot children.JCardiovascElectrophysiol1997;8:1349—56.

[39] KoyakZ,deGrootJR,BoumaBJ,etal.Symptomaticbutnot asymptomaticnon-sustained ventriculartachycardiais asso- ciatedwithappropriateimplantable cardiovertertherapy in tetralogyofFallot.IntJCardiol2013;167:1532—5.

[40] Alexander ME, Walsh EP, Saul JP, Epstein MR, Triedman JK.Valueofprogrammedventricularstimulation inpatients with congenital heart disease. J Cardiovasc Electrophysiol 1999;10:1033—44.

[41] KhairyP, Landzberg MJ, Gatzoulis MA, et al. Value ofpro- grammed ventricular stimulation after tetralogy of fallot repair:amulticenterstudy.Circulation2004;109:1994—2000.

[42] Khairy P, Harris L, Landzberg MJ, et al. Implantable cardioverter-deﬁbrillators in tetralogy of Fallot. Circulation 2008;117:363—70.

[43] BerulCI,VanHareGF,KerteszNJ,etal.Resultsofamulticenter retrospectiveimplantablecardioverter-deﬁbrillatorregistryof pediatricandcongenitalheartdiseasepatients.JAmCollCar- diol2008;51:1685—91.

[44] JordanCP,FreedenbergV,WangY,CurtisJP,GlevaMJ,Berul CI. Implant and clinical characteristics for pediatric and

congenitalheartpatientsinthenationalcardiovasculardata registry implantable cardioverter deﬁbrillator registry. Circ ArrhythmElectrophysiol2014;7:1092—100.

[45]KoyakZ,deGrootJR,VanGelderIC,etal.Implantablecar- dioverterdeﬁbrillatortherapyinadultswithcongenitalheart disease:whoisatriskofshocks?CircArrhythmElectrophysiol 2012;5:101—10.

[46]Vehmeijer JT, Brouwer TF, Limpens J, et al. Implantable cardioverter-deﬁbrillatorsinadultswithcongenitalheartdis- ease: a systematic review and meta-analysis. Eur Heart J 2016;37:1439—48.

[47]Witte KK, Pepper CB, Cowan JC, ThomsonJD, English KM, Blackburn ME. Implantable cardioverter-deﬁbrillator therapy in adult patients with tetralogy of Fallot. Europace 2008;10:926—30.

[48]Bordachar P, Marquie C, Pospiech T, et al. Subcutaneous implantable cardioverter deﬁbrillators in children, young adultsandpatientswithcongenitalheartdisease.IntJCardiol 2016;203:251—8.

[49]Jarman JW,LascellesK,WongT,MarkidesV,ClagueJR,Till J. Clinical experience ofentirely subcutaneous implantable cardioverter-deﬁbrillators in children and adults: cause for caution.EurHeartJ2012;33:1351—9.

[50]OkamuraH,McLeodCJ,DeSimoneCV,etal. Rightparaster- nal lead placement increases eligibility for subcutaneous implantablecardioverter deﬁbrillatortherapy inadultswith congenitalheartdisease.CircJ2016;80:1328—35.

[51]Pospiech T, Roubertie F, Jalal Z, Bordachar P, Thambo JB.

New technique for surgical epicardial implantation of a cardioverter-deﬁbrillatorinchildrenandadultswithcongeni- talheartdisease.AnnThoracSurg2016;102:615—9.

[52]FurushimaH,ChinushiM,SugiuraH,etal.Ventriculartachy- cardialateafterrepairofcongenitalheartdisease:efﬁcacy ofcombinationtherapywithradiofrequencycatheterablation andclassIIIantiarrhythmicagentsandlong-termoutcome.J Electrocardiol2006;39:219—24.

[53]Gonska BD, Cao K, RaabJ, EigsterG, Kreuzer H.Radiofre- quency catheter ablation of right ventricular tachycardia late after repair of congenital heart defects. Circulation 1996;94:1902—8.

[54]Morwood JG, Triedman JK, Berul CI, et al. Radiofrequency catheterablation ofventriculartachycardiainchildren and young adults with congenital heart disease. Heart Rhythm 2004;1:301—8.

[55]ZeppenfeldK,SchalijMJ,BartelingsMM,etal.Catheterabla- tionofventriculartachycardiaafterrepairofcongenitalheart disease: electroanatomic identiﬁcation of the critical right ventricularisthmus.Circulation2007;116:2241—52.

[56]KapelGF,SacherF,DekkersOM,etal.Arrhythmogenicanatom- icalisthmusesidentiﬁedbyelectroanatomicalmappingarethe substrateforventriculartachycardiainrepairedtetralogyof Fallot.EurHeartJ2016[Inpress].

[57]Kapel GF, Reichlin T, Wijnmaalen AP, et al. Left-sided ablation of ventricular tachycardia in adults with repaired tetralogyofFallot:acaseseries.CircArrhythmElectrophysiol 2014;7:889—97.

[58]Atallah-Yunes NH, Kavey RE, Bove EL, et al. Postoperative assessment of a modiﬁed surgical approach to repair of tetralogyofFallot.Long-termfollow-up.Circulation1996;94:

II22—6.

[59]DietlCA,Cazzaniga ME, DubnerSJ, Perez-BalinoNA, Torres AR,FavaloroRG.Life-threateningarrhythmiasandRVdysfunc- tion aftersurgical repairof tetralogyofFallot. Comparison betweentransventricularandtransatrialapproaches.Circula- tion1994;90:II7—12.

[60]Hascoet S, AcarP, Boudjemline Y. Transcatheter pulmonary valvulation: current indications and available devices. Arch CardiovascDis2014;107:625—34.

(9)

[61]GiannopoulosNM,ChatzisAK,KarrosP,etal.Earlyresultsafter transatrial/transpulmonaryrepairoftetralogyofFallot.EurJ CardiothoracSurg2002;22:582—6.

[62]MoralesDL,ZafarF,FraserJr CD.Tetralogy ofFallotrepair:

therightventricleinfundibulumsparing(RVIS)strategy.Semin ThoracCardiovascSurg2009:54—8.

[63]SfyridisPG,KirvassilisGV,PapagiannisJK,etal.Preservationof rightventricularstructureandfunctionfollowingtransatrial- transpulmonaryrepairoftetralogyofFallot.EurJCardiothorac Surg2013;43:336—42.