EHRA/AEPC CONSENSUS STATEMENT Europace(2013)15,1337–1382 doi:10.1093/europace/eut082 Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population: EHRA and AEPC-Arrhythmia Working Group joint consensus statement Josep Brugada1*, Nico Blom2, Georgia Sarquella-Brugada3, Carina Blomstrom-Lundqvist4, John Deanfield5, Jan Janousek6, Dominic Abrams7, Urs Bauersfeld8†, Ramon Brugada9, Fabrizio Drago10, Natasja de Groot11, Juha-Matti Happonen12, Joachim Hebe13, Siew Yen Ho14, Eloi Marijon15, Thomas Paul16, Jean-Pierre Pfammatter17, and Eric Rosenthal18 1PaediatricArrhythmiaUnit,CardiologyDepartment,HospitalSantJoandeDe´u-HospitalCl´ınic,UniversityofBarcelona,08036Barcelona,Spain;2DepartmentofPediatric Cardiology,LeidenUniversityMedicalCenterandAcademicalMedicalCenterAmsterdam,2300RCLeiden,TheNetherlands;3PaediatricArrhythmiaUnit,CardiologyDepartment, HospitalSantJoandeDe´u,UniversityofBarcelona,08950Barcelona,Spain;4DepartmentofCardiology,UppsalaUniversity,s-75236Uppsala,Sweden;5CardiothoracicUnit,Great OrmondStreetHospital,GreatOrmondStreet,WC1N3JHLondon,UK;6Children’sHeartCentre,UniversityHospitalMotol,15006Prague,CzechRepublic;7Cardiac Dow E2UBU91C2l8a9neDm2ac7iver7t0bedrp7,iorinaoEsBproivuttrhamyreGyso,msec3peiunoe7seltuln0a`aoro,n9gP9GfyGGePedGeDeerinoaodm¨ivetritraitagtsiitineccinrosysigHcn;ePC,1oCno4De,smCanpGertapidpteeriaiadrdrolr,moilataoIumncnagnsdHyeMty,nioRt;oCtus1ertp7hospPiiefdtlhedaa’CoIdrlrn,lecraov7ihnraeg5d’tsysI9iintco0iHUsglc8otaoniactgPsiruiytpoda´,t,riieRtoCiB,asol,ilhoPo,yFiagUlmardlylaindr,e`nBeiUodvcnrrieenoc’osr;iamvs,1Hie6G0tpDryo0tsior0seiotopn5pyfni5atHHoaar-FtfleoI,midBlussBIepeimBonrniGtksintcati,iiloo,na3anfn1o0n,Pd7,1d0e0I0Ht2d0Iam1iB3elay1letps;Gr5riei1nncir1Mrk,iDCoaiSAlnUewaCa,prni,dUtaoizSivrolSetpelemAlrraolgsia;egneint8yn;yMdLta1;oC0neoaAnddefndrindCzIrontihnrant1yaer8i,sltdEnchSHvishoWmieveolloieisa3nFgpCaayU6itk,aCNanurElihe,lPrtti,0aa,¨lMdsPt0Um,ree2eKKdd9un;iii0snca’s1itdMHn5rHePieceCra,olsrs,CCspiisp3nihati0krCaitliad1ld,al5irZ,ForeGdiulR¨nno´iroluosgaicyvytnUh’tasdeasn,;rc&ni8dv1ud03eaSlCa3rmHtrs2eTi,etnRZyTahteroeuhH¨strmereoSiacfaNsuorhsprcr,’egihtHSEteahwlCrloe,eyicesGrtptlzDnareeitonteoeradpplrrla,s,hgan;S-ryIdnAtEsm;si1uoegelr7ounmEgstHt,y-, by guest on Nnloaded from London,UK ovem Onlinepublish-ahead-of-print12July2013 ber 14, 2014 Inchildrenwithstructurallynormalhearts,themechanismsofarrhythmiasareusuallythesameasintheadultpatient.Somearrhythmiasare particularlyassociatedwithyoungageandveryrarelyseeninadultpatients.Arrhythmiasinstructuralheartdiseasemaybeassociatedeither withtheunderlyingabnormalityorresultfromsurgicalintervention.Chronichaemodynamicstressofcongenitalheartdisease(CHD)might create anelectrophysiological andanatomicsubstrate highlyfavourable forre-entrantarrhythmias. Asageneralrule,prescriptionofantiarrhythmicdrugsrequiresacleardiagnosiswithelectrocardiographicdocumentationofagivenar- rhythmia.Risk–benefitanalysisofdrugtherapyshouldbeconsideredwhenfacinganarrhythmiainachild.Prophylacticantiarrhythmicdrug therapyisgivenonlytoprotectthechildfromrecurrentsupraventriculartachycardiaduringthistimespanuntilthediseasewilleventually ceasespontaneously.Inthelastdecades,radiofrequencycatheterablationisprogressivelyusedascurativetherapyfortachyarrhythmiasin children andpatientswith or without CHD. Evenin young children, procedures can be performed with high success rates andlowcom- plication rates as shown by several retrospective and prospective paediatric multi-centre studies. Three-dimensional mapping and non- fluoroscopic navigation techniques and enhanced catheter technology have further improved safety and efficacy even in CHD patients withcomplex arrhythmias. Duringlastdecades,cardiacdevices(pacemakersandimplantablecardiacdefibrillator)havedevelopedrapidly.Thepacinggeneratorsize hasdiminishedandthepacingleadshavebecomeprogressivelythinner.Thesedevelopmentshavemadeapplicationofcardiacpacinginchil- dren easieralthoughno dedicatedpaediatric pacingsystems exist. ----------------------------------------------------------------------------------------------------------------------------------------------------------- Keywords Paediatrics † Arrhythmias † Antiarrhythmicdrugs † Radiofrequencyablation † Electrical devices Peerreviewers:FarreJeronimo,KriebelThomas,MavrakisIraklis,NapolitanoCarlo,SanataniShubhayan,ViskinSami *Correspondingauthor:E-mail:[email protected] †Dr.UrsBauersfeldpassedawayduringpreparationofthemanuscript. PublishedonbehalfoftheEuropeanSocietyofCardiology.Allrightsreserved.&TheAuthor2013.Forpermissionspleaseemail:[email protected]. 1338 J.Brugadaetal. Anatomy of the conduction system arrangement of the atrial appendages, and in some AV septal defects. When occurring in a structurally normal heart, the of the heart pattern of the cardiac conduction system can take one of three anatomic forms: atrial-axis discontinuity, nodal-ventricular discon- Conduction system in normally tinuity, or intraventricular discontinuity (Figure 1C). The last form structured hearts is extremely rare. The association of congenital complete heart Thesinusnodeisusuallylocatedimmediatelysubepicardiallyinthe blockwithmaternalconnectivetissuediseaseiswelldocumented. terminal groove (sulcus terminalis) on the lateral margin of the Mostcommonly,theAVnodewaslackingandtherewasassociated junction between the superior caval vein and the right atrium fibrosis ofthesinus nodein severalcases.2,3 (Figure1A).Itisspindle-shaped,withataperingtailinthemajority of hearts. In about one-tenth of individuals, it is shaped like a Accessoryatrioventricularconnections horseshoe and straddles the crest of the right atrial appendage. AccessoryAVconnections havebeenlocatedboth instructurally At theborders,thenodalcellsare adjacenttoworking myocytes normal hearts and in hearts with congenital malformations. in places andshorttongues of transitional cells inter-digitatewith These anomalous muscle strands breach the separation of atrial ordinary musculature in others. The tail of the sinus node pene- fromventricularmyocardiumatanypointaroundtheAVjunctions trates postero-inferiorly into the musculature of the terminal (Figure2).Themajorityofleft-sidedparietalpathwaysruncloseto crest to varying distances. Apart from the occasionally long tail, theepicardialaspectofthefibroushingeofthemitralvalve.Incon- and the tongues of transitional cells, no histologically specialized trast, accessory pathways along the right parietal junction either pathways are seen intheinternodal musculature. cross an area of deficiency in the fibrofatty tissues or traverse Inthenormalheart,theatrialmusculatureconstitutesaseparate more peripherally though the fatty tissues of the AV groove. myocardial mass relative to the ventricular musculature apart Some right-sided pathways may arise from a node-like structure from one muscular connection—the bundle of His. The areas of (nodeofKent)atitsatrialorigin.‘Mahaimphysiology’canbepro- contiguityattheatrioventricular(AV)junctionsaroundtheorifices duced by such histologically specialized right-sided pathways that of theAV valvesprovidethe separation. connectwiththeAVconductionsystemviaabundlethatdescends D ThetriangleofKochisthegrosslandmarktothepositionofthe in the right parietal wall. The pathways are hence described as ow AanVglenoidsed(eFliimguirteed1Bp)o.sVteierwioerdlyfrboymthtehecoringthintuaattriioanl aospfetchte, tahtetactrhi-- ‘laizteridofcaosncidcuuclatrio’ncotinssnueec,tiwoinths.itSsuvcahriaousslinagppoefllahtiisotnoslo,sghicoaulllydsbpeedciias-- nloaded from msbionerundstesroefpotftuhmtehe(Eaultssrotiaacnkhgnlioaenwisnvatalhvseet,hhtehineEguetsleitnanecdho(ianannnorufidluTgseo))d.oaTrfohte,hieanntosteerptihtoaerl tcsiconrngipuntiesivchetesldyt,htfehroeAmyVartnehoebdeectltoaesrrsiblcaubn‘eMdlllaeehdatoinmotdhfioebvvereen’nt.rtirTcicuhulealarrlaansttedeprftausdmciri.ceuDcltoely-- by guest on N leaflet of the tricuspid valve. The mouth of the coronary sinus is ventricular accessory connections, respectively, highlighting their ovem uloscuaatlelydtaatktehne aapsetxhewhbearseethoef ttehnedotnriaonfgTleo,dwaritohintsheertsAiVntonotdhee caroennreecgtuiolanrlywitfhoutnhde cinonndourcmtioalnhtiesasrutess, (eFsipguerceial2ly). iTnhenseeonfiabtreess. ber 14, 2014 central fibrous body. On one side, the compact AV node lies So-calledseptalaccessoryconnectionsarebetweenatrialandven- against the central fibrous body whereas on the other side it has tricular myocardium at the offset attachments of the leaflets of aninterfaceoftransitionalcellswithatrialmyocardium.Theexten- mitralandtricuspidvalves.Afurthersubsetofaccessorypathways sion of the node into the central fibrous body, the penetrating has been described as being located close to the penetrating bundle of His, is then completely encased within fibrous tissues. bundle (‘intermediate septal’ or para-Hisian pathways). Another TheAVconductionbundle,stillwithinafibroussheath,continues type, atrio-Hisian connections (originally designated as ‘atriofasci- toashortnon-branchingportionbeforeitbecomesthebranching cular’) traverse through the central fibrous body, connecting bundle. Although sandwiched between the membranous septum atrial myocardium with the node-bundle axis distal to the nodal and themuscular ventricular septum, the branching bundleis dis- region. posed towards the left in many hearts (Figure 1), resulting in the Further variants of accessory connections are those related to cord-like right bundle branch passing through the septum before coronary venous structures instead of being related to the inser- emerging in the subendocardium on the right ventricular (RV) tions of the AV valves or the conduction system. For example, side. The left bundle branch descends in the subendocardium of they are associated with aneurysmal dilation of the coronary the ventricular septum. Having descended the septum as bundles sinus or aneurysmal formation of the anterior cardiac vein, of conduction tissue surrounded by fibrous tissue sheaths, the where broad bands of muscular connections surround the bundle branches then continue into the so-called Purkinje mouth oftheaneurysm. network thatallowinterfacewithventricular myocardium. Conduction system in congenitally malformed hearts Congenital heart block Congenital complete heart block can occur in congenitally mal- Sinus node formed hearts or in otherwise normal hearts.1 Complete block Themajorityofmalformedheartshavetheatrialchambersintheir associated with a cardiac defect is most frequently seen in the usual position (situs solitus) with a regular location of the sinus anomaly of congenitally corrected transposition, isomeric node. Abnormal positions of the sinus node have been found in Pharmacologicalandnon-pharmacologicaltherapyforarrhythmiasinthepediatricpopulation 1339 D ow nloaded from by guest on N ovem ber 14, 2014 Figure1 (A)Diagramofthecardiacconductionsystem.(B)TherightatriumisopenedtoshowthetriangleofKochdelimitedbythehinge lineofthetricuspidvalveanteriorly(brokenline),thetendonofTodaro(dottedline)posteriorly,andthecoronarysinus(CS)inferiorly.The sinusnodeliesintheterminalcrestatitsantero-lateraljunctionwiththesuperiorcavalvein(SCV).(C)Thesefourpanelsdepictthenormal components of the atrioventricularconduction system and the variants of interruption thatare the anatomic substrates of congenital heart block. AV,atrioventricular;BB,branchingbundle; LBB,leftbundlebranch;ER,Eustachianridge;EV,Eustachianvalve;ICV,inferiorcavalvein; LA,leftatrium;LV,leftventricle;RA,rightatrium;RV,rightventricle;Trans.,transitional. hearts with juxtaposition of the atrial appendages and in hearts thatdeviatestheterminalcrest.4Rightjuxtapositionismuchrarer withanatrialarrangementotherthantheusual.Leftjuxtaposition but doesnotaffect thelocationofthesinus node. in which the right atrial appendage lies alongside the left atrial Abnormal arrangement of the atrial chambers themselves also appendagetotheleftsideofthearterialpediclehasananteriorly affectsthelocationofthesinusnode.Whentheatriaarearranged displacedsinusnodeowingtothedistortionoftheatrialanatomy inmirrorimageofnormal(situsinversus),therightatriumandthe 1340 J.Brugadaetal. Figure2 DiagramoftheAVjunctionsdepictingvarioustypesofaccessoryconnections.AV,atrioventricular;LBB,leftbundlebranch;RBB, rightbundlebranch. Dow nloaded from si(c‘iansuapsrlrenanoniadg’ee),matrheenertoenoatfrheethbleeilafttmesirodaerlptohefromtlhoiegniapclaacltliryeensrtti.sgIhnanthdea,atcrroitasrlrweasiptphpoeinsnoddimnaggeelrys-, otrgicyTuholaefrdFsaiesltlportitabluisdtiedofienrecotcftbltyehcceaouAmsVepaacrodanebdfleeuccwttiiionthnthahexeiavsreitnnsthrwiecitauhrlatsirsowselaiptthteudtmevtreisanla-- by guest on N bilateral sinus nodes.2 Terminal crests, however, are lacking in cardinal feature of tetralogy of Fallot. Most ventricular septal ovem hateraiarltsapwpiethndaisgoemse(r‘picolyasrpralenngieam’).eAntlthoofugthheinmtohirsphgorolougpicablillyateleraftl doenfsecotfs,twhehemtheemrbinrainsooluastiosnepotrumot.hTerhwesisee,aarreetleorcmateeddipnertihmeeemnbvriar-- ber 14, 2014 superior caval veins can be present, usually the sinus node is not nous defects since they have a fibrous component or remnant of found in its anticipated position. In some hearts a remnant of themembranousseptumattheirposteroinferiorborderthatcon- specialized tissue is found in the inferior atrial wall near the AV tains the AV conduction bundle (Figure 3A). The non-branching junction whilein otherheartssuch tissuecannot beidentified. bundle is longer than in normal hearts and the normal leftward shift of the bundle still brings it into the LV outflow tract making Atrioventricularconduction system this part of the defect the most critical area for avoiding injury Mostcongenitalheartlesionsaresimpleholesinthecardiacseptum to theconductionsystem.5 orabnormalventricularoriginsofthegreatarteries.Thesemalfor- Defects with completely muscular borders, termed muscular mationshavelittleeffectontheproperalignmentofatrialandven- defects, have varying relationships with the conduction axis de- tricular septal structures and, generally, a regular posteriorly pendingontheirlocationwithintheseptum(Figure3A).Thosesitu- situatedAVconductionsystemistobeexpected.Thekeyprerequis- ated between the ventricular outlets are remote from the itetoaregularsystemisconcordantconnectionattheAVlevel(i.e. conduction axis, whereas defects in the apical trabecular part are the morphologically right atrium connectsto the morphologically in the environs of the ramifications of the bundle branches. RV and the morphologically left atrium connects to the morpho- Defects opening to the inlet part of the RV need to be distin- logicallyleftventricle(LV).Whenassociatedwithmirror-imagedar- guished from those perimembranous defects that have an exten- rangementoftheatrialappendages(situsinversus),theseheartshave sive posteroinferior incursion. The conduction axis runs in the mirror-imageddistributionoftheAVconductionaxis. anterosuperior quadrant of the margin of a muscular inlet defect, instarkcontrasttotheposteroinferiorlocationfoundwithaperi- Heart defects with normallyaligned septalstructure membranous inlet defect. When both a perimembranous defect Themorecommonmalformationsinthisgroupareheartswithan andamuscularinletdefectexistinthesameheart,theconduction isolated ventricular septal defect, with AV septal defect, and with axistraversesthe muscularbridge separatingthedefects. tetralogyof Fallot. Except for those heartswith AV septal defect, Defects situated immediately beneath both arterial valves the triangle of Koch remainsa good landmark for the locationof (doublycommittedandjuxta-arterialdefects)haveavaryingrelation- the AVnode.5 ship to the conduction system depending on its posteroinferior Pharmacologicalandnon-pharmacologicaltherapyforarrhythmiasinthepediatricpopulation 1341 D ow nloaded from by guest on N ovem tFhiegucoruers3eo(Af)thDeiaAgrVamcosnhdouwctiniognthtiesssueepst.aTlahsepeficbtrooufsthteissruigeht(garterieunm)aatndthveenptorsicteler.oT-ihnefetryiopresmoafrVgiSnDo(fytehlelowpesrhimapeebsr)anaoreusshVoSwDnainburteslatthioenAtVo ber 14, 2014 conduction bundle. (B) This diagram shows usual atrial arrangement with discordant AV connections with the morphologically LV opened. TheAVconductionbundlepassesantero-superiortotheLVoutletanddescendsalongtheanteriormarginofVSD.(C)TheAVnodeisab- normallylocated.(D)TheAVnodeislocatedinthemuscularflooroftherightatriuminheartswith‘tricuspidatresia’wherethereisabsenceof therightAVconnection.(E)WhenviewedfromtheaspectoftherudimentaryRV,theAVconductionbundlepassesalongthemarginofthe ventricularseptaldefect (VSD)thatisnearesttotheacutecardiacmargin.AV,atrioventricular;VSD,ventricularseptaldefect;RV,rightven- tricle;LV,leftventricle;SCV,superiorcavalvein;ICV,inferiorcavalvein;MV,mitralvalve. margin.Iftheposteroinferiorrimismuscular,theconductionaxisis arrangement, hearts with left-hand topology in the setting of iso- protectedbythemusclebutitisvulnerableintheareaoffibrouscon- mericatrialappendagesandsomevarietiesofheartswithuniven- tinuitybetweenarterialandAVvalvesintheperimembranoustype. tricular AV connection. Hearts with AV septal defect usually have a wide separation Heartswithstraddlingofthetricuspidvalvehavetheposteroin- between atrial and ventricular septal structures. The landmarks ferior part of the ventricular septum deviated to the right of the of the triangle of Koch no longer delineate the position of the cardiaccrux.TheconnectingAVnodeissituatedposteroinferiorly connecting AV node.5 Instead, the connecting AV ventricular but is displaced to a position of the atrial wall that is nearest the nodeisdisplacedposteroinferiorlyattheatrialsideofthejunction point at which the ventricular septum rises to meet the tricuspid between atrial and ventricular septa (Figure 3B). The penetrating orifice at the AV junction.5 The penetrating bundle passes bundle pierces through the conjoined valvar attachment at the throughthehingeofthetricuspidvalveinthisregionandcontinues cardiac crux. The non-branching bundle is long and runs on the to a long non-branching segment before dividing into the bundle crestoftheventricular septum. branches. HeartswithusualatrialarrangementanddiscordantAVconnec- Heartdefectswithmalalignementoftheseptalstructures tions(suchascongenitallycorrectedtransposition)haveaventricular These include hearts with straddling tricuspid valve, hearts with arrangement similar to those with isomeric arrangement of the discordant AV connection in the setting of lateralized atrial atrialappendagesinassociationwithleft-handventriculartopology. 1342 J.Brugadaetal. Thedistributionoftheconductionsystemisalsosimilar.5Inthese heartdisease(CHD)thatincombinationcreateanelectrophysio- hearts,theanterosuperiorandright-sidedventricularchamberisa logical and anatomic substrate highly favourable for reentrant morphologicallyLV(Figure3B).TheconnectingAVnodeislocated arrhythmias. intheatrialwallrelatedtotheanterolateralquadrantofthemitral Epidemiology and pathophysiology of valve (Figure 3C). The penetrating bundle runs in the region of fibrous continuity between the mitral valve and the valve of the arrhythmias in structurally normal heart posterior great artery. A long, non-branching bundle then Supraventriculararrhythmias courses anterior to the outflow tract of the posterior great Population-based study reported a prevalence of supraventricular arterybeforedescendingalongtheanterosuperiormarginofaven- arrhythmia(SVA)of2.25/1000personswithanannualincidencein tricularseptaldefecttobranchintothebundlebrancheswiththe children ,19yearsofageof13/100000.Thismayunderestimate left bundle branch descending down the right aspect of the ven- the true frequency due to the sporadic nature of symptoms in tricular septum, whereas the right bundle branch penetrates the manypatients,andspontaneousresolutionofsymptomsininfants septum to emerge on the left side (Figure 3B). Occasionally, a never diagnosed as supraventricular tachycardia (SVT). In infancy, secondAVnodeispresent.Thisistheregularnodewithinthetri- SVT results predominantly from accessory pathways and a small angle of Koch. A sling of conduction tissues may sometimes be numberofectopicatrialtachycardia.Inteenagelife,thereisasignifi- formedwhentheregularnodealsoconnectswiththeventricular cant increase in the prevalence of atrioventricular nodal reentry bundle branches. Rarely, only the regularly situated node makes tachycardia(AVNRT)particularlyinfemales. the connectionwiththe ventricles. Hearts with univentricular AV connection include those with Atrioventricular reentrytachycardia double-inlet connection, together with those having absence of Atrioventricularreentrytachycardia(AVRT)isfacilitatedbyamus- either the right or left AV connections. Those that are significant cular accessory pathway(s) spanning the fibrous AV junction and in having an abnormal disposition of the conduction axis are providing continuity between atrial and ventricular myocardium, hearts with the atria connected to a dominant LV and those atasiteelectrophysiologicallydistinctfromtheAVnodeandprox- with a solitary indeterminate ventricle.5 Essentially, hearts with imalHis–Purkinjesystem(AVN/His).Suchconnectionshavebeen D dsineogpmtAuinVman.nTotdhueLsVa,thetuhaserutasalclwyuittehhamdvoearugbainlnea-linpalnoettseictrioioonnrnlyoecfttliohocenartheiagdvhetvAaeVcnotonrrincifieucclaetr-. d2w0easywcsretiboeekrdsegginereststhastefioodrnme.vIstetlhohapesinsbugebehsnturmaintaefenfrorhreedaacrttch,eanstsoofrarmilyuaprlelaytohrfwetgahryeesss.6esiSnppgaotbnhy-- ownloaded from Ft(htrreoicmuveshpneitdrrieca,utrtleahrseiasb)eupanntuddmleth.peWedrhofoemrnaintteahsnetthrvieegnhvttarilAcvlVaericsaototnafncleehcfmttimeonnotritpsohaobelsnoetgenyrt, tdraeondceeuovmeulesonptreeldagt,reearsltsihnioolnuifgehorefinmpwaainhthsawtuapnycroerpftuoanrincti.toionnofinpatiinefnatnscysymisptowmelsl by guest on N the AV node is found in the muscular floor of the right atrium The exact epidemiology of accessory pathways (APs) can best ovem (bFoigrudreer3oDf).tIhnebosethptsaelttdinegfesc,tthtehadtesicsenndeianrgesbtunthdeleapcaustseesctaordtihaec boeloagpypsrteucdiyataenddbryadasiosefrsesqmueenntcyofapbalattieionnts(EuPnSd/eRrFgAoi)n.7g,8eBleecttwroepehny5si5- ber 14, 2014 margin, irrespective of the location of rudimentary RV and 60% of AP(s) will be manifest on the surface electrocardio- (Figure 3E). Hence, the ventricular course of the conduction axis gram (ECG) as varying degrees of ventricular pre-excitation,8 the in double-inlet LVandin‘tricuspid atresia’ is comparable. Wolff–Parkinson–White (WPW) ECG pattern or WPW syn- In summary,the cardiac conductionsystemboth in structurally drome in symptomatic individuals. The degree of pre-excitation normal hearts and in malformed hearts shows variability that can isdependentonmultiplefactors:theanterogradeconductionvel- account for some of the rhythm abnormalities. Cardiac surgeons, ocity of the pathway relative to the AVN/His; the position of the electrophysiologists, and other interventionists should be knowl- AP atrial insertion relative to the sinus and AV nodes; intra-atrial edgeable of the locations of the specialized conduction system conduction time and refractoriness and the quality of input and whether in repairing the cardiac malformations or in modifying outputoftheAPultimatelydependentonthespatial-geometricar- the sinusorAV nodes. rangementbetweenthe atriaandventricles. In10583childrenundergoingEPS/RFAreportedbythePaediat- ricElectrophysiologySociety (www.paces.org) between1991and Pathophysiology and epidemiology 2003,7AVRTwasthemechanismin67%,ofwhich (cid:2)50%ofpath- of arrhythmias in children ways were located on the left free wall, 30% on the septum and 20% on the right free wall. Pre-excited tachycardia may occur In children with structurally normal hearts the mechanisms of during antidromic AVRT but also during AVNRT, atrial flutter arrhythmias are usually the same as that in the adult patient, al- (AFL)oratrialfibrillation(AF)wheretheAPisabystandernotes- though certain arrhythmias are particularly associated with young sentialto the arrhythmiamechanism. age and very rarely seen in adult patients. However, accessory pathways, atrial foci, and dual AV nodal physiology represent the Atrialfibrillation in association with accessory pathways substrate of the vast majority of paediatric arrhythmias in normal Atrialfibrillationoccursmorefrequentlyinpatientswithmanifest hearts. Arrhythmias in structural heart disease may be associated pre-excitationthanthosewithconcealedAPs.Themostcommon either with the underlying abnormality, or result from surgical mechanism of AF initiation is degeneration from AVRT. The im- intervention and the chronic haemodynamic stress of congenital portance of AF in association with pre-excitation is the potential Pharmacologicalandnon-pharmacologicaltherapyforarrhythmiasinthepediatricpopulation 1343 forrapidanterogradeconductionviaanAPwithashortrefractory Atrioventricular nodal reentry tachycardia associated with 2:1 period initiating ventricular fibrillation (VF). However, sudden transient conduction block is present in 17% of children during cardiac death (SCD) secondary to pre-excited AF remains rare. EPS, a muchgreaterproportionthanseen inadults(9%). Detailed analysis of 184 asymptomatic children with WPW ECG pattern after baseline EPS and a median follow-up of 57 months, Ectopic atrial tachycardia found life-threatening arrhythmias (documented pre-excited AF Ectopic atrial tachycardia is a rare cause of SVT in children with shortest pre-excited R–R interval ,250ms) in 19 (10.3%), accounting for 3.7–5.7% undergoing EPS,7,8 although may be of whom the majority reported atypical or minimal symptoms. morecommon ininfants.Atrial tachycardia inchildrenistypically AnAPeffectiverefractoryperiod(ERP)of ≤240msandmultiple automatic in nature, displaying enhanced phase 4 automaticity pathways identified thoseathighest risk.9 and ‘warm up/cool down’ behaviour often with wide fluctuations in atrial rate secondary to autonomic tone.10 The mechanism is Accessory pathwayswith uniqueelectrophysiological properties typically one of centrifugal atrial activation away from a single Atriofascicular(Mahaim)accessorypathways.Atriofascicularpathways source, although multifocal atrial tachycardia (MAT)/chaotic atrial (AFP)areconsideredaduplicateofthenormalconductionsystem, rhythm is well recognized and may have the ECG appearance of with an atrial insertion point on the lateral tricuspid annulus and different P-wave morphologies or may be indistinguishable from distal insertion point at the terminal end of the right-sided con- AF. The site of origin is varied including right and left atrial ductingsystem(fascicle).Thesepathwaysexhibitslow,decremen- appendages, pulmonary vein ostia and crista terminalis. Due to tal anterograde conduction, such that pre-excitation may be their incessant nature, LV dysfunction, potentially severe in minimal or absent during sinus rhythm but becomes evident nature, is frequently seen. Spontaneous resolution is common in duringatrialpacingorAVRT.TheQRSmorphologyduringtachy- those presenting ,3 years of age (78%), but much less in older cardiaisbroadduetoanterogradeconductionexclusivelyviathe childrenandadolescents(16%).10,11 AFPandretrogradeconductionviathetrueAVN/Hisorrarelyvia asecond pathway. Junctional ectopictachycardia Permanent junctional reciprocating tachycardia. Permanent junctional Congenitaljunctionalectopictachycardia(JET)isbelievedtoresult Dow rAreeVctrRipoTrgor(ac2da)tei,nfagdcetilcaitcraehtmyecdeanrbtdayialac(noPJnRAdTPu)cttriheoapntr.etTsyehpneictsaAllaPysidmseammlloopnsrtsotcproaotmretsmiooonnnollyyf fmcreoasmysaancatcbenploeatrrtametreanloaraundtdoecmfeaalsettirecairttyejuianntc,rteoiosrpnocallnosrseaetteotsoa,autrtheoemmHaotiisrcebtoucnonedm.lemA,noaninnldy- nloaded from lotoescrtoaiutgemrda,daienlthctohoeungdphuocmsttiaoeyrnobsiesepfvtoaiaulnrtdehgeaiotAnoVtchNloe/rsHesisittoepsr.tohIndeutccaoicnrhgoyncaaarrnydaiarsrinoaunws- sseheonwsinatrhaotsheerpnreasrerontwingco,m6plemxoQntRhSs owfitahgev.arTiahbeleERCRGintytepricvaalllsy, by guest on N QRScomplexonthesurfaceECG,withtheretrogradeP-waveim- and either ventriculoatrial (VA) dissociation or less commonly ovem mwofietPhdJiiRnatTethlypeaprAtriPeccu(ellaodrinnlyggiRnthPientfaafconhltlysocwaanrinddgiay)Qo.uDRnSugedcuthoeildttrhoeens,ilnoscewevsescraoenntLdVnuactdtuiyorsne- 1bble:oe1cnk,VsAuagngdceosatneddpu.ocLtteieonfntt.iavleRnartorrelieclyu,flaoJrErTdmysmaftuaenyrcntabiolenanawtsisa-oSscSriAaet/peaondrtti-weSdSitBhinhA1aV5s ber 14, 2014 function may be present at diagnosis, which typically resolves of94 (16%)childrenwith JET,with fatalityseen in4patients.12 with suppression of pathway activity. Spontaneous AP regression hasbeendocumentedinover20% ofchildrenwith PJRT. Atrial flutter Atrial flutter in children is rare and most frequently seen in the neonatal period. The ECG appearance of tricuspide isthmus- Atrioventricular nodal reentrytachycardia dependantflutterissimilartothatseenintheadult,withabaseline The substrate for AVNRT is two electrophysiologically distinct pathways (dual AV nodal physiology) within the triangle of Koch; of continuous regular atrial activity and morphology suggesting either clockwise or counter clockwise rotation around the a superiorly and posteriorly located ‘fast’ pathway which demon- tricuspid annulus. strates rapid impulse conduction but a long ERP and a ‘slow’ pathway located more inferiorly and anteriorly with slower impulseconductionbut shorterERP. Atrial fibrillation ThemostcommonmechanismofAVNRTinchildrenisantero- Atrialfibrillationisextremelyrareinchildrenandadolescentswith gradeslowpathwayactivationfollowedbyretrogradeactivationof structurally normal hearts and its presence should immediately theatriaviathefastpathway(slow–fast)andanterogradeventricular warn about the possibility of a genetic origin. It is most typically activationoccurringshortlyafterviatheHis–Purkinjesystem.This associatedwithorganizedSVTsuchasAVRTorAVNRTdegener- producesanarrowcomplexQRStachycardiawithP-wavesvisible atingintoAF.Similartootherincessantarrhythmias,persistentAF as a discrete deflection in the terminal portion of the QRS inadolescentsmayleadtoLVdysfunction.Rapidlyfiringatrialfoci complexinleadV1,andashortinterval(,70ms)betweentheearli- (often multiple) located during EPS at the pulmonary veins, crista estventricularandatrialsignalsatEPS.Inthelesscommonatypical terminalis and left atrium have been shown to initiate paroxysms AVNRT(fast–slow)thecircuitisreversedandearliestatrialactiva- of irregular atrial tachycardia indistinguishable from AF on the tionseeninthelowrightatrium,producingalongRPtachycardiaon surface ECG. Irregular atrial tachycardia appears less likely to de- thesurfaceECGwithaninvertedP-waveshortlybeforethefollow- generate into AF in adolescents compared to adults probably ingQRScomplex. duetoage-relateddifferencesinatrialfibrosisandrefractoriness.13 1344 J.Brugadaetal. Ventriculararrhythmias functional conduction block or wave front collision within Ventricular tachycardia (VT) is rare in children representing only ventricularmyocardium. 1.8% of children undergoing EPS.8 Ventricular tachycardia in chil- dren is typically associated with a structurally normal heart, al- Bidirectional ventriculartachycardia though those presenting with VT require careful evaluation for Bidirectional ventricular tachycardia is the hallmark arrhythmia of early manifestationsofunderlying cardiac disease. catecholaminergicpolymorphicventriculartachycardia(CPVT),al- Ventriculartachycardiaiswelldescribedininfancy,andalthough thoughmayalsobeseeninAndersen–Tawilsyndromeanddigitalis symptoms are less common compared to older children (22 vs. toxicity. Bidirectional ventricular tachycardia results from delayed 34%), andmaybe incessant leading toventricular dysfunction. In- after depolarization induced triggered activity occurring alterna- fantile VT demonstrates a left bundle morphology suggesting a tivelyinthePurkinjefibresoftherightandleftbundlebranches.16 RV origin in 86% of cases, and shows a high rate of spontaneous The surface ECG displays a characteristic pattern beat-to-beat resolution(89%). 1808 alteration in QRS polarity consistent with the alternate sitesofPurkinje fibreactivation. Ventricularoutflowtractventricular tachycardia OutflowtractVTmostfrequentlyoriginatesfromtheRVoutflow Foetal arrhythmias tract,andlesscommonlytheleft(includingthesinusesofValsalva), Many different arrhythmia mechanisms may be identified in the and represents a clinical spectrum from regular ectopy to foetus including AVRT, atrial and JET and TdP secondary to QT non-sustainedandsustainedVT.Themechanismisusuallyadrener- prolongation. Poor rate control precipitates cardiac failure and gically mediated triggered activity caused by cyclic adenosine hydropsfetalis, frequentlyassociated with apoor prognosis. monophosphate (cAMP) induced after depolarizations that are sensitive to fluxes in intracellular calcium. Due to antagonism of Epidemiology and pathophysiology cAMP by adenosine, outflow tract VT is typically adenosine- of arrhythmias in congenital heart disease sensitive. Symptoms range from absent to severe including Junctional ectopictachycardia syncopeandventriculardysfunction.14The12-leadECGinVTtyp- Junctional ectopic tachycardia is a malignant tachyarrhythmia that D ically shows a left (or right) bundle branch pattern and inferiorly ow dopocaiarrrliitleggtyiicenntr,aencndlodaoansfxedaainstc;oatiitntvothtahrmeteaioicQcpnaaerRlrdlcSyioimanmcdesimoisstmrtbipenrahncapottnplowoifnurgigotsyhmsmedapeatftymhouecmpoarnlHeasmdtnirsidecattcebehtluseahncnedtiasrleemoxpc.ahhecAayntsstssiroiiibttfleeuoegegooain-ffl mhImctaeooriasdsnrtittaohsdpc,seouohflmceimsicatmototsenor,dyanarllowtyyhfibotochyuacprgcnadhuusirasamsctceifmaorafoniteleugu,rerstenyv,spitauhearriliggoavhibfcaelarcerliaasrbncdiotnoiodcarlrypluselodteceigtnemiioagx,pnisahetgirsogeahf(tsleueecrrseoesln,eatvglboheeoannlsvngieteoa)1rfl. by guest on Nnloaded from reported in 29% of children with RV VT undergoing EPS. These post-operative troponin T or creatine kinase, longer ventilatory ovem ttyhpoesse osefenRVinOaurrthflyotwhmtoragcetnicVTrigshhtovueldntrbiceuldariffecraerndtioiamteydopfraothmy sohuocpcwpueorvretarf,taeinsrdmaohnisygthfkreiinnqdouteronoftplyiscuorbrgeseqerruyvireefdomraeftncetor.ncPglooenssutit-raseulrohgfiecaaarvlteJnEdtTerifcemucltaasyr; ber 14, 2014 (ARVC),whichmayattimes be difficult. septal defect (4%), AV septal defect repair (2%), and complete repairoftetralogyofFallot(22%).17 Fascicular ventricular tachycardia Post-surgicalJETismostlikelyduetoenhancedautomaticityin FascicularVTisareentrantarrhythmiathatinvolvestheleftfasci- thebundleofHis,andseveralpotentialaetiologieshavebeenpro- cles(typicallyposterior,butinrarecasesanterior)producingright posed,including(1)placementofsuturelinesintheareaoftheAV bundlebranchblock(RBBB)QRSmorphologyandleft,superioror node giving rise to haemorrhage, oedema or an inflammatory right, inferior axis during VT, respectively. Fascicular VT is highly response, (2) direct damageto theAV node itself,or (3)longitu- sensitive to verapamil (but not adenosine), one of the identifying dinal stretch of the AV node area caused by cardiac surgery characteristics of this arrhythmia, suggesting a calcium-dependent during exposure of a ventricular septal defect and/or resection mechanism. Similar to outflow tract VT, symptoms in children ofmusclebundlesto relieveRVoutflow-tractobstruction. may be absent or include syncope and tachycardia induced ventricular dysfunction. Post-operative atrial arrhythmia in congenital heart disease Torsadedespointes Torsadedespointes(TdP)isapolymorphicVTcharacterizedbya Early post-operativearrhythmia QRSmorphologythatappearstorotatearoundanimaginarybase- Tachycardiasarisingaftersurgicalrepairofcongenitalheartdefects line,andistypicallyassociatedwithcongenitallongQTsyndrome are caused by electro-pathological alterations secondary to the (LQTS) in children. Torsade is initiated by subendocardial focal congenitaldefect, aconsequenceofcardiacsurgery,orthe result activity commonly manifest as a short-long-short RR pattern on of haemodynamic abnormalities in the post-operative period. In the surface ECG, followed by successive reentrant excitation of a large cohort of children (N¼580) undergoing paediatric ventricular myocardium with the classical ECG appearance sec- surgery for CHD, early post-operative arrhythmias occurred in ondary to the bifurcation of the rotating wave front as a result 51,18 including SVT (N¼21), JET (N¼12), complete atrio- oflocalizedfunctionalconductionblock.15Torsadefrequentlyter- ventricular block (N¼10), VT (N¼3) and AF (N¼5). Death minates spontaneously either due to the development of further occurred in 15 of them. The most important risk factor for Pharmacologicalandnon-pharmacologicaltherapyforarrhythmiasinthepediatricpopulation 1345 development of early post-operative tachycardias in this popula- patient group were AFL, AF or ectopic atrial rhythms and are tionwasthetypeof surgicalprocedure. most likely the result of damage to the (i) sinus node and its blood supply, (ii) interatrial conduction pathways, (iii) AV node Late post-operative arrhythmia and its blood supply, and (iv) atrial muscle, caused by the Late post-operative tachycardias are mainly atrial arrhythmias in- extensivenessofthe surgicalprocedure. cluding AFL and intra-atrial reentrant tachycardia, which may Thefrequencyofsinusnodedysfunctionandatrialtachycardias arise months to years after cardiac surgery. They are most often after the Senning procedure was comparable with the Mustard observed afterFontan, Mustard,andSenning procedureor repair procedure. Nowadays, the atrial redirection procedure has been of tetralogy of Fallot. Atrial reentrant tachycardias also develop replaced by an arterial switch operation (Jatene procedure). in patients with ventricular septal defect, most likely as a result Follow-up studies have demonstrated that this surgical technique of atrial enlargement. Development of late post-operative atrial is associated with a lower incidence of atrial tachyarrhythmias tachycardia is additionally influenced by various patient- and (5%) and preserved sinus node function. This may be due to the procedure-relatedvariablesincludingthecomplexityofcongenital fact that the Jatene procedure requires limited operation in the heart defects, the number of surgical procedures performed, atria. In addition, the operation is also performed in the neonatal haemodynamicstatus,andtimeaftercardiacsurgery.Atrialtachy- period and it is therefore less likely that the patient has had a cardiapresentinglateaftersurgicalrepairinthispatientgroupare prior surgical atrial septectomy requiring atrial sutures which typically reentrant in the majority of cases around surgical scars. maydamagethe sinusnode orits bloodsupply. Precipitating factors for development of atrial tachycardias in the setting of congenital heart defects are the presence of prosthetic Arrhythmias in atrialseptal defect materials and electro-pathological alterations of the atrial Pre-operativeatrialtachycardiasinchildrenwithostiumsecundum architecture. atrialseptaldefectsareuncommon.Developmentofthesetachy- cardiasisassociatedwitholderage,shuntsize,andseverityofpul- Arrhythmias inFontancirculation monary hypertension. Pre-operative EPSs performed in children The Fontan procedure is aimed at re-directing systemic venous with ostium secundum atrial septal defects revealed sinus node D blood directly into the pulmonary circulation without passing dysfunction, AV node dysfunction, abnormalities in atrial conduc- ow tthormoousgihngthtehesurbigphutlmatorinuamrytvoenthtreicpleu.lmThoinsairsyaacrctoemryp,leisihtheedrbdyiraencatsly- ttiaoten,adnedverleofpramcteonrtinoefss.reTehnetsreanetlectatrcohpyaarthrhoylothgmicaialsaltaenrdatiaornesfmacoilsi-t nloaded from oacrorimsuinmsginogdnuairnincogolndtdehureitp.fiartEiseatrnlt3ys0tuandcdahyeysragraorfhitnyegtrhsmcuariargdseira(ycm.osustrgteyrpyicaarlley mAFoLr)e, llmiokaieadlsy.2at0shEeiatrrhelyassuslubtreogeefnraytsrhmiaolawsytnrperttehcvahetnceatluetshceterdoobpcyacturhirgorhelotn-gsciiecdaeoldfaltvtaoeclrhuaymtaioernrohsvyaetrhre-- by guest on N ThemostfrequentcomplicationobservedlateaftertheFontan partly reversible aftersurgical repairofthe atrial septal defect. ovem prereoncterdaunrtetaischaytcraiarldriae)e.nRtirsaknftatcatcohryscfaorrdaiatr(iaAlFrLe,enAtFr,anantdtacinhtyrcaa-artdriiaasl defAetcrtisalarteacfhryeaqrurehnyttlhymeianscoaufnteterresdurcgoicmalplriceaptaioirnso.fInaatrdiadlitisoenpttaol ber 14, 2014 inpatientswithFontancirculationincluderightatrialenlargement, pre-existing electropathological alterations, damage to atrial elevated atrial pressure, dispersion of atrial refractoriness, sinus musclebundlescausedbytheatrialincisionsfurtherfacilitatesde- node dysfunction, older age at the time of cardiac surgery, eleva- velopment of atrial tachycardias. The incidence of late post- tion of pulmonary pressure, low oxygen saturation, preoperative operative tachycardias in children with ostium secundum atrial arrhythmias, and a longer time after cardiac surgery. As time septal defects is variable, ranging from 8 to 71%. It is more fre- after cardiac surgery passes by, there is an increasein arrhythmia quently observed in patients who also had tachycardias pre- propensity;anincidenceof21%hasbeenreportedduringafollow- operatively.AtrialflutterandAFarethemostfrequentlyoccurring upperiodof15yearsafter the Fontan surgery.19 arrhythmias. Late post-operative tachycardias are more common The presence of conduits, long sutures lines or scar tissue inpatientswhoalsohaveanabnormalpulmonaryvenousdrainage. increase the likelihood of development of intra-atrial reentrant Theoccurrenceofpost-operativearrhythmiasisalsoinfluencedby tachycardiasastheycanserveasbarriersofthereentrantcircuits. thesurgicalprocedure;alowerincidenceoftachyarrhythmiashas beenreportedafterconversionofthecannulationtechniquefrom Arrhythmias intransposition ofthe greatarteries cannulation through the right atrial appendage to direct cannula- Before surgery, a variety of abnormalities in cardiac rhythm have tion of the superior caval vein. Arrhythmogenecity of cardiac beenobservedinchildrenwithtranspositionofthegreatarteries surgery is supported by studies demonstrating that tachyarrhyth- includingsinusbradycardia,sinoatrialblock,sinoatrialWenckebach mias in children after transcatheter closure of atrial septal defect block,junctionalescaperhythms,andprematureatrialdepolariza- areuncommon. tions. In 1964, the Mustard procedure was introduced as physio- logic correction of the transposition of the great arteries. This Arrhythmias in tetralogyofFallot surgicalbaffleprocedureisextensiveandrequireslongintra-atrial Surgical repair of tetralogy of Fallot can be performed through suturelines.Thereportedincidenceofbothbradyarrhythmiaand eitheratransatrialortransventricularapproach.Thetransatrialap- tachyarrhythmiaafterthissurgicalprocedurewashigh(30–100%). proach is nowadays preferably used because it is associated to a The incidence of SCD was also considerable high, ranging from reduced risk of ventricular arryhthmias. In the post-operative 2 to 8%. Post-operative tachycardias commonly observed in this period, SVTs are an important cause of morbidity. They have 1346 J.Brugadaetal. beenreportedafterbothtransventricularandtransatrialrepairsof Hypertrophic cardiomyopathy tetralogy of Fallot. The incidence of SVTs is associated with pul- Hypertrophiccardiomyopathyisoneofthemostcommongenetic monary regurgitation, atrial volume overload, and older age at cardiovascular disorders, affecting 1 in 500 people in the general the time of surgery or previous palliation with a Waterston or population. Hypertrophic cardiomyopathy is defined by the pres- Pottsanastomosis. ence of asymmetric LV hypertrophyand myocyte disarray usually VentriculartachycardiasmaybethecauseofSCD,whichoccurs affectingtheseptum.However,HCMisadiseaseofvariablepene- in 1–3% in the operatedFallot patients. Risk factors for develop- trance and expressivity, and the disease pattern can range from ment of post-operative VTs include older age at intracardiac severe hypertrophy and disarray to minimal changes, from septal repair, longer interval after cardiac surgery, increased RV systolic hypertrophy to other less commonforms (apical) and from SCD pressure,andmoderatetoseverepulmonaryregurgitationorven- to asymptomatic individuals. Nevertheless, HCM is the most tricular dysfunction. The ventricular septal defect, ventriculotomy common cause of premature SCD in the young, especially in the scar and outflow patch are often part of the reentrant circuit of young athlete.26 The disease is considered inherited in 90% of ventricular tachyarrhythmias inthis patient group. thecases,generallywithanautosomaldominantpatternoftrans- mission, except for cases with mutations in mitochondrial DNA Post-operativeventriculararrhythmias (mtDNA),whichhave a maternal transmission.27,28 in congenital heart disease Mutationshavebeendescribedinseveralgenesencodingessential Isolatedventricular prematurebeats frequentlyoccurin the early sarcomeric proteins, heavy chain b-myosin (MYH7) and myosin- periodaftercardiacsurgeryandtheyareoftentheresultofhypo- bindingproteinC(MYBPC3),heavychaina-myosin(MYH6),tropo- kalemia. Sustained VTs are rare and they commonly arise in the ninI(TNNI3),troponinT(TNNT2),a-tropomyosin(TPM1),essential settingofmyocardialischaemiaormyocardialinfarction.Develop- myosinlightchains(MYL3),regulatorylightchain(MYL2),titin(TTN), mentofVTsarefacilitatedbydisruptionoftheventricularmyocar- anda-actin(ACTC).29Mutationshavealsobeendetectedingenes dium caused by (1) areas of scar due to the ventriculotomy, implicatedinthemetabolismofthehemeandFe2+group,andin (2)fibrotictissueasaresultoflong-lastingcyanosis,or(3)valvular genes involved in mitochondrial bioenergetics. Genetic studies of regurgitationcausingventriculardilatation.Ventriculartachycardias families with LV hypertrophy have shown metabolic cardiomyop- D aremainlyobservedaftercorrectionoftetralogyofFallotandLV athieswithmutationsinthePRKAG2andLAMP2genes.Recently,mis- ow odeufteflcotws sturacchtadseftercatnssbpuotsitthioenyaolsfothaerisgereinatoathrteerriteysp,euonfivceonntgriecnuiltaarl sae-nascetinmhuatavteiobnesetnhadtecsacursibeeddefienctHivCeMin.teNraecxtiiloinn(bNeEtwXeNe)nisneaxcilainrdainadc nloaded from hescneaatrrrsatsn,todrcoirupcbruolietss-tohouefttllieacttemRpVaot,esatr-nioadlpsevreliakntetivreicpuValtaTcrshesinesvpotaalnvldedevcefoencnttdrsiuc.iutTlsoh.teoRmriseky- Zfro-dUmispcfoupnrrctoieltspegrineesntehenartat,thmeaduswtaaitctihoruinncsitahhlaefvusenacnrtcoiootmnbeeteorenp.3trh0ootuecgthtcatordpiarcedZic-dtitshces by guest on N factors for developing sustained VT are older age at the time of severityofthephenotypebecauseindividualswithdifferentdegrees ovem sdtauycrnhgaeymcryaic,rdlsoitaanstguaesrr,eadanusdsruaptmriooenldoontogfapbtoeiostnth-oesufmrtghaiceinaQlcafRouSlsloecwoom-fuSppCl,eDpxo.oVobersnehtrarviecemudloainr- o(mSfuDht)aytpmioeanryt.rTbohepihspyirsedosureenwttoitinhthtaeheignrtseeaarmtveeernftpaimroenidlyoisfdpmeosospidtiitiofeynicnatgorgreysniunedgsdtaehnneddspeaomaltyhe- ber 14, 2014 patientswithcongenitalheart defects. morphisms,whichrequiremoreexhaustivestudiestoachieveafull understanding. It is assumed that interruption of mitochondrial Genetics in paediatric arrhythmias energy metabolism in the heart is the cause of HCM in patients with sarcomeric contraction disruption; this sheds some light on The role of inheritance in arrhythmias has been largely demon- severalclinicalobservationssuchasheterogeneity,variabilityinclin- stratedingeneticaswellasinepidemiologicalstudies.Geneticre- icalpresentation,andasymmetryinhypertrophy. search has shown that inherited arrhythmias can be caused by RiskstratificationforSCDinHCMpatientsremainsatthefore- mutations ingenesmainlyencodingfourtypes ofproteins: sarco- front ofclinicalresearch.Left ventriclewall thicknessz-score .6 meric, which cause mainly hypertrophic cardiomyopathy (HCM); andanabnormalbloodpressureresponsetoexerciseareconsid- cytoskeletal, which cause mainly dilated cardiomyopathy (DCM); ered clinical factors for SD in children. Differentiating HCM from desmosomal, which cause mainly ARVC; and ion channels, which ‘athlete’s heart’ remains a challenge for an important percentage cause electrical diseases (or channelopathies). This last group of cases. Electrocardiogram criteria, echocardiography, and includes LQTS, Brugada syndrome (BrS), short QT syndrome genetic analysis as well as detraining can successfully resolve (SQTS), CPVT, and AF. Several of thesediseases arehighly lethal someofthesecases.31 in the early years. The use of genetics enables the identification of mutations responsiblefor thesephenotypes.21–24 Arrhythmogenic rightventricularcardiomyopathy Arrhythmogenic right ventricular cardiomyopathy is an inherited Cardiomyopathies cardiomyopathy characterized by RV dysfunction and ventricular Cardiomyopathies are heart diseases induced by mutations in arrhythmias. Patients with ARVC show fibrofatty replacement of genes that encode contractile and structural proteins as well as RV wall. However, ARVC may involve both ventricles and in proteins for cardiac energy production. They are responsible for veryisolatedcasesonlytheLV.Thispathologicalalterationispro- lethal arrhythmogenic disorders in pediatric population, mainly gressiveandwillgenerateRVdysfunctionandventriculararrhyth- HCM andarrhythmogenic cardiomyopathy (ARVC).25 mias,includingSCD.ThediagnosisofARVDisbasedonaseriesof