Pharmacological and non-pharmacological therapy for arrhythmias in the pediatric population ...

46 Pages·2013·8.44 MB·English

Europace Advance Access published July 12, 2013
EHRA/AEPC CONSENSUS STATEMENT
Europace
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,
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Juha-Matti Happonen12, Joachim Hebe13, Siew Yen Ho14, Eloi Marijon15, ow
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Thomas Paul16, Jean-Pierre Pfammatter17, and Eric Rosenthal18 loa
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1PaediatricArrhythmiaUnit,CardiologyDepartment,HospitalSantJoandeDe´u-HospitalCl´ınic,UniversityofBarcelona,08036Barcelona,Spain;2DepartmentofPediatric fro
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Cardiology,LeidenUniversityMedicalCenterandAcademicalMedicalCenterAmsterdam,2300RCLeiden,TheNetherlands;3PaediatricArrhythmiaUnit,CardiologyDepartment, h
HospitalSantJoandeDe´u,UniversityofBarcelona,08950Barcelona,Spain;4DepartmentofCardiology,UppsalaUniversity,s-75236Uppsala,Sweden;5CardiothoracicUnit,Great ttp
OrmondStreetHospital,GreatOrmondStreet,WC1N3JHLondon,UK;6Children’sHeartCentre,UniversityHospitalMotol,15006Prague,CzechRepublic;7Cardiac ://e
ElectrophysiologyDivision,DepartmentofCardiology,Children’sHospital,Boston,02115MA,USA;8MedizinischeFakulta¨t,KinderspitalZu¨rich,8032Zu¨rich,Switzerland; u
9CardiovascularGeneticsCenter,Institutd’Investigacio´ Biome`dicaGirona-IdIBGi,17003Girona,Spain;10ArrhythmiaUnit,PediatricCardiologyandHeartSurgeryDepartment, rop
BambinoGesu`PediatricHospitalandResearchInstitute,Palidoro,00055Fiumicino,Italy;11DepartmentofCardiology,ErasmusMC,3015Rotterdam,TheNetherlands; ace
12DepartmentofPediatricCardiology,Children’sHospital,UniversityofHelsinkiandHelsinkiUniversityCentralHospital,00290Helsinki,Finland;13CenterforElectrophysiology, .o
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28277Bremen,Germany;14CardiacMorphologyUnit,RoyalBromptonHospitalandImperialCollegeLondon,SW36NP,UK;15ParisCardiovascularResearchCenter,Inserm fo
UU9n7iv0e,rEsiutyro,3p7e0an99GGeoo¨rtgtiensgePno,mGpeidrmouanHyo;s1p7Piteadl,r7ia5t9ic0c8aPrdarioisl,oFgrya,nUcen;iv1e6DrseitpyaortfmBeernnt,o3f0P1e0diBaetrrinc,CSwaridtzioelrolagnyda;nadndInt1e8EnvsievleinCaaCrheilMdreednic’sinHe,oCsphiitladlr,eGn´usyU’sn&iveSrtsTityhoHmoassp’itHalo,sGpeitoarl,gS-AE1ug7uEsHt- rdjou
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Inchildrenwithstructurallynormalhearts,themechanismsofarrhythmiasareusuallythesameasintheadultpatient.Somearrhythmiasare g
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particularlyassociatedwithyoungageandveryrarelyseeninadultpatients.Arrhythmiasinstructuralheartdiseasemaybeassociatedeither st o
withtheunderlyingabnormalityorresultfromsurgicalintervention.Chronichaemodynamicstressofcongenitalheartdisease(CHD)might n J
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create anelectrophysiological andanatomicsubstrate highlyfavourable forre-entrantarrhythmias. ly
2
Asageneralrule,prescriptionofantiarrhythmicdrugsrequiresacleardiagnosiswithelectrocardiographicdocumentationofagivenar- 3
, 2
rhythmia.Risk–benefitanalysisofdrugtherapyshouldbeconsideredwhenfacinganarrhythmiainachild.Prophylacticantiarrhythmicdrug 0
1
3
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.
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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].
Page 2 of 46 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
D
pathways are seen intheinternodal musculature. cross an area of deficiency in the fibrofatty tissues or traverse o
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Inthenormalheart,theatrialmusculatureconstitutesaseparate more peripherally though the fatty tissues of the AV groove. nlo
a
myocardial mass relative to the ventricular musculature apart Some right-sided pathways may arise from a node-like structure de
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from one muscular connection—the bundle of His. The areas of (nodeofKent)atitsatrialorigin.‘Mahaimphysiology’canbepro- fro
contiguityattheatrioventricular(AV)junctionsaroundtheorifices duced by such histologically specialized right-sided pathways that m
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of theAV valvesprovidethe separation. connectwiththeAVconductionsystemviaabundlethatdescends ttp
ThetriangleofKochisthegrosslandmarktothepositionofthe in the right parietal wall. The pathways are hence described as ://e
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AV node (Figure 1B). Viewed from the right atrial aspect, the tri- ‘atriofascicular’ connections. Such a sling of histologically specia- ro
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angle is delimited posteriorly by the continuation of the attach- lizedconductiontissue,withitsvariousappellations,shouldbedis- ce
ment of the Eustachian valve, the tendon of Todaro, into the tinguished from the classic ‘Mahaim fibre’. The latter directly .ox
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sinus septum (also known as the Eustachian ridge). The anterior connects the AV node or bundle to the ventricular septum. De- rd
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border of the triangle is the hingeline (annulus) of the septal scriptively, theyare better labelled nodoventricular and fasciculo- u
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leaflet of the tricuspid valve. The mouth of the coronary sinus is ventricular accessory connections, respectively, highlighting their als
usually taken as the base of the triangle, with the AV node connection with the conduction tissues (Figure 2). These fibres .org
located at the apexwhere the tendon of Todaro inserts into the are regularly found in normal hearts, especially in neonates. b/
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central fibrous body. On one side, the compact AV node lies So-calledseptalaccessoryconnectionsarebetweenatrialandven- gu
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against the central fibrous body whereas on the other side it has tricular myocardium at the offset attachments of the leaflets of st o
aninterfaceoftransitionalcellswithatrialmyocardium.Theexten- mitralandtricuspidvalves.Afurthersubsetofaccessorypathways n J
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sion of the node into the central fibrous body, the penetrating has been described as being located close to the penetrating ly
2
bundle of His, is then completely encased within fibrous tissues. bundle (‘intermediate septal’ or para-Hisian pathways). Another 3, 2
TheAVconductionbundle,stillwithinafibroussheath,continues type, atrio-Hisian connections (originally designated as ‘atriofasci- 01
3
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 Page 3 of 46
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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
Page 4 of 46 J.Brugadaetal.
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Figure2 DiagramoftheAVjunctionsdepictingvarioustypesofaccessoryconnections.AV,atrioventricular;LBB,leftbundlebranch;RBB, http
rightbundlebranch. ://e
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sinusnodeareontheleftsideofthepatient.Inheartswithisomer- ThedistributionoftheAVconductionaxisinheartswithtetral- .ox
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ic arrangement of the morphologically right atrial appendages ogyofFallotisdirectlycomparablewithheartswithisolatedven- rd
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(‘asplenia’),therearebilateralterminalcrestsand,correspondingly, tricularseptaldefectbecauseadefectintheventricularseptumisa u
bilateral sinus nodes.2 Terminal crests, however, are lacking in cardinal feature of tetralogy of Fallot. Most ventricular septal rnals
hearts with isomeric arrangement of the morphologically left defects,whetherinisolationorotherwise,arelocatedintheenvir- .org
atrial appendages (‘polysplenia’). Although in this group bilateral ons of the membranous septum. These are termed perimembra- b/
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superior caval veins can be present, usually the sinus node is not nous defects since they have a fibrous component or remnant of g
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found in its anticipated position. In some hearts a remnant of themembranousseptumattheirposteroinferiorborderthatcon- st o
specialized tissue is found in the inferior atrial wall near the AV tains the AV conduction bundle (Figure 3A). The non-branching n J
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junction whilein otherheartssuch tissuecannot beidentified. bundle is longer than in normal hearts and the normal leftward ly
2
shift of the bundle still brings it into the LV outflow tract making 3
, 2
Atrioventricularconduction system this part of the defect the most critical area for avoiding injury 01
Mostcongenitalheartlesionsaresimpleholesinthecardiacseptum to theconductionsystem.5 3
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 Page 5 of 46
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Figure3 (A)Diagramshowingtheseptalaspectoftherightatriumandventricle.ThetypesofVSD(yellowshapes)areshowninrelationto .org
thecourseoftheAVconductiontissues.Thefibroustissue(green)atthepostero-inferiormarginoftheperimebranousVSDabutstheAV b/
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conduction bundle. (B) This diagram shows usual atrial arrangement with discordant AV connections with the morphologically LV opened. g
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TheAVconductionbundlepassesantero-superiortotheLVoutletanddescendsalongtheanteriormarginofVSD.(C)TheAVnodeisab- es
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normallylocated.(D)TheAVnodeislocatedinthemuscularflooroftherightatriuminheartswith‘tricuspidatresia’wherethereisabsenceof n
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therightAVconnection.(E)WhenviewedfromtheaspectoftherudimentaryRV,theAVconductionbundlepassesalongthemarginofthe u
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ventricularseptaldefect (VSD)thatisnearesttotheacutecardiacmargin.AV,atrioventricular;VSD,ventricularseptaldefect;RV,rightven- 2
3
tricle;LV,leftventricle;SCV,superiorcavalvein;ICV,inferiorcavalvein;MV,mitralvalve. , 2
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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.
Page 6 of 46 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.
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Hearts with univentricular AV connection include those with Atrioventricular reentrytachycardia ow
double-inlet connection, together with those having absence of Atrioventricularreentrytachycardia(AVRT)isfacilitatedbyamus- nlo
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either the right or left AV connections. Those that are significant cular accessory pathway(s) spanning the fibrous AV junction and de
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in having an abnormal disposition of the conduction axis are providing continuity between atrial and ventricular myocardium, fro
hearts with the atria connected to a dominant LV and those atasiteelectrophysiologicallydistinctfromtheAVnodeandprox- hm
with a solitary indeterminate ventricle.5 Essentially, hearts with imalHis–Purkinjesystem(AVN/His).Suchconnectionshavebeen ttp
dominant LV usually have an anteriorly located ventricular described in the developing human heart, normally regressing by ://e
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septum.Thus,heartswithdouble-inletconnectionhaveaconnect- 20weeksgestation.Ithasbeeninferredthatfailureofthesepath- rop
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ingAVnodeattheacutemarginalpositionoftherightAVorifice. waystoregressformsthesubstrateforaccessorypathways.6Spon- ce
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From here, the bundle perforates the valvar attachment to enter taneous regression of pathway function in infancy is well xfo
the ventricular septum. When the right AV connection is absent documented, although in what proportion of patients symptoms rd
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(tricuspidatresia)andthedominantventricleisofleftmorphology, redeveloplaterinlife remainsuncertain. urn
the AV node is found in the muscular floor of the right atrium The exact epidemiology of accessory pathways (APs) can best als
(Figure 3D). In both settings, the descending bundle passes to the beappreciatedbyassessmentofpatientsundergoingelectrophysi- .org
border of the septal defect that is nearest the acute cardiac ologystudyandradiofrequencyablation(EPS/RFA).7,8Between55 by/
margin, irrespective of the location of rudimentary RV and 60% of AP(s) will be manifest on the surface electrocardio- gu
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(Figure 3E). Hence, the ventricular course of the conduction axis gram (ECG) as varying degrees of ventricular pre-excitation,8 the st o
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in double-inlet LVandin‘tricuspid atresia’ is comparable. Wolff–Parkinson–White (WPW) ECG pattern or WPW syn- J
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In summary,the cardiac conductionsystemboth in structurally drome in symptomatic individuals. The degree of pre-excitation ly 2
normal hearts and in malformed hearts shows variability that can isdependentonmultiplefactors:theanterogradeconductionvel- 3, 2
account for some of the rhythm abnormalities. Cardiac surgeons, ocity of the pathway relative to the AVN/His; the position of the 01
3
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 Page 7 of 46
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 D
minimal or absent during sinus rhythm but becomes evident o
nature, is frequently seen. Spontaneous resolution is common in w
duringatrialpacingorAVRT.TheQRSmorphologyduringtachy- n
those presenting ,3 years of age (78%), but much less in older lo
cardiaisbroadduetoanterogradeconductionexclusivelyviathe childrenandadolescents(16%).10,11 ade
AaFsPecaonnddrpeatrtohwgraayd.econductionviathetrueAVN/Hisorrarelyvia d fro
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Junctional ectopictachycardia h
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Permanent junctional reciprocating tachycardia. Permanent junctional Congenitaljunctionalectopictachycardia(JET)isbelievedtoresult ://e
reciprocating tachycardia (PJRT) represents a small proportion of from abnormal automaticity at, or close to, the His bundle, and uro
AVRT (2) facilitated by an AP that typically demonstrates only mayaccelerateordecelerateinresponsetoautomatictone.Anin- pa
c
retrograde, decremental conduction. The AP is most commonly cessant pattern and faster junctional rates are more commonly e.o
x
located in the posteroseptal region close to the coronary sinus seen in those presenting ,6 months of age. The ECG typically fo
ostium, although may be found at other sites. In tachycardia an- rd
shows a rather narrow complex QRS with variable RR intervals, jo
terograde conduction is via the AVN/His producing a narrow and either ventriculoatrial (VA) dissociation or less commonly urn
QmwieRthdSiinactoetmhlyepplAerxPeco(elnodintnhggeRtshPuertfaafcochellyoEcwCariGndgi,aw)Q.itDRhSutehdeutoerettthrooegsirlnoacdweesscPao-nwntdanuvaecttuiimorne- 1bl:o1ck,VAandcoandpuoctteionnt.ialRarorelely,foJErTmmataeyrnableanatsis-oScSiAat/eandti-wSSitBh hAaVs bals.org/
of PJRT particularly in infants and young children, severe LV dys- been suggested. Left ventricular dysfunction was reported in 15 y g
function may be present at diagnosis, which typically resolves of94 (16%)childrenwith JET,with fatalityseen in4patients.12 ues
with suppression of pathway activity. Spontaneous AP regression t on
J
hasbeendocumentedinover20% ofchildrenwith PJRT. Atrial flutter uly
Atrial flutter in children is rare and most frequently seen in the 23
Atrioventricular nodal reentrytachycardia neonatal period. The ECG appearance of tricuspide isthmus- , 201
dependantflutterissimilartothatseenintheadult,withabaseline 3
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
Page 8 of 46 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
D
gically mediated triggered activity caused by cyclic adenosine hydropsfetalis, frequentlyassociated with apoor prognosis. ow
monophosphate (cAMP) induced after depolarizations that are nlo
a
sensitive to fluxes in intracellular calcium. Due to antagonism of Epidemiology and pathophysiology de
d
cAMP by adenosine, outflow tract VT is typically adenosine- of arrhythmias in congenital heart disease fro
sensitive. Symptoms range from absent to severe including m
Junctional ectopictachycardia h
syncopeandventriculardysfunction.14The12-leadECGinVTtyp- ttp
ically shows a left (or right) bundle branch pattern and inferiorly Junctional ectopic tachycardia is a malignant tachyarrhythmia that ://e
directed axis; the QRS morphology may predict the exact site of most commonly occurs after surgical correction of congenital uro
heartdefects,althoughacongenitalvariantalsoexists(seeabove). pa
origin, and intracardiac mapping demonstrates a centrifugal ce
It is associated with numerous variables including age less than 1 .o
pattern of activation consistent with a focal mechanism. A site of x
month,historyofcardiacfailure,higherbodytemperature,longer fo
originclosetotheperimembranousseptumandelectrophysiologi- rd
cardiopulmonarybypasstime,typeofcardioplegia,higherlevelsof jo
cally and anatomically distinct from the His bundle has been u
post-operative troponin T or creatine kinase, longer ventilatory rn
rttyhepopeosserteosdefeinRnVi2n9O%aurrtohflfyoctwhhmildtorragecentniwcViTtrhigshRhtVovuVeldTntrbuicenudledarrifgfeocrianergndtiEoiaPmteSyd.oTpfhraeothsmey soucpcpuorrtaftaenrdahniyghkiinndotroofpiscurrgeeqruyirefomrencto.nPgoenstit-asulrhgiecaarltJEdTefemctasy; bals.org/
(ARVC),whichmayattimes be difficult. however,ismostfrequentlyobservedafterclosureofaventricular y gu
septal defect (4%), AV septal defect repair (2%), and complete e
s
repairoftetralogyofFallot(22%).17 t on
Fascicular ventricular tachycardia J
Post-surgicalJETismostlikelyduetoenhancedautomaticityin u
FascicularVTisareentrantarrhythmiathatinvolvestheleftfasci- ly
thebundleofHis,andseveralpotentialaetiologieshavebeenpro- 2
cles(typicallyposterior,butinrarecasesanterior)producingright posed,including(1)placementofsuturelinesintheareaoftheAV 3, 2
bundlebranchblock(RBBB)QRSmorphologyandleft,superioror 01
node giving rise to haemorrhage, oedema or an inflammatory 3
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 Page 9 of 46
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
D
setting of congenital heart defects are the presence of prosthetic Arrhythmias in atrialseptal defect o
w
materials and electro-pathological alterations of the atrial Pre-operativeatrialtachycardiasinchildrenwithostiumsecundum nlo
a
architecture. atrialseptaldefectsareuncommon.Developmentofthesetachy- de
d
cardiasisassociatedwitholderage,shuntsize,andseverityofpul- fro
Arrhythmias inFontancirculation monary hypertension. Pre-operative EPSs performed in children m
h
The Fontan procedure is aimed at re-directing systemic venous with ostium secundum atrial septal defects revealed sinus node ttp
blood directly into the pulmonary circulation without passing dysfunction, AV node dysfunction, abnormalities in atrial conduc- ://e
u
throughthesubpulmonaryventricle.Thisisaccomplishedbyanas- tion,andrefractoriness.Theseelectropathologicalalterationsfacili- ro
p
a
tomosingtherightatriumtothepulmonaryartery,eitherdirectly tate development of reentrant tachyarrhythmias and are most ce
.o
or using a conduit. Early tachyarrhythmias (most typically AFL), likelytheresultofatrialstretchcausedbyright-sidedvolumeover- x
fo
arising during the first 30 days after cardiac surgery are more load.20Earlysurgerymaypreventtheoccurrenceoftachyarrhyth- rd
jo
commoninolder patients undergoingsurgery. mias asithas beenshown thatelectropathological alterationsare u
rn
ThemostfrequentcomplicationobservedlateaftertheFontan partly reversible aftersurgical repairofthe atrial septal defect. als
procedure is atrial reentranttachycardia (AFL, AF, andintra-atrial Atrial tachyarrhythmias after surgical repair of atrial septal .org
reentranttachycardia).Riskfactorsforatrialreentranttachycardias defects are frequently encountered complications. In addition to b/
y
inpatientswithFontancirculationincluderightatrialenlargement, pre-existing electropathological alterations, damage to atrial gu
e
elevated atrial pressure, dispersion of atrial refractoriness, sinus musclebundlescausedbytheatrialincisionsfurtherfacilitatesde- st o
n
node dysfunction, older age at the time of cardiac surgery, eleva- velopment of atrial tachycardias. The incidence of late post- J
u
tion of pulmonary pressure, low oxygen saturation, preoperative operative tachycardias in children with ostium secundum atrial ly
2
arrhythmias, and a longer time after cardiac surgery. As time septal defects is variable, ranging from 8 to 71%. It is more fre- 3, 2
after cardiac surgery passes by, there is an increasein arrhythmia quently observed in patients who also had tachycardias pre- 01
3
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
Page 10 of 46 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-
D
kalemia. Sustained VTs are rare and they commonly arise in the ninI(TNNI3),troponinT(TNNT2),a-tropomyosin(TPM1),essential o
w
settingofmyocardialischaemiaormyocardialinfarction.Develop- myosinlightchains(MYL3),regulatorylightchain(MYL2),titin(TTN), nlo
mentofVTsarefacilitatedbydisruptionoftheventricularmyocar- anda-actin(ACTC).29Mutationshavealsobeendetectedingenes ade
dium caused by (1) areas of scar due to the ventriculotomy, implicatedinthemetabolismofthehemeandFe2+group,andin d fro
(2)fibrotictissueasaresultoflong-lastingcyanosis,or(3)valvular genes involved in mitochondrial bioenergetics. Genetic studies of m
h
regurgitationcausingventriculardilatation.Ventriculartachycardias families with LV hypertrophy have shown metabolic cardiomyop- ttp
aremainlyobservedaftercorrectionoftetralogyofFallotandLV athieswithmutationsinthePRKAG2andLAMP2genes.Recently,mis- ://e
u
outflowtractdefectsbuttheyalsoariseinothertypeofcongenital sensemutationsthatcausedefectiveinteractionbetweennexilinand ro
p
defects such as transposition of the great arteries, univentricular a-actinhavebeendescribedinHCM.Nexilin(NEXN)isacardiac ace
hearts, double-outlet RV, and ventricular septal defects. The re- Z-discproteinthathasacrucialfunctiontoprotectcardiacZ-discs .ox
entrantcircuitsof latepost-operativeVTs involveventriculotomy fromforcesgeneratedwithinthesarcomere.30 ford
scars or prosthetic materials like patches and conduits. Risk Upuntilpresent,mutationshavenotbeenthoughttopredictthe jou
rn
factors for developing sustained VT are older age at the time of severityofthephenotypebecauseindividualswithdifferentdegrees als
surgery, longer duration of post-surgical follow-up, poor haemo- of hypertrophy or with a greater predisposition to sudden death .org
dynamicstatus,andprolongationoftheQRScomplex.Ventricular (SD)maybepresentinthesamefamilydespitecarryingthesame b/
y
tachycardiasareassumedtobethemaincauseofSCDobservedin mutation.Thisisduetotheinterventionofmodifyinggenesandpoly- gu
e
patientswithcongenitalheart defects. morphisms,whichrequiremoreexhaustivestudiestoachieveafull st o
n
understanding. It is assumed that interruption of mitochondrial J
u
Genetics in paediatric arrhythmias energy metabolism in the heart is the cause of HCM in patients ly
2
with sarcomeric contraction disruption; this sheds some light on 3, 2
The role of inheritance in arrhythmias has been largely demon- severalclinicalobservationssuchasheterogeneity,variabilityinclin- 01
3
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