Citation for published version (APA): Luijendijk, P. (2014). Aortic coarctation: late complications and treatment strategies

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1 UvA-DARE (Digital Academic Repository) Aortic coarctation: late complications and treatment strategies Luijendijk, P. Link to publication Citation for published version (APA): Luijendijk, P. (2014). Aortic coarctation: late complications and treatment strategies General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvA-DARE is a service provided by the library of the University of Amsterdam ( Download date: 03 Sep 2018

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3 Abstract Aorticcoarctationisacommoncongenitalcardiovasculardefect,whichcanbediagnosedoverawide rangeofagesandwithvaryingdegreesofseverity.surgeryhasproventobeaneffectivetreatment forthemanagementofnativeaorticcoarctation,andremainsthetreatmentofchoiceinneonates. Balloon angioplasty with or without stenting has evolved rapidly over the past decade. Balloon angioplasty is the treatment of choice in children with recoarctation, and currently available immediateresultsinnativecoarctationaresimilarwithregardtogradientreductionascomparedto surgery.however,bothtreatmentoptionscarrytheriskofrestenosisandaorticwallcomplications, especiallyafterballoonangioplastywithoutstentinginnativecoarctation.ontheotherhand,stent implantationhasshownexcellentshorttermresultsinbothchildrenbeyondinfancyandinadults withnativecoarctation.inpatientswithrecurrentcoarctationwhoareathighsurgicalrisk,balloon angioplasty and stent repair offer a less invasive and equally effective method. Stent repair is preferredoverballoonangioplastyinadultsandoutgrownchildrenwitharecurrentcoarctation,as theriskforrecoarctationandaneurysmformationseemstobelower.datawithregardtolongterm outcome after percutaneous treatment strategies are scarce. This review summarizes the current insights in the efficacy and safety of both surgical and transcatheter treatment options for aortic coarctation.

4 Surgical versus percutaneous treatment in CoA Introduction: Aorticcoarctationisacongenitalstenosisorocclusionoftheaorta,usuallylocatedintheregionof the ligamentum arteriosum. 1 The worldwide incidence of aortic coarctation is approximately 4 in livebirths,whichcorrespondsto58%ofallcongenitalheartdefects.Itcanbediagnosedover awiderangeofagesanddegreesofseverity,andwithvariouspresentations.aorticcoarctationis most often diagnosed at age 36 months. A small proportion is not diagnosed until adolescent or adultage. 1 Over the past 5 decades, the spectrum of therapeutic options for the treatment of native aorticcoarctationhasexpandedsubstantially.surgicalrepairofaorticcoarctationwasperformedfor the first time in 1944 by Crafoord and Nylin. 2 The surgical treatment of coarctation has improved substantially since then. However, compared with the normal population, survival is reduced in patientsaftersuccessfulrepairbeforetheageof5yearswithonly91%oftheoperatedpatientsalive at the age of 20, and 80% at the age of 4050 years. 36 Another factor that affects survival in a negativemannerisdelayeddiagnosis,assurvivalisdecisivelyaffectedbytheageatrepair,which explainswhyearlyrepairisstilladvocatedinthesepatients. 3;710 Despitethesefindingssurgicalrepair isstilladvocatedinpatientsdiagnosedatolderagebecauseofareducedcardiovasculareventrisk and improved survival. 10, 11 Lifelong surveillance is mandatory in all coarctation patients, even in thosewhounderwentsuccessfulrepair,astheyremainatriskforrecoarctationoraorticaneurysm formation. 3;6;10;11 Moreover, significant morbidity persists after surgical repair due to systemic hypertension, accelerated coronary atherosclerosis, aortic dissection, stroke and congestive heart failure. 6;1216 Thesurgicalapproachesdevelopedoverthepastdecadesincludeendtoendanastomosis, subclavian flap aortoplasty, aortoplasty using a synthetic patch, interposition graft placement and the extended endtoend anastomosis. 36 Over the past two decades, percutaneous treatment optionshavebecomeanalternativeforsurgery.balloonangioplastywasfirstperformedinthe1980s andtheuseofballoonexpandableendovascularstentsbecameavailableinthe1990s. 17;18 Advances inoperatorexperiencesandballoonandstenttechnologyhaveimprovedthesuccessrateandsafety oftranscatheter treatment. Severalstudieshavebeenperformedtoassessthefeasibilityofthese percutaneousapproaches,butlongtermfollowupremainsscarcewithregardtotheoccurrenceof aortic aneurysm formation, recurrent stenosis and the general cardiovascular morbidity and mortality after percutaneous treatment. This review summarizes current insights with regard to treatmentoptionsforcoarctationpatientsinanerainwhichtheroleofpercutaneoustreatmentis evolving. Surgicalrepair Endtoendanastomosis Surgical repair of aortic coarctation by endtoend anastomosis was first described in 1947 by CrafoordandNylin. 2 Repairofaorticcoarctationwithendtoendanastomosisischaracterizedbya low mortality rate and a low recoarctation rate during longterm followup. 19; The extended endtoend anastomosis was introduced more recently, and has shown good shortterm and intermediateterm results. 25;26 This approach is characterized by the fact that an endtoend anastomosis is created to the inferior aspect of the aortic arch. The resulting wide anastomosis achievedprovidesmaximumreliefofsystemicafterloadandreducestherecurrencerate.whenthe 3

5 distalaorticarchandisthmusarehypoplastic,theresultingextendedanastomosisislimitedonlyby thediameteroftheaorticarchitself,allowingformaximumgrowthpotential.inthiscontext,the extended anastomosis actually relieves hypoplasia of the distal arch, which is an great advantage whencomparedtothestandardendtoendanastomosis. 27 The ACC/AHA guidelines currently advise an intervention in patients with a peakto peak coarctation gradient > 20 mmhg or in patients with a peak topeak gradient < 20 mmhg with radiologicalevidenceofsignificantcoarctationandcollateralflow. 28 Theextendedendtoendanastomosisisnowadaysthepreferredtechniqueininfantsandin patientswithamilddegreeofhypoplasiaofthedistalarch.theadvantagesofthistechniqueinclude preservationoftheleftsubclavianartery,resectionofductaltissue,andtheuseofautologoustissue whichallowsvesselgrowthalongwiththepatient. 19 Surgicalrepairofprimarycoarctationremains currently the preferred treatment in the neonatal and paediatric period, despite the fact that outcomeislessfavourableinpatientswithassociatedcardiaclesions. Subclavianflapsurgery Subclavianflapsurgeryisthesecondmostfrequentlyperformedsurgicaltechniqueinbothneonates andinfants. 29 Advantagesofsubclavianflaprepairincludetheuseofautologoustissuewhichhasthe potentialtogrowalongwiththepatient.furthermore,thistechniquecreatesatensionfreerepairin whichtheneedforextensiveaorticresectionandmobilizationislimited.despitethebenefitsofthe subclavianflapprocedure,majorconcernsremainevenaftersuccessfulrepairincludingtheriskof aorticaneurysmformationandrecoarctation.theefficacyofthesubclavianflapprocedurehasbeen a topic of debate, as the recoarctation rate is higher compared to endtoend anastomosis. 30;31 Freedomfromrestenosiswas8789%after5yearsfollowupinpatientswhounderwentsubclavian flapsurgeryascomparedto8695%inthosewhounderwentextendedendtoendanastomosis. 20;32 Barreiro et al. recently reported that 11% of patients who underwent subclavian flap surgery requiredreinterventionbecauseofrecoarctationduringameanfollowupof8months. 29 Thecause of this increased risk of recoarctation is related to the fact that ductal tissue is left in situ in the majority of the cases. Therefore, many centers favour the extended endtoend anastomosis procedureoversubclavianflapsurgery. 29 Patchangioplasty Dacron patch angioplasty was introduced in the 1960s and is characterized by successful gradient resolution, avoidance of harm to the intercostal arteries and a low risk for restenosis because of resection of circumferential suture lines. 33;34 A major disadvantage of this technique is the high incidenceofaorticaneurysmformationinadultspatients;32%inacohortdescribedbyalakuljuet al. 35 Accordingtothisstudy,theriskofaneurysmformationincreasedduringlongtermfollowup, whichwaslaterconfirmedbyparksetal.whoreportedthattheriskofaorticaneurysmformation roseto51%duringfollowup. 36 Theuseoflargepatcheswasshowntoplayaroleinaorticaneurysm formation,possiblyduetothefactthatpatientswhowereoperatedatanolderagetendtorequire largerpatchesandtendhavehigherbloodpressureascomparedtoyounginfants. 36 Lateaneurysm formation after patch angioplasty, a potentially fatal complication because it may lead to aortic dissection, is more prevalent in female patients operated after 2 years of age and in pregnant women. 37 The mechanism behind aneurysm formation after patch angioplasty is thought to be

6 Surgical versus percutaneous treatment in CoA causedbythefactthatapartoftheaortaisreplacedbyamaterialwithatensilestrengththatdiffers fromthatoftheaorta Whentheaorticpulsewavereachesthestiff,lesscompliantgraft,itis thought that the turbulence is transmitted to the elastic aorta opposite and adjacent to the graft causingprogressiveweakeninganddilatationoftheaorticwall. Walhout et al. recently compared outcome after patch aortoplasty and endtoend anastomosisforaorticcoarctationin262children. 41 Incontrasttopreviousstudies,thisstudydidnot report a significant difference between these treatment strategies with regard to the risk of recoarctation or aortic aneurysm formation. This might be related to the fact that in the patch angioplastygrouponlypolytetrafluoroehtylene(ptfe)patcheswereusedandnodacronpatches.it hasbeenhypothesizedthatthegiantcellinfiltrationthatisoftenseenwithdacrongraftscausesan inflammatoryresponsethatincreasestheriskforaorticaneurysmformation. 42;43 WithPTFEpatches this infiltration is substantially less and PTFE is therefore advocated when performing patch angioplasty. However, the results of this study need to be interpreted with caution, as it was a retrospectivestudycoveringalmostthreedecadesinwhichbothsurgicaltechniqueshaveimproved. Overall patch angioplasty is therefore not the treatment of choice in patients with an aortic coarctation. Endovasculartreatmentofaorticcoarctation Balloonangioplastyinchildren Sos et al. were the first to report about the feasibility of dilating an aortic coarctation in a post mortem study. 44 The technique of balloon angioplasty involves expansion of the constricted coarctation site, which results in rupture of the intima and injury of the media. 45 The first in vivo experience with this technique in humans was reported by Singer et al. in 1982 who reported successful balloon angioplasty in a newborn with aortic coarctation. 46 Balloon angioplasty was initiallyusedinneonatesandinfantswithheartfailurewhowereatahighriskforsurgery,butits indication was later extended to include children, adolescents and adults as well However, as opposedtothegoodresultsofballoonangioplastyinbothchildrenandadultswithadiscretetype coarctation, less favourable outcomes have been reported in patients with isthmic hypoplasia or diffusestenosisthatincludestheaorticarch Postprocedural complications after balloon angioplasty in children include injury at the percutaneous access site, elastic recoil or restenosis, and uncontrolled damage of the aortic wall resultinginaorticaneurysmformation. 49;5153 However,theexactmechanismfortheincreasedriskof aorticaneurysmformationafterballoonangioplastyisstillunclear.ithasbeenhypothesizedthatthe presenceofcysticmedialnecrosis,whichisfoundinresectedcoarctationsegmentsinalmosttwo third of patients, might be causative for the development of aortic aneurysms in patients after surgery, balloon angioplasty and stent implantation. 54 Other factors involved in aortic aneurysm formation after balloon angioplasty include larger balloon size, because overstretching of the coarctationareamightcauseintimamediatearsandasaconsequenceaorticaneurysmformation andrupture. Asecondwellknowncomplicationafterballoonangioplastyistheoccurrenceofrestenosis, which is found in 1015% of all children and adults who are treated with balloon angioplasty for nativeaorticcoarctation. 51 Raoetal.reportedthatneonatesandinfantsareparticularlyatriskfor restenosisduetothelargeamountofmyoblastsaroundthecoarctationsite. 55 Additionally,ithas 3

7 beensuggestedthattheincreasedrestenosisriskmaybecausedbythefactthatballoonangioplasty causesinjurytotheaorticintimaandmedia.asaconsequence,recoilandharmfulscartissuemight causerestenosis Inanonrandomizedretrospectivestudyinchildren(age12±10years),18%of thepatientswhounderwentballoonangioplastyhadprocedurerelatedcomplications,ascompared to50%ofthepatientsaftersurgery. 57 After3yearfollowupthenumberofaorticcomplicationssuch as restenosis and aneurysm formation was 21% in the balloon angioplasty group of which 26% required reintervention versus no longterm complications in the surgical repair group. 57 These findingswereconfirmedintwoprospectiverandomizedcontrolledtrialsinwhichbothtechniques wereequallysuccessfulinreducingtheaorticgradient.however,theriskofrecoarctationandaortic aneurysm formation was higher in the balloon angioplasty group as compared to the surgical group. 50;58 Basedonaliteraturereview,Wongetal.reportedasystematicdecisionanalysistocompare balloonangioplastyandsurgeryinchildrenofdifferentagegroups.balloonangioplastywasfoundto bepreferableoversurgeryinthenonneonatalcoarctationpatients,whereasballoonangioplastyin neonates remains controversial. 59 The current AHA guidelines state that balloon angioplasty is recommendedinchildrenbeyondtheageof46monthsinpatientswithagradient>20mmhgand withasuitableanatomy. 60;61 Inconclusion,thesefindingsdemonstratethatballoonangioplastyis effectiveinrelievingtheaorticgradientinchildrenbeyondtheneonatalperiod.however,theriskof recoarctationorruptureandaorticaneurysmformationistoohigh.ingeneral,itcanbeconcluded thatballoondilatationshouldbeavoidedinchildrenandneonatesasitislesseffectiveandtherisk forcomplicationsistoohigh. Balloonangioplastyinadultswithnativecoarctation Balloonangioplastyinthemanagementofadolescentsandadultsremainsatopicofdebate.Overall gradientreductionisacceptableafterballoondilatation.howeverpostproceduraloutcomeisoften suboptimalwitharesidualgradientof20mmhgormorein9%ofthecases. 8;62 Thesefindingsare important, as it has been shown that the recoarctation risk is lower in patients with a post proceduralgradientoflessthan10mmhg. 63;64 Walhoutetal.evaluated85patients(age1455years)withadiscreteaorticcoarctation12± 7 years after balloon angioplasty. 65 Fawzy et al. reported results for 29 patients (age 1571 years) after balloon angioplasty with similar characteristics of the coarctation 8.5 ± 3 years after balloon angioplasty.inthesetwostudiesoverallsixpatientsunderwentrepeatinterventionforrecoarctation and four patients demonstrated aortic aneurysm formation at the dilation site. Walhout et al. reported that the occurrence of recoarctation was 3% in their population. 62 The risk of aortic aneurysmatthedilatationsitewasclearlylowerascomparedtootherstudiesinwhichtheriskwas varyingbetween50%intheearlydaysand1.8and6%asdescribedinlaterstudies Thereduced riskofaorticaneurysmformationinthesestudiesmightbeexplainedbythefactthatonlypatients withadiscrete shelflike lesionwereincludedashasbeenpreviouslyhypothesizedbytanouset al. 69 Despitetheselongtermcomplications,severalstudieshaveshownthatballoonangioplasty isasafeandeffectiveinadultswithnativecoarctation.recoarctationriskafterballoonangioplasty hasbeenshowntobelowerinadultsascomparedtochildren. 55 Resultsafterballoonangioplastyin adults with native coarctation are comparable with surgery, and the longterm need for

8 Surgical versus percutaneous treatment in CoA reinterventionisrelativelylow.however,asstenttreatmentisevolvingovertime,itappearsthatthe roleofballoonangioplastyseemstodeclineforadultswithnativecoarctation.balloonangioplastyis thereforecurrentlylimitedtopaediatricpatientswithadiscreterecoarctationorolderchildrenand adultswithsystemicconditionssuchasconnectivetissuediseaseorturnersyndrome,orinpatients inwhomthearterialaccesssiteisnotsuitableforstentintroduction. 60;70 Balloonangioplastyforrecurrentcoarctation Recurrentcoarctationisacommoncomplicationaftersurgicalcorrection,withanincidenceof16up to60%. 21;71 Thedefinitionofrecurrentcoarctationisaresidualgradientabove2030mmHgatthe coarctation site. Singer et al. were the first to describe treatment of recurrent coarctation with balloon angioplasty, with acceptable early and intermediate term results. 46 However, several complicationshavebeendescribedinotherstudiesafterballoondilatationforrecoarctationsuchas aortic dissection, restenosis, aortic rupture and complications at the femoral access site. 54;68;72;73 Surgicalreinterventionisrequiredin550%ofthesepatients Balloonangioplastyseemstobesafeandeffectiveininfantswitharecurrentcoarctation,to avoidrepeatsurgery. 65 However,Yetmanetal.reportedthatamong90patients(medianageof1.1 years) who underwent balloon angioplasty for recoarctation, 31% required rereintervention. 76 Severalriskfactorsexistforrecoarctationafterballoonangioplasty,includingageatinitialrepair<2 3months,weightatinitialrepair<5kg,residualductiletissue,andtheuseofsilksutureattheinitial repair. 77 Thesefindingsdemonstratethattheeffectivenessofballoonangioplastyforrecoarctationin infancyremainsatopicofdebate. In children with recurrent coarctation, balloon angioplasty was effective in 6790% of the patientswithamortalityrateof0.72.5%. 72;78 Themortalityrateissignificantlylowerascompared the 7% mortality after surgical repair for recoarctation. 72;79 Long termfollowup results were reviewed by Yetman et al. in a large series of children after balloon angioplasty for aortic recoarctation. The immediate outcome after balloon angioplasty was excellent with a residual gradient < 20 mmhg in 88% of the cases. However, in 31% of the 90 cases reintervention was needed.balloonangioplastywasnotparticularlysuccessfulinchildrenwithcomplexmultilevelleft sided obstruction, which suggests that those are less suitable for balloon angioplasty because of persistingabnormalflowintheaorticarch.failureofballoonangioplastyinpatientswithisolated recoarctation was only found in patients after surgical repair with endtoend anastomosis. These findings are attributed to the extended reconstruction in which the site of obstruction is located moreproximaltothetransversearch. 76 Reichetal.describedlongtermfollowupdataafterballoon angioplastyforrecoarctationinchildren,whichdemonstratedalowcomplicationrateaswellasa lowriskofaorticaneurysmformation. 80 AlthoughReichetal.statethatballoonangioplastyshould betheinitialtreatmentinallrecoarctationpatients,restenosiswasmoreoftenfoundinchildrenin whichreinterventionswereperformedatanolderage.therefore,balloonangioplastyseemsmore suitable for the treatment of restenosis during infancy, as it avoids the need for repeat surgery. 65 Balloonangioplastymaybeusefultopreventtheneedforstentimplantationentirely,orpostpone stentimplantationuntiladultagewhenstentingwithadultsizedstentsisfeasible. 80 3

9 Stentimplantation Stentimplantationinchildren De Lezo et al. published the first experiences of treating severe aortic coarctation with balloon expandablestents.ithasbeensuggestedthatstentingafterballoonangioplastylowerstheriskfor complicationsandhasa beneficialeffectonlongtermsurvival Encouraging results havebeen reportedafterstentimplantationfortheinitialtreatmentofaorticcoarctation,especiallyinchildren older than 6 years of age, adolescents and adults. 64;82;83;8597 However, primary stenting has an important limitation, which is the failure to adapt to the growing vessel in a child. In order to overcomethisproblem,redilatationduringfollowuphasbeendescribed. 82;83;98 Thisapproachmight benecessaryingrowingchildren,andhasbeenshowntobesafeandeffectivewhereassurgerymay beassociatedwithamuchhighercomplicationrate. 99 Endoproliferativerestenosishasbeendescribedin18%ofyounginfants,especiallyafterthe useofsmalldiameterstents. 99 Forthisreason,itisimportanttoconsiderthemaximumsizeastent canbe(re)dilated,inordertopreventaniatrogenicobstructioncausedbyasmalldiameterstent. 100 However, more important is that implantation of adultsized stents in children is associated with significantvascularcomplications,whichmayrequiresurgicalstentremovaloraorticreconstruction. Chisolmetal.reportedthattheuseofadultsizedstentsislegitimateinpatientsabove15kgand evenbetween1015kg. 101 However,Rosenthaletal.donotadvocatestentimplantationinchildren lessthan25kgduetodifficultieswiththesizeofthedeliverysheath. 102 Thanopoulosetal.suggested that if stent repair in children is considered, bare metal stents should be favoured over covered stentsinchildrenastheycanberedilatedmoreeasily,andinsertionismorefeasiblethroughsmaller Mullins sheaths. 101;103;104 Moreover, covered stents seem to be more suitable in children with a complexanatomy,withaorticaneurysms,andwithcomplicationsduetostentimplantationsuchas aorticdissection. 105;106 Theuseofbioabsorbablestentsthatadapttothegrowingchildmightbean alternative in children, nevertheless, results with regard to the use of these stents in children are limited. 107 In conclusion, these findings demonstrate that immediate results regarding gradient reduction after stent repair in children are promising. In our opinion, stent implantation remains complicatedinchildrenbelowtheageof810years,duetoseveralmajorlimitationssuchasvascular complications, difficulties with sheat delivery and the fact that children are not yet full grown. 82;83;90;91;108 Additionally,theriskoflateaneurysmformationseemstobehigherinveryyoung children,especiallyinthosewithahypoplasticarch. 109 ThecurrentAHAguidelinesstatethatstent repairisonlyrecommendedinneonateswithacomplexaorticarchobstruction,whichexistsdespite surgicalorcatheterinterventionalattemptsandinhighrisksurgicalpatients. 60 Stentrepairmightbe analternativeinchildrenbeyondtheageof810yearsthatarefullgrown.however,aslongterm dataarelackingthisremainsamatterofdebate.therefore,surgery,withamortalityrateof<1%, remainsthetreatmentofchoiceinbothneonatesandchildrenyoungerthen810yearsofagein whichimplantationofanadultsizedstentisnotpossible. 19;20;110 Stentimplantationinadultpatientswithnativecoarctation In a small percentage of patients, coarctation of the aorta is not diagnosed until adult age. The diagnosis is usually made in the workup for a heart murmur, decreased peripheral pulses, or therapyresistant hypertension. In particular, hypertensive patients may present with decreased

10 Surgical versus percutaneous treatment in CoA exercise tolerance or intermittent claudication due to arterial insufficiency of the legs, either spontaneouslyorafterinitiationofantihypertensivetherapy. 6 Inthemajorityofcasesopensurgical repair is the treatment of choice. 110 Native coarctation patients have an intact aorta at the coarctation site,withoutfibroticorcalcifiedscartissue.surgicalriskislowerinnativecoarctation patientsascomparedtorecoarctationpatientsbecausetherearenoconcernswithregardtopleural orperiaorticscartissueduetoprevioussurgicalprocedures.however,nativecoarctationinadults canbeassociatedwithothercomplicatingfactors.forexample,significantcollateralisationaround thesiteofcoarctationcanoccurinsomepatientsthatpresentwithnativecoarctationatolderage. The risk for surgical bleeding is significantly increased in these patients. Percutaneous treatment mightbeasafeandeffectivealternativeinthesehighriskpatients Wheatly et al. treated 16 native coarctation patients with balloon angioplasty followed by balloonexpandablecoveredstentimplantation,andreporteda100%immediatesuccessratewith regardtogradientresolution.postoperativeserialctimagingdemonstratedminorstentmigrationin only one patient, which required reintervention after 14 months. 116 Tanous et al. utilized covered stents in the management of 22 native coarctation patients, and routine angiographic and hemodynamicassessmentwasperformedafterstentimplantation. 69 Thegradientimmediatelyafter stent placement was maintained during a median followup of 1 year, as was the blood pressure reductionandthelowerneedforantihypertensivemedication. 69 Holzeretal.provideddatafrom oneofthelargestprospectiveregistriesonstentimplantationinbothchildrenandadultswitheither nativeorrecurrentcoarctation. 117 Thesedatademonstratea96%immediatesuccessrateafterstent implantation, and a longterm success rate of 77% over 1860 months followup. A substantial number of patients were followed with either CT or MRI over a mean followup of 1.1 years (3.6 monthsto4.8years)whichallowedassessmentoflongtermcomplications.in5%ofthepatients procedurerelated events occurred. Approximately 12% of these patients required a repeat interventionduringfollowup,whichiscomparablewiththereinterventionratesaftersurgerywhich varybetween6and20%. 117 Stent implantation has proven to reduce the recoarctation risk more then balloon angioplasty alone, as it prevents overdilatation and vascular wall injury and therefore results in a lower degree of elastic recoil. However, underdeployment of stents increases the risk of stent migration, which in some cases may require emergency vascular surgery. 89; Restenosis after implantationofcoveredstentsoccurredin3outof22casesasdescribedinastudybytanousetal., which is comparable with recoarctation risk after implantation of bare metal balloon expandable stents. 69;83;104;121 The risk of aortic aneurysm formation after coarctation stenting in adults appears to be limited,althoughfollowupwithdetailedcardiovascularimagingisoftenlackinginpublishedseries, The reported risk of aortic aneurysm formation is less than 10% after stent implantation, as compared to 17% in patients after balloon angioplasty alone, and 51% in patients after surgical repair. 64;109;122 Aorticdissectionorruptureisararebutpotentiallydevastatingcomplicationofstent implantationforaorticcoarctation.animportantriskfactorforthiscomplicationisadvancedage. Although it has been suggested that the use of covered stents might avoid aortic dissection or rupture,thisisnotnecessarilythecaseasaorticrupturehasbeendescribedaftertheuseofcovered stents. 123 Awarenessoftheriskofaorticdissectionorruptureisextremelyimportant,asitneedsto bemanagedimmediatelybydeploymentofadditionalcoveredstents. 124 Therefore,itisnecessaryto 3

11 continuously monitor stent deployment using simultaneous radial artery access, which allows fast recognitionofhemodynamicinstability,aorticdissectionorrupture,aswellasfemoralarteryaccess complications. 125 Stentfractureisuncommonaftercoarctationstentingbuthasbeendescribedfor thecp TM stent.adequatetreatmentisrecommendedinpatientswithastentfracture,evenifthey areasymptomatic,asaorticaneurysmformationmightoccuratthefracturesite. 84;104;126;127 Designof the CP TM stent has however been changed to reduce the risk for stent fracture and its consequences. 126 Stent technology has evolved rapidly in the past few years, including balloon expanding stents, by incidence self expanding stents and the well known polytetrafluoroethylene covered stents.covered stents are currently recommended as first line intervention in endovascular managementofaorticcoarctationinvariousclinicalconditionssuchnativeaorticcoarctation,stent fracture and recoarctation and aneurysm formation after both surgical and percutaneous procedures.coveredstentswereparticularlyused withanincreasingfrequencyincriticalpatients withaorticwallaneurysmsafterprevioussurgeryorepercutaneoustreatment.however,theuseof coveredstentsiscurrentlyalsoincreasinginpatientswithaprimaryaorticcoarctation,incomplex coarctationpatients,inpatientsatanolderage(>65yearsofage)orinpatientswithpreviousstent relatedcomplications. 104 Coveredstentsseemtobeparticularlyeffectivebecauseoftheir sealing effectonthestenoticareawhichisparticularlyhelpfulinpatientswithaorticwallaneurysmsstent fracturesandeveninpatientswithanaorticrupture. 61 Forthisreason,coveredstentsareprimary effectiveinpreventingaorticdissectionorruptureofthevesselwall.theuseofcoveredstentsis currently indicated in fullgrown patients, as covered stents can only be dilated up to a certain diameter and the fact that redilatation might damage the polytetrafluroethlene covering material. 104;119;128 Inconclusion,theseintermediatetermresultsdemonstratethatstenttreatmentissafeand effectiveinpatientspresentingatadultagewithnativecoarctation.stentimplantationresultsina sustainedreductionofthegradientandareductionofaorticwallcomplicationscomparedtoballoon angioplastyalone. 118 Balloonangioplastyversusstentimplantationinadultswithnativeaorticcoarctation Whetherballoonangioplastyaloneorprimarystentingisthemosteffectivetreatmentadultnative coarctationpatientsremainstobeatopicofdebate.ithasbeensuggestedthatstentimplantation might reduce the complication rate and improve longterm survival in the adult population Balloonangioplastyhasshowntobeeffectiveinreducingthegradientacrossthecoarctationsitein adults. 121; However,apreviousreportdemonstratesresidualgradientsrangingbetween8±10 mmhg up to 18±15mmHg and of > 20 mmhg in approximately 728% of all cases after balloon angioplasty. 121;131 Zabaletal.reportedthattheresidualgradientwassignificantlylowerinthegroup that underwent stent implantation as compared to after balloon angioplasty alone (2.7±4.3 vs 10.7±10.8 mg, respectively). The results for balloon angioplasty were particularly poor in patients withanondiscretetypecoarctation,wherearesidualgradient>20mmhgwasseenin57%ofthe cases, while none of the cases after stent repair had a residual gradient. Among patients with discretetypecoarctation,aresidualstenosiswasobservedinonly9.3%ofthecohortafterballoon angioplasty.primarystentingisthereforeadvocatedinpatientswithacomplexanatomysuchasin patientswithtubularcoarctationoristhmichypoplasia. 64;134;135 Moreover,stentrepairisfavourable

12 Surgical versus percutaneous treatment in CoA inpatientswithadiscretetypecoarctationandaresidualgradientafterballoonangioplastyof>10 mmhg. 64 Stentimplantationhasproventoreducetheriskofrecoarctationascomparedtoballoon angioplasty, because it prevents overdilatation and thereby aortic wall injury and in addition, it results in a lower degree of elastic recoil. The incidence of recoarctation after baremetal stent implantationislimitedtoapproximately1outof16,whichissimilarafterimplantationofcovered stents. 104 Aortic aneurysm formation is a common complication after surgical and percutaneous treatmentofaorticcoarctation.theriskofaneurysmformationisthoughttobehigherafterballoon angioplasty then after stenting. The estimates for risk of aortic aneurysm formation after balloon angioplasty in adults are varying between 0 55%. The risk of aortic aneurysm after balloon angioplastywassignificantlylowerduringintermediatefollowupintwopreviouslypublishedstudies bijfawzyandwalhoutetal. 8;62 Theseresultsmightbecausedbythefactthatonlydiscretetypeor shelflikelesionswereincluded. Theoverallriskforaorticaneurysmformationseemstobeaslowas10%inpatientsafter coarctationstenting,ascomparedto17%inpatientsafterballoonangioplastyand51%inpatients after surgical repair of aortic coarctation. 64;109;119;136 Horlick et al. observed a reduction of post stenoticdilatationinthethoracicaorta,whichmightlimittheriskofaorticaneurysmformationor rupture. Stent repair seems to reduce recoarctation risk and might additionally prevent aortic aneurysm formation as compared to balloon angioplasty alone in adult patients presenting with native aortic coarcation. Percutaneous treatment with primary stenting seems therefore currently thetreatmentofchoicefornativeadultcoarctationpatients. 69 Stentimplantationforrecoarctationatadultage Approximately10%ofpatientswhounderwentsurgicalrepairforcoarctationasaninfantdevelop recoarctation at adult age. 137 These patients often present with associated aortic anomalies, for example aortic aneurysm formation or pseudoaneurysm formation. In addition to the complex aorticpathology,thesepatientsoftenhavealargecollateralnetworkofintercostalarteriesaswellas pleuraladhesionsduetothepreviousoperation.asaconsequence,reinterventioninthesepatients isusuallyachallenge.therefore,alessinvasiveapproachmightbeadvocatedinthesepatientsas excellentresultshavebeendescribedinthesehighriskpatients. 69;138 Stent implantation was initially introduced as a safe alternative to surgery, especially in patients with aortic recoarctation after surgery. Several periprocedural complications have been describedsuchasdeath,immediateorlatedissection,stentrecoil,recoarctationandaorticrupture, as well as complications at the femoral access site. 54;68;72;73;98;139;140 However, longterm followup withctormriimagingdemonstratesthatstentimplantationisaneffectivetechniqueforrecurrent coarctation of the aorta. 141 Stenting for aortic recoarctation is associated with a lower risk of recurrent coarctation and aortic aneurysm formation. 69 The current AHA guidelines recommend stent implantation for recoarctation therefore in all patients with an aortic recoarctation and a gradient>20mmhgwhichareofsufficientsizeforsafestentplacementandinwhichexpansionto anadultsizeispossible. 60 3

13 Comparingballoonangioplasty,surgeryandstentrepairinchildrenandadultswithnativeaortic coarctation Adirectcomparisonbetweenthethreemaintreatmentstrategiesinaorticcoarctationischallenging, aslimiteddataareavailablewithregardtoshorttermandlongtermfollowupcomplicationsand adverseeventswithregardtotherelativelynewpercutaneoustreatmentstrategies.outcomeafter balloon angioplasty has been compared to surgery in previous studies. 50;142;143 However, data regardingthecomparisonofsurgeryversusstentrepairarescarce. The initial treatment effect is usually evaluated by the gradient reduction after repair. However,datawithregardtoresidualgradientsaftersurgicalrepairarelacking.Theinitialeffectof treatmentasdeterminedbythepercentageofpatientswitharesidualgradientof<20mgranges between85100%intheballoonangioplastygroupand94100%afterstentrepair.(table1) Table 1 demonstrates that the reintervention rate in patients after surgical repair is on average 13% (range 1123%) as compared to 21% (331%) after balloon angioplasty. The reinterventionratewasespeciallyhighinpatientstreatedwithballoonangioplastyduringinfancy. Thehighreinterventionrate,whichisonaverage18%(034%)inthestentgroupiscausedbythe fact that elective redilatations have been performed in growing children. In 2011, Forbes et al. publisheddataofanobservationalstudyperformedbytheccisconsortiumtocomparesafetyand efficacyofsurgicalrepair,balloonangioplastyandstentrepairofnativecoarctationinpatientswitha meanageof15years(range263years).inthisstudywitha meanfollowuprangingfrom1860 months, stent repair was superior to surgical repair and balloon angioplasty with regard to immediatecomplicationsinchildrenaged612yearsweighing>10kg.aorticwallcomplicationsof any type occurred significantly more often in the balloon angioplasty group as compared to the surgeryorstentrepairgroup.aorticaneurysmformationafterballoonangioplastyandstentrepair usually occurs usually within the first year after percutaneous treatment, in contrast to surgical repair. 118;144 Aorticaneurysmformationwithinthesurgicalrepairgroupwasexclusivelyfoundinthe subclavian flap and patch angioplasty group. 144 The increased risk of aneurysm formation in the balloon angioplasty group is in agreement with data from Cowley et al. based on a randomized comparisonofballoonangioplastyversussurgeryinchildrenwithnativecoarctation. 143 However,in this study the need for reintervention was also increased in the balloon angioplasty group as comparedtothesurgicalrepairgroup,whichwasnotconfirmedinthecciscpopulation.theriskof acute complications was lowest after stent repair as compared to after surgery or balloon angioplasty.atshorttermandintermediatefollowup,stentingandsurgeryweresuperiortoballoon angioplasty with regard to hemodynamic outcome and aortic arch diameters. However, planned reinterventionsweremostoftenobservedinthestentgroup.overall,acutemortalityiscomparable betweenthethreestrategies;lessthan12%foreach.theoverallmortalityratesinstudieswitha followup of 5 years or less, is ranging between 02.6%. However, Reich et al. demonstrated a mortalityrateof8.1%inpatientswhounderwentballoonangioplastyafter8.4yearsfollowup.the overallmortality30yearsaftersurgeryisreportedtobe23.7%asdescribedbytorosalazaretal. These findings and the overall mortality rates in table 1 demonstrate that the overall mortality is increasingsignificantlyinstudieswithalongerfollowup.

14 Surgical versus percutaneous treatment in CoA Table 1. < 20 mmhg Vacular Study (year) Age Age Follow-up Overall Mortality % % % % % % Surgery

15 ExpertOpinionand5yearview Thisreviewsummarizesthewidevarietyoftreatmentoptionsforaorticcoarctationinvolvingsurgical approachesandpercutaneoustreatmentmodalitiesincludingballoonangioplastyandstentrepair. Althougharangeofstudieshavebeenpublishedonthetreatmentofcoarctation,itremainsdifficult tocomparethesetreatmentstrategies,asmostpublisheddataarebasedonretrospectivestudies biasedbyoperatororinstitutionalpreferences.arecentlypublishedcochranereviewdemonstrated thatnorandomizedtrialswereavailabletocomparesurgeryandstentrepair,whichemphasizethe needforrandomizeddatatocomparedifferenttreatmentstrategies. 145 Consideringthatdatathat areavailable,wehavetobeawarethateachtechniquehashaditsownevolutionandlearningcurve, andthereisalargedifferencewithregardtothelengthoffollowupavailableaftereachtreatment option,withapproximately10yearsafterstentrepair,20yearsafterballoonangioplasty,andupto 50yearsaftersurgery. 75 Furthermore,aorticarchimagingwithCTorMRIorcardiaccatheterizationis notroutinelyperformedafterpercutaneousrepair,whichresultsinsuboptimalscreeningforlong termcomplications. 136 Duetotheselimitations,decisionmakingremainschallenging,andthechoice for the most effective and safe treatment option may depend on an individual patient s age and clinicalscenario.(figure1) Figure1:Overviewofanalgorithmforthedifferenttreatmentstrategiesininfants,childrenandadultswithan aorticcoarctation.

16 Surgical versus percutaneous treatment in CoA Surgeryisstillthetreatmentofchoiceininfantswithamortalityrateoflessthan1%.Moreover, surgeryremainsthetreatmentofchoiceinchildrenbeyondtheneonatalperiod.balloonangioplasty isnotadvocatedinneonatesandchildrenduetoahigherreinterventionrateduetorestenosisand anincreasedriskforaorticruptureandaorticaneurysmformationascomparedtosurgicalrepair. 50;58 Although studies in children after neonatal age weighing more then 15 kg have shown that stent implantation seems to be a safe and effective treatment for primary and recurrent coarctation, surgeryremainsthetreatmentofchoice. 73;146 Themainreasonforwhichsurgeryfavoursstentrepair istheincreasedriskforcomplicationsafterstentrepairinchildrenthatarenotoutgrown,whichis usually below the age of 810 years. 82;83;90;108 Frequent complications after stent repair involve difficultieswithsheatdelivery,vascularcomplications,restenosisandaorticaneurysmformationand failuretoadapttothegrowingchildforwhichredilatationisnecessary. 82;83;90;91 Percutaneous treatment has become an acceptable treatment modality in the adult population.balloonangioplastyandendovascularstentrepairremaintechnicallychallenging,butare safeandundoubtedlyeffectiveinappropriatelyselectedpatients.theroleofballoonangioplastyin adultsseemstobelimitedtopatientsinwhichtheaccesstostentingisnotavailable.stentrepairis currentlythemainstayofpercutaneoustreatmentinadultswithnativeandrecurrentcoarctation,as itpreventsvesselelasticrecoilandreducestheneedforreintervenionsinthefuture. 147 Theuseof bioabsorbable stents may be a promising technique in the setting of coarctation stenting. 148 This revolutionarytechniquemayenabletheuseofstenttreatmentininfantsandstillpreventtheneed forredilatationinagrowingchild. Futurestudiesshouldfocusonthelongtermfollowupforaorticcomplications,morbidity and mortality after each of the available treatment strategies. It has been shown that overall mortalityratesarecomparablebetweensurgicalrepair,balloonangioplastyandstentplacement. 75 Althoughfollowupafterpercutaneoustreatmentishistoricallyshorterthanaftersurgery,mortality rates remain significantly lower after percutaneous treatment than during 30 year followup after surgical repair for aortic coarctation. 3 Although mortality rates are higher after surgical repair, reinterventionriskremainshigherafterstentrepair. 66 Mostreinterventionsinvolveredilatationdue to underdilatation during the initial treatment, whereas the overall risk after redilatation remains lowerascomparedtoafterrepeatsurgery. 89 Data with regard to the periprocedural risks and the intermediate complications such as aneurysmformationandtheneedforreinterventionarenowavailable.percutaneoustreatmentof aorticcoarctationisnowadayssafeandeffectiveinbothchildrenandadultsduetomajoradvances inendovasculartechnology.however,thesepatientsremainatriskforrecoarctationandaneurysm formation. Adequate surveillance by CT or MRI is therefore necessary in all patients, both for the individual patientasfortheoverallassessmentof longtermoutcomeafterthevarioustreatment modalities. Additionally it is known that onethird of the patients remain hypertensive even after successfulendovasculartreatment,andleftventriculardysfunctiondoesnotresolveinallpatients. Thesefindingsdemonstratethatinformationwithregardtodiseaserelatedmorbidityandlongterm outcome is necessary for an adequate decision strategy in the era of transcatheter treatment for aorticcoarctation. 3

17 ŽƌƟĐĐŽĂƌĐƚĂƟŽŶ >ĂƚĞĐŽŵƉůŝĐĂƟŽŶƐĂŶĚƚƌĞĂƚŵĞŶƚƐƚƌĂƚĞŐŝĞƐ Percutaneous treatment in native CoA Percutaneous treatment in recurrent CoA D E J K F G L M H I Figure2:Overviewofadultsdiagnosedwithbothnativeandrecurrentaorticcoarctation. AͲBPatientdiagnosedattheageof26yearswithanativeaorticcoarctation.(A:beforestenting,B:after stenting). CͲDPatientwithanativeaorticcoarctationdiagnosedattheageof28yearswithsignificantcollateralisation (C:beforestentingD:afterstenting). EͲFPercutaneoustreatmentofanativecoarctationdiagnosedattheageof20years(E:beforestenting; F:afterstenting). GͲHPercutaneoustreatmentofsignificantrecoarctationattheageof28yearsafterasubclavianflap procedureduringchildhood.(g:beforestenting,h:afterstenting) IͲJPercutaneoustreatmentofrecoarctationoccuringattheageof45years,afterendͲtoendanastomosis duringchildhood.(i:beforestenting,j:afterstenting). ϱϰ

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