Title:First-in-humanexperienceofanewgenerationtransfemoraltranscatheteraorticvalveforthetreatmentofsevereaorticregurgitation:theJ-Valvetransfemoralsystem.

Authors:MarkHensey,MB,BCh,BAO;DaleJMurdoch,MBBS;JanarthananSathananthan,MBChB;AbdullahAlenezi,M.D;GnaliniSathananthan,M.D;RobertMoss,

MBBS;PhilippBlanke,M.D;JonathonLeipsic,M.D;DavidAWood,M.D;AnsonCheung,

M.D;JianYe,M.D;JohnGWebb,M.D

DOI:10.4244/EIJ-D-18-00935

Citation:HenseyM,MurdochDJ,SathananthanJ,AleneziA,SathananthanG,MossR,BlankeP,LeipsicJ,WoodDA,CheungA,YeJ,WebbJG.First-in-humanexperienceofa

newgenerationtransfemoraltranscatheteraorticvalveforthetreatmentofsevere

aorticregurgitation:theJ-Valvetransfemoralsystem.EuroIntervention2018;Jaa-4852018,doi:10.4244/EIJ-D-18-00935

Manuscriptsubmissiondate:20September2018

Revisionsreceived:30October2018Accepteddate:16November2018

Onlinepublicationdate:20November2018

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First-in-humanexperienceofanewgenerationtransfemoraltranscatheter

aorticvalveforthetreatmentofsevereaorticregurgitation:theJ-Valve

transfemoralsystem

MarkHenseyMBBChBAO

DaleJMurdochMBBS

JanarthananSathananthanMBChB

AbdullahAleneziMD

GnaliniSathananthanMD

RobertMossMBBS

PhilippBlankeMD

JonathonLeipsicMD

DavidAWoodMD

AnsonCheungMD

JianYeMD

JohnGWebbMD

CentreforHeartValveInnovation,StPaul’sHospital,UniversityofBritish

Columbia,Vancouver,Canada

Runningtitle:

First-in-humantransfemoralJ-Valvesystem

AddressforCorrespondence:

JohnWebbMD,St.Paul’sHospital,1081BurrardStreet,Vancouver,BC,Canada

V6Z1Y6

Email:john.webb@vch.ca

Telephone:+16048068804

Disclosures:

Drs.Blanke,LeipsicandWood,andWebbareconsultantstoandreceiveresearch

supportfromEdwardsLifesciences.DrCheungisaconsultanttoAbbott

Disclaimer : As a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been published immediately upon acceptance as it was received. The content of this article is the sole responsibility of the authors, and not that of the journal

Vascular,MedtronicandNeovasc.DrYeisaconsultanttoEdwardsLifesciences

andJCMedical.

Wordcount:1339

Classifications:

Aorticregurgitation

Femoral

TAVI

Fundingstatement:

Nofundingsources

Abreviations:

TAVI–Transcatheteraorticvalveimplantation

AS–Aorticstenosis

TA–Transapical

AR–AorticRegurgitation

TF–Transfemoral

NYHA–NewYorkHeartAssociation

LV–Leftventricular

TEE-Transesophagealechocardiography

TTE–Transthoracicechocardiography

Disclaimer : As a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been published immediately upon acceptance as it was received. The content of this article is the sole responsibility of the authors, and not that of the journal

Introduction

Transcatheteraorticvalveimplantation(TAVI)isnowwellestablishedinthe

contemporarymanagementofsevereaorticstenosis(AS)withamultitudeof

valvedesignsavailable.Thetransapical(TA)J-Valvesystem(JCMedicalInc.,

Burlingame,California,USA)haspreviouslybeenshowntobeeffectiveforthe

treatmentofbothsevereASandaorticregurgitation(AR)(1,2).

TheJ-Valvetranscatheteraorticvalveconsistsofthevalveandthreeu-shaped

‘anchorrings’(Figure1A)andisdeployedinatwo-stepprocess.Firstthe

anchorringsareopenedabovethenativevalveandareretracted(TA)or

advanced(transfemoral)intothevalveapparatusallowingautomaticanatomic

alignmentintheaorticsinusesandclaspingofthenativevalveleaflets(Figure

1C),thiscanbevisualisedonfluoroscopy.Oncepositioned,theself-expanding

valveisthendeployedwithintheanchorringsandsecuresthenativevalve

leaflets(Figure1D).Thevalveisnotrecapturable.Thetransfemoral(TF)

valveisdeliveredbyan18Frsteerabledeliverysystem(Figure1B).Wepresent

thefirst-in-humanexperienceoftheTFJ-Valvesystemforthetreatmentof

severeAR.

Methods

A42-year-oldmalewithpriorsubaorticmembranerepairpresentedwith

recurrentheartfailurehospitalizationsduetosevereAR(NewYorkHeart

Association(NYHA)ClassIV)andhighdiureticrequirements.Echocardiography

revealednormal(LV)systolicfunction,anLVend-diastolicdiameterof66mm

andanon-calcifiedtricuspidaorticvalvewithsevereAR(Figure2A).Invasive

cardiaccatheterizationrevealednormalcoronaryarteriesandraisedLVend-

diastolicpressureof35mmHg.Hehadmultiplecomorbiditiesincludingmorbid

obesity(BMI>50kg/m2),diabetesandstageIVchronickidneydisease(eGFR

29ml/minper1.73m2).STSpredictedriskofmortalitywas7.8%andthepatient

wasdeemedatprohibitiveriskforsurgicalaorticvalvereplacementorTATAVI

bythemultidisciplinaryHeartTeam.Preoperativevalvesizingwith

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computedtomographywasnotoptimalduetoelevatedbodymassindex

andattemptstoreducecontrastloadtolowertheriskofacutekidney

injury,thereforeintraoperativetransesophagealechocardiography(TEE)

wasperformedtoconfirmsizing.TEEisnotrequiredfordeploymentofthe

valve.

Rightcommonfemoralarterialaccesswasgainedandan18Fsheathinserted.

TheaorticvalvewascrossedandasmallSafariwire(BostonScientific,

Marlborough,Massachusetts,USA)wasplacedintheleftventricle.A28mmJ-

valvesystemwasadvancedoverthewireintotheaorticrootanddeployed

withouttheneedforrapidpacing.Deploymentofthevalveprovedchallenging

duetothesmallsizeofthesinotubularjunctionwhichinteractedwiththevalve’s

anchorrings,howeverastablepositionwasattained(Figures2Cand2D).

Followingvalvedeploymenttherewasanimmediateimprovementin

haemodynamics.EchocardiographyandaortographyrevealednosignificantAR

(Figure2B),howevertheaorticportionofthevalveframeappearedunder-

expandedonfluoroscopy(Figure2D).Webelievethatthiswasduetorotation

ofthedeliverysystemfollowingdeploymentoftheanchorrings,butprior

tovalvedeployment,resultinginthetwistingofsutureconnectionsatthe

topofthevalve.Meantransaorticgradientontransthoracicechocardiography

(TTE)was39mmHgwithnoAR.Post-dilatationoftheTAVIvalvewas

subsequentlyperformedwitha25mmballoonandresultedinfullexpansionof

thevalveframeandareductionofthemeangradientto16mmHg(Figures2E

and2F).

Results

Thepatientremainedintubatedfor8daysduetohighrespiratorysupport

requirementsandrequiredtemporaryintermittenthaemodialysis.Ondischarge

thepatientwaseuvolaemic,hadNYHAclassIIsymptoms,improvedrenal

function(eGFR>50)andnodiureticrequirements.At30-dayfollow-upthe

patientremainedNYHAClassIIandremainedoffdiuretics.TTErevealedamean

gradientof18mmHgwithnoARandnormalLVsystolicfunction.

Disclaimer : As a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been published immediately upon acceptance as it was received. The content of this article is the sole responsibility of the authors, and not that of the journal

Discussion

TheJ-ValveTFsystemofferspotentialforthetreatmentofsevereASandpure

ARanddespiteadifficultpost-proceduralcourse,deliveredapromisingclinical

resultinthiscase.Under-expansionofthevalve,asoccurredinthiscase,can

bepreventedbyavoidingrotationofthedeliverysystemafterdeployment

oftheanchorrings.Changestothedeliverysystemarealsobeingmadeto

addressthisissue.ATFapproachislessinvasivethanTAaccesswhilst

preservingtheleaflet-securingandanatomicpositioningabilitiesoftheJ-Valve

system.Theseleaflet-securingpropertiesofferpossibleadvantages,notonlyin

thetreatmentofpureAR,butalsomayalsoofferasolutiontothetreatmentof

patientswitheithernativeASorbioprostheticvalvefailureathighriskof

coronaryobstructionastheanchorringsmayretractthenativeorbioprosthetic

valveleafletstoavoidobstructingthecoronaryostia(3);thisrequiresfurther

investigation.Additionallythevalvetodatehasdemonstratedalow

pacemakerrateofapproximately5%(1,2),likelyduetotherelativelyhigh

deploymentwithintheanchorrings.

Limitations

ThisisasinglecasestudyandtheTFJ-Valvesystemrequiresvalidationwith

furtherclinicaldataandlarge-scaleclinicaltrials.

Conclusions

TheTFJ-Valvesystemisanoveltranscatheterheartvalvesystemwithleaflet

securinganchorrings,whichmaybewellsuitedtopatientswithnon-calcified

aorticvalvediseaseandthoseatriskofcoronaryobstruction.Furtherclinical

experienceisrequired.

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Impactondailypractice

TheTFJ-Valveisnotcurrentlyavailableoutsideofclinicalstudies,howeveritis

apotentiallyadvantageousdeviceincertainclinicalsituations.

Figure1.TransfemoralJ-ValveSystem.A)Valveconsistingofbovinepericardial

leafletswithinnitinolstentframedeployedwithinnitinolanchorring.B)J-Valve

steerabletransfemoraldeliverysystem.Outerdiameterof18Frwithminimal

femoralaccessdiameterof5.5mm.C)Illustrationofanchorringdeployment

withinnativevalvecuspswithanatomicalignmentandleafletgrasping.D)

Deploymentofself-expandingJ-Valvewithinanchorring.E)Valvesizingchart.A

31mmvalveisalsoindevelopment

Figure2.Transesophagealechocardiography(TEE)andfluoroscopyofJ-Valve

deployment.A)TEEpre-deploymentshowingsevereaorticregurgitation.B)TEE

post-deploymentshowingtrivialparavalvularaorticregurgitation.C)

Fluoroscopyofanchordeploymentintonativevalvecusps.D)Fluoroscopyof

deployedvalveintoanchorrings.D)Post-dilatationofvalvewith25mmnon-

compliantballoon.E)Finalaortogramshowingwell-deployedvalvewithno

aorticregurgitation.

Disclaimer : As a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been published immediately upon acceptance as it was received. The content of this article is the sole responsibility of the authors, and not that of the journal

References:

1. LiuH,YangY,WangW,ZhuD,WeiL,GuoK,ZhaoW,YangX,ZhuL,GuoY,

WangW,WangC.Transapicaltranscatheteraorticvalvereplacementforaortic

regurgitationwithasecond-generationheartvalve.TheJournalofthoracicand

cardiovascularsurgery.2018;156(1):106-16.

2. ZhuL,GuoY,WangW,LiuH,YangY,WeiL,WangC.Transapical

transcatheteraorticvalvereplacementwithanoveltranscatheteraorticvalve

replacementsysteminhigh-riskpatientswithsevereaorticvalvediseases.The

Journalofthoracicandcardiovascularsurgery.2018;155(2):588-97.

3. YeJ,LeeAJ,BlankeP,WebbJ.Thefirsttransapicaltranscatheteraortic

valve-in-valveimplantationusingtheJ-valvesystemintoafailedbiophysio

aorticprosthesisinapatientwithhighriskofcoronaryobstruction.

Catheterizationandcardiovascularinterventions:officialjournaloftheSociety

forCardiacAngiography&Interventions.2018.

Disclaimer : As a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been published immediately upon acceptance as it was received. The content of this article is the sole responsibility of the authors, and not that of the journal

Disclaimer : As a public service to our readership, this article -- peer reviewed by the Editors of EuroIntervention - has been published immediately upon acceptance as it was received. The content of this article is the sole responsibility of the authors, and not that of the journal