Targeting the tricuspid valve: A new therapeutic challenge.

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ArchivesofCardiovascularDisease(2016)109,1—3

Availableonlineat

ScienceDirect

www.sciencedirect.com

SCIENTIFIC

EDITORIAL

Targeting

the

tricuspid

valve:

A

new

therapeutic

challenge

La

valve

tricuspide

:

un

nouveau

déﬁ

thérapeutique

Patrizio

Lancellotti

a,b,∗

,

Khalil

Fattouch

c

,

Raluca

Dulgheru

a

a_Department_of_Cardiology,_Heart_Valve_Clinic,_University_of_Liège_Hospital,_University

Hospital,GIGACardiovascularSciences,CHUduSartTilman,1,avenuedel’Hôpital,4000 Liège,Belgium

b_Gruppo_Villa_Maria_Care_and_Research,_E.S._Health_Science_Foundation,_Lugo_(RA),_Italy c_Department_of_{Cardiovascular}_Surgery,_GVM_Care_and_Research,_Maria_Eleonora_Hospital,

DepartmentofSurgeryandCancer,UniversityofPalermo,Palermo,Italy

Received9November2015;accepted9November2015 Availableonline18December2015

KEYWORDS Tricuspidvalve; Regurgitation; Treatment; Percutaneous approach MOTSCLÉS Valvetricuspide; Régurgitation; Traitement; Approchepercutanée

Often dysfunctional, difﬁcult to assess with ultrasound techniques, with fewer

out-come data andmore contradictory results than theother valvediseases, the tricuspid

valve (TV)is the most challenging valve for the clinician [1—3]; it is often called the

‘‘forgottenvalve’’.WhileTVstenosis isratheruncommon,TVregurgitation(TR)is

fre-quent,butstillpoorlydeﬁned.TrivialTRisfrequentlydetectedbyechocardiographyin

normal subjects. Pathological TR is more often secondary, rather than resulting from

a primary valve lesion (intrinsic morphopathological changes of the TV complex) [4].

CausesofprimaryTRareinfectiveendocarditis,rheumaticheartdisease,carcinoid

syn-drome,myxomatousdisease,endomyocardialﬁbrosis,Ebstein’sdisease,thoracictrauma,

pacemakerleads/cathetersinterferingwithleaﬂetcoaptationanddrug-inducedvalve

dis-ease. Secondary TRis mainlycaused by dilationof thetricuspid annulusandtethering

of the TV leaﬂets secondary to right ventricular dysfunction caused by chronic

pres-sure (i.e. left-sidedheart disease or pulmonary hypertension)or volumeoverload (i.e.

atrial septaldefects or intrinsic disease of the right ventricle[RV]) [5]. Some authors

distinguish a third entity, at the border between primary and secondary TR, so-called

‘‘idiopathic’’TR,inwhich annularenlargement(possiblyof degenerativeaetiology,but

withnormal leaﬂet morphology) playsthe centralrole inTR genesis [6].‘‘Idiopathic’’

Abbreviations: 3D,three-dimensional;CMR,cardiacmagneticresonance;CT,computedtomography;RV,rightventricle/ventricular; TR,tricuspidvalveregurgitation;TV,tricuspidvalve.

∗_{Corresponding}_author._Department_of_Cardiology,_Heart_Valve_Clinic,_University_of_Liège_Hospital,_University_Hospital,_GIGA_{Cardiovascular}

Sciences,CHUduSartTilman,1,avenuedel’Hôpital,4000Liège,Belgium.

E-mailaddress:plancellotti@chu.ulg.ac.be(P.Lancellotti). http://dx.doi.org/10.1016/j.acvd.2015.11.001

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2 P.Lancellottietal.

TRis more often observed in elderly patients with atrial

ﬁbrillation,butthediagnosiscanonlybemadeafter

exclu-sionof other potentialcauses of TR. Distinction between

theseentitiesrepresentstheﬁrststepintheimaging

assess-mentofTR,aselegantlyhighlightedinthecurrentissueof

thejournalbyHuttinetal.[7].

Echocardiographyisthekeyimagingmethodforthe

eval-uationofTR.Infact,themanagementofpatientswithTR

largelyintegrates theresults of echocardiography; it

pro-videsdetailedanatomicalandfunctional information,and

clariﬁesthemechanismsthatplayaroleinTR[4].Presence

ofvegetations,leaﬂetthickeningandretraction(carcinoid,

rheumaticanddrug-inducedvalvedisease),prolapsing/ﬂail

leaﬂets (myxomatous or post-traumatic disease) or

dys-plastic TV with a distance between the tricuspid septal

leaﬂetinsertionpoint toanteriormitralleaﬂet>8mm/m2

(Ebstein’sdisease)wouldplead forprimaryTR.Secondary

TRis conﬁrmed by measurement of the tricuspid annular

dimensions,TVdeformation,RVfunctionandremodelling,

andsystolicpulmonaryarterypressure.Signiﬁcanttricuspid

annulardilatationisdeﬁnedbyadiastolicdiameter≥40mm

or≥21mm/m2 _(cut-off _derived _from _surgical _studies) _in

thefour-chambertransthoracicview.SigniﬁcantTV

tether-ing,basedonpostoperativeresidualTRafterTVrepairfor

secondary TR, is deﬁned as a coaptation distance>8mm

(distance between the tricuspid annular plane and the

point of coaptation in mid-systole from the apical

four-chamber view), a tenting area>1.63cm2 _and _a _tethering

distance>0.76cm. Similar to mitral regurgitation, mixed

formsofTRmaybeencounteredinadvancedstagesofthe

disease.Inthesecases,three-dimensional(3D)

echocardi-ographymayplayacrucialroleinoutliningtheTRaetiology

[4].

Colour Doppler echocardiographynot only detects the

presenceofregurgitation,butalsopermitsan

understand-ing of the mechanisms of regurgitation (very eccentric

jets may favour primary TR while central jets favour

secondaryTR)andquantiﬁcationofitsseverityand

reper-cussions.Practically,theevaluationofTRrequirestheuseof

differentechocardiographic modalities (M-mode,Doppler,

two-dimensional/3D and transoesophageal

echocardiogra-phy), should integrate multiple variables and should be

supported by clinical data. The width of the vena

con-tracta seems to be the most reliable quantitative index;

a vena contracta diameter>7mm is a good marker of

severeTR.Theproximalﬂowconvergencemethodhasbeen

poorlyvalidated,butretainedcriteriaforsevereTR

affect-ing patient outcome are an effective regurgitant oriﬁce

area>40mm2_and_a_regurgitant_volume_>₄₅_mL_[8]_._In_their

review,Huttin etal.emphasized theneed to accountfor

respiration-inducedchangesinTRseverity,andthe

neces-sitytore-evaluatethepatientsafteroptimizationofloading

conditions, especially when isolated TV surgery is

con-templated. The authors alsooutlined the complementary

usefulnessofcardiac computedtomography (CT)and

car-diacmagneticresonance(CMR)intheassessmentofpatients

withTR[7].

Special attention was also given to the relationship

betweenTRandRVfunction.Theauthorsreiteratedthatthe

RV,beinga volume-pump,toleratesanincreasein volume

overloadratherwell.Signiﬁcant TRmaythusbeclinically

silent foraprolonged period,duringwhich progressiveRV

dilatation and dysfunction may develop [3]. This has led

tothegeneralprinciplethatsurgeryshouldbecarriedout

earlyenoughtoavoidirreversibleRVdysfunction[2,3].

How-ever,theloaddependencyofallechocardiographicandCMR

derivedvariablesofRVfunction,andthefactthatsomemay

bealteredevenintheabsenceofRVcontractiledysfunction,

representnon-negligiblelimitationstothepredictionofRV

functionimprovementaftercorrectivesurgery[7].

Eventually,theTRpatientmaybemanagedwith

diuret-ics for symptoms, and only considered for surgery after

advanced RV dysfunction, even when liver dysfunctionor

cirrhosishasdeveloped.Itshouldbenosurprise,therefore,

thatresultsfromtheSocietyofThoracicSurgeonsDatabase

indicatedthatTVsurgeryisthemosthigh-riskvalve

oper-ation in terms of morbidity and mortality [9]. Although

mitralvalvesurgeryhasevolvedoverthepastfewdecades

towardsprogressivelyearlierintervention,eveninselected

asymptomatic patients, nosuchevolution hasoccurred in

TVsurgeryasyet[2,3].Therelativepaucity ofarticleson

theTVcomparedwithleft-sidedvalvesandthelackof

ran-domizedtrialshaveallcontributedtointensifythisproblem.

Actually,inpatientsscheduledformitralvalvesurgery,TR

isfarfromuncommon.Historically,TRsecondarytomitral

valve disease was thought to improve after mitral valve

surgery; this led to a conservative non-surgical approach

toTR.However,recentstudieshaveclearlychallengedthis

concept, showing excess cardiovascular events when not

treated. Therefore, mitral valve surgery alone cannot be

expectedtoresultineffectiveTRcontrol[10].

The current European and Americanguidelines for the

management of valvular heart disease suggest that TV

surgeryisrecommendedforpatientswithsevereTR

under-goingleft-sidedvalvesurgery(ClassI),andthatTVsurgery

canbevaluableforpatientswithatleastmoderateTRwith

tricuspidannulardilation(ClassIIa)[2,3].RecurrenceofTR

longafterTVplastyisnotasuncommon(ashighas60%at5

years),andsurgerymaybeneededinupto20%ofpatients

after10years[11].Inthesepatients,asreoperationonthe

TVcarriesaveryhighsurgicalrisk,percutaneousapproaches

mightbecomevaluablealternativesinthenearfuture.

Areviewofthetechniquescurrentlyavailableanda

com-prehensivedescriptionofseveralcasesfromexperienceat

Bichat Hospital have been provided in the current issue

of thejournalby Bouletietal.[12].Sofar, transcatheter

interventions for TV disease have been mainly suggested

forpatientswithadegeneratingbioprosthesis,withmixed

results [13]. Indeed, valve-in-valve reimplantation

proce-duresaresubjecttofewercomplicationsthanvalve-in-ring

procedures,inwhich signiﬁcantparavalvularregurgitation

is commoninincompleterigid rings.Valve-in-nativevalve

implantation is more technically challenging. This is the

result,in part, ofthe absenceof arigid landing zonefor

valvedeployment,suchasinaorticstenosis,aswellasthe

varietyofannulardimensions thatmayoccurinsevereTR

[14]. This has recently led tosome experiencewith

het-erotopic placement of transcatheter aortic valves in the

inferiorvenacavainthosepatientswithrefractory

periph-eralsignsofRVfailure[15].Althoughshort-termresultsare

encouraging,long-termstudiesareneeded.Bicuspidization

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Targetingthetricuspidvalve:Anewtherapeuticchallenge 3

authors.Othernewertechniques,suchastheFORMArepair

system(EdwardsLifesciences,Irvine,CA,USA)andthe

Mil-lipedesystem(Millipede,LLC,AnnArbor,MI,USA)arealso

reportedasmeanstoextendcurrentpercutaneousoptions

toTRreduction.Theoptionoftransjugularuseofthe

Mitr-aClip system (AbbottVascular Inc.,Santa Clara, CA, USA)

toattemptleaﬂettetheringanddecreasefunctionalTRhas

alsobeenoutlined,althoughsuchanapproachmaybe

ques-tionableincase ofseveretricuspidannulusdilatation and

widemalcoaptationgaps.

Currently,thereisnosingletherapeuticapproachforthe

percutaneoustreatmentofTR,althoughanincreasing

num-ber of patients with severe TR exist. General agreement

regarding appropriate patient selection, optimal indexof

treatment andstandardized imagingapproach

(echocardi-ography,CMR,CT)isnecessary forthesepatients.Clinical

andtechnicalchallengesassociatedwithpercutaneous

ther-apiesofTRarepreventivefeatures,andrepresentthenext

frontiersthatclinicianswillneedtoovercome.

Disclosure

of

interest

Theauthorsdeclarethattheyhavenocompetinginterest.

References

[1]IungB,BaronG,ButchartEG,etal.Aprospectivesurveyof patientswithvalvularheartdiseaseinEurope:theEuroHeart Surveyonvalvularheartdisease.EurHeartJ2003;24:1231—43. [2]Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guidelineforthemanagementofpatientswithvalvularheart disease: executivesummary: a reportof theAmerican Col-legeofCardiology/AmericanHeartAssociationTaskForceon PracticeGuidelines.JAmCollCardiol2014;63:2438—88. [3]VahanianA, Alﬁeri O, AndreottiF,et al. Guidelines on the

managementofvalvularheartdisease(version2012):theJoint TaskForce ontheManagementofValvularHeart Diseaseof theEuropeanSocietyof Cardiology (ESC)and the European AssociationforCardio-ThoracicSurgery(EACTS).EurHeartJ 2012;33:2451—96.

[4]LancellottiP,TribouilloyC,HagendorffA,etal. Recommenda-tionsfortheechocardiographicassessmentofnativevalvular regurgitation:anexecutivesummaryfromtheEuropean Asso-ciation of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging2013;14:611—44.

[5]Lancellotti P, Magne J. Tricuspid valve regurgitation in patients with heart failure: does it matter? Eur Heart J 2013;34:799—801.

[6]MutlakD,LessickJ,ReisnerSA,AronsonD,DabbahS,Agmon Y.Echocardiography-basedspectrumofseveretricuspid regur-gitation: the frequency of apparently idiopathic tricuspid regurgitation.JAmSocEchocardiogr2007;20:405—8. [7]HuttinO,VoilliotD,MandryD,VennerC,JuillièreY,Selton-Suty

C.Allyouneedtoknowaboutthetricuspidvalve:tricuspid valveimagingandtricuspidregurgitationanalysis.Arch Car-diovascDis2016;109:67—80.

[8]Topilsky Y, Nkomo VT, Vatury O, et al. Clinical outcome ofisolated tricuspid regurgitation.JACC Cardiovasc Imaging 2014;7:1185—94.

[9]RankinJS,HammillBG,FergusonJrTB,etal.Determinantsof operativemortalityinvalvularheartsurgery.JThorac Cardio-vascSurg2006;131:547—57.

[10]GoldstoneAB,HowardJL,CohenJE,etal.Naturalhistoryof coexistenttricuspidregurgitationinpatientswith degenera-tivemitralvalvedisease:implicationsforfutureguidelines.J ThoracCardiovascSurg2014;148:2802—9.

[11]Kim JB, Jung SH, Choo SJ, Chung CH, Lee JW. Clinical and echocardiographic outcomes after surgery for severe isolated tricuspid regurgitation. J Thorac Cardiovasc Surg 2013;146:278—84.

[12]BouletiC,JuliardJM,HimbertD,etal. Tricuspidvalve and percutaneousapproach:nolongertheforgottenvalve! Arch CardiovascDis2015;109:55—66.

[13]BenthamJ,QureshiS,EickenA,GibbsJ,BallardG,Thomson J. Earlypercutaneous valvefailure within bioprosthetic tri-cuspidtissuevalvereplacements.CatheterCardiovascInterv 2013;82:428—35.

[14]O’NeillWW,O’NeillBP.Transcathetertricuspidvalve interven-tion:thenextfrontier.JAmCollCardiol2015;65:1196—8. [15]LautenA,Ferrari M,HekmatK,et al.Heterotopic

transcat-heter tricuspid valve implantation: ﬁrst-in-man application of a novelapproach to tricuspidregurgitation. Eur HeartJ 2011;32:1207—13.