017-AHA科学声明：左心疾病引起的儿童肺动脉高压的临床管理和移植考虑 2024

Circulation:HeartFailure

AHASCIENTIFICSTATEMENT

ClinicalManagementandTransplant

ConsiderationsinPediatricPulmonary

HypertensionDuetoLeftHeartDisease:AScientificStatementFromtheAmericanHeartAssociation

RachelK.Hopper,MD,Chair;GeorgHansmann,MD,PhD;SethA.Hollander,MD;AnneI.Dipchand,MD;OscarvanderHave,MD;ColleenIler,ACCNS-P;CynthiaHerrington,MD;ErikaB.Rosenzweig,MD;JuanC.Alejos,MD;

KarinTran-Lundmark,MD,PhD,ViceChair;onbehalfoftheAmericanHeartAssociationCouncilonCardiopulmonary,CriticalCare,Perioperative&Resuscitation;CouncilonClinicalCardiology;andCouncilonCardiovascularStrokeNursing

ABSTRACT:Childrenwithleftheartdiseaseareatriskfordevelopingpulmonaryhypertension,initiallysecondarytopulmonaryvenoushypertensionthatcanprogresstoincludeelevatedpulmonaryvascularresistance,knownascombinedpre-andpostcapillarypulmonaryhypertension.Elevatedpulmonaryvascularresistancemayposearisktotherightventricleofanewlytransplantedheartbecauseofincreasedafterloadandisanimportantconsiderationforhearttransplanteligibility.However,theepidemiology,pathophysiology,optimaldiagnosticandtreatmentapproaches,andthresholdsforpulmonaryvascularresistanceinpulmonaryhypertensionassociatedwithleftheartdiseaseremainunclearbecauseoflackofevidence,particularlyinpediatrics.Theresultisheterogeneitywithrespecttohemodynamicassessment,useofpulmonaryvasodilatortherapies,andhearttransplantlisting.Thisscientificstatementaimstosynthesizetheavailabledataandhighlightareasofgeneralconsensusaswellasimportantknowledgegaps.

KeyWords:AHAScientificStatements.heartdiseases.hypertension,pulmonary.pediatrics.transplantation

I

nmanycountries,pediatrichearttransplantation(HTx) isstandardtherapyforend-stageheartfailureinchil- dren,whichinmostcasesiscausedbycongenital heartdiseaseorcardiomyopathy.Associatedpulmonaryhypertension(PH)canbeanabsoluteorrelativecontra-indicationtoHTx,dependingonthelevelofelevationofpulmonaryvascularresistance(PVR)andotherclinicalfactors.ElevatedPVRmaydetercentersfromconsid-eringachildforHTxalone,raisingtheconsiderationofcombinedheart-lungtransplantation,becauseoftheriskofpostoperativerightheartfailurefromincreasedafter-loadtotherightventricle(RV)ofthenewlytransplantedheart.However,long-termsurvivalissignificantlybetterwithHTxcomparedwithcombinedheart-lungtransplan-tation;inaddition,increasedPVRsecondarytoleftheartdiseasenormalizesaftertransplantinmostcases.1

WhereasassessmentofPVRispartofthestandardHTxevaluationinmostcenters,thereislittleconsensusregardingPVRthresholdsforHTxlisting,particularlyinchildren,largelybecauseoflackofdata.Recogni-tionofthepotentialnegativeeffectofelevatedPVRonHTxoutcomesandthegoaltoavoidlungtransplanta-tionhaveledtopreventionandmanagementstrategies,includinguseofpulmonaryvasodilatortherapies.Theevolutionofventricularassistdevices(VADs)andtheircapacitytoreduceleftatrial(LA)andleftventricular(LV)end-diastolicpressurehavealsobroadenedthearmamentariumoftherapeuticsusedtotreatPHinthepediatricHTxcandidate.ThesestrategiesmayalsobeusedtotreatpersistentPHandRVdysfunctionintheearlypost-HTxperiod,ifneeded.Clinicalquestionsandmanagementdilemmasencounteredwhenassessing

©2024AmericanHeartAssociation,Inc.

Circulation:HeartFailureisavailable

at/journal/circheartfailure

CircHeartFail.2024;17:e000086.DOI:10.1161/HHF.0000000000000086TBD20241

HopperetalPediatricPHDuetoLeftHeartDisease

CircHeartFail.2024;17:e000086.DOI:10.1161/HHF.0000000000000086TBD20242

childrenwithelevatedPVRforHTxarehighlightedinFigure1.

Thelackofconsensusregardingevaluationandman-agementofelevatedPVRinchildrenwithheartfailurebeforeHTxresultsinbroadpracticeheterogeneity.2Thisscientificstatementaimstoreviewtheavailabledataonhemodynamics,pathophysiology,andmanagementofPHsecondarytoleftheartdiseaseinchildrenbeforeandafterHTx,identifyknowledgegaps,andhighlightareasforfutureresearchtoidentifyandstandardizebestpracticesforoptimalpatientoutcomes.Managementofpatientswithsingleventriclephysiologyisbeyondthescopeofthisscientificstatementandwillnotbediscussed.

CLASSIFICATIONANDPATHOBIOLOGYOFPHINPEDIATRICLEFTHEARTDISEASE

HemodynamicDefinitionsofPH

In2018,theWorldSymposiumonPulmonaryHyperten-sion(WSPH)issuedarevisionofthedefinitionofPHfromameanpulmonaryartery(PA)pressure(mPAP)

≥25mmHgto>20mmHg.3ThiswasincorporatedintothepediatricPHrecommendationspublishedby

theWSPHin20184andtheEuropeanPediatricPulmo-naryVascularDiseaseNetwork,5althoughitisunclearwhetheramildmPAPelevationof21to24mmHgisclinicallyrelevantinchildrenandadolescents.PulmonaryarterialhypertensionisclassifiedasWSPHgroup1PH:aformofprecapillaryPHthatischaracterizedbyhighmPAPwithelevatedPVRandnormalPAwedgepressure(PAWP).InPHduetoleftheartdisease(WSPHgroup2),themajordriverissystolicordiastolicdysfunctionoftheleftventricle,leadingtoLAhypertensionandpulmo-naryvenouscongestionorhypertension,withelevatedmPAPandPAWP(postcapillaryPH).Congenitalleft-sidedobstructivelesions,suchasmitraloraorticvalvestenosis,canalsocauseLApressureelevationandpost-capillaryPH.PatientswithpostcapillaryPHcandevelopelevatedPVR,resultingincombinedpre-andpostcapil-laryPHwithfeaturesofWSPHgroups1and2(Table1).

ClassificationofPHDuetoLeftHeartDisease

ThebroaddiagnosescontributingtoPHinleftheartdiseaseinchildrenarepresentedinFigure2,andincludeabnormalitiesanatomicallylocatedbetweenthepul-monarycapillariesandthethoracicdescendingaorta.LeftheartfailurecanbefurtherdividedbyLVejection

Figure1.Clinicalquestionsandmanagementdilemmasinevaluationandtreatmentofchildrenwithleftheartdiseaseandelevatedpulmonaryvascularresistance.

Manyquestionsremainregardingtheapproachtothepediatricpatientwithleftheartdiseaseandelevatedpulmonaryvascularresistance,

includingclinicalriskfactors,hemodynamicassessmentbycardiaccatheterizationwithacutevasoreactivitytesting,andapproachtomedicalmanagementandtransplanteligibility.Thequestionmarkshighlightareasofuncertaintyandpracticeheterogeneitythatwouldbenefitfromfurtherstudy.

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Table1.HemodynamicDefinitionsofPulmonaryHypertension

Definitions*†

Invasivemeasures*†

WSPHgroup

Pulmonaryhyper-tension(PH)*†

mPAP>20mmHg

1–5

Precapillary

PH*†or

pulmonaryarterialhypertension

mPAP>20mmHg

PAWP≤15mmHg

PVRi≥3WUm2(adults:PVR>2WU‡)

1,3,4,and5

Isolated

postcapillaryPH*†

mPAP>20mmHg

PAWP>15mmHg

PVRi<3WUm2(adults:PVR<2WU‡)dTPG<7mmHg(optional)

2and5

Combinedpost-

andprecapillaryPH

mPAP>20mmHg

PAWP>15mmHg

PVRi≥3WUm2(adults:PVR>2WU‡)dTPG≥7mmHg(optional)

2and5

Hemodynamicdefinitionsaccordingtothe2018WorldSymposiumonPul-monaryHypertension(WSPH)3andthe2022EuropeanSocietyofCardiology/EuropeanRespiratorySocietyguidelinesonpulmonaryhypertension(PH)inadults.17dTPGindicatesdiastolictranspulmonarypressuregradient;PAWP,pul-monaryarterywedgepressure;andPVRi,pulmonaryvascularresistanceindexedforbodysurfacearea.

*ThedefinitionsofthePHsubtypesapplyonlywhencardiacindexiseithernormalordecreased,andnotinhyperdynamicstateswithsubstantiallyincreasedcardiacindex(eg,high-doseprostacyclinanalogueinfusion,sepsis).

†ThedefinitionofPHhaschangedtoalowermeanpulmonaryarterialpres-sure(mPAP)cutoffvalue(mPAP>20mmHg)andnowalsoincludesthepulmo-naryvascularresistancecutoffvalueof3WU(adults)and3WU·m2(children)todistinguishprecapillaryfromisolatedpostcapillaryPH.

‡EuropeanSocietyofCardiology/EuropeanRespiratorySocietyguidelinesonly.

AdaptedwithpermissionfromSimonneauetal3andHumbertetal.17©Copy-right2023EuropeanRespiratorySociety.

fractionstatus(ie,heartfailurewithpreservedejectionfractionversusheartfailurewithreducedejectionfrac-tion[HFrEF]).Accordingtothe2018WSPHclassifica-tion,3PHduetoleftheartdisease(WSPHgroup2PH)includesthefollowingsubgroups:

2.1:PHduetoheartfailurewithpreservedejectionfraction

2.2:PHduetoHFrEF

2.3:Valvularheartdisease

2.4:Congenital/acquiredcardiovascularconditionsleadingtopostcapillaryPH

ChildrencandevelopPHsecondarytoLVmyocar-dialdysfunctionorfailure(systolic,diastolic,orboth)orbecauseofunderlyingcongenitaloracquiredheartdis-easeswithpreservedorreducedLVejectionfraction.6Inchildren,heartfailurewithpreservedejectionfractionismostcommonlyassociatedwithcongenitalhypoplasiaofleft-sidedstructures(suchastheShonecomplex,hypo-plasticleftheartvariants,orrestrictivecardiomyopathies)orcongenitalleftinflow/outflowobstructivelesions(suchasmitralstenosis,cortriatriatum,orchronicmitralregur-gitation).7RheumaticheartdiseaseaffectingthemitralvalveisacommonacquiredcauseofWSPHgroup2PHinlow-tomiddle-incomecountries,butitislesscom-monindevelopednations.8Pulmonaryveinstenosisisan

importantcauseofWSPHgroup2PH,butitisnotdis-cussedinthisarticle,becausepatientswithpulmonaryveinstenosisarenottypicallyconsideredforisolatedHTx.CongenitaloracquiredLVoutflowobstructions,suchasaorticstenosisorcoarctationoftheaorta,aremorelikelytopresentwithHFrEFinchildren.OthercausesofHFrEFincludedilatedandhypertrophiccardiomyopa-thies,whichcanbecongenital/inheritedoracquired.7,9Inaddition,patientswithcomplexcongenitalheartdisease(WSPHgroup5.4PH),suchasShonecomplexwithshunts,candevelopcombinedpre-andpostcapillaryPHofvaryingseveritybecauseofthevariabilityinunderlyinghemodynamicsandrepairstrategies.3,4

PathobiologyofPHinLeftHeartDisease

ChronicpulmonaryvenouscongestionandresultingPHcanleadtoconstrictionandremodelingofthepulmonaryvasculature,resultinginelevatedPVR(Figure2).Precap-illaryvasoconstrictionmaybeaprotectivereflextopreventpulmonaryedemawhenPApressureiselevatedbecauseofcongestion,atleastintheearlyphasesofdisease.10ThetimingandprecisemechanismsunderlyingPAremodel-ingremainunclearbutlikelyincludeincreasedwallstressandmyogeniccontractionleadingtosmoothmusclecellproliferation,aswellasgeneticandmetabolicfactors.11,12ThisremodelingischaracterizedhistologicallybymedialthickeningofPAsand,lessfrequently,intimalfibrosis.13Inchildrenwithpulmonaryvenoushypertensionbecauseofcongenitalmitralstenosis,extensivemedialhypertrophyofthePAshasbeenreported,14withthemedialthicknesscorrelatingwithdegreeofPH.15Despitetheseverityofvascularremodelinginmitralstenosis,thePApressuretypicallynormalizesaftersurgicalintervention,suggest-ingreversibilityofvascularchanges.14,16Giventhehighriskassociatedwithlungbiopsyinchildrenwithheartfail-ureandPH,lessinvasivediagnostictestsareneededtocharacterizevascularremodelingbeforeHTxandassessreversibility,suchasserumbiomarkersoradvancedimag-ingmodalities.

EpidemiologyofPHinPediatricLeftHeartDisease

Accordingtothe2022EuropeanSocietyofCardiology/EuropeanRespiratorySocietyguidelines,PHduetoleftheartdiseaserepresentsthemostprevalentformofPHinadults,accountingfor65%to80%ofcases.17How-ever,epidemiologicandoutcomedataonPHduetoleftheartdiseaseinchildrenaresparse,becausethispopula-tionisrarelyincludedinpediatricPHregistries.Arecentregistryofchildrenwithacutedecompensatedheartfail-ureadmittedtocardiacintensivecareunitsidentifiedPHin6%ofhospitalencounters,whichwasmorecommoninpatientswithcongenitalheartdiseasethanthosewith-out.18Differencesinpathogenesis,age,severity,duration,

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Figure2.Mechanismsofpulmonaryhypertensionduetoleftheartdisease.

Pathogenesesunderlyingleft-sidedheartdiseaseinchildrenandadolescentsincludebothcongenitalandacquiredstructuralanomaliesoftheleftoutflowandinflowtractsaswellasprimarycausesofsystolicanddiastolicheartfailurewithbothpreservedandreducedejectionfraction.Elevationofpulmonaryvenouspressureisacommonconvergingpointforallpathogeneses,whichistypicallyprecededbyelevationofleft

atrialpressure.Elevationsofpulmonaryvenouspressurearepropagatedontothearterialsidethroughalveolarcapillaries,causingpostcapillarypulmonaryhypertension(PH).InthesettingofchronicpostcapillaryPH,precapillarypulmonaryvasoconstrictionandarterialremodelingcan

givewaytoelevatedpulmonaryvascularresistance(PVR),causingcombinedpre-andpostcapillaryPH.FactorscontributingtoreversibilityofPVRremainunclear.

andmanagementofheartdiseasealllikelyaffectthedegreeofseverityandpotentialforreversibilityofcom-binedpre-andpostcapillaryPHinchildren.

HEMODYNAMICCONSIDERATIONSFORHTx

CardiacCatheterization

WhereascardiaccatheterizationisnotrecommendedforroutinesurveillanceinchildrenbeforeHTx,itisrec-ommendedinthesettingofconcernforPH.19PracticevariationexistsregardingcardiaccatheterizationforhemodynamicassessmentbeforeHTxbecauseoflackofdatatosupportrecommendationsbutmaybeunder-taken,atleastinpart,todifferentiatebetweenisolated

postcapillaryorcombinedpre-andpostcapillaryPH(Table1),byPVRandothermeasures.ThePVRiscal-culatedasthemeantranspulmonarypressuregradi-entdividedbypulmonarybloodflow.Inchildren,PVRisindexedforbodysurfacearea(PVRi),andreportedinindexedWoodunits(iWU;mmHg·L·min·m2,WU·m2).Despitepotentialusefulness,theremaybelimitationstopre-HTxinvasivehemodynamicassessmentinchildren,intermsofapproach,calculations,andproceduralrisk,includingthefollowing:(1)accuratemeasurementofcar-diacoutputmaybechallenginginthesettingofseverelyreducedventricularfunctionorconfoundedbypresenceofaVAD;(2)thereisnoconsensusregardinguseofcal-culatedFick(usuallywithassumedoxygenconsumption)versusmeasuredthermodilutionmethodsfordetermina-tionofcardiacoutput2;(3)sedationoranesthesiaforthe

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procedureaffectsbothpulmonaryandsystemicvascularresistanceanddoesnotreflectbaselineconditions;(4)thereisalackofstandardizationofprotocolsformonitor-ingandpressuremeasurements;and(5)theprocedurecarriesrisk,especiallyincriticallyillchildren.

Thediastolictranspulmonarypressuregradient(dTPG),alsocalleddiastolicpressuregradient,iscal-culatedbysubtractingthePAWPfromthediastolicPApressure.BecausedTPGisadirectlymeasuredindica-torofprecapillarypulmonaryvasculardisease,itislesssensitivetoflowmetrics(confounders)andlargelyinde-pendentofRVstrokevolume.StudiesinadultssuggestdTPGispreferablefortheassessmentoftheprecapillarycomponentinWSPHgroup2PH.20,21Onepediatricstudyfoundhighpre-HTxdiastolicpressureindices(diastolicPApressureanddTPG)wereassociatedwithhigherriskofearlygraftlossafterHTx,whereasPVRiwasnot.22

AcuteVasoreactivityTesting

Acutevasoreactivitytesting(AVT)canbeperformedduringcardiaccatheterizationtoassessresponseofthepulmonaryvascularbedtovasodilatorsandassessPHreversibility.The2016InternationalSocietyforHeartLungTransplantationguidelinesrecommendperformingAVTifPAsystolicpressureis≥50mmHgandeithertranspulmonarypressuregradientis≥15mmHgorPVRis>3WUwhilemaintainingsystolicbloodpressure>85mmHg.19ThereisnostandardizedapproachtoAVTinchildrenbeforeHTx.Mostcentersuseinhalednitricoxide(iNO)eitheraloneorincombinationwith100%oxygen,iftheyassessacutevasoreactivityinpatientswithelevatedPVRiatbaseline.2However,thereisapaucityofdataontheoptimalapproach.Patientswithcombinedpre-andpostcapillaryPHmayrequireareductioninLVafterloadtoachieveoptimizationofPVRi,sosomecentersusenitroprussideormilrinone,eitheraloneorincombinationwithiNO,toassesschangesinPVRi.23,24ThepotentialriskofAVTisacutepulmonaryedemafromworsen-ingLAandpulmonaryvenoushypertension,although1studydemonstratedthatiNOdecreasedPApressureandPVRinchildrenwithbaselineLApressure>15mmHgwithoutasubstantialincreaseinLApressure.25Becausetherearenostudiestoguideabsolutecontra-indicationsforAVT,cliniciansshouldcarefullyweighrisksandbenefitsoftestingpatientswithsevereLAhyperten-sion,especiallyinthesettingofhemodynamicinstabilityorpreexistingpulmonaryedema,andexercisecautionifthePAWPisgreatlyelevated.

UnlikeforWSPHgroup1PH(pulmonaryarterialhypertension),therearenoaccepteddefinitionsofposi-tiveAVTforWSPHgroup2PH.The24thBethesdacon-ferencestatedthataPVR>6WUthat“decreasesby50%withhemodynamicmaneuvers”wasacceptablefororthotopictransplant,basedonlimitedadultdataatthetime.26Arecentpracticesurveyofpediatricphysicians

revealedthathalfofrespondingcentersconsideraPVRicutoff<6iWUafterAVTasacceptabletoproceedwithHTx.2However,PVRialonemaybeinsufficienttointerprethemodynamicresponsetoAVT.Forexample,AVTusuallyincreasespulmonarybloodflow(denominator)butmayalsoleadtoadisproportionateriseinLApressure(andPAWP)ifthereisunmaskedLVdiastolicdysfunction.Thiscausesadecreaseinmeantranspulmonarypres-suregradient(numerator),and,assuch,thePVRi.ThedropinthecalculatedPVRimaythenbemorereflectiveofrestrictiveLVphysiologythanvasoreactivityandwouldindicateacontraindicationtopulmonaryvasodilatoruse.Forthisreason,PVRimustbeconsideredincontextofcompletehemodynamicdata.Somecentersincludebothtranspulmonarypressuregradient(mean,diastolic,orboth)andPVRi27–30ascriteriainHTxevaluation.Clini-calexperiencesuggestslackofresponsetoAVTmaynotprecluderesponsetolonger-termpulmonaryvaso-dilatortherapy,and,conversely,areactivevascularbedmaybecomeunresponsiveovertime.Considerationsaffectingresponsetolonger-termpulmonaryvasodila-tortherapymayincludeAVTresponse,butalsootherfactors,suchasthepatient’sage(eg,<1yearismorereversible30),underlyingdiagnosis,durationofleftheartdisease,andothercomorbidities,includinglungdisease,previouspost-tricuspidshunt,orgeneticconditions.

PVRANDHTxOUTCOMES

Sincethe24thBethesdaconferencein1993recom-mendedfixedPVR>6WUasanexclusioncriterionforHTx,anumberofpediatricstudieshaveevaluatedtheeffectofelevatedPVRionpost-HTxoutcomes,primar-ilyretrospectivecohortstudiesofpatientsfromthemid-1980stoearly2000s.SomereportedastrongstatisticalassociationbetweenelevatedpretransplantPVRiandmortalityrisk,27–29,31,32whereasothersfoundnoeffectofPVRionoutcomes32–36(Table2).

Reasonsforthestrikingdiscrepanciesremainunclear,butlikelyreflectheterogeneityofpatientpopu-lations,analysismethods,PVRicutoffsused,inclusionofAVT,post-HTxmanagement,outcomesevaluated,andtimeperiod.ThereisnocleareraeffectofelevatedPVRiaffectingoutcomesmoregreatlybeforewidespreadavailabilityofVADsandpulmonaryvasodilatortherapies. Fewstudieshaveexaminedwhetherpost-HTxdeathresultedfromrightheartfailureorPHandlackcon-sensusregardingwhetherelevatedpre-HTxPVRicor-respondedtopost-HTxRVfailure.29,31OnerecentstudyfoundnoassociationbetweenelevatedPVRiandgraftfailure,insteadfindingthepresenceofmultiplehigh-riskclinicalcriteriatobepredictive.34Anotherstudycorre-latedincreasingnumberofhigh-riskclinicalfactorswithcumulativemortalityrisk.33InadditiontoPVRi,contribu-torsmayincludeprimarycardiacdiagnosis,mechanicalcirculatorysupport,endorgandysfunction,comorbidities,

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Table2.StudiesReportingOutcomesofPediatricPatientsWithElevatedPulmonaryVascularResistanceBeforeHeartTransplant

Study

Years

N

Agerange

PVRicutoff(WU·m2)

AVT

included

Conclusions

Addonizio

etal36(1989)

1984–1988

30

5d–18y

6

No

NodifferenceinmortalityratesinpatientswithelevatedPVRunlesshighPVRwascombinedwithinotropedependence(1-ysurvival30%vs84%inthosewithouteitherriskfactor)

Bandoetal27(1993)

1982–1992

67

1d–18y

4andTPG

>15mmHg

No

ElevatedTPGwasariskfactorforearly(30-d)death

Huangetal28(2004)

1986–2001

165

0–22y

6andTPG

<15mmHg

Yes

RiskofisolatedRVgraftfailureincreasedby1.2-foldforevery1iWUinmaximalPVR

Daviesetal33(2008)

1995–2005

3502

0–21y

6

No

PVRi>6alonewasnotassociatedwithearly(<30d)orlate(1y)death

Hoskoteetal29(2010)

2000–2006

129

0–18y

6andTPG

<15mmHg

Yes

PVRi>6(despitereactivity)andRCMdiagnosispredictedpostoperativeRVfailure;PVRi(butnotRVfailure)independentlypredictedlong-termsurvival

Ofori-Amanfo

etal31(2011)

1984–2005

263

0.1–25.4y

6

Yes

ElevatedPVRwasassociatedwithworse3-mo,1-y,andoverallsurvival;AVTnonrespondershadincreasedriskofrightheartfailureafterHTx

Auerbach

etal34(2012)

1993–2006

189

0–23.6y

6

Yes

PVRi>6(reactiveornot)wasnotasignificantriskfactorforgraftloss

Buddheetal30(2012)

1994–2010

1322

0–18y

TPG>12

No

Increasedmortalityrateat1and3moinrecipientswithPH>1yofage;noeffectonmortalityrateinchildren<1yofage;noimprovementwithrecentavailabilityofpulmonaryvasodilatortherapy

Chiuetal37(2012)

1984–2010

158

0.3–17.8y

6

Yes

ROCanalysisidentifiedPVRi929iWUandAUC0.863asoptimalcutoffforriskofincreased30-dmortality(AUC0863);nocleareffectofvasoreactivity

Chiuetal35(2015)

1987–2011

1943

0–18y

6,9

No

PVRiwasnotasignificantpredictorofoutcomes;nosurvivaldifferencewithpropensity-matchedHTxrecipients

Maxwelletal32(2015)

2002–2012

3523

0–18y

3.37

No

ROCanalysisidentifiedPVRi337iWU(AUC0.69)asdichotomizedvari-ablepredictingearly(30-d)death,butnotascontinuousvariable

Richmond

etal38(2015)

1993–2011

1909

0.1–18y

NA

No

InpediatricHTxrecipientswithoutcongenitalheartdisease,elevatedPVRididnotaffectsurvivalafterHTx;pre-HTxPVRi>5iWUin24%ofcohort

Balakrishnan

etal39(2021)

2014–2019

97

1–18y

4

No

PVRhadnoeffectonearlyorlatesurvivalinsingle-centercohort

AUCindicatesareaunderthecurve;AVT,acutevasoreactivitytesting;HTx,hearttransplantation;iWU,indexedWoodunits;PVR,pulmonaryvascularresistance;PVRi,pulmonaryvascularresistanceindexedforbodysurfacearea;RCM,restrictivecardiomyopathy;ROC,receiveroperatingcharacteristic;RV,rightventricle;andTPG,transpulmonarygradient.

donormatchingconsiderations,andimmunosuppres-sionmodalities.ThisbegsthequestionastowhethertheearlieroutcomesstudiedresulteddirectlyfromelevatedPVRiorifPVRimay,inpart,haveservedasasurrogatefordurationorseverityofheartfailure.AnotherrecentstudyfoundnoeffectofPVRionpost-HTxoutcomes,butincludedonlyafewpatientswithPVRi>6iWU.39However,ifcentersapplyempiricPVRicutoffs,theuse-fulnessofretrospectivestudiesmaybelimited.PatientswithelevatedPVRiareoftenmanageddifferentlythanpatientswithlowPVRi,withintensivepulmonaryvasodi-latortherapyandmechanicalsupport,thedetailsofwhicharenotalwaysreportedindatabaseorregistry-basedstudies.Therefore,thelackofassociationbetweenPVRiandpost-HTxmortalityriskinalarge,multicenterpedi-atriccohortof>1900childrenthatincluded24%withPVRi>5iWUprimarilysuggeststhatcurrentmanage-mentstrategiescanbesuccessfultoovercomeelevatedPVRitofacilitateHTx.38

Thereremainsalackofconsensusregardingwhether,ortowhatdegree,PVRelevationshouldbeconsidered

relevantforHTxwithrespecttopost-HTx