heart failure in renal transplant recipients - kdigo.org · all paents had symptomac chf (nyha...

GregKnollMDMScProfessorofMedicine,UniversityofO9awa

SeniorScien<st,O9awaHospitalResearchIns<tuteCo-Chair,KDIGOGuidelinefortheEvalua<onofCandidatesforKidneyTransplanta<on

KDIGOControversiesConferenceonHeartFailureinChronicKidneyDisease

May27,2017

HeartFailureinRenalTransplantRecipients

KDIGO

Outline

•  PrevalenceofLVDysfunc<onatReferral/Transplanta<on•  Pre-TransplantLVFunc<onandTransplantOutcomes•  EffectofKidneyTransplanta<ononLVFunc<on•  TreatmentofCHF(ACE/ARBs)intheKidneyTransplantPopula<onKDIGO

PrevalenceofLVDysfunc<onatReferral/Transplanta<on

KDIGO

N=4214evaluatedandlistedforTransplantN=2,718hadgated-SPECTif:age>50,historyofCVdisease,DM

EvenwiththeSelec<onBiasthatExistswithTransplantReferral

24.9%hadLVEF≤50%10.5%hadLVEF≤40%

LVEF≤30%:MedianSurvival~36months

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LVEF≤30%hadstrongestassocia<onwithmortality

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ForeachpercentincrementinLVEF-adjustedmortalityriskdecreasedby2.5%

InaHighlySelectedWait-ListPopula<onLVFunc<onStronglyAssociatedwithMortality

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>50%

30-40%

40-50%

<30%

LVEF

N=739hadanechoandwereassessedfortransplanta<on

LVFunc<onNormal,n=613(85.5%)

Mildlyimpaired,n=57(7.9%)

Moderatelyimpaired,n=30(4.2%)

Severelyimpaired,n=17(2.4%)

LVEF≤30%:MedianSurvival~1year

14.5%hadLVEF≤50%

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RegionalWallMo<onAbnormali<esAssociatedwithSurvivalMedianSurvival~3yearsKDIGO

EF<45%:18.2%at<meoftransplanta<on

MeanEFinthisGroup:36.7±6.7%

MeanTimetoCardiac-RelatedDeath:1.5±1.7years

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LVSystolicDysfunc<oninthosewhoSurvivedLongEnoughtobeTransplantedwasalsoAssociatedwithMortality

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WhatistheEffectofKidneyTransplanta<ononLVFunc<on?

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UremicCardiomyopathy–CommonFeatures1.  AllPa<entshadSymptoma<cCHF(NYHAClassIII/IV)2.  NormalCoronaryArteriesonAngiogram3.  DiffuseHypokinesiswithlowEF4.  LVDilata<on5.  SymptomsCompletelyResolvedPost-Transplant6.  Post-TxLVshowednormalwallmo<onorminimalhypokinesis

withsignificantimprovementinEF

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Parfreyetal,Transplanta/on,60:908,1995

N=102DialysisPa<entswhoUnderwentKidneyTransplanta<on

SystolicDysfunc<on:12%Pre-Transplant-0%Post-TransplantNormalEcho:17%Pre-Transplant-36%Post-Transplant

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Pa<entswithSystolicDysfunc<onShowedSignificantImprovement

AretheImprovementsJustFrom:ImprovedBPcontrol?

Normaliza<onoftheHgb?Correc<onofVolumeOverload?Thrombosis/ClosureofAVF?

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N=103Pa<entswithLVEF<40%MeanEF31.6±6.7%~HalfhadLVEF<30%

Medianof2hospitaliza<onsforCHFbeforeTxEvalua<on

51%hadCAD–MostRevascularizedPre-TxandNonehadInducibleIschemiaatTime

ofTransplanta<on

N=72(70%)ImprovedwithLVEF≥50%byOneYearMeanEF58.8±6.8%

N=16(15%)ImprovedwithLVEF40-50%MeanEF42.1±2.4%

N=16(15%)DidNotImprove(LVEF<40%)MeanEF31.6±4.9%

Overall,86%hadIncreaseinLVEFofatLeast5%(byMUGA)Pre-TxLVEF<30%:68%hadPost-TxLVEF>50%

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TimeonDialysisPre-TransplantonlyFactorAssociatedwithFailuretoImproveLVFunc<on

EveryOneMonthIncreaseinDialysisTimeDecreasedLikelihoodofNormalizingLVFunc<onby18%

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FailuretoImproveLVwasAssociatedwithReducedSurvival

Group2/3MedianSurvival~1.5-2.5yrsKDIGO

1.  Laietal.Theeffectofrenaltransplanta<ononleqventricularfunc<oninhemodialysispa<ents.ClinNephrol18:74,1982

2.  Flemingetal,Improvedcardiacfunc<onaqerrenaltransplanta<on.PostgraduateMedicalJournal61:525-528,1985

3.  VandenBroeketal.Improvedleqventricularfunc<onaqerrenaltransplanta<on.MedJAust;154:279,1991

4.  Aboumaetal.Reveersalofmyocardialdysfunc<onfollowingrenaltransplanta<on.Transplanta/onProceedings;25:1034,1993.

5.  Sahagun-Sanchezetal,TheEffectofkidneytransplantonCardiacfunc<on:Anechocardiographicperspec<ve.Echocardiography18(6),2001

6.  Melchoretal.Kidneytransplanta<oninpa<entswithventricularejec<onfrac<onlessthan50%:featuresandpos9ransplantoutcome.Transplanta/onProceedings;34:2539-2540,2002

7.  Oppertetal.Improvementofleqventricularfunc<onandarterialbloodpressure1yearaqerSPK.Transplanta/onProceedings;34:2251-2252,2002

8.  Dudziakaetal.CardiovascularEffectsofSuccessfulRenalTransplanta<on:A30-MonthStudyonLeqVentricularMorphology,SystolicandDiastolicFunc<ons.Transplanta/onProceedings;37(2):1039–1043,2005

9.  Vaidyaetal.EffectofRenalTransplanta<onforChronicRenalDiseaseonLeqVentricularMass;TheAmericanJournalofCardiology;Volume110,Issue2,2012,Pages254–257

10. ……

11. …..

Mul<pleStudieshaveShownImprovementinLVFunc<onwithKidneyTransplanta<on

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NoSignificantDifferenceinanyoftheCardiacParametersMeasuredPropor<onwithLVHinbothGroupswas68%anddidnotChangeinFollow-up

MeanChangeinEjec<onFrac<onPerYear

2.1%peryear -0.4%peryear

MeanChangeinLVMIPerYear

-3.6%peryear 2.8%peryear

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EffectofTransplanta<ononLVFunc<on

• MostReportshaveDemonstratedImprovementinLVFunc<onPostKidneyTransplanta<on•  Publica<onBias?Pa<entSelec<onBias?

•  Keyistoselectthosewhowillmostlikelyimprove:•  Pure“uremic”cardiomyopathy

•  Diffusehypokinesiswithnormalcoronaries

•  An<cipatedshortdialysisdura<on•  Livingdonor;Deceaseddonor(localalloca<onrules/donorrate)

•  AbsenceofRWMAandischemia•  Ques<onableroleofcorrec<ngischemiainasymptoma<cpa<ents

•  Overallburdenofdisease‘low’

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WhatistheIncidenceandOutcomeofdenovoCHFFollowingKidneyTransplanta<on?

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N=638TransplantPa<entsfreefromCVDiseaseat1-YearPost-Transplanta<on

3.6%at5-Years12.1%at10-Years21.6%at20-Years

IncidentRateofCHF:2-5xhigherthanGeneralPopula<on(Framingham)IncidentRateofIHD:SimilartotheGeneralPopula<on(Framingham)

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HemoglobinandBPstronglyAssociatedwithdenovoCHF

RiskofCHFIncreasedasHemoglobinDeclined RiskofCHFIncreasedasBPIncreasedDBP>>>SBP

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DenovoCHFAssociatedwithWorseSurvival

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ExcludedPa<entswithaHistoryofCHF

32.3%

18.3%

CHFIncidenceat36-monthsAge>60-28.8%BMI>30-25.4%Diabetes-25.1%Angina-30.7%MI-37.7%DGF-25.7%

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IndependentCorrelatesofdenovoCHF

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MortalityaqerCHFDiagnosis14.5%at1-year21.2%at2-Years

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CHFMostCommonCVDiagnosis16%ofallPost-TransplantAdmissionsandIncreasingsince2005

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TreatmentofCHF:ACE-InhibitorsandARBsintheKidneyTransplantPopula<on

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Observa<onalDataisConflic<ng

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N=70Pa<entswithPersistentLVH6-12MonthsPost-TransplantRandomizedtoLisinoprilorNoTherapy

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EffectModifica<onPresentLisinoprilAppearedtoOnlyWorkinPa<entsReceivingCyclosporine

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LargestACE/ARBRCTinKidneyTransplantRecipientsStoppedEarlyfor‘Fu<lity’MeanFollow-up20-months

Rela<velyLow-Risk:Diabetes11%,CVD15%,MeanProteinuria130mg/day

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Knolletal,TheLancetDiabetes&Endocrinology;4(4):318-326,2016

N=212KidneyTransplantRecipientsRandomizedtoRamiprilorPlacebo(Blinded)MeanFollow-up48-months(LongestFollow-Up7Years)

FairlyHigh-Risk:Diabetes43%,Hypertension93%,Hyperlipidemia67%,CVD25%,Age>60yrs34%,Pr>0.5g/day43%

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NoDifferenceinOverallSurvival

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NoDifferenceinCVEvents

17/103=16.5%17/109=15.6%

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SignificantDeclineinHgbOverTimeinRamiprilGroup

ACE-InhibitorsarenotBenigninthisPopula<on

MeanDifferenceatEndofTrial:-14g/L(-22to-7g/L)

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AdverseEventsMoreCommononRamipril

BlindedStudyDrugStoppedBecauseofAdverseEventRamipril-9%Placebo-2%

P=0.03


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StudyInclusionCriteria-RCT

-ACEorARB-≥1-YearofFollow-up-ReportedClinically

ImportantOutcome(e.g.Death,Graqlossetc)

N=8TrialsInvolvingn=1,502Pa<entsExceptforPaolezStudy,NoneTargetedCHForLVFunc<on

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MortalityNearlyIden<calinACE/ARBvsControlACE/ARB:35/754=4.6%Control:36/748=4.8%

KDIGO

Summary1.  Approximately15to25%ofpa<entsreferredforkidneytransplantevalua<on

haveevidenceofLVdysfunc<on.

2.  Manyreportshaveshownimprovementsincardiacfunc<onparametersaswellasresolu<onofsymptoma<cCHFfollowingkidneytransplanta<on

3.  LVdysfunc<onatthe<meoftransplanta<onand‘failuretonormalize’LVfunc<onarebothimportantriskfactorsforpooroutcomes.Selec<ngappropriatecandidateswhowillul<matelyimproveisnotstraigh{orwardandwillrequirefurtherstudy.

4.  denovoCHFiscommonpost-transplantandisassociatedwithinferiorgraqandpa<entoutcomes

5.  Withrespecttotreatment,thereremainsinsufficientevidencewhetherACE/ARBsimproveclinicaloutcomesinkidneytransplantrecipients.FurtherRCTsusingACE/ARBwillbechallengingifnotimpossibletoconductgivenknownbenefitsinthenon-CKDpopula<on,‘perceived’benefitintransplantpa<entsandtheircommonuseasan<-hypertensivesinthispopula<on.

KDIGO

GregKnollMDMScProfessorofMedicine,UniversityofO9awa

SeniorScien<st,O9awaHospitalResearchIns<tuteCo-Chair,KDIGOGuidelinefortheEvalua<onofCandidatesforKidneyTransplanta<on

KDIGOControversiesConferenceonHeartFailureinChronicKidneyDisease

May27,2017

HeartFailureinRenalTransplantRecipients

KDIGO

heart failure in renal transplant recipients - kdigo.org · all paents had symptomac chf (nyha...

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