Cardiacspecificbiomarkersfordiagnosisandprognosisinpa3entswithkidneydisease

Thepast,presentandfuture

ChristopherdeFilippi,MDVice-ChairAcademicAffairs

InovaHeartandVascularIns=tuteVirginia,USA

KDIGO

Disclosures

Researchgrants:Abbo@Diagnos3cs,Amgen,FujiRebio,OrthoDiagnos3cs,Prevencio,RocheDiagnos3csAdvisoryboard/Consul3ng/Honorarium/Royal3es:Alere,FujiRebio,Metabolomics,OrthoDiagnos3cs,RocheDiagnos3cs,SiemensHealthcare,UpToDate,WebMDEndpointCommi@ee/DSMB:Radiometer,Quin3les

KDIGO

Cardiacspecifictroponinassays

•  DiagnosisofnonSTeleva3onmyocardialinfarc3onintheeraofthehighsensi3veassays

•  Futuredirec3onstoimprovediagnos3caccuracy

•  Evolu3onfrom“falseposi3ve”toindependentprognos3cator

•  Associa3onswithunderlyingstructuralheartdiseaseintheabsenceofmyocardialinfarc3on

KDIGO

Casepresenta=on#1 History

“62yrmalewithESRDdevelopspalpita8onsandchestpainwithin2-3hoursofcomple8ngdialysis.Cardiaccathandechocardiogram14monthsearliershowednoCAD,moderateaor8cstenosisanda

NormalLVEF”KDIGO

Casepresenta=on#1 PhysicalExam

“BP71/49,HR158,respira8on22,Lungscleartoauscula8on,cardiactachyirregularrateandrhythm,2/6systolicmurmur

heardthroughouttheprecordium,norubsorgallops”

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Casepresenta=on#1 ECG

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Casepresenta=on#1 EchoandCardiacCatheteriza3on

SevereLVH

Aor3cStenosis

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Casepresenta=on#2 History

“A62-year-oldmalepresentedtotheemergencydepartmentwithchestpainradia8ngdownhisleTarmthatlasted40 minutesandawakenedhim3 hourspriortoarrival.Itwasassociatedwith

shortnessofbreath,nausea,anddiaphoresis.

Younoteahistoryofhypertensionandhypercholesterolemiacontrolledwithhydrochlorothiazideandatorvasta8n.

Inaddi8on,hehaschronicrenalfailure,forwhichhetellsyouthathisdoctorthinkshemightsoonrequiredialysis.”

JaffeA,SaraJ.TrendsCardiovascMed.2015;25:655-6

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Casepresenta=on#2 PhysicalExam

“Hisbloodpressureis149/89 mmHgandheartrateis86bpm.Onausculta8on,bothheartsoundsareaudibleandnormal,althoughyoudono8ceafourthheartsoundandbibasilarralesonthechestposteriorlyalongwithbilateralpedaledematothelevelofthe

mid-shinsandmildjugularvenousdistension.”

JaffeA,SaraJ.TrendsCardiovascMed.2015;25:655-6

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Casepresenta=on#2 ECG

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Casepresenta=ons Relevantlaboratoryfindings

Case Presen=ngcTn 2ndcTn eGFR

cTnI(ng/ml) hs-cTnT(ng/L) cTnI hs-cTnT

#1 0.02 14.5 ESRDonHD

#2 36.2 39.0 23ml/min/1.73m2KDIG

O

Baselinelevelsofsensi=veandhscTnassaysatpresenta=oninpa=entswithfinaldiagnosisotherthanacutemyocardial

infarc=on

Twerenboldetal.Circula3on.2015;131:2041-2050

n=447

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CriteriaforAcuteMyocardialInfarc3on•  Detec3onofariseand/orfallofcardiacbiomarkervalues

[preferablycardiactroponin(cTn)]withatleastonevalueabovethe99thpercen3leupperreferencelimit(URL)andwithatleastoneofthefollowing:–  Symptomsofischemia.

–  NeworpresumednewsignificantST-segment–Twave(ST–T)changesornewlembundlebranchblock(LBBB).

–  DevelopmentofpathologicalQwavesintheECG.

–  Imagingevidenceofnewlossofviablemyocardiumornewregionalwallmo3onabnormality.

–  Iden3fica3onofanintracoronarythrombusbyangiographyorautopsy.

J Am Coll Cardiol. 2012;60:2427-63

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Differen3a3onoftypeofMIaccordingtothecondi3onofthecoronaryarteries

J Am Coll Cardiol 2012;60:1581-98

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ThirdUniversalDefini3onofMyocardialInfarc3on

J Am Coll Cardiol 2012;60:1581-98 J Am Coll Cardiol. 2012;60:2427-63

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hs-cTnIconcentra3onatpresenta3oninsuspectedACSStra3fiedbyrenalfunc3on(A)andadjudicatedindexdiagnosisstra3fiedbyrenalfunc3on(B)

Miller-HodgesEetal.Circula3on.2018;137:425-435

N=371027653822

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PerformanceoftheEuropeanSocietyofCardiology0/1-houralgorithmusinghigh-sensi=vitycardiactroponinTinpa=entswithrenaldysfunc=onandnormalrenalfunc=on

Twerenboldetal.Circula3on.2018;137:436-451

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Diagnos=cperformanceofhs-cTnTinpa=entswithrenaldysfunc=onandnormalrenalfunc=on

Twerenboldetal.Circula3on.2018;137:436-451

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Cardiacspecifictroponinassays

ü DiagnosisofnonSTeleva3onmyocardialinfarc3onintheeraofthehighsensi3veassays

•  Futuredirec3onstoimprovediagnos3caccuracy

•  Evolu3onfrom“falseposi3ve”toindependentprognos3cator

•  Associa3onswithunderlyingstructuralheartdiseaseintheabsenceofmyocardialinfarc3on

KDIGO

CardiacTroponinT:SmallerMoleculesinPa=entswithEnd-StageRenalDiseasethanaQerOnsetofAcuteMyocardialInfarc=on

MinglesAMetal.ClinChem.2017;63:683–690

WesternBlotAnalysisAcuteMI ChronicESRD

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Cardiacspecifictroponinassays

ü DiagnosisofnonSTeleva3onmyocardialinfarc3onintheeraofthehighsensi3veassays

ü Futuredirec3onstoimprovediagnos3caccuracy

•  Evolu3onfrom“falseposi3ve”toindependentprognos3cator

•  Associa3onswithunderlyingstructuralheartdiseaseintheabsenceofmyocardialinfarc3on

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Prognos=cvalueofcardiactroponininpa=entswithCKDwithoutsuspectedACS

Asystemicreviewandmeta-analysis

MichosEDetal.AnnInternMed2014;161:491–501

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Associa=onofhighsensi=vecTnTwithLVHandLVEFTheCRICStudy

hscTnT(ng/L)

P<0.001 P<0.001

MishraR.AmJkidneyDis2013;61:701-9

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Incidentheartfailurebasedonhs-cTnTlevelTheCRICStudy

BansalN.JAmSocNephrol2015;26:946-56

Medianfollow-up=6yearsIncidentHFevents=320

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Natriure3cpep3deassays

•  InfluenceofGFRonlevelsandfrac3onalextrac3onofBNPandNT-proBNP

•  Physiologicassocia3onsofnatriure3cpep3delevelsinpa3entswithkidneydisease

•  Diagnos3caccuracyofnatriure3cpep3delevelsforacutedecompensatedheartfailure

KDIGO

Natriure=cpep=delevelsacrosstheeGFRcon=nuum

RolandR.J.vanKimmenadeetal.JACC2009;53:884-890

HTNpa3entsundergoingevalua3onforrenalarterystenosis,butsubsequentlyexcluded(n=165)

Soliddotsindicatelemkidney,opendotsindicaterightkidney

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Correla=onsBetweenFrac=onalExtrac=onandGFRintheLeQandtheRightKidney

RolandR.J.vanKimmenadeetal.JACC2009;53:884-890

BNP

NT-proBNP

Soliddotsindicatelemkidney,opendotsindicaterightkidney

KDIGO

Natriure3cpep3deassays

ü InfluenceofGFRonlevelsandfrac3onalextrac3onofBNPandNT-proBNP

•  Physiologicassocia3onsofnatriure3cpep3delevelsinpa3entswithkidneydisease

•  Diagnos3caccuracyofnatriure3cpep3delevelsforacutedecompensatedheartfailure

KDIGO

Rela=onshipofrenalfunc=onwithleQventricularend-diastolicwallstresswithBNP

Pa3entsweredividedintoter3lesaccordingtotheEDWSlevel(firstter3le:<33kdynes/cm2,secondter3le:33–55,thirdter3le:>55)

MeaneGFR:normals=78,CKD=44,ESRD=5

NiizumaSetal.ClinChem2009;55:1347-1353

n=58n=57n=41

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Natriure3cpep3deassays

ü InfluenceofGFRonlevelsandfrac3onalextrac3onofBNPandNT-proBNP

ü Physiologicassocia3onsofnatriure3cpep3delevelsinpa3entswithkidneydisease

•  Diagnos3caccuracyofnatriure3cpep3delevelsforacutedecompensatedheartfailure

KDIGO

DiagnosisandprognosisofacuteheartfailurewithNT-proBNP

McCulloughPetal.JAmCollCardiol2018;71:1201-1203

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Influenceofrenalfunc=onandageonNT-proBNPfordiagnosisofacuteheartfailureinpa=entswithshortnessofbreath

TheIconReloadedStudy

Januzzi,JLetal.JAmCollCardiol2018;71:1191-1200

KDIGO

Conclusions

ü ThecardiacspecificbiomarkerscTnI,cTnT,BNP,andNT-proBNParefrequentlyincreasedinpa3entswithCKDwithandwithoutanacuteevent.

ü Elevatedcardiacspecificbiomarkerstypicallyreflectcardiovascularpathophysiologymorethanimpairedrenalclearance

ü ThetestsremainaccurateforAMIandacuteheartfailure,respec3vely,albeitwithamodestreduc3oninaccuracyandomenaneedtoconsiderhighercutoffs.

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