Ulrika Birgersdotter-Green, MD, FHRSProfessor of MedicineDivision of Cardiology

University of California, San Diego

BiomarkersandArrhythmias/Devices

Disclosures

Honoraria, Research Grants, Medtronic

Honoraria, Research Grants, St. Jude Medical

Honoraria, Research Grants, Biotronik

Outline

• BiomarkersinAtrialFibrillation

• BiomarkersinCardiacResynchronizationTherapy

• BiomarkersinDiagnosisofDeviceInfections

BiomarkersinAtrialFibrillation

• AFisthemostcommonclinicalarrhythmiaandtheprevalenceisprojectedtoincreasemarkedlyinthecomingdecades

• AFisindependentlyassociatedwithuptotwo-foldhigherriskofdeath

• AFhasbeenestimatedtocontributeto130000deathseachyear

• Establishedriskscoreforischemicstroke;CHA2DS2-VASc

• Overall,useofbiomarkershasnotbeenintegratedintoclinicalmanagementofAF

BiomarkersinAtrial FibrillationGuidelineRecommendations

Recommendationforpredictionofstrokeandbleedingrisk

• Troponinisprognosticinpatientswithatrialfibrillation,correlatingwithincreasedcardiovasculareventssuchasischemicstroke,TIA,acutecoronarysyndrome,acuteheartfailure,majorbleedinganddeath

BiomarkersinAtrial FibrillationTroponin

• Howdoyouimplementthisfindingclinically?

• CantroponinhelpdetectincreasedriskofAF?

BiomarkersinAtrial FibrillationTroponin

Notenoughdata

Noclearbenefit

• CantroponinhelppredictpostopAF?

• Cantroponin aidinAFpatientswhopresentwithchestpain,r/o MI?

BiomarkersinAtrial FibrillationTroponin

Chang, Kay-Won, et al., The American Journal of Medicine, Vol 130, No 12, December 2017

• CantroponinhelpdetectincreasedriskofAF?

BiomarkersinAtrial FibrillationTroponin

Notenoughdata

Noclearbenefit• CantroponinhelppredictpostopAF?

• Cantroponin aidinAFpatientswhopresentwithchestpain,r/o MI?

• RiskstratificationinnewinsetAF?

BiomarkersinAtrial FibrillationTroponin

Chang, Kay-Won, et al., The American Journal of Medicine, Vol 130, No 12, December 2017

• Similartotroponin,BNPandNT-proBNP haveshowntobeassociatedwithAFincidence,postoperativeAFandprognosisinAF

• IthasalsobeenassociatedwithdiagnosisofheartfailureinAFandpredictingsuccessofDCcardioversionforAFCirclethisbulletonasecondclick

• Howtoimplementclinically?

BiomarkersinAtrial FibrillationTroponin

BiomarkersinAtrial FibrillationB-TypeNatriuretic Peptide

Chang, Kay-Won, et al., The American Journal of Medicine, Vol 130, No 12, December 2017

BiomarkersinAtrial FibrillationST2

Chang, Kay-Won, et al., The American Journal of Medicine, Vol 130, No 12, December 2017

BiomarkersinAtrial FibrillationABCDeathRiskScore

Hijazi Z, et al., European Heart Journal (2018) 39, 477–485

BiomarkersinCardiacResynchronizationTherapy

• Cardiacresynchronizationtherapy(CRT)isan effectivetherapyforselectedpatientswithheartfailure

• CRTreducesmortalityandimprovesmorbidity

• CRTishasaClassIindicationinpatientswithLVEF≤35%,QRSduration ≥150 mswithLeftBundleBranchBlock(LBBB)morphologyandonoptimalmedicaltherapy(OMT)

• However,anon-responserateof20%–40%existsandhasremainedunchangedoverthelastdecade,despiteextensiveresearch

• Couldbiomarkershelppredictreversalofadversecardiacremodeling?

BiomarkersinCardiacResynchronizationTherapy

BiomarkersinCardiacResynchronizationTherapy

Moher D, Liberati J, Altman DG, The PRISMA Group (2009).

Results:• ConsistentobservationinallECMbiomarkerbehaviorbeforeandafterCRTimplantationwasnot observedbetweenstudies.LowertypeIandtypeIIIcollagensynthesisbiomarkers(N-terminalpropeptides oftypeIandIIIprocollagens)expressiondemonstratedreplicatedabilitytopredictreverseleftventricularremodeling

BiomarkersinCardiacResynchronizationTherapy

BiomarkersinCardiacResynchronizationTherapy

Nauffal V, et al., PLoS One. 2017 Apr 7;12(4):e0175205

BiomarkersinCardiacResynchronizationTherapy

ChangesinCT-apelin andNT-proBNP levelsaccordingtoresponsetoCRT

Kosztin A, et al., Journal Biomarkers Vol 22, 2017 Issue 3-4.

BiomarkersinDiagnosisofDeviceInfections

• WorldwideimplantationratesofCardiacImplantableElectronicDevices(CIED)areestimatedat1,250000pacemakersand410000ICDsperyearwithanannualincreaseofabout5%

• Increaseimplantationrateshaveresultedinincreasedcomplicationratesandspecificallyadisproportionateincreaseindeviceinfections

• CIEDinfectionsareassociatedwithsignificantmorbidity,highermortalityandincreasedcosts

BiomarkersinDiagnosisofDeviceInfections

• Insuspecteddevicepocketinfectionsanearlydiagnosisandsubsequentcompletedeviceandleadremovalisimportanttoavoidprogressiontosepsisorendocarditis

• Diagnosingapocketinfectioncanbechallengingaspatientsmaypresentwithmild/fewsymptomsorlackofclearcutsignsoflocalinfection

• ConventionalinflammationrelatedbiomarkerssuchasWBCorESRhavelowsensitivitytopocketinfections.Aretherebetterbiomarkers?

BiomarkersinDiagnosisofDeviceInfections

Comparisonofsensitivityandspecificityforrelevantbiomarkersapplyingestablishedoroptimizedcut-offvalues.

Lennerz C, et al., PLoS One. 2017 Mar 6;12(3):e0172384

Conclusions

• BiomarkersinAtrialFibrillation– showingsomepromise,willbeinterestingtoseeiftheABCriskscoregetsclinicaltraction

• BiomarkersinCardiacResynchronizationTherapy– wearealongwayfromidentifyinganybiomarkersthatcanhelppredictnonresponse

• BiomarkersinDiagnosisofDeviceInfections– seemsreasonable tocheckaPCTlevelinthemorechallengingdiagnosticcases