2022 ADA共识报告：心力衰竭——被低估的糖尿病并发症（英文原本版）.docx

HeartFailure:AnUnderappreciatedComplicationofDiabetes.AConsensusReportoftheAmericanDiabetesAssociationHeartfailure(HF)hasbeenrecognizedasacommoncomplicationofdiabetes,withaprevalenceofupto22%inindividualswithdiabetesandincreasingincidencerates.DataalsosuggestthatHFmaydevelopinindividualswithdiabetesevenintheabsenceofhypertension,coronaryheartdisease,orvalvularheartdiseaseand,assuch,representsamajorcardiovascularcomplicationinthisvulnerablepopulation;HFmayalsobethefirstpresentationofcardiovasculardiseaseinmanyindividualswithdiabetes.Giventhatduringthepastdecade,theprevalenceofdiabetes(particularlytype2diabetes)hasrisenby30%globally(withprevalenceexpectedtoincreasefurther),theburdenofHFonthehealthcaresystemwillcontinuetorise.ThescopeofthisAmericanDiabetesAssociationconsensusreportwithdesignatedrepresentationfromtheAmericanCollegeofCardiologyistoprovideclearguidancetopractitionersonthebestapproachesforscreeninganddiagnosingHFinindividualswithdiabetesorprediabetes,withthegoaltoensureaccesstooptimal,evidence-basedmanagementforallandtomitigatetherisksofseriouscomplications,leveragingpriorpolicystatementsbytheAmericanCollegeofCardiologyandAmericanHeartAssociation.BriefOverviewofScopeandNeedTraditionally,thepreventionandmanagementofchroniccomplicationsinindividualswithtype1(T1D)andtype2(T2D)diabeteshavebeenfocusedonnephropathy,retinopathy,neuropathy,andatheroscleroticcardiovasculardisease(ASCVD)(includingischemicheartdisease,stroke,andperipheralvasculardisease)(1).However,heartfailure(HF)hasbeenrecognizedasacommoncomplicationofdiabetes,withaprevalenceofupto22%inindividualswithdiabetesandincreasingincidencerates(2-4).Thisrecognitionstemsinpartfromtrialsfocusedoncardiovascularsafetyofnewerdrugstotreatdiabetes.DataalsosuggestHFmaydevelopinindividualswithdiabetesevenintheabsenceofhypertension,coronaryheartdisease,orvalvularheartdiseaseand,assuch,representsamajorcardiovascularcomplicationinthisvulnerablepopulation(5).Giventhatduringthepastdecade,theprevalenceofdiabetes(particularlyT2D)hasrisenby30%globally(6)(withprevalenceexpectedtoincreasefurther),theburdenofHFonthehealthcaresystemwillcontinuetorise.ThescopeofthisAmericanDiabetesAssociation(ADA)consensusreportwithdesignatedrepresentationfromtheAmericanCollegeofCardiology(ACC)istoprovideclearguidanceandtorecommendbestapproachestogeneralinternists,primarycareproviders,andendocrinologistsforHFscreening,diagnosis,andmanagementinindividualswithT1D,T2D,orprediabetestomitigatetherisksofseriouscomplications,leveragingpriorpolicystatementsbytheACC(7)andAmericanHeartAssociation(AHA)(2).ThisconsensusreportwasdevelopedbythewritinggroupconvenedbyADAwithrepresentationfromACCthroughaseriesofconferencecalls,emails,andindependentworkfromMarch2021throughMarch2022.HFEpidemiologyPrevalenceandIncidenceofHFAmongIndividualsWithDiabetesTheepidemiologicassociationbetweenHFanddiabetesiswellrecognized(SUPPlementarvTabIe1)(2,3).Resultsofseverallongitudinalobservationalstudiesofpopulation-basedcohortswithdiabetesandprediabetes,includingFraminghamHeartStudy(8),FirstNationalHealthandNutritionExaminationSurvey(NHANESI)EpidemiologicFollow-upStudy(9),ReykjavikStudy(10),andtheScottishdiabetesmellitusregister(3),haveshownatwo-tofourfoldincreasedriskofHFamongmenandwomenwithdiabetesorprediabetescomparedwiththosewithout(8,10).Additionally,HFwasthemostcommonfirstpresentationofcardiovasculardiseaseinindividualswithT2Dwhenevaluatedincontemporarycohortsincludingmillionsofpeoplewithlinkedprimarycare,hospitaladmission,diseaseregistry,anddeathcertificaterecordsinEngland.T2DwasanindependentriskfactorforincidentHFandincreasedHF-associatedmorbidityandmortalityduringamedian5.5-yearfollow-upperiod(2,3).ThesedataarefurthersupportedbyrecentevidencefromtheUKProspectiveDiabetesStudy(UKPDS),withincidenceratesofupto11.9per1,000patient-yearsover10yearsoffollow-up(H).TheincidenceandprevalenceofHFarealsoincreasedamongpatientswithT1D,ashighlightedbyfindingsfromtheScottishdiabetesmellitusregister(3),whiletheSwedishNationalDiabetesRegistry(12)alsoreportedatwotofivetimeshighercrudeincidencerateofHFhospitalizationandmortalityformenandwomenwithT1Dcomparedwiththosewithoutdiabetes(3,13)andhigherprevalenceofdiastolicdysfunction(14).Inarecentsystematicreviewincluding12millionglobalparticipants,investigatorsfoundthatHFmaybeevenmoreprevalentamongmenandwomenwithT1DthanamongthosewithT2D(4).ThedeleteriousrelationshipbetweendiabetesandHFpersistsafteradjustmentforageandrelevantcomorbidities(15).WhilealongerdurationofdiabetesisclearlylinkedtohigherriskforincidentHF,theassociationbetweendiabetesandHFisobservedeveninindividualswithrecent-onsetdiabetesoryoungerage(14,16).GlycemiccontrolandinsulinresistancearestronglyassociatedwithriskforincidentHF,suggestingacontinuousrelationshipbetweenanybloodglucoseabnormalityandHFriskandHFprognosis(10,11,17)(SUPPIememarVTabIe1).PrevalenceandIncidenceofDiabetesAmongPeopleWithHFTherelationshipbetweendiabetesandHFhasauniquebidirectionalassociation.Forexample,insulinresistanceisprevalentin>60%ofindividualswithHF(18)andnew-onsetdiabetesiscommonamongthosewithHF,asshowninseverallargecohorts(19,20,21)(SUPPIementarVTabIe2).GivenheightenedriskfordiabetesinthosewithHF,itisnotsurprisingthatdataindicateahighprevalenceofdysglycemiainthispopulation,withprevalencerangingfrom20%incommunity-basedcohorts(22)to34%inpharmacologicalinterventiontrialsforsystolicHF(23-27),andupto47%inacutedecompensatedHF(28-30).Race-relateddifferenceshavealsoemergedintheprevalenceofdiabetesinindividualswithHF.Severalstudieshavefoundtheprevalenceofdiabetestobe47-56%forBlack,Hispanic,andNativeAmericanindividualswithHFQI-33).Similarly,amongindividualswithimpairedmyocardialdiastolicrelaxation,diabetesismorecommoninBlack(40.5%)andHispanic(40.9%)individualscomparedwithWhitecounterparts(27.2%)(33).Moreover,intheAsianSuddenCardiacDeathinHeartFailure(ASIAN-HF)registry,41.3%ofindividualsfrom11AsianregionssufferingfromHFwerealsoaffectedbydiabetes(34).Clearerdataareneededregardingrace-relatedimpactsonhealthandriskfortheintersectionofdiabetesandHF.FewstudieshavedirectlycomparedtheprevalenceandincidenceratesofdiabetesinpeoplewithHFandreducedejectionfraction(HFrEF)versusthosewithpreservedejectionfraction(HFpEF).However,inastudyofhospitalizedindividualswithHF,prevalenceofdiabeteswas40%amongbothHFrEFandHFpEFpatients(35).MorespecificdataregardingdistributionofdiabetesburdenamongthosewithHFrEFandHFpEFareneeded.KeyPointsBothT1DandT2DincreasetheriskofdevelopingHFacrosstheentirerangeofglucoselevels,butHFmaybemoreprevalentinpeoplewithT1DcomparedwithT2D.ThereisincreasedincidencerateofHFamongpeoplewithdiabetesevenafteradjustmentforageandcomorbidities.HFmaybethefirstpresentingcardiovascularcomplicationinindividualswithdiabetes.RiskFactorsTheriskfactorsforHFinbothT2DandT1Dincludediabetesduration,poorglycemiccontrol,uncontrolledhypertension,hyperlipidemia,higherBMI,microalbuminuria,renaldysfunction,ischemicheartdisease,andperipheralarterydisease(2,12,13).Currenttrendssuggestcontrolofmodifiableriskfactorsispoorinthosewithdiabetes(36),emphasizingtheimportanceofcarefulreviewofeachduringclinicalvisits.AnoverviewoftheirimpactonHFispresentedinSUPPIementarVMatnriaLPathophysiologyThepathophysiologyofHFinindividualswithdiabetesiscomplexandreflectstheinteractionsofmultipleriskfactorsactinginconcertwithdysregulatedSUbceIIuIarpathwaysthatextendbeyondtheconsequencesofdiabetes-associatedhyperglycemia,allleadingtofunctionalandstructuralchangesinthediabeticheart,asillustratedinSUPPlernemarVFia1.uDiabeticcardiomyopathy,definedasventriculardysfunctionintheabsenceofcoronaryarterydisease(CAD)andhypertension(37),isanincreasinglyrecognizedentity.SeveralpotentialmechanismscontributingtothedevelopmentofHFindiabetesincluderenin-angiotensin-aldosteronesystem(RAAS)activation,mitochondrialdysfunction,oxidativestress,inflammation,changesinintracellularcalciumhomeostasis,increasedformationofadvancedglycationendproducts,andmyocardialenergysubstratealterationsincludingincreasedfreefattyacidutilization,decreasedglucoseutilization,andincreasedoxygenconsumption,resultingindecreasedcardiacefficiency(2,15,37-40)(SUPPIementarVFia1).Despitetheincreasedratesoffattyacidutilization,triglyceridesandotherlipidmetabolites(e.g.,ceramides,diacylglycerol,etc.)accumulateinthemyocardiumofindividualswithdiabetes(15,41).Thesederangementsinmyocardiallipidandglucosemetabolismareincreasinglyrecognizedasanearlyeventinthedeteriorationofdiabetes-relatedcardiacfunction(££).Ultimately,theseresultinmaladaptivefibrosis,microvascularrarefaction,Iipotoxicity,anddecreasednitricoxideavailability,leadingtofurthercardiovasculardysfunction.WhilethepredominantmechanismsforHFrEFareconsideredtobedirectmyocardialinjuryduetoassociatedCADorhypertension,aunifyingtheoryofthepathophysiologyofHFpEFsuggestsacentralroleforendothelialandmicrovasculardysfunction(42).Wepointthereadertoreviewarticles(15,43)andscientificstatements(2)thatdescribethesemechanismsindetail.WhileindividualswithT1DexhibitselectstructuralfeaturescharacteristicofanearlyHFpEFphenotypereflectiveofincreasedleftventriclestiffness(38),therearealsonotableHFsimilaritiesbetweenT1DandT2D.Sharedmechanismsincludecardiovascularautonomicneuropathy(38,44),specificallyassociatedwithimpairedleftventriclediastolicrelaxationinbothpeoplewithT2D(45)andpeoplewithT1D(40),andcoronarymicrovasculardysfunction(46-48)withtheassociatedfunctionaland/orstructuralabnormalitiesofthecoronarymicrovasculature(47,49)resultinginmyocardialperfusionimpairment(39,40).SexdifferencesinendothelialandmicrovascularfunctionmayalsoplaypivotalpathogenicrolesintheetiologyofHFinwomenwithdiabetes(50).Accumulatingevidenceshowsthatwomenwithdiabetesexhibitgreaterendothelial(51),coronarymicrovascular(52),anddiastolic(48)abnormalitiescomparedwithmenwithdiabetes.UnderlyingmechanismsfortheincreasedriskofHFinwomenwithdiabetesarenotentirelyclear,butsexhormones,adifferentspectrumofcardiovascularriskfactors,and/ordifferencesinprescriptionpatternsbetweenmenandwomenmayplayarole(53).FurtherresearchisneededtoclarifytheexactmechanismscontributingtothisexcessHFriskinwomenwithdiabetes(particularlyT1D)andidentifyappropriatesex-specificpreventionandtreatmentstrategies.KeyPointsIndividualswithdiabetesmaydevelopudiabeticcardiomyopathy,definedasleftventricularsystolicordiastolicdysfunctionintheabsenceofothercauses(suchasCADorhypertension),withexcessriskinwomen.BothHFpEFandHFrEFmaybepresentindiabetes.ThepathophysiologyofHFinindividualswithdiabetesreflectscomplexinteractionsbetweennumerouspathwayswithdeleteriouseffectsonmyocardialremodelingandmusclefunction.HF:DiagnosisandClinicalStagesHFrepresentsacontinuumofcardiacstructuralabnormalityanddysfunctionandassociatedcardiovascularrisk.UsefulmeansbywhichtoclassifythevariousstagesofHFhavebeenarticulatedbytheACC/AHA/HFSA(HeartFailureSocietyofAmerica)HFguidelines(54)andrecentlyaffirmedbytheUniversalDefinitionandClassificationofHeartFailuretaskforce(55).DetectionofpeopleathighriskforHF(stageA)orthosewithstageBHF(withoutsymptomsbutwitheitherstructural/functionalcardiacabnormalitiesorelevatedbiomarkersnatriureticpeptidesortroponin)wouldpermitearlierimplementationofeffectivestrategiestopreventordelaytheprogressiontoadvancedHFinindividualswithdiabetes,suchasoptimizinguseofRAASinhibitorsand-blockersorearlierinitiationofothertherapieswithmorerecentlyprovenabilitytopreventprogressionofHFsuchassodiumglucosecotransporter2(SGLT2)inhibitors(SGLT2i).However,theimplementationofavailablestrategiestodetectasymptomaticHFhasbeensuboptimal,highlightingopportunitiesformorewidespreadawarenessofthesubjectandneedformoreassiduousapplicationofbeneficialtherapiesinsuchindividuals.Althoughechocardiographymightidentifysignsofmaladaptiveleftventricularremodeling,itsroutineusehasnotbeenconsideredcost-effectiveandthushasnotbeensystematicallyrecommendedforasymptomaticindividuals,includingthosewithdiabetes.Ontheotherhand,theadditionofrelativelyinexpensivebiomarkertestingaspartofthestandardofcaremayhelptorefineHFriskpredictioninindividualswithdiabetes(Table1).Table1BiornarkerSandC)PtirnalCiJtoffSforincidentHFindiabetesCohortThousand&1Study(58)PooledcohortfromAtherosclerosisRiskinCommunities(ARIC),DallasHeartStudy(DHS),andMulti-EthnicStudyofAtherosclerosis(MESA)(56)EXAMINE(57)StVincenfsScreeningtoPreventHeartFailure(STOP-HF)(59)NT-PrOBNPSeleCtedPreVemionOfCardiaCeveNtsiraPoPUIaTiOnOfdiabeticPatientSWithoUtACohorthistoryofCardiacdisease(PONTIAC)(60)CanagliflozinCardiovascularAssessmentStudy(CANVAS)(131,211)AllHRandORvaluesareshownwith95%Cl.HHF,hospitalizationforHF;HR,hazardratio;hs-cTN,high-sensitivitycardiactroponin;LV,leftventricular;OR,oddsratio.MACE:hospitaladmissionsforacutecoronarysyndrome,HF,stroke,andcardiacrevascularizationanddeath.StageA:IndividualsatRiskforHFThepresenceofestablisheddiabetesindicatesthatanindividualisatriskforHF,andthesepatientsshouldbeconsideredinthestageAcategoryandatheightenedriskforprogressiontolaterstagesofHF.Inthisstage,theachievedcontrolofglycemiaandotherriskfactorsmaymodify(orinsteadamplify)riskforclinicalHF.TheseriskfactorsarediscussedaboveinHfepidemiologyandinSUPPIementarVMaterialandshouldbeconsideredwhenevaluatinganindividualwithdiabetes.KeyPointsAnyonewithadiagnosisofdiabetesandtheriskfactorsshowninFiQ.1isinthestageAcategoryofHF.StageB:Pre-HF/EarlyDetectionACC/AHA(2,55)stageBHFislinkedtoincreasedrisksofcardiovascularandall-causemortality,aswellasprogressiontomoreadvancedstagesofovertHF(2,54)(Fig,1),andmaybereferredtoasupre-HF.nManyindividualswithdiabetescanbeclassifiedinstageB(54).Figure1STACEAMZfar.STAGCBMRKtl4Ur4rSTAGEC/D Oe*lt> H>rrtrmM“rMZ MD CAD Sei WOH Ortbopnra FarMyMMlMKtUnMl JyIeM We<ftMligMe Weigbl Rc LVy*Molkactic0 LVdAMtllc4)fMtio LVhypertrophy Chb<rmUrgremH ValvularJbeA>e IocrtAMdfiUia(PrrMBreaMViewIargeDownIoadslideStepwiseapproachforscreeninganddiagnosisacrossHFstages.CXR,chestX-ray;HFpEF,heartfailurewithpreservedejectionfraction;HFrEF,heartfailurewithreducedejectionfraction;hs-cTN,high-sensitivitycardiactroponin;JVD,jugularveindistension;LV,leftventricle.Inrecognitionoftheimportanceofbiomarkerstosupportthedetectionofcardiacdysfunctionatanearlystage,thedefinitionofstageBintherecentUniversalDefinitionandClassificationofHeartFailurewasrevisedtoincludeasymptomaticindividualswithatleastoneofthefollowing:1)evidenceofstructuralheartdisease,2)abnormalcardiacfunction,or3)elevatednatriureticpeptidelevelsorelevatedcardiactroponinlevels(55).Thisapproachiscompatiblewiththe2017ACC/AHAHFFocusedUpdate,whichissuedaclassIlarecommendationforuseofnatriureticpeptidemeasurementtoidentifyHFatanearlystage(2).SubclinicalStructuralHeartDiseaseSubclinicalchangesthatmaybepresentinstageBincludeventricularsystolicordiastolicdysfunction,LVhypertrophy,chamberenlargement,valvulardisease,and/orevidenceofincreasedfillingpressures.BiomarkersforDetectionofStageBHFSpecifictoindividualswithdia