心力衰竭糖尿病患者急性心肌梗死后无法回避的难题.ppt

心力衰竭-糖尿病患者急性心肌梗死后无法回避的难题,吴永健中国医学科学院中国协和医科大学心血管病研究所阜外心血管病医院,糖尿病患者急性心肌梗死后心力衰竭,Theprevalenceofheartfailureisabout12%inpeoplewithType2diabetesascomparedtoonly3.2%innon-diabeticsubjectsAt6months,theincidenceofHFwas24%(n=10)inthediabeticsand11%(n=30)inthenon-diabetics(P=0.015)At5years,therateofHFincreasedto43%(n=18)inthediabeticsandto20%(n=57)inthenon-diabetics(P=0.001).,HeartfailureinType2diabeticpatientsfollowingACS,Circulation2000;102:1014-1019,CHFeventrate(%),0,5,10,15,20,25,0,3,6,9,12,15,18,21,24,DM+,CVD+,DM-,CVD+,DM+,CVD-,DM-,CVD-,Months,AcuteCoronarySyndrome,PredictorsofHFatMultivariateCoxAnalysis(6months),Circulation.2019;110:1974-1979,糖尿病急性心肌梗死后HF,糖尿病急性心肌梗死后早期HF的机制,糖尿病急性心肌梗死后早期HF的机制,DiabetesandcongestiveHFindependentofCAD,EndocrineReviews2019;25:543-567,Smallvesseldisease,Diabeticcardiomyopathy,Leftventriculardysfunction,Cardiacautonomicneuropathy,Cardiacinsulinresistance,糖尿病急性心肌梗死后晚期HF的机制,Diabetesmellituscanacceratetheprogressionofpost-infarctiongeneticregulatoryexpressioninuntreatedStreptozotocin-inducedDiabeticRatModel-GeneticfindingsintheremotezoneofLVfreewallpostacutemyocardialinfarctionGuang-YuanSong1,Yong-JianWu1*,Yue-JinYang1,Jian-JunLi1,RuiLi2,Ru-TaiHui3,Han-JunPei1,Zhen-YanZhao1Fromthe1CenterofCoronaryHeartDisease,3CenterofHypertension,CardiovascularInstituteCenterofCoronaryHeartDisease,DepartmentofCardiology,CardiovascularInstitute(2)AMIinnon-diabeticrats(N-DM+AMI);(3)Shamindiabeticrats(DM+Sham);(4)Shaminnon-diabeticrats(N-DM+Sham).ExperimentalprotocolisshowninFigure1,Bothdiabeticandnon-diabeticratsweresubjectedtoleftanteriordescendingcoronaryartery(LADCA)ischemiafor1-56dayswithoutreperfusion.Transmissionelectronmicroscopy(TEM)wasutilized10weeksafterDMinduction.Two-dimensionalechocardiographywasutilizedtoobtainLVdimensionsandLVpercentfractionalshorteningatbaseline,DM10weeks,andat1d,7d,14d,28d,56dafterAMI;hemodynamicstudieswasperformedatbaseline,DM10weeks,andat1d,28dafterAMI;andthentheremotezonetissuesofLVfreewallweretakenassamplesatday1,7,14,28,and56postAMIforgenechipmicroarrayanalysis;inaddition,heart-to-bodyweightratioandmassonstrichromestainingwasmeasuredasanindexofcardiachypertrophyandfibrosisatbaseline,DM10weeks,andat1d,7d,14d,28d,56dafterAMI.,Aminalsweresacrificedjustafterechocardiographicassessment,andtheremotezonetissuesofLVfreewallweretakenassamplesatday1,7,14,28,and56postAMI.Accordingtopreviousstudies,weusedthesamplepoolingstrategiesformicroarrayanalysisinordertoreducethewholecostofthestudy.RNAfractionsfromthethreeratsineachgroupatthetimepointwerebalancedpooledforGeneChipanalysis.SignificantdifferentexpressiongeneswerefilteredfromAffymetrixGenechipU2302.0arraybyGCOSsoftware(P0.01).Geneticchangespostmyocardialinfarctionwereclassifiedbyhierarchicalclustering.Andthen,thedifferentialexpressionsof10selectedtranscriptsidentifiedbythemicroarraywereexaminedingreaterdetailbyRealTime-PCR.,GeneChipMicroarrayAnalysisandRealTime-PCR,HierarchicalClusteringGeneclusteringwasanalyzedbyusingCluster3.0andEisensoftware-Treeview.Inthisstudy,hierarchicalclusteranalysesweredoneusingtheClusterprogram(completelinkageclustering)andresultsweredisplayedusingTreeView.Thecriterionforfilteringoutageneisbaseduponthepercentageofexpressionvaluesforthatgenewhichhaveatleastaminimumfold-changefromthemedianexpressionvalueforthatgene.(Ifthedatasetcontains250ormoreexperiments,thenthemeanwillbeusedinsteadofthemedianforcomputationalefficiency.)Iflessthan50percentageofexpressionvaluesmeettheminimumfold-changerequirement,thenthegeneisfilteredout.Then164genesexpressionwerechosenfortheclustering,inwhichwefound118genesintheforegonegeneticdatabase,suchasleucine-richPPR-motifcontaining(IL-6signalingpathway),procollagentypeI,VI,VIII,andXV,fibronectin1,RT1,andTIMP-1,thatassociatedwithpost-infarctioncardiacremodeling,etc.,HierarchicalClustering,Accordingtohierarchicalclustering,wefindthatthemolecularregulatoryexpressionrelatedtocardiacremodelingintheremotezonetomyocardialinfarctionisquitedifferentastimeelapsesinbothdiabeticandnon-diabeticrats.Thegeneexpressionatday1and7postAMIinbothgroupsissimilar,whilethegeneticchangesatday14postAMIindiabeticratsandtheonesatday14and28innon-diabeticratsareclassifiedintothesamecluster.Andthenthegeneticchangesatday28and56postAMIindiabeticratsandtheonesatday56innon-diabeticratsareclassifiedintothesamecluster.,Eight-and20-wkechocardiographydataforthe20-wkWistar-Kyoto(WKY)andGoto-Kakizaki(GK)heartfailuregroupsexpressedasaratiooftheirrespectiveshamgroups.*P0.05,8wkGKvs.8wkWKYgroups,ChangesinEF(A),IZWMSI(B),andLVvolumes(CandD)during6monthsafterAMIinpatientswith(solidline)andwithout(dashedline)diabetes(*P0.01vsbaseline,byANOVAanalysis),Circulation.2019;110:1974-1979,糖尿病和急性心肌梗死早期HF的特点,糖尿病和急性心肌梗死相关发现,早期心衰的治疗策略,b/a受体拮抗剂的应用,EPICEPILOGEPISTENT早期应用可以显著减少DM患者1年死亡率对于胰岛素使用，死亡率减少50%,两组室壁运动异常节段评分指数,两组左心室舒张末容积（ml）,TheHyperglycemia:IntensiveInsulinInfusionInInfarction(HI-5)Study,ActivationofPPARenhancesmyocardialglucoseoxidationandimprovescontractilefunctioninisolatedworkingheartsofZDFrats,AmJPhysiolEndocrinolMetab289:E328E336,2019,Cardiacfunctionandratesofsubstrateoxidation.A:cardiacpowerinthepresenceof5mMglucoseand5mMglucose0.4mMoleate(shadedarea)assubstrates.B:myocardialoxygenconsumption(MVO2)with5mMglucoseand5mMglucose0.4mMoleatepresentassubstrates.C:glucoseoxidation(Ox)ratesintheinthepresenceof5mMglucoseand5mMglucose0.4mMoleateassubstrates.D:oleateoxidationrate.FunctionswereassessedinisolatedperfusedworkingheartsfromfedZL-V(),ZL-A(OE),ZDF-V(),andZDF-A()rats(6063daysold)during40minofaerobicperfusion.ValuesaremeansSEfor1013independentobservationsineachtreatmentgroup,InductionofDMDMwasinducedwithasingleintraperitonealinjectionofSTZ(65mg/kgin0.1mmol/L,pH4.5sodiumcitratebuffer)18.Ageandbodyweightmatchedratsthatusedasnon-diabeticcontrolswereinjectedwiththesamedoseofsodiumcitratebuffer(0.1mmol/L,pH4.5).AllanimalsingroupsDMwithserumglucoselevels300mg/dl(16.8mmol/L),polyuriaandweightlosswereincludedinthestudy.Theratswiththeserumglucoselevel300mg/dloncewereeliminatedfromthestudy.,WeightBody(A)andSerumGlucoseLevels(B)inSTZ-induceddiabeticrats.*P0.001comparedwithnondiabeticrats.DM3d=3daysafterDMinduction,DM7d=7daysafterDMinduction,etc.,PictureA-DshowthemyocardiumofSTZ-induceddiabeticheartsfor10weeks(thearrowsshowthehistopathologicalchanges);PictureEandFshowthemyocardiumofnon-diabetichearts.mitochondrialdamage(swellinganddisruptedcristae),cardiacmusclefibers,thebasallaminaofregionalsmallvessels,glycogenparticles,lipiddroplets.,TEMTheseresultsindicatethattherealreadywerehistopathologicalandultrastructuralchangesrelatedtoDMintheheart10weeksafterSTZinjection.,ExperimentalAMI10weeksafterDMinduction,AMImodelsweremadeaspreviouslydescribed.Sham-operatedratsingroup(3)andgroup(4)weretreatedsimilarlyexceptthatthesuturearoundthecoronaryarterywasnottied.,Fiftysix-dayKaplan-Meiersurvivalcurvesrepresentingpercentageofsurvivingratsin4groups.SurvivalindiabeticratsafterAMIwassignificantly(P0.01)lessthanthatobservedinshamgroup,andsimilarly,the28-daysurvivalwassignificantlyattenuatedindiabeticratssubjectedtoAMIcomparedwithnon-diabeticoneswithAMI(P0.05).,EarlyandProlongedSurvival,Cardiachypertrophy,Thedataabouthearttobodyweightratiosandtheheartweighttotibiallengthratiosarepresented.,HW,heartweight;BW,bodyweight;TL,tibiallength.HW/BW=hearttobodyweightratio;HW/TL=heartweighttotibiallength.ThedatainbracketmeanstheincreasedproportionofHW/BWandHW/TLchangescomparedwithDM70d.*P0.05vs.DM70dinthesamegroup;*P0.001vs.DM70dinthesamegroup.P0.01vs.N-DM+AMIatthesametimepoint;P0.001vs.N-DM+AMIatthesametimepoint.,CONCLUSIONThedifferentpatternsofthegeneticchangesinthisuntreatedSTZ-induceddiabeticnon-perfusionmyocardialinfarctionratmodelmightsuggestthatDMcouldacceratetheprogressionofpost-infarctioncardiacremodelinginSTZ-induceduntreateddiabeticratmodel.,糖尿病患者急性心肌梗死后死亡,Survivalimprovements.KaplanMeiersurvivalcurvesfrom2019and2019aredisplayedforcohortswithandwithoutDM.Thehighlightedareareferstosurvivalimprovementwithineachgroupbetween2019and2019,糖尿病患者PCI术后,Measurementsofepicardialcoronaryflow,myocardialreperfusion,andfinalinfarctsizefordiabeticpatients(whitebars)andnondiabeticpatients(blackbars),AmJCardiol2019;100:206210,Adjustedmyocardialbloodflow(MBF)reservemeasuredbyPET,Circulation2019;111:2291-2298,IS,IR,IGT,T2DM,T2DM+HT,0.0,1.0,2.0,3.0,*,*,*p0.001,p=0.002,MBF,mLmin-1g-1,Coronarycirculatorydysfunctionworsenswithincreasingseverityofinsulinresistance,Endothelial