總醫(yī)院心衰課件

心力衰竭

--糖尿病患者急性心肌梗死后無(wú)法回避的難題

吳永健中國(guó)醫(yī)學(xué)科學(xué)院中國(guó)協(xié)和醫(yī)科大學(xué)心血管病研究所阜外心血管病醫(yī)院TheGreatWallInternationalCongressofCardiology2008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)inthe

non-diabetics(P=0.001).HeartfailureinType2diabeticpatientsfollowingACSCirculation2000;102:1014-1019CHFeventrate(%)051015202503691215182124DM+,CVD+DM-,CVD+DM+,CVD-DM-,CVD-MonthsAcuteCoronarySyndromeDiabetesincreasestheriskofHFby82%andadverselyaffectstheprognosisOASISRegistry(n=8013)OR(95%CI)PAge,y1.0513(1.0284–1.0746)0.0001PeakCK,U/L1.0002(1.0001–1.0002)0.0004Six-monthLVdilation,mL1.0104(1.0038–1.0170)0.0021Diabetes1.8026(1.0374–3.1321)0.0366PredictorsofHFatMultivariateCoxAnalysis

(6months)Circulation.2004;110:1974-1979糖尿病急性心肌梗死后HF糖尿病患者急性心肌梗死早期心衰晚期心衰糖尿病急性心肌梗死后早期HF的機(jī)制舒張功能障礙糖尿病心肌病變心臟收縮協(xié)調(diào)性下降糖尿病急性心肌梗死后早期HF的機(jī)制微循環(huán)障礙，組織水平灌注不良心肌抗缺血生存能力降低，自我恢復(fù)減低心肌代謝障礙，胰島素抵抗更加明顯血糖升高，影響血流動(dòng)力學(xué)DiabetesandcongestiveHFindependentofCADEndocrineReviews2004;25:543-567DiabetesSmallvesseldiseaseDiabeticcardiomyopathyLeftventriculardysfunctionSymptomaticheartfailureCardiacautonomicneuropathyCardiacinsulinresistance糖尿病急性心肌梗死后晚期HF的機(jī)制梗死區(qū)心肌收縮的恢復(fù)降低左室重構(gòu)更趨明顯Diabetesmellituscanacceratetheprogressionofpost-infarctiongeneticregulatoryexpressioninuntreatedStreptozotocin-inducedDiabeticRatModel-GeneticfindingsintheremotezoneofLVfreewallpostacutemyocardialinfarctionGuang-YuanSong1,Yong-JianWu1*,Yue-JinYang1,Jian-JunLi1,RuiLi2,Ru-TaiHui3,Han-JunPei1,Zhen-YanZhao1Fromthe1CenterofCoronaryHeartDisease,3CenterofHypertension,CardiovascularInstitute&Fu-WaiHospital,PekingUnionMedicalCollegeandChineseAcademyofMedicalSciences,Beijing100037,China.Fromthe2GenminixInformaticsLtd.Co*Thecorrespondingauthor:Yong-JianWu,MD,PhD;CenterofCoronaryHeartDisease,DepartmentofCardiology,CardiovascularInstitute&Fu-WaiHospital,PekingUnionMedicalCollegeandChineseAcademyofMedicalSciences,167BeiLiShiRd,Beijing,100037,P.R.China.E-mail:fuwaihospital@StudyDesign217Sprague-Dawley(SD)ratswererandomizedintooneofthefourfollowinggroups:(1)AMIindiabeticrats(DM+AMI);(2)AMIinnon-diabeticrats(N-DM+AMI);(3)Shamindiabeticrats(DM+Sham);(4)Shaminnon-diabeticrats(N-DM+Sham).ExperimentalprotocolisshowninFigure1Bothdiabeticandnon-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-bodyweightratioandmasson’strichromestainingwasmeasuredasanindexofcardiachypertrophyandfibrosisatbaseline,DM10weeks,andat1d,7d,14d,28d,56dafterAMI.Aminalsweresacrificedjustafterechocardiographicassessment,andtheremotezonetissuesofLVfreewallweretakenassamplesatday1,7,14,28,and56postAMI.Accordingtopreviousstudies,weusedthesamplepoolingstrategiesformicroarrayanalysisinordertoreducethewholecostofthestudy.RNAfractionsfromthethreeratsineachgroupatthetimepointwerebalancedpooledforGeneChipanalysis.SignificantdifferentexpressiongeneswerefilteredfromAffymetrixGenechipU2302.0arraybyGCOSsoftware(P<0.01).Geneticchangespostmyocardialinfarctionwereclassifiedbyhierarchicalclustering.Andthen,the

differentialexpressionsof10selectedtranscriptsidentifiedbythemicroarraywereexaminedingreaterdetailbyRealTime-PCR.GeneChipMicroarrayAnalysisandRealTime-PCRHierarchicalClusteringGeneclusteringwasanalyzedbyusingCluster3.0andEisensoftware-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.

HierarchicalClusteringAccordingtohierarchicalclustering,wefindthatthemolecularregulatoryexpressionrelatedtocardiacremodelingintheremotezonetomyocardialinfarctionisquitedifferentastimeelapsesinbothdiabeticandnon-diabeticrats.Thegeneexpressionatday1and7postAMIinbothgroupsissimilar,whilethegeneticchangesatday14postAMIindiabeticratsandtheonesatday14and28innon-diabeticratsareclassifiedintothesamecluster.Andthenthegeneticchangesatday28and56postAMIindiabeticratsandtheonesatday56innon-diabeticratsareclassifiedintothesamecluster.Eight-and20-wkechocardiographydataforthe20-wkWistar-Kyoto(WKY)andGoto-Kakizaki(GK)heartfailuregroupsexpressedasaratiooftheirrespectiveshamgroups.*P<0.05,8wkGKvs.8wkWKYgroupsChangesinEF(A),IZWMSI(B),andLVvolumes(CandD)during6monthsafterAMIinpatientswith(solidline)andwithout(dashedline)diabetes(*P<0.01vsbaseline,byANOVAanalysis)Circulation.2004;110:1974-1979糖尿病和急性心肌梗死早期HF的特點(diǎn)發(fā)病率高微小的心肌梗死即可誘發(fā)HF持續(xù)時(shí)間長(zhǎng)治療反應(yīng)差老年患者尤其是女性易發(fā)HF糖尿病和急性心肌梗死相關(guān)發(fā)現(xiàn)HF的發(fā)生與糖尿病的病程極其伴隨的危險(xiǎn)因素有關(guān)尿微量白蛋白升高，腎功能惡化是HF發(fā)生強(qiáng)有力的預(yù)測(cè)因子肥胖是重要的影響因素早期心衰的治療策略常規(guī)治療更要積極，強(qiáng)度加大（利尿劑的使用）再灌注治療早期再灌注能否受益？

Ⅱb/Ⅲa受體拮抗劑中藥針對(duì)血糖異常的治療（InsulinfocusorGlucemiafocus）萬(wàn)爽力Ⅱb/Ⅲa受體拮抗劑的應(yīng)用EPICEPILOGEPISTENT

早期應(yīng)用可以顯著減少DM患者1年死亡率

對(duì)于胰島素使用，死亡率減少50%糖尿病患者AMI再灌注治療時(shí)同時(shí)使用可能改善微循環(huán)灌注，從而改善預(yù)后兩組室壁運(yùn)動(dòng)異常節(jié)段評(píng)分指數(shù)梗塞24小時(shí)內(nèi)一周二周一月三月六月一年通心絡(luò)組1.75521.69691.61251.50851.40521.37671.3254對(duì)照組1.73901.75741.74631.70831.64751.53801.4890P值0.69450.15240.00430.00010.00010.00240.0378兩組左心室舒張末容積（ml）梗塞24小時(shí)內(nèi)一周二周一月三月六月一年通心絡(luò)組n=60138.17±23.77150.86±21.91150.36±26.24150.71±27.57143.12±29.95145.27±27.93148.91±30.67對(duì)照組n=52146.43±33.13160.48±24.54163.39±24.68164.10±27.11165.6±30.92162.38±32.65166.79±33.58P值0.210.090.040.040.0020.0090.046TheHyperglycemia:IntensiveInsulinInfusionInInfarction(HI-5)StudyResultsAtotalof240subjectswererecruited.Insulin/dextroseinfusiondidnotreducemortalityattheinpatientstage(4.8vs.conventional3.5%,P=0.75),3months(7.1vs4.4%,P=0.42),or6months(7.9vs.6.1%,P0.62).Therewas,however,alowerincidenceofcardiacfailure(12.7vs.22.8%,P=0.04)andreinfarctionwithin3months(2.4vs.6.1%,P=0.05).WhenanalyzedbymeanBGLachievedduringthefirst24h,mortalitywasloweramongsubjectswithameanBGL8mmol/l,comparedwithsubjectswithameanBGL8mmol/l(2vs.11%at6months,P=0.02)ActivationofPPARenhancesmyocardialglucoseoxidationandimproves

contractilefunctioninisolatedworkingheartsofZDFratsAmJPhysiolEndocrinolMetab289:E328–E336,2005Cardiacfunctionandratesofsubstrateoxidation.A:cardiacpowerinthepresenceof5mMglucoseand5mMglucose0.4mMoleate(shadedarea)assubstrates.B:myocardialoxygenconsumption(MV˙O2)with5mMglucoseand5mMglucose0.4mMoleatepresentassubstrates.C:glucoseoxidation(Ox)ratesintheinthepresenceof5mMglucoseand5mMglucose0.4mMoleateassubstrates.D:oleateoxidationrate.FunctionswereassessedinisolatedperfusedworkingheartsfromfedZL-V(?),ZL-A(OE),ZDF-V(),andZDF-A(■)rats(60–63daysold)during40minofaerobicperfusion.ValuesaremeansSEfor10–13independentobservationsineachtreatmentgroup謝謝?。?！InductionofDMDMwasinducedwithasingleintraperitonealinjectionofSTZ(65mg/kgin0.1mmol/L,pH4.5sodiumcitratebuffer)18.Ageandbodyweightmatchedratsthatusedasnon-diabeticcontrolswereinjectedwith