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Advancementofdiagnosisandtherapyincardiomyopathies
心肌病诊治进展
LIAOYu-HuaInstituteofCardiology,UnionHospital,TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnology,Wuhan,China精选课件ContemporaryDefinitionsandClassificationoftheCardiomyopathies
(2006AHA)
Cardiomyopathiesareaheterogeneousgroupofdiseasesofthemyocardiumassociatedwithmechanicaland/orelectricaldysfunctionthatusually(butnotinvariably)exhibitinappropriateventricularhypertrophyordilatationandareduetoavarietyofcausesthatfrequentlyare
genetic.Cardiomyopathieseitherareconfinedtotheheartorarepartofgeneralizedsystemicdisorders,oftenleadingtocardiovasculardeathorprogressiveheartfailure–relateddisability.MaronBJ,etal.Circulation,2006,113:1807-1816精选课件ClassificationCardiomyopathiescanbemosteffectivelyclassifiedasprimary:
genetic,mixed(geneticandnongenetic),acquired;and
secondaryPrimarycardiomyopathiesarethosesolelyorpredominantlyconfinedtoheartmuscleandarerelativelyfewinnumberSecondary
cardiomyopathiesshowpathologicalmyocardialinvolvementaspartofalargenumberandvarietyofgeneralizedsystemic(multiorgan)disordersMaronBJ,etal.Circulation,2006,113:1807-1816精选课件MaronBJ,etal.Circulation,2006,113:1807-1816精选课件DilatedCardiomyopathyDilatedformsofcardiomyopathyarecharacterizedbyventricularchamberenlargementandsystolicdysfunctionwithnormalLVwallthickness;usuallydiagnosisismadewith2-dimensionalechocardiographyDCMisacommonandlargelyirreversibleformofheartmusclediseasewithanestimated
prevalenceof1:2500;itisthethirdmostcommoncauseofheartfailureandthemostfrequentcauseofhearttransplantationMaronBJ,etal.Circulation,2006,113:1807-1816精选课件DCMphenotypewithgeneticoccurrencAbout20%to35%ofDCMcaseshavebeenreportedasfamilial,althoughwithincompleteandage-dependentpenetrance,andlinkedtoadiversegroupof20lociandgenes.DCMisalsocausedbyanumberofmutationsinothergenesencodingcytoskeletal/sarcolemmal,nuclearenvelope,sarcomere,andtranscriptionalcoactivatorproteins.ThemostcommonoftheseprobablyisthelaminA/Cgene,alsoassociatedwithconductionsystemdisease,whichencodesanuclearenvelopeintermediatefilamentprotein.MaronBJ,etal.Circulation,2006,113:1807-1816精选课件DCMphenotypewithsporadicoccurrenceInfectiousagents,particularlyviruses(coxsackievirus,adenovirus,parvovirus,HIV);bacterial;fungalrickettsial;myobacterial;andparasiticOthercausesincludetoxins;chronicexcessiveconsumptionofalcohol;chemotherapeuticagents;metalsandothercompounds;autoimmuneandsystemicdisorders;pheochromocytoma;neuromusculardisorderssuchasDuchenne/BeckerandEmery-Dreifussmusculardystrophies;andmitochondrial,metabolic,endocrine,andnutritionaldisordersMaronBJ,etal.Circulation,2006,113:1807-1816精选课件Criteria
①leftventricularend-diastolicdimension(LVEDd)>2.7cm/m2②leftventricularejectionfraction(LVEF)<45%and/orfactionalshortening
<25%
Exclusion:①hypertension,②CHD,③long-termoverdosedrinkingalcohol,④persistencesupraventriculararrhythmia,⑤systemicdisease,⑥pericardialdisease,⑦congenitalheartdisease,⑧pneumocardialdisease
DiagnosticcriteriaofidiopathicdilatedcardiomyopathyManolioTA,etal.AmJCardiol,1992,69:1459–66精选课件①diagnosticcriteriaofdilatedcardiomyopathy②Thediagnosisoffamilialdilatedcardiomyopathyis
made:1.inthepresenceoftwoormoreaffectedindividualsinasinglefamily2.orinthepresenceofafirst-degreerelativeofadilatedcardiomyopathypatient,withwelldocumentedunexplainedsuddendeathat<35yearsofageDiagnosis
offamilialdilatedcardiomyopathyMestroniL,etal.
EuroHeartJ,1999,20:93–102精选课件①diagnosticcriteriaofdilatedcardiomyopathy
②immunologicmarkers—anti-heartantibodiesaremainmarkers1including:anti-ANTAb、anti-ß1-receptorAb、anti-MHCAb、anti-M2-receptorAb
Secondarymarkersincluding:
persistentviralinfectionTh2cellpredominancecytokinesgenetypeofhumamleucocyteantigenDiagnosis
ofimmune
dilatedcardiomyopathy
1苑海涛,廖玉华等.临床心血管病杂志,2000,16:313-315精选课件AnalysisofautoantibodyindilatedcardiomyopathyANT31*(64.6%)4(8.3%)64.6%91.7%β126*(54.2%)4(8.3%)54.2%91.7%M220*(41.7%)3(6.3%)41.7%93.7%MHC23*(47.9%)2(4.2%)47.9%95.8%
positiveofautoantibodyinDCM
AHAinDCMPeptides
DCMgroup
(n=48)
HDgroup
(n=48)
sensitivity
specificity
n(%)n(%) ComparedwithHDgroup*p<0.005苑海涛,廖玉华.临床心血管病杂志,2000,16:313精选课件ImmunopathogenesisinDCMVoltage-gatingCa-channelsCa-overloadCelldamageCardiacdilationReceptor-gatingCa-channelsVirusinfectionandautoimmunityresponseDCMAnti-ANT-AbAnti-ß1-RAb精选课件TreatmentofDCM1、Conventionaltreatmentofheartfailure2、Preventembolism3、PreventSCD4、Improvecardiacmetabolism5、Cardiacresynchronizationtherapy6、Cardiactransplantation7、ImmunologictherapyinDCM精选课件1.β-receptorblockerToinhibittheanti-β1-Abmediatedmyocardiualdamage,especiallyinearlystageEspeciallysuitforthepatientswithtachycardiaorventriculararrhythmias,orwithanti-β1-AbpatientsDose:metroprolol6.25mgBidto12.5~100mgBid,slowlytitrateBlockedautoantibodiesresponse(1)精选课件
MDCtrial
Patients345,MGn=177andPGn=16816-75yearsofage
Metoprolol10mg/day→100~150mg/day
therapyofHF:digitalis、diuretics、ACEI
Followingup18months
MetoprololisindicatedtoimprovequanlityoflifeinheartfailurewithDCMβ-receptorblocker
clinicaltrialinDCMWaagsteinF,etal.Lancet,1993,342:1441-46
精选课件2.DiltiazemFrequeceofAnti-ANTantibodyispositiveabout60%-95%Mechanism:Anti-ANTantibodyincreasedCacurrentofmyocardialcell.DiltiazemcouldinhibittheantibodymediatedmyocardialdamageandprotectmyocardiumDiltiazemmightbeusedinearlystageofDCMDosage:diltiazem30mgtid
Blockedautoantibodiesresponse
(2)精选课件CalciumantagonistclinicaltrialinDCMDiDitrialPatients186,DGn=92andPGn=9418~70yearsofagetheadjuncttherapyofdiltiazem60~90mgtidonstandardtreatmentDiDitrialisshowedtoimprovecardiacfunction,exercisecapacityandsubjectivestatusinDCMFigullaHR.Circulation,1996,94:346-352.精选课件CalciumantagonistclinicaltrialinDCMISDDCtrialToevaluateeffectsofdiltiazemonheartfunctionandprognosisinDCMMultiplecentre,random,placebo-control
Followingup6~12monthsPatients221,PGn=107andDGn=114,46±12yearsofageDiltiazem60~90mg/dayorVitB160mg/day
TherapyofHF:digoxine,diuretics,ACEILiaoYH.IntJCardiol,1998,64:25-30.精选课件ISDDCtrial
PrognosisanalysisinDCM
PlaceboDiltiazemn=107n=114Outpatienttreatment63(58.9)102(89.5)***
Repeatedhospitalization44(41.1)12(10.5)***Death12(11.2)4(3.5)**Comparedwithplacebogroup**p<0.05,***p<0.01LiaoYH.IntJCardiol,1998,64:25-30.精选课件
BeforeAfterLVEDd>70mm(n=28)
LVEDd77.61±5.3874.50±8.92*
EF27.68±11.6933.71±12.64*
LVEDd<70mm(n=86)
LVEDd61.34±4.9156.88±5.32**
EF38.76±8.7546.07±7.88**
Comparedwithbeforetreatment,*p>0.05,**p<0.01
ISDDCtrialSubgroupanalysisofheartfunctionLiaoYH.IntJCardiol,1998,64:25-30.精选课件HeartimageafterdiltiazemtreatedDCM2000-8-11CTR0.451999-1-18CTR0.51998-9-17CTR0.6精选课件ISDDCtrialconclusionLiaoYH.IntJCardiol,1998,64:25-30.diltiazemissafeandeffectiveinthetreatmentofDCMtheactionmechanismmightbeinterventioninantibody-mediatedmyocardialdamageandprotectionofmyocardiumdiltiazemismoresuitablefortreatmentof
theearlystageinDCM
精选课件PathogenesisandtreatmentinDCMß1-blocksDiltiazemVoltage-gatingCa-channelsCa-overloadCelldamageCardiacdilation
Receptor-gatingCa-channelsVirusinfectionandautoimmunityresponseAnti-ANT-AbAnti-ß1-RAbTherapyofHFDCMHFnoHFSevereHFLiaoYH.2001精选课件ImmunoadsorptionofautoantibodiesAnti-β1-adrenoceptorantibodyremovedbyimmunoadsorptioninpatientswithDCM,meanwhiletreatmentofheartfailureFollow-uponeyear,LVEFincreasing15%(22.3±3.3%to37.9±7.9%)
andLVEDddecreasing14.5%(74.5±7.1to63.7±6.0mm)inDCMgroup;LVEF(23.8±3.0to25.2±5.9%)noimprovement
andLVEDddecreased3.8%incontrolgroupTheclinicaltrialconfirmedthatremovingtheautoantibodiesmightimproveheartfunctioninDCMMüllerJ,etal.Circulation,2000,101:385-39SchimkeI,etal.JClinApher,2005,20:137-42精选课件ImmunomodulatingtherapyImmunomodulatingtherapywithintravenousimmunoglobulin2g/kginpatientswithchronicheartfailurewithin6monthsrecentlydiagnosedDCMAftertreated6monthsand12months,LVEFincreasing(0.25±0.08to0.41±0.17/6monthand0.42±0.14/12month)inpatientswithDCMThefindingsuggestsimmunoglobulinmight
regulatethebalanceofinflammatoryfactorand
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