阜外心肌病診治進展英

Advancementofdiagnosisandtherapyincardiomyopathies

心肌病診治進展

LIAOYu-HuaInstituteofCardiology,UnionHospital,TongjiMedicalCollegeofHuazhongUniversityofScienceandTechnology,Wuhan,China精選課件ContemporaryDefinitionsandClassificationoftheCardiomyopathies

（2006AHA）

Cardiomyopathiesareaheterogeneousgroupofdiseasesofthemyocardiumassociatedwithmechanicaland/orelectricaldysfunctionthatusually(butnotinvariably)exhibitinappropriateventricularhypertrophyordilatationandareduetoavarietyofcausesthatfrequentlyare

genetic.Cardiomyopathieseitherareconfinedtotheheartorarepartofgeneralizedsystemicdisorders,oftenleadingtocardiovasculardeathorprogressiveheartfailure–relateddisability.MaronBJ,etal.Circulation，2006，113:1807-1816精選課件ClassificationCardiomyopathiescanbemosteffectivelyclassifiedasprimary:

genetic,mixed(geneticandnongenetic),acquired;and

secondaryPrimarycardiomyopathiesarethosesolelyorpredominantlyconfinedtoheartmuscleandarerelativelyfewinnumberSecondary

cardiomyopathiesshowpathologicalmyocardialinvolvementaspartofalargenumberandvarietyofgeneralizedsystemic(multiorgan)disordersMaronBJ,etal.Circulation，2006，113:1807-1816精選課件MaronBJ,etal.Circulation，2006，113:1807-1816精選課件DilatedCardiomyopathyDilatedformsofcardiomyopathyarecharacterizedbyventricularchamberenlargementandsystolicdysfunctionwithnormalLVwallthickness;usuallydiagnosisismadewith2-dimensionalechocardiographyDCMisacommonandlargelyirreversibleformofheartmusclediseasewithanestimated

prevalenceof1:2500;itisthethirdmostcommoncauseofheartfailureandthemostfrequentcauseofhearttransplantationMaronBJ,etal.Circulation，2006，113:1807-1816精選課件DCMphenotypewithgeneticoccurrencAbout20%to35%ofDCMcaseshavebeenreportedasfamilial,althoughwithincompleteandage-dependentpenetrance,andlinkedtoadiversegroupof20lociandgenes.DCMisalsocausedbyanumberofmutationsinothergenesencodingcytoskeletal/sarcolemmal,nuclearenvelope,sarcomere,andtranscriptionalcoactivatorproteins.ThemostcommonoftheseprobablyisthelaminA/Cgene,alsoassociatedwithconductionsystemdisease,whichencodesanuclearenvelopeintermediatefilamentprotein.MaronBJ,etal.Circulation，2006，113:1807-1816精選課件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精選課件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精選課件①diagnosticcriteriaofdilatedcardiomyopathy②Thediagnosisoffamilialdilatedcardiomyopathyis

made:1.inthepresenceoftwoormoreaffectedindividualsinasinglefamily2.orinthepresenceofafirst-degreerelativeofadilatedcardiomyopathypatient,withwelldocumentedunexplainedsuddendeathat<35yearsofageDiagnosis

offamilialdilatedcardiomyopathyMestroniL,etal.

EuroHeartJ，1999，20:93–102精選課件①diagnosticcriteriaofdilatedcardiomyopathy

②immunologicmarkers—anti-heartantibodiesaremainmarkers1including:anti-ANTAb、anti-?1-receptorAb、anti-MHCAb、anti-M2-receptorAb

Secondarymarkersincluding：

persistentviralinfectionTh2cellpredominancecytokinesgenetypeofhumamleucocyteantigenDiagnosis

ofimmune

dilatedcardiomyopathy

1苑海濤，廖玉華等.臨床心血管病雜志，2000,16:313-315精選課件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苑海濤,廖玉華.臨床心血管病雜志,2000,16:313精選課件ImmunopathogenesisinDCMVoltage-gatingCa-channelsCa-overloadCelldamageCardiacdilationReceptor-gatingCa-channelsVirusinfectionandautoimmunityresponseDCMAnti-ANT-AbAnti-?1-RAb精選課件TreatmentofDCM1、Conventionaltreatmentofheartfailure2、Preventembolism3、PreventSCD4、Improvecardiacmetabolism5、Cardiacresynchronizationtherapy6、Cardiactransplantation7、ImmunologictherapyinDCM精選課件1．β-receptorblockerToinhibittheanti-β1-Abmediatedmyocardiualdamage,especiallyinearlystageEspeciallysuitforthepatientswithtachycardiaorventriculararrhythmias,orwithanti-β1-AbpatientsDose：metroprolol6.25mgBidto12.5～100mgBid,slowlytitrateBlockedautoantibodiesresponse(1)精選課件

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

精選課件2．DiltiazemFrequeceofAnti-ANTantibodyispositiveabout60%-95%Mechanism：Anti-ANTantibodyincreasedCacurrentofmyocardialcell.DiltiazemcouldinhibittheantibodymediatedmyocardialdamageandprotectmyocardiumDiltiazemmightbeusedinearlystageofDCMDosage：diltiazem30mgtid

Blockedautoantibodiesresponse

(2)精選課件CalciumantagonistclinicaltrialinDCMDiDitrialPatients186,DGn=92andPGn=9418~70yearsofagetheadjuncttherapyofdiltiazem60~90mgtidonstandardtreatmentDiDitrialisshowedtoimprovecardiacfunction,exercisecapacityandsubjectivestatusinDCMFigullaHR.Circulation,1996,94:346-352.精選課件CalciumantagonistclinicaltrialinDCMISDDCtrialToevaluateeffectsofdiltiazemonheartfunctionandprognosisinDCMMultiplecentre,random,placebo-control

Followingup6~12monthsPatients221,PGn=107andDGn=114,46±12yearsofageDiltiazem60~90mg/dayorVitB160mg/day

TherapyofHF:digoxine,diuretics,ACEILiaoYH.IntJCardiol,1998,64:25-30.精選課件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.精選課件

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.精選課件HeartimageafterdiltiazemtreatedDCM2000-8-11CTR0.451999-1-18CTR0.51998-9-17CTR0.6精選課件ISDDCtrialconclusionLiaoYH.IntJCardiol,1998,64:25-30.diltiazemissafeandeffectiveinthetreatmentofDCMtheactionmechanismmightbeinterventioninantibody-mediatedmyocardialdamageandprotectionofmyocardiumdiltiazemismoresuitablefortreatmentof

theearlystageinDCM

精選課件PathogenesisandtreatmentinDCM?1-blocksDiltiazemVoltage-gatingCa-channelsCa-overloadCelldamageCardiacdilation

Receptor-gatingCa-channelsVirusinfectionandautoimmunityresponseAnti-ANT-AbAnti-?1-RAbTherapyofHFDCMHFnoHFSevereHFLiaoYH.2001精選課件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精選課件ImmunomodulatingtherapyImmunomodulatingtherapywithintravenousimmunoglobulin2g/kginpatientswithchronicheartfailurewithin6monthsrecentlydiagnosedDCMAftertreated6monthsand12months,LVEFincreasing（0.25±0.08to0.41±0.17/6monthand0.42±0.14/12month）inpatientswithDCMThefindingsuggestsimmunoglobulinmight

regulatethebalanceofinflammatoryfactorand