心肌病的分类英文幻灯课件.pptx

1、NormalDilatedHypertrophicRestrictiveArrhythmogenicRight VentricularSystoleDiastoleClassification of CardiomyopathiesPrimary Cardiomyopathies(predominantly involving the heart)GeneticMixed*AcquiredHCMARVC/DLVNCConductionDefectsMitochondrialmyopathiesDCMRestrictive(non-hypertrophiedand non-dilated)Inf

2、lammatory(myocarditis)Stress-provoked（”tako-tsubo”）PeripartumTachycardia-inducedInfants of insulin-dependentDiabetic mothersCirculation 2006;113:1807-1816Ion Channel DisordersLQTSBrugadaSQTSCPVTAsian SUNDS*Predominantly nongeneticPRKAG2DanonGlycogenStorageSecondary CardiomyopathiesInfiltrativeStorag

3、eToxicityEndomyocardialInflammatory(granulomatous)EndocrineCardiofacialNeuromuscular/neurologicalNutritional deficiencyAutoimmune/collagenElectrolyte imbalanceConsequence of Cancer therapyCirculation 2006;113:1807-1816Gene Mutations Associated with Multiple Phenotypes of Cardiomyopathies-Myosin heav

4、y chainCardiac troponin T-TropomyosinCardiac myosin bindingProtein CCardiac troponin I ActinTitinDesminMuscle LIM proteinTelethoninDesmoplakinPlakoglobinGenePhenotypesHCMDCMRCMARVC/DSarcomere proteinsZ-disc proteinDesmosome proteinIntermediate filamentsHypertrophic Cardiomyopathy About half of cases

5、 show familial occurrence.About half of familial HCM have gene mutations of sarcomere proteins(25%of total HCM).Specific(Secondary)cardiomyopathies often show HCM phenotype.Storage:Fabrys disease Inflammatory:Sarcoidosis HCV cardiomyopathyCoxsackie B virusAdenovirusHepatitis C virusDilated Cardiomyo

6、pathy Myocarditis Viral Infection and Phenotypes of CardiomyopathiesCirculation 1995;92:2519-2525Biochem Biophys Res Commun 1996;222:678-682Lab Inv.2000;80:1137-1142Hypertrophic CardiomyopathyViral Infection of the HeartDiffuseCHF/DCMSystolic HFRegionalAneurysmSubendocardialRCMDiastolic HFARVC/DLV A

7、neurysmRandomHypertrophy/HCMVirusReceptorMyocyteFibroblastCompleterecoveryDiffusehypokinesisRegionalabnormalitySubendocardiallesionsIncreasedwall thicknessUnclassifiedabnormalityViral MyocarditisCHF/DCMSystolic HFHCMRCMARVC/DDiastolic HFHepatitis C Virus LV AneurysmARVCHCMDCMMyocarditisMatsumori A C

8、irc Res 2005;96:144-147Hypertrophic Obstructive Cardiomyopathy Associated with HCV InfectionHECoreA-2Immunohistochemical Staining of HCV Core Antigen in the Heart of a Patient with HCM Apical Hypertrophic Cardiomyopathy Associated with HCV InfectionEndomyocardial Biopsy in Patients with HCM with HCV

9、 InfectionA Patient with HCM,Hepatitis and Nephritis Associated with HCV InfectionBiopsy Finding in a Patient with Hypertropic Cardiomyopathy,Hepatitis and NephritisKidneyHeartLiverAcute HepatitisChronic HepatitisLiver CirrhosisMyocardialFibrosisDCMAcute MyocarditisChronicInflammationHepaticFailureH

10、CCHCM85%20%6%4%HCV HepatitisHCV CardiomyopathiesAn Atypical Variant of Fabrys Disease in Men with Left Ventricular Hypertrophy.Nakao S et al NEJM 1995;333:288-293 Fabrys disease is an X-linked recessive disorder that results from a deficiency of -galactosidase.Seven of the 230 patients(3%)of HCM.Fab

11、rys Disease Presented as HCM Alpha-galactosidase activity 0.7 n moles/hr/ml (Normal 4.8-17.6 n moles/hr/ml)IVST 20 mmLVPWT 11 mmLVEDD 58 mmLVESD 45 mmLVEF 45%UCG201 Tl ScintigraphyIncreased uptake at IVS and anterior wallIncreased LV cavity compared to those of1.5 yr before.Heart Disease in Friedrei

12、chs Ataxia Observation of a Case for Half a Century.Kawai C,Kato S et al Jpn Circ J 2000;64:229-236IVST 14mmLVPWT 12mmDisarrangement of bizzare-shapedmyocardial fibers with hypertrophy and interstitial fibrosis Hypertrophic Cardiomyopathy as a Manifestation of Cardiac Sarcoidosis.Matsumori A et al J

13、pn Circ J 2000;64:679-683 Six of 82(7.3%)patients with sarcoidosis have echocardiographic abnormality.Four of 82(4.8%)showed phenotype of HCM.ASH:2 cases,APH:1 caseDepar tment of Cardiovascular Medicine,Kyoto University LV Aneurysm in a Patient with HCV CardiomyopathyVT,Hepatitis C(IFN Rx),Lymphaden

14、opathy FH:Hepatitis C,HCC in 2 brothers UCG:IVS 16mm,LVPW 13mm,LVDd 47mm,LVDs 37mm,EF 36%RAOEDESMT 52 MDetection of HCV RNA in Heart Tissues from Patients with ARVCnPositive nFrequencyWHF Council ofCardiomyopathiesNational CardiovascularCenter,Japan63922433.0%66.7%44.4%TotalImmunohistochemical Stain

15、ing of HCV Core Protein in the Heart from Patients with ARVC/DGenetic Background of the Host Influences the Phenotype of CardiomyopathiesHLA and HCMHLA-DRW4 antigen linkage in patients with hypertrophic obstructive cardiomyopathy Matsumori A et al.Am Heart J.1981;101:14-16.HLA in hypertrophic cardio

16、myopathy and rheumatic heart disease Matsumori A et al.Jpn Circ J 1979;43:445-449HL-A and Hypertrophic Cardiomyopathy Matsumori A et al.Am Heart J 1979;97:428-431 Frequencies of DPB1 Alleles in PatientsWith HCV-Associated Cardiomyopathy and ControlsBoth DPB1*0401 and DPB*0901 was significantly assoc

17、iated with HCV-HCM(*P 0.05),whereas none of DPB1 allele demonstrated significant association with HCV-DCMShichi D,Matsumori A,et al.Int J Immunogenet 2008;35:37-43 DPB1alleleHCV-HCM(2n=76)HCV-DCM(2n=42)Control(2n=264)*0201 0.145 0.143 0.205*03010.053 0.095 0.057*04010.079*0.024 0.023*05010.368 0.381

18、 0.413*06010.013 0.004*09010.184*0.119 0.095Association with Polymorphic of DP-Chain in HCV-HCMShichi D,Matsumori A,et al.Int J Immunogenet 2008;35:37-43 PositionAmino acidresidueCases(n=38)+-DP 8DP 9DP 11DP 36DP 55DP 57DP 76LeuPheGlyAlaAlaGluMetControls(n=132)+-OR(95%CI)PPc 6 6 63131 6 6129129129 7

19、 7129129 3 3 3125125 3 3323232 7 73232 0.12(0.03-0.52)0.12(0.03-0.52)0.12(0.03-0.52)4.03(1.32-12.35)4.03(1.32-12.35)0.12(0.03-0.52)0.12(0.03-0.52)0.0040.0040.0040.0170.0170.0040.0040.0080.0120.0080.0340.0510.0080.012(Pockets)(6)(9)(6)(9)(9)(-)(4)The polymorphic residues from DPB1 alleles located in

20、P9 pockets(at position 36A and 55A)showed positive associations with HCV-HCM.In contrast,five polymorphic residues showed significant negative associations:76M in P4 pockets;8L and 11G in P6 pockets;9F in P9 pockets and 57E adjacent to P9 pocket.Quite interestingly,all the residues showing significa

21、nt positive or negative associations composed of DPB1*0401.The Susceptible Gene Mapping for HCV-DCM and HCMwith Microsatellite Markers throughout the HLA regionOdds RatioCorrected PSusceptibility to HCV-DCM was mapped at the locus spanning from NFKBlL1 to BAT1 loci within the HLA class III subregion

22、.HCV-HCM was associated with DPB1 alleles.The candidate genes may encode molecules involved in the immunity and inflammation.Shichi D et alTissue Antigen2005:66:200HCMDCMHLA and HCV Infection Our study provides new and suggestive information on the immunological involvement of DPB1 gene in the HCV-H

23、CM development.The polymorphic amino acids residues by which the DP chain adopt specificity pocket appear to influence on disease-susceptibility at the allelic manner level.The existence of different risk alleles among HCV-related diseases including chronic liver disease,asymptomatic carrier and HCV

24、-DCM suggests that each clinical outcome may arise from distinct pathogenic conditions on the basis of differential HLA-mediated immune responses.Etiology of HCMHCMGeneticInflammatorySarcomereStorageVirusUnknownEtiology of DCMDCMGeneticInflammatorySarcomereStorageVirusUnknownEtiology of ARVC/DARVC/D

25、GeneticInflammatoryVirusUnknownDefinition and Classifications of CardiomyopathiesI.Etiological ClassificationA.GeneticB.InfectiousC.NutritionalD.UnknownII.Anatomical(Structural)ClassificationA.Dilated a.LV b.RVB.Hypertrophica.Septum b.Diffuse c.Free wall d.ApexIII.Physiological(mechanical)Classifica

26、tionA.Systolic failure/dysfunctionB.Diastolic failure/dysfunctionC.BothD.Normal functionIV.Electrical ClassificationA.Ion channel disordersB.Conduction system diseaseC.OthersDefinition and Classifications of CardiomyopathiesISFC ClassificationProposed ClassificationDCM(with viral infection)DCM(with

27、gene mutation)HCM(with gene mutation and outflow obstruction)Apical HCM(with unknown causes)Apical HCM(with HCV infection)ARVC/D(with gene mutation)ARVC/D(with HCV infection)Long QT SyndromeI B,II A a,III AI A,II A a,III AI A,II B a,III B I D,II B d,III BI B,II B d,III BI A,II A b,III AI B,II A b,II

28、I AI A,，IV AI.EtiologicalA.GeneticB.InfectionsC.NutritionalD.UnknownII.Anatomical(Structural)A.Dilated a.LV b.RVB.Hypertrophica.Septum b.Diffuse c.Free wall d.ApexIII.Physiological(mechanical)A.Systolic failure/dysfunctionB.Diastolic failure/dysfunctionC.Both D.Normal FunctionIV.Electrical Classific

29、ationA.Ion channel disordersB.Conduction system diseaseC.OthersDepartment of Cardiovascular Medicine,Kyoto UniversityViral Infection of the HeartDiffuseCHF/DCMSystolic HFRegionalAneurysmSubendocardialRCMDiastolic HFARVC/DLV AneurysmRandomHypertrophy/HCMVirusReceptorMyocyteFibroblastDepartment of Car

30、diovascular Medicine,Kyoto UniversityHypertrophic Obstructive Cardiomyopathy Associated with HCV InfectionDepartment of Cardiovascular Medicine,Kyoto UniversityAn Atypical Variant of Fabrys Disease in Men with Left Ventricular Hypertrophy.Nakao S et al NEJM 1995;333:288-293 Fabrys disease is an X-li

31、nked recessive disorder that results from a deficiency of -galactosidase.Seven of the 230 patients(3%)of HCM.Department of Cardiovascular Medicine,Kyoto UniversityDetection of HCV RNA in Heart Tissues from Patients with ARVCnPositive nFrequencyWHF Council ofCardiomyopathiesNational CardiovascularCen

32、ter,Japan63922433.0%66.7%44.4%TotalDepartment of Cardiovascular Medicine,Kyoto UniversityFrequencies of DPB1 Alleles in PatientsWith HCV-Associated Cardiomyopathy and ControlsBoth DPB1*0401 and DPB*0901 was significantly associated with HCV-HCM(*P 0.05),whereas none of DPB1 allele demonstrated signi

33、ficant association with HCV-DCMShichi D,Matsumori A,et al.Int J Immunogenet 2008;35:37-43 DPB1alleleHCV-HCM(2n=76)HCV-DCM(2n=42)Control(2n=264)*0201 0.145 0.143 0.205*03010.053 0.095 0.057*04010.079*0.024 0.023*05010.368 0.381 0.413*06010.013 0.004*09010.184*0.119 0.095Department of Cardiovascular Medicine,Kyoto UniversityEtiology of DCMDCMGeneticInflammatorySarcomereStorageVirusUnknown