廖玉华阜外心肌病诊治进展英.ppt

Advancement of diagnosis and therapy in cardiomyopathies 心肌病诊治进展 LIAO Yu-HuaInstitute of Cardiology,Union Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan,China 1Contemporary Definitions and Classification of the Cardiomyopathies（2006AHA2006AHA）Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually(but not invariably)exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic.Cardiomyopathies either are confined to the heart or are part of generalized systemic disorders,often leading to cardiovascular death or progressive heart failurerelated disability.Maron BJ,et al.Circulation，2006，113:1807-1816 2ClassificationCardiomyopathies can be most effectively classified as primary:genetic,mixed(genetic and nongenetic),acquired;and secondary1.Primary cardiomyopathies are those solely or predominantly confined to heart muscle and are relatively few in number2.Secondary cardiomyopathies show pathological myocardial involvement as part of a large number and variety of generalized systemic(multiorgan)disordersMaron BJ,et al.Circulation，2006，113:1807-1816 3Maron BJ,et al.Circulation，2006，113:1807-1816 4Dilated CardiomyopathyDilated forms of cardiomyopathy are characterized by ventricular chamber enlargement and systolic dysfunction with normal LV wall thickness;usually diagnosis is made with 2-dimensional echocardiographyDCM is a common and largely irreversible form of heart muscle disease with an estimated prevalence of 1:2500;it is the third most common cause of heart failure and the most frequent cause of heart transplantationMaron BJ,et al.Circulation，2006，113:1807-1816 5DCM phenotype with genetic occurrencAbout 20%to 35%of DCM cases have been reported as familial,although with incomplete and age-dependent penetrance,and linked to a diverse group of 20 loci and genes.DCM is also caused by a number of mutations in other genes encoding cytoskeletal/sarcolemmal,nuclear envelope,sarcomere,and transcriptional coactivator proteins.The most common of these probably is the lamin A/C gene,also associated with conduction system disease,which encodes a nuclear envelope intermediate filament protein.Maron BJ,et al.Circulation，2006，113:1807-1816 6DCM phenotype with sporadic occurrenceInfectious agents,particularly viruses(coxsackievirus,adenovirus,parvovirus,HIV);bacterial;fungal rickettsial;myobacterial;and parasitic Other causes include toxins;chronic excessive consumption of alcohol;chemotherapeutic agents;metals and other compounds;autoimmune and systemic disorders;pheochromocytoma;neuromuscular disorders such as Duchenne/Becker and Emery-Dreifuss muscular dystrophies;and mitochondrial,metabolic,endocrine,and nutritional disordersMaron BJ,et al.Circulation，2006，113:1807-1816 7Criteria left ventricular end-diastolic dimension（LVEDd）2.7cm/m2 left ventricular ejection fraction（LVEF）45%and/or factional shortening 25%Exclusion：hypertension,CHD,long-term overdose drinking alcohol,persistence supraventricular arrhythmia,systemic disease,pericardial disease,congenital heart disease,pneumocardial disease Diagnostic criteria of idiopathic dilated cardiomyopathyManolio TA,et al.Am J Cardiol，1992，69：145966 8 diagnostic criteria of dilated cardiomyopathy The diagnosis of familial dilated cardiomyopathy is made:1.in the presence of two or more affected individuals in a single family2.or in the presence of a first-degree relative of a dilated cardiomyopathy patient,with well documented unexplained sudden death at 35 years of ageDiagnosis of familial dilated cardiomyopathyMestroni L,et al.Euro Heart J，1999，20:93102 9 diagnostic criteria of dilated cardiomyopathy immunologic markers anti-heart antibodies are main markers1 including:anti-ANT Ab、anti-1-receptor Ab、anti-MHC Ab、anti-M2-receptor Ab Secondary markers including：persistent viral infectionTh2 cell predominancecytokines genetype of humam leucocyte antigenDiagnosis of immunedilated cardiomyopathy 1 苑海涛，廖玉华等.临床心血管病杂志，2000,16:313-31510Analysis of autoantibody in dilated cardiomyopathyANT 31*(64.6%)4(8.3%)64.6%91.7%1 26*(54.2%)4(8.3%)54.2%91.7%M2 20*(41.7%)3(6.3%)41.7%93.7%MHC 23*(47.9%)2(4.2%)47.9%95.8%positive of autoantibody in DCM AHA in DCM Peptides DCM group(n=48)HD group(n=48)sensitivity specificity n (%)n (%)Compared with HD group *p0.005苑海涛,廖玉华.临床心血管病杂志,2000,16:31311Immunopathogenesis in DCMVoltage-gating Ca-channelsVoltage-gating Ca-channelsCa-overload Ca-overload Cell damageCell damageCardiac dilation Cardiac dilation Receptor-gating Ca-Receptor-gating Ca-channelschannelsVirus infection and autoimmunity Virus infection and autoimmunity responseresponseDCMA An nt ti i-A ANNT T-A Ab bA An nt ti i-1 1-R RA Ab b12Treatment of DCM1、Conventional treatment of heart failure 2、Prevent embolism3、Prevent SCD 4、Improve cardiac metabolism 5、Cardiac resynchronization therapy6、Cardiac transplantation7、Immunologic therapy in DCM131-receptor blocker To inhibit the anti-1-Ab mediated myocardiual damage,especially in early stageEspecially suit for the patients with tachycardia or ventricular arrhythmias,or with anti-1-Ab patientsDose：metroprolol 6.25mg Bid to 12.5100 mg Bid,slowly titrate Blocked autoantibodies response(1)14MDC trialPatients 345,MG n=177 and PG n=168 16-75 years of age Metoprolol 10mg/day 100150mg/daytherapy of HF：digitalis、diuretics、ACEIFollowing up 18 months Metoprolol is indicated to improve quanlity of life in heart failure with DCM-receptor blocker clinical trial in DCMWaagstein F，et al.Lancet，1993，342:1441-46 152 DiltiazemFrequece of Anti-ANT antibody is positive about 60%-95%Mechanism：Anti-ANT antibody increased Ca current of myocardial cell.Diltiazem could inhibit the antibody mediated myocardial damage and protect myocardiumDiltiazem might be used in early stage of DCMDosage：diltiazem 30 mg tid Blocked autoantibodies response(2)16Calcium antagonist clinical trial in DCMDiDi trialPatients 186,DG n=92 and PG n=94 1870 years of age the adjunct therapy of diltiazem 6090mg tid on standard treatment DiDi trial is showed to improve cardiac function,exercise capacity and subjective status in DCM Figulla HR.Circulation,1996,94:346-352.17Calcium antagonist clinical trial in DCMISDDC trialTo evaluate effects of diltiazem on heart function and prognosis in DCMMultiple centre,random,placebo-controlFollowing up 612 monthsPatients 221,PG n=107 and DG n=114,4612 years of ageDiltiazem 6090 mg/day or Vit B1 60mg/dayTherapy of HF:digoxine,diuretics,ACEILiao YH.Int J Cardiol,1998,64:25-30.18ISDDC trial Prognosis analysis in DCM Placebo Diltiazem n=107 n=114Outpatient treatment 63(58.9)102(89.5)*Repeated hospitalization 44(41.1)12(10.5)*Death 12(11.2)4(3.5)*Compared with placebo group*p0.05,*p 70 mm(n=28)LVEDd 77.615.38 74.50 8.92*EF 27.68 11.69 33.71 12.64*LVEDd0.05,*p0.01 ISDDC trialSubgroup analysis of heart functionLiao YH.Int J Cardiol,1998,64:25-30.20Heart image after diltiazem treated DCM2000-8-112000-8-11CTR 0.45CTR 0.451999-1-181999-1-18CTR 0.5CTR 0.51998-9-171998-9-17 CTR 0.6 CTR 0.621ISDDC trial conclusion Liao YH.Int J Cardiol,1998,64:25-30.Fdiltiazem is safe and effective in the treatment of DCMFthe action mechanism might be intervention in antibody-mediated myocardial damage and protection of myocardiumFdiltiazem is more suitable for treatment of the early stage in DCM 22Pathogenesis and treatment in DCM1-blocksDiltiazemVoltage-gating Ca-channelsCa-overload Cell damageCardiac dilation Receptor-gating Ca-channelsVirus infection and autoimmunity responseAnti-ANT-AbAnti-1-RAbTherapy of HFDCMHFno HFSevere HFLiao YH.200123Immunoadsorption of autoantibodies Anti-1-adrenoceptor antibody removed by immunoadsorption in patients with DCM,meanwhile treatment of heart failureFollow-up one year，LVEF increasing 15%（22.33.3%to37.97.9%)and LVEDd decreasing 14.5%（74.5 7.1 to 63.7 6.0 mm）in DCM group；LVEF（23.8 3.0 to 25.2 5.9%）no improvement and LVEDd decreased 3.8%in control group The clinical trial confirmed that removing the autoantibodies might improve heart function in DCMMller J,et al.Circulation，2000，101:385-39Schimke I,et al.J Clin Apher，2005，20:137-4224Immunomodulating therapyImmunomodulating therapy with intravenous immunoglobulin 2g/kg in patients with chronic heart failure within 6 months recently diagnosed DCM After treated 6 months and 12 months,LVEF increasing（0.250.08 to 0.410.17/6 month and 0.420.14/12 month）in patients with DCMThe finding suggests immunoglobulin might regulate the balance of inflammatory factor and anti-inflammatory factor and improve heart functionMcNamara DM,et al.Circulation，2001，103:2254-925Dilated phase of HCMHave a good prognosis,80 patients can survive 10ys,some patients sudden deathSome patients will Dilated phase of hypertrophic cardiomyopathy-Complicated LV enlargement and heart failurePossible causes:myocardial ischemia,alchhol letion,viral infectionThe incidence of dilated stage of HCM is about 14%16%,heart failure is one major cause of death,prognosis poor Chemical ablation of interventricular septum should strictly control the indication in HCM patients 26summary Immunologic therapy might delay process of immune DCM during early stageDilated phase is a natural process of HCM,we should strictly control the indication of chemical ablation in HCM patients Heart failure or sudden death is final end-result Investigation of etiology and pathogenesis in cardiomyopathies have important value for therapy of cardiomyopathies Prevention and cure of heart failure form A stage and B stage the load is heavy while the way is long27后面内容直接删除就行资料可以编辑修改使用资料可以编辑修改使用资料仅供参考，实际情况实际分析28主要经营：课件设计，文档制作，网络软件设计、图文设计制作、发布广告等秉着以优质的服务对待每一位客户，做到让客户满意！致力于数据挖掘，合同简历、论文写作、PPT设计、计划书、策划案、学习课件、各类模板等方方面面，打造全网一站式需求29The user can demonstrate on a projector or computer,or print the presentation and make it into a film to be used in a wider field30