廖玉華阜外心肌病診治進(jìn)展英文

1、Advancement of diagnosis and therapy in cardiomyopathies 心肌病診治進(jìn)展,LIAO Yu-HuaInstitute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China,Contemporary De

2、finitions and Classification of the Cardiomyopathies（2006AHA）,Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invar

3、iably) 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 di

4、sorders, often leading to cardiovascular death or progressive heart failure–related disability.,Maron BJ, et al. Circulation，2006，113:1807-1816,Classification,Cardiomyopathies can be most effectively classified as primar

5、y: genetic, mixed (genetic and nongenetic), acquired; and secondaryPrimary cardiomyopathies are those solely or predominantly confined to heart muscle and are relatively few in numberSecondary cardiomyopathies show pat

6、hological myocardial involvement as part of a large number and variety of generalized systemic (multiorgan) disorders,Maron BJ, et al. Circulation，2006，113:1807-1816,,Maron BJ, et al. Circulation，2006，113:1807-1816,Dilat

7、ed Cardiomyopathy,Dilated forms of cardiomyopathy are characterized by ventricular chamber enlargement and systolic dysfunction with normal LV wall thickness; usually diagnosis is made with 2-dimensional echocardiography

8、DCM 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 transplantation,Maron

9、 BJ, et al. Circulation，2006，113:1807-1816,DCM phenotype with genetic occurrenc,About 20% to 35% of DCM cases have been reported as familial, although with incomplete and age-dependent penetrance, and linked to a divers

10、e 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

11、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,DCM phenotype with sporadic

12、occurrence,Infectious agents, particularly viruses (coxsackievirus, adenovirus, parvovirus, HIV); bacterial; fungal rickettsial; myobacterial; and parasitic Other causes include toxins; chronic excessive consumption of

13、alcohol; chemotherapeutic agents; metals and other compounds; autoimmune and systemic disorders; pheochromocytoma; neuromuscular disorders such as Duchenne/Becker and Emery-Dreifuss muscular dystrophies; and mitochondria

14、l, metabolic, endocrine, and nutritional disorders,Maron BJ, et al. Circulation，2006，113:1807-1816,Criteria ① left ventricular end-diastolic dimension（LVEDd） >2.7cm/m2② left ventricular ejection fraction（LVEF）<4

15、5% and/or factional shortening <25% Exclusion：① hypertension, ② CHD, ③ long-term overdose drinking alcohol, ④ persistence supraventricular arrhythmia, ⑤ systemic disease, ⑥ pericardial disease, ⑦ congenital heart d

16、isease, ⑧ pneumocardial disease,Diagnostic criteria of idiopathic dilated cardiomyopathy,Manolio TA, et al. Am J Cardiol，1992，69：1459–66,① diagnostic criteria of dilated cardiomyopathy② The diagnosis of familial dilated

17、 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 su

18、dden death at <35 years of age,Diagnosis of familial dilated cardiomyopathy,Mestroni L, et al. Euro Heart J，1999，20: 93–102,① diagnostic criteria of dilated cardiomyopathy ② immunologic markers —anti-heart antibodie

19、s are main markers1 including: anti-ANT Ab、anti-ß1-receptor Ab、anti-MHC Ab、anti-M2-receptor Ab Secondary markers including： persistent viral infectionTh2 cell predominancecytokines genetype of humam leucoc

20、yte antigen,Diagnosis of immunedilated cardiomyopathy,1 苑海濤，廖玉華等. 臨床心血管病雜志，2000, 16:313-315,Analysis of autoantibody in dilated cardiomyopathy,ANT 31*(64.6%) 4 (8.3%) 64.6% 91.7%β1 26*(5

21、4.2%) 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

22、 DCM group (n=48) HD group (n=48) sensitivity specificity n (%) n (%),Compared with HD group * p<0.005,,,,苑海濤,廖玉華. 臨床心血管病雜志, 2000,16:313,Immunopathogenesis in

23、DCM,Voltage-gating Ca-channels,Ca-overload Cell damageCardiac dilation,Receptor-gating Ca-channels,Virus infection and autoimmunity response,DCM,Anti-ANT-Ab,Anti-ß1-RAb,,,,,,,Treatment of DCM,1、Conventional treatm

24、ent of heart failure 2、 Prevent embolism3、 Prevent SCD 4、 Improve cardiac metabolism 5、 Cardiac resynchronization therapy6、Cardiac transplantation,7、Immunologic therapy in DCM,1．β-receptor blocker To inhibit the an

25、ti-β1-Ab mediated myocardiual damage, especially in early stageEspecially suit for the patients with tachycardia or ventricular arrhythmias, or with anti-β1-Ab patientsDose：metroprolol 6.25mg Bid to 12.5～100 mg Bid, sl

26、owly titrate,Blocked autoantibodies response (1),,MDC trialPatients 345,MG n=177 and PG n=168 16-75 years of age Metoprolol 10mg/day →100~150mg/daytherapy of HF：digitalis、diuretics、ACEIFollowing up 18 months Metop

27、rolol is indicated to improve quanlity of life in heart failure with DCM,β-receptor blocker clinical trial in DCM,Waagstein F，et al. Lancet，1993，342:1441-46,2． DiltiazemFrequece of Anti-ANT antibody is positive about 60

28、%-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： dil

29、tiazem 30 mg tid,Blocked autoantibodies response (2),Calcium antagonist clinical trial in DCM,DiDi trialPatients 186, DG n=92 and PG n=94 18~70 years of age the adjunct therapy of diltiazem 60~90mg tid on standard

30、treatment DiDi trial is showed to improve cardiac function, exercise capacity and subjective status in DCM,Figulla HR. Circulation,1996,94:346-352.,Calcium antagonist clinical trial in DCM,ISDDC trialTo evaluate effect

31、s of diltiazem on heart function and prognosis in DCMMultiple centre, random, placebo-controlFollowing up 6~12 monthsPatients 221, PG n=107 and DG n=114, 46±12 years of ageDiltiazem 60~90 mg/day or Vit B1 60mg/

32、dayTherapy of HF: digoxine, diuretics, ACEI,Liao YH. Int J Cardiol, 1998, 64:25-30.,ISDDC trial Prognosis analysis in DCM,,Placebo Diltiazem n=107 n=1

33、14Outpatient treatment 63 (58.9) 102 (89.5)*** Repeated hospitalization 44 (41.1) 12 (10.5)***Death 12 (11.2) 4 (3.5)**Compared with plac

34、ebo group ** p<0.05, *** p<0.01,,,,Liao YH. Int J Cardiol, 1998, 64:25-30.,,Before After LVEDd> 70 mm(n=28) LVEDd 77.61±5.38 74.50

35、 ±8.92* EF 27.68 ± 11.69 33.71 ± 12.64* LVEDd0.05, ** p<0.01,ISDDC trialSubgroup analysis of heart function,,,,Liao YH. Int J Cardiol, 1998, 64:25-30

36、.,Heart image after diltiazem treated DCM,2000-8-11CTR 0.45,1999-1-18CTR 0.5,1998-9-17 CTR 0.6,ISDDC trial conclusion,Liao YH. Int J Cardiol, 1998, 64:25-30.,diltiazem is safe and effective in the treatment of DCM

37、the action mechanism might be intervention in antibody-mediated myocardial damage and protection of myocardiumdiltiazem is more suitable for treatment of the early stage in DCM,Pathogenesis and treatment in DCM,Immunoad

38、sorption of autoantibodies,Anti-β1-adrenoceptor antibody removed by immunoadsorption in patients with DCM, meanwhile treatment of heart failureFollow-up one year，LVEF increasing 15%（22.3±3.3% to37.9±7.9 %) an

39、d 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 t

40、he autoantibodies might improve heart function in DCM,Müller J, et al. Circulation，2000，101:385-39Schimke I,et al. J Clin Apher，2005，20:137-42,Immunomodulating therapy,Immunomodulating therapy with intravenous im

41、munoglobulin 2g/kg in patients with chronic heart failure within 6 months recently diagnosed DCM After treated 6 months and 12 months, LVEF increasing （0.25±0.08 to 0.41±0.17 /6 month and 0.42±0.14/ 12 mo

42、nth ）in patients with DCMThe finding suggests immunoglobulin might regulate the balance of inflammatory factor and anti-inflammatory factor and improve heart function,McNamara DM, et al. Circulation，2001，103:2254-9,Dila

43、ted phase of HCM,Have 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 cau

44、ses: 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 sh

45、ould strictly control the indication in HCM patients,summary,Immunologic therapy might delay process of immune DCM during early stageDilated phase is a natural process of HCM, we should strictly control the indication o

46、f 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