廖玉华阜外心肌病诊治进展英文.ppt

Advancement of diagnosis and therapy in cardiomyopathies 心肌病诊治进展,LIAO Yu-Hua Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China,Contemporary Definitions 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 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,Classification,Cardiomyopathies can be most effectively classified as primary: genetic, mixed (genetic and nongenetic), acquired; and secondary Primary cardiomyopathies are those solely or predominantly confined to heart muscle and are relatively few in number Secondary cardiomyopathies show pathological 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,Dilated 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 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 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 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,DCM phenotype with sporadic occurrence,Infectious 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 disorders,Maron BJ, et al. Circulation，2006，113:1807-1816,Criteria 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 cardiomyopathy,Manolio TA, et al. Am J Cardiol，1992，69：145966, 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 family 2. or in the presence of a first-degree relative of a dilated cardiomyopathy patient, with well documented unexplained sudden death at 35 years of age,Diagnosis of familial dilated cardiomyopathy,Mestroni L, et al. Euro Heart J，1999，20: 93102, 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 infection Th2 cell predominance cytokines genetype of humam leucocyte antigen,Diagnosis of immune dilated cardiomyopathy,1 苑海涛，廖玉华等. 临床心血管病杂志，2000, 16:313-315,Analysis of autoantibody in dilated cardiomyopathy,ANT 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, 2000,16:313,Immunopathogenesis in DCM,Voltage-gating Ca-channels,Ca-overload Cell damage Cardiac dilation,Receptor-gating Ca-channels,Virus infection and autoimmunity response,DCM,Anti-ANT-Ab,Anti-1-RAb,Treatment of DCM,1、Conventional treatment of heart failure 2、 Prevent embolism 3、 Prevent SCD 4、 Improve cardiac metabolism 5、 Cardiac resynchronization therapy 6、Cardiac transplantation,7、Immunologic therapy in DCM,1-receptor blocker To inhibit the anti-1-Ab mediated myocardiual damage, especially in early stage Especially suit for the patients with tachycardia or ventricular arrhythmias, or with anti-1-Ab patients Dose：metroprolol 6.25mg Bid to 12.5100 mg Bid, slowly titrate,Blocked autoantibodies response (1),MDC trial Patients 345,MG n=177 and PG n=168 16-75 years of age Metoprolol 10mg/day 100150mg/day therapy of HF：digitalis、diuretics、ACEI Following up 18 months Metoprolol is indicated to improve quanlity of life in heart failure with DCM,-receptor blocker clinical trial in DCM,Waagstein F，et al. Lancet，1993，342:1441-46,2 Diltiazem Frequece 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 myocardium Diltiazem might be used in early stage of DCM Dosage： diltiazem 30 mg tid,Blocked autoantibodies response (2),Calcium antagonist clinical trial in DCM,DiDi trial Patients 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.,Calcium antagonist clinical trial in DCM,ISDDC trial To evaluate effects of diltiazem on heart function and prognosis in DCM Multiple centre, random, placebo-control Following up 612 months Patients 221, PG n=107 and DG n=114, 4612 years of age Diltiazem 6090 mg/day or Vit B1 60mg/day Therapy 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=114 Outpatient 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, * p0.01,Liao YH. Int J Cardiol, 1998, 64:25-30.,Before After LVEDd 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 trial Subgroup analysis of heart function,Liao YH. Int J Cardiol, 1998, 64:25-30.,Heart image after diltiazem treated DCM,2000-8-11 CTR 0.45,1999-1-18 CTR 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 the action mechanism might be intervention in antibody-mediated myocardial damage and protection of myocardium diltiazem is more suitable for treatment of the early stage in DCM,Pathogenesis and treatment in DCM,Immunoadsorption of autoantibodies,Anti-1-adrenoceptor antibody removed by immunoadsorption in patients with DCM, meanwhile treatment of heart failure Follow-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 DCM,Mller J, et al. Circulation，2000，101:385-39 Schimke I,et al. J Clin Apher，2005，20:137-42,Immunomodulating therapy,Immunomodulating 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 DCM The 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,Dilated phase