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1、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,Contemporary Definitions and Classification of the Cardiomyopathies（2019AHA）,Cardiomyopathies are
2、 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 conf
3、ined 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，2019，113:1807-1816,Classification,Cardiomyopathies can be most effectively classified as primary: genetic, mixed (geneti
4、c and nongenetic), acquired; and secondaryPrimary cardiomyopathies are those solely or predominantly confined to heart muscle and are relatively few in numberSecondary cardiomyopathies show pathological myocardial involvement as part of a large number and variety of generalized systemic (multiorgan)
5、 disorders,Maron BJ, et al. Circulation，2019，113:1807-1816,Maron BJ, et al. Circulation，2019，113:1807-1816,Dilated Cardiomyopathy,Dilated forms of cardiomyopathy are characterized by ventricular chamber enlargement and systolic dysfunction with normal LV wall thickness; usually diagnosis is made wit
6、h 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 transplantation,Maron BJ, et al. Circulation，2019，113:1807-1816,DCM ph
7、enotype 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
8、 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，2019，113:1807-1816,DCM phenotype with
9、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
10、 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，2019，113:1807-1816,Criteria left ventricular end-diastolic dimension（LVE
11、Dd） 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 crite
12、ria 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 family2. or in the presence of a first-de
13、gree 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，2019，20: 93102, diagnostic criteria of dilated cardiomyopathy immunologic markers anti-heart antibodies are
14、 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 antigen,Diagnosis of immunedilated cardiomyopathy,1 苑海涛，廖玉华等. 临床心血管病杂志，2000, 16:313-315,Analysis
15、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 (%)
16、,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 damageCardiac dilation,Receptor-gating Ca-channels,Virus infection and autoimmunity response,DCM,Anti-ANT-Ab,Anti-1-RAb,Treatment of DCM,1、Conventional treatment of h
17、eart failure 2、 Prevent embolism3、 Prevent SCD 4、 Improve cardiac metabolism 5、 Cardiac resynchronization therapy6、Cardiac transplantation,7、Immunologic therapy in DCM,1-receptor blocker To inhibit the anti-1-Ab mediated myocardiual damage, especially in early stageEspecially suit for the patients w
18、ith 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),MDC trialPatients 345,MG n=177 and PG n=168 16-75 years of age Metoprolol 10mg/day 100150mg/daytherapy of HF：digitalis、diuretics、ACE
19、IFollowing 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 DiltiazemFrequece of Anti-ANT antibody is positive about 60%-95%Mechanism： Anti-ANT antibody increased Ca current
20、 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),Calcium antagonist clinical trial in DCM,DiDi trialPatients 186, DG n=92 and PG n=94
21、 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,2019,94:346-352.,Calcium antagonist clinical trial in DCM,ISDDC trialTo evaluate effects of di
22、ltiazem 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, ACEI,Liao YH. Int J Cardiol, 2019, 64:25-30.,ISDDC trial Prog
23、nosis 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, * p0.01,Liao YH. Int J Cardiol, 2019, 64:25-30.,Before After LVEDd 70 mm(n=28) LVEDd 77.615.38 74.50
24、 8.92* EF 27.68 11.69 33.71 12.64* LVEDd0.05, * p0.01,ISDDC trialSubgroup analysis of heart function,Liao YH. Int J Cardiol, 2019, 64:25-30.,Heart image after diltiazem treated DCM,2000-8-11CTR 0.45,2019-1-18CTR 0.5,2019-9-17 CTR 0.6,ISDDC trial conclusion,Liao YH. Int J Cardiol, 2019, 64:25-30.,dil
25、tiazem is safe and effective in the treatment of DCMthe 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,Immunoadsorption of autoantibodies,An
26、ti-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
27、3.8% in control group The clinical trial confirmed that removing the autoantibodies might improve heart function in DCM,Mller J, et al. Circulation，2000，101:385-39Schimke I,et al. J Clin Apher，2019，20:137-42,Immunomodulating therapy,Immunomodulating therapy with intravenous immunoglobulin 2g/kg in p
28、atients 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-in
29、flammatory factor and improve heart function,McNamara DM, et al. Circulation，2019，103:2254-9,Dilated 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 failur
30、ePossible 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,summary,Immunolog
31、ic 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 long,
