1. 14.02.2010kvs04e.ppt1 Cardiomyopathies Oliver Rácz, 2011

2. 14.02.2010kvs04e.ppt2 Definition? Idiopathic pathological processes ??? Primary = monogenic, mostly AD with low penetrancy and expressivity (in the past often nondiagnosed) Secondary – known causes CMs can be combined with other heart and circulatory conditions!

3. 14.02.2010kvs04e.ppt3 Classification Dilated systolic dysfunction (DCM, COCM – dilated, congestive cardiomyopathy) Hypertrofic diastolic dysfunction with or without outflow obstruction (HNCM a HOCM - hypertrophic nonobstructive/obstructive cariodiomyopathy) Restrictive Impaired elasticity of the ventricular walls, diastolic and systolic dysfunction. RCM - restrictive cardiomyopathy

4. 14.02.2010kvs04e.ppt4 Secondary CMs Specific diseases of the myocard - 1 Toxic Cobalt salts added to the beer (and other) Anticancer drugs Alcoholic CM (?) Nutritional deficiencies m. Keshan – Se deficiency B group vitamin deficiency (beri-beri)

5. 14.02.2010kvs04e.ppt5 Secondary CMs Specific diseases of the myocard - 2 Metabolic Diabetes mellitus Kidney failure - uremia Neuromuscular diseases ? Muscular atrophies, Friedreich etc. ??? Hereditary conditions! Infiltration with cells, abnormal substances Leukemia, glycogenoses, lipid storage diseases Infections ? Diphteria, viroses Inflammation or alteration?

6. 14.02.2010kvs04e.ppt6 Secondary CMs Specific diseases of the myocard - 3 Electrolyte disturbances? Potassium, magnesium ? Endocrine diseases hyperthyreosis, hypothyreosis, suprarenal d. Connective tissue pathologies lupus erytematodes and many others Heart damage in immune disturbances

7. 14.02.2010kvs04e.ppt7 Dilated, congestive – bad prognosis Hereditary, see later Common in alcoholics Dilated ventricles Systolic dysfunction of the left ventricle – low EF, congesction in the pulmonary circulation Later diastolic dysfunction of the left and failure of the right ventricle Valvular regurgitation Arrythmias Clot formation in the ventricles, danger of embolisation – systemic and pulmonary

8. 14.02.2010kvs04e.ppt8 HYPERTROPHIC (HNCM, HOCM) – mostly good prognosis Abnormal histology of the myofibrills Hypertrophy is compensatory Contractility is good, EF is normal or even increased Diastolic dysfunction of the left ventricle – slow relaxation after systole Arrythmias The muscular hypertrophy often affects the interventricular septum and causes outflow obstruction = subvalvular aortic stenosis

9. 14.02.2010kvs04e.ppt9 RESTRICTIVE CMs – rare in Europe The ventricular wall is rigid Severe diastolic dysfunction, tachycardia, dyspnoe. Often also right ventricle failure Valvular dysfunction Known etiology Cardiac muscle infiltration with anormal sbstances - amyloidosis, hemocromatosis, glycogenoses... Genetic ? Endomyocardial fibrosis – tropical disease Fibroelastosis of the myocardium – rare children disease of unknown etiology

10. 14.02.2010kvs04e.ppt10 HEREDITARY CONDITIONS AND CMs HYPERTROFIC CMH1- gene for he heavy chain of  -myosin (ch. 14) Gene for troponin T (ch. 1q3) Gene for  -tropomyozín (ch. 15q2) DILATED Gene for dystrophin Gen for lamin A ??? See later Gene for actin BUT ALSO – Duchenne, mitochondrial diseases, and „arytmogenic dysplasia of the left ventricle“

11. 14.02.2010kvs04e.ppt11 NEW KNOWLEDGE Prevalence  40/100 000 (SR  2000!) Screening is recommended (children, relatives) OMIM – 37 data about DCM, more about HCM Sometimes withou any logical connection to the heart– lamin gene mutations MUTATIONS IN DCM 1A Arg60Gly Leu85Arg Glu161Lys Asn195Lys Glu203Gly Arg571Ser Ser573Leu 1-bp del 959T 1-bp ins 28A

12. 14.02.2010kvs04e.ppt12 LAMIN? Lamins (A,B,C) are parts of the inner layer of the nuclear membrane – responsible to proper form of the nucleus Lamins A and C are coded on gene LMNA, locus 1q21.2 – 21.3, 24 exons The difference between the proteins is the result of alternative RNA processing (A: 74 kD – 664 aminoacids, C: 65 kD and 98 aminoacids less)

13. 14.02.2010kvs04e.ppt13 LAMIN??? – crazy! Different expression in the tissues, different interactions with other genes…, different diseases Dilated CMs with conduction abnormalities Lipodystrophy Neuropathy Progeric conditions! (Werner) Restrictive dermopathy ??? Obesity is some ethnic groups ??? 1908 C/T