1. Cardiomyopathies
Oliver Rácz, 2011
kvs04e.ppt

2. 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!
kvs04e.ppt

3. Classification Dilated Hypertrofic Restrictive
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
kvs04e.ppt

4. 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)
kvs04e.ppt

5. 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?
kvs04e.ppt

6. 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
kvs04e.ppt

7. 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
kvs04e.ppt

8. 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
kvs04e.ppt

9. 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
kvs04e.ppt

10. HEREDITARY CONDITIONS AND CMs
HYPERTROFIC
CMH1- gene for he heavy chain of b-myosin (ch. 14)
Gene for troponin T (ch. 1q3)
Gene for a-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“
kvs04e.ppt

11. NEW KNOWLEDGE Prevalence  40/100 000 (SR  2000!)
MUTATIONS IN DCM 1A
Arg60Gly
Leu85Arg
Glu161Lys
Asn195Lys
Glu203Gly
Arg571Ser
Ser573Leu
1-bp del 959T
1-bp ins 28A
Prevalence  40/ (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
kvs04e.ppt

12. 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)
kvs04e.ppt

13. 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
kvs04e.ppt