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Cardiomyopathies
Oliver Rácz, 2011
14.02.2010
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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!
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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
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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)
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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?
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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
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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
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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
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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
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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“
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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
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MUTATIONS
IN DCM 1A
Arg60Gly
Leu85Arg
Glu161Lys
Asn195Lys
Glu203Gly
Arg571Ser
Ser573Leu
1-bp del 959T
1-bp ins 28A
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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)
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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
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