Cardiomiopatia Dilatativa
(DCM)
• Dilatazione e depressa funzione di pompa del ventricolo
sinistro/e destro
• EF < 45%, LVEDD > 117% corretto per eta’ e BSA
• Causa di of CHF, aritmie, sudden death, trapianto
• Prevalenza: 1 in 500-2500 individui
• 2-3 millioni di pazienti negli US
• mortalita’: 28,807 nel 1998 (American Heart Association
website)
• Causa?
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CMPD IDIOPATICA: EZIOPATOGENESI
2
FATTORI
GENETICI
MUTAZIONI
DEL DNA
MH
C
ALTERAZIONI
DEL SISTEMA
IMMUNITARIO
AUTOANTICORP
I ANTI T-linfociti
INFEZIONE
VIRALE
MIOCARDITE
INTERFERENZA
CON LA RISPOSTA
IMMUNE
PROTEINE
ALTERATE
FUNZIONE
MIOCARDICA
ALTERATA
PERSISTENZ
A VIRALE
CARDIOMIOPATIA DILATATIVA
CMPD: SINTOMI
•
•
•
•
•
•
Nessuno (scoperta occasionale: ECGG, ECO, RX)
dispnea
astenia
palpitazioni
angina
sincopi/presincopi
CMPD: esame obiettivo
• Polso piccolo/alternante
• itto esteso e sollevante, spostato sull’AA, in VI
spazio
• turgore giugulare (onda “a” e “v” ++)
• II tono polmonare ++
• 3° e 4° tono
• rigurgito mitralico/tricuspidale
• epatomegali
• edemi
Pedigrees of Families With Different Forms of
Familial Dilated Cardiomyopathy:
Phenotypic Heterogeneity
Mestroni,Sinagra et al., JACC 1999
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Components of Myocyte Cytoarchitecture
Desmin
Titin
Dystrophin
Dystrophin-associated
glycoprotein
complex
Actin-associated
cytoskeleton
Actin
Beta MHC
Troponin T Z band
Alpha-tropomyosin
Sarcolemma
Sarcomere
Emerin
Lamins A and C
Nuclear membranes
Nucleus
Nuclear
envelope
Nuclear
pore
Cytoplasm
Fatkin,et al. N Eng J Med 1999 ;341:1715 (modified)
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DCM: molecular epidemiology
GENE
•cardiac troponin T
• titin
PHENOTYPE
DCM
DCM
FREQUENCY
? 5%
?
• desmin
DCM, CDDC, MD
? 0-1% (exon 8)
• b-myosin heavy chain
DCM
? 5%
• cardiac actin
DCM
< 1%
• a-tropomyosin
DCM
? < 1%
• dystrophin
XLDC
~ 37%
• lamin A/C
DCM, CDDC, EDMD, LGMD
? (~ 40% in CDDC)
• metavinculin
DCM
< 1%
• d-sarcoglycan
DCM (~CK)
4%, pediatric pts
• G4.5 (tafazzin)
congenital DCM, LVNC
?
⇧CK
pediatric pts
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DCM: molecular epidemiology
Phenotype
Chromosomal
location
6q12-q16
LOCUS OMIM
9q13
CMD1B
600884
(with mitral prolapse)
10q21-q23
CMD1C
601493
Autosomal recessive FDC
unknown
Autosomal dominant FDC with
6q23
CMD1F
Autosomal dominant FDC with
2q14-q22
CMD1H 604288
conduction defects
3p22-p25
CMD1E
601154
Autosomal recessive with retinitis
6q23-q24
CMD1J
605362
Autosomal dominant FDC
605582
212110
602067
skeletal muscle disease
pigmentosa and deafness
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Genes associated with DCM
•Cardiac troponin T
•Titin
•Tinin-cap (teletonin)
•Cardiac Myosin-Binding Protein C
•Cardiac b-myosin heavy chain
•Cardiac actin
a-tropomyosin
Cypher/ZASP
MLP
a-actinin 2
Cysteine-glycine-rich protein 3 (MLP)
Cardiac a-myosin heavy chain
•Desmin
•Dystrophin
• d-sarcoglycan
a-dystrobrevin
•Desmoplakin
•Metavinculin
•Lamin A/C
•LAP2
Pospholamban
•G4.5 (tafazzin)
Changing Mortality in DCM
Heart Muscle Disease Registry - Trieste
Deaths/HTx
1,0
,8
p<0.0001
,6
Cohort 1988-1994
(n=249)
,4
Cohort 1978-1987
(n=99)
,2
p<0,0001
0,0
0
36
72
108
follow-up (months)
144
180