L’amiloidosi: il danno cardiaco
e le conseguenze
C. Quarta, C. Rapezzi
Eleventh International Symposium
HEART FAILURE & Co.
MORTE IMPROVVISA
SUDDEN DEATH
Reggia di Caserta, 29-30 aprile 2011
“.. an infiltrative CMP that looks like hypertrophic
or hypertensive heart disease..”
Apo A
immunoglobulin
Lysozime
TTR
Terminology and Classification of Amyloidoses
Amyloid protein
Precursor
Syndrome or involved tissue
AL
immunoglobulin Primary / Myeloma
associated
light chain
ATTR
Transthyretin
Familial (PAF)
Senile (wilde type TTR)
AA
Serum AA
Secondary, reactive
A ß2M
ß2 microglobulin
Hemodyalisis associated
AApo AII
AFib
Alys
Apolipoprotein AII
Fibrinogen  chain
Lysozyme
Familial
Familial
Familial
….
Aß
APrP
….
Aß protein precursor
Prion protein
….
Alzheimer’s desease, aging
Spongioform encephalopathies
Amyloid Heart Disease: Therapeutic Strategies
chemotherapy
AL
high dose chemotherapy
autologous stem cell
transplantation
heart transplantation
Hereditary
ATTR
SSA
Liver transplantation
Heart & liver transplantation
“new stabilizer drugs”
treatment of heart failure
heart transplantation
Restrictive filling pattern, n
(%)
Dip-plateau morphology of RV
pressure tracing, n (%)
AL
(n=157)
ATTR
(n=61)
SSA
(n=15)
P
Value
82/150 (55)
22/59 (37)
4/14 (29)
0.024
1 (2)
1 (3)
1/12 (8)
0.329
Rapezzi et al, Circulation 2009:120:1203-1212
CONIGLIO
Perugini et al, Heart 2006;92:343-349
Baseline characteristics of pts with amyloidotic
CMP (Bologna & Pavia, n=233)
AL
(n=157)
SSA
(n=15)
ATTR
(n=61)
p
Value
LBBB, n (%)
6/146 (4)
6 (40)
4/60 (7)
<0.001
Total QRS score, mV
92 ± 36
120 ± 37
112 ± 34
<0.001
Low QRS voltage, n (%)
88/146 (60)
6 (40)
15/60 (25)
<0.001
Any infarct pattern, %
101/146 (69)
41/59 (69)
0.98
LV mass among men (g)
339 ± 106
513 ± 162 392 ± 150
<0.0001
Diastolic IVS (mm)
16 ± 3
20 ± 4
17 ± 4
<0.0001
LV ejection fraction (%)
53 ± 13
44 ± 15
58 ± 13
<0.0001
Restrictive filling
pattern, n (%)
82/150 (55)
4/14 (29) 22/59 (37)
10 (66)
Rapezzi et al, Circulation 2009;120:1203-1212
0.02
MACE
OVERALL
FREESURVIVAL
SURVIVAL
AL
ATTR
SSA
100%
75%
50%
AL
ATTR
SSA
25%
0%
Log Rank
Rank p
Log
p=
= 0.0001
0.0048
0
0
at risk
AL 157
131
ATTR 61
57
SSA 15
14
22
44
years
years
66
88
69
53
28
26
76
36
27
9
10
21
15
10
34
1
75
11
Rapezzi et al, Circulation 2009;120:1203-1212
Vascular localization
AL 79%
ATTR 21%
SSA 0%
p<0,0001
Inflammation
AL 14%
ATTR 3%
SSA 33%
p 0,014
Rapezzi et al, Circulation 2009;120:1203-1212
Different prognosis and functional impairment
•Direct toxic effect of circulating light chains
•Coronary (microvascular) involvement
•Duration/rapidity of amyloid accumulation
•………
?
Sudden death