Eleventh International SymposiumHEART FAILURE & Co.

MORTE IMPROVVISASUDDEN DEATH

Reggia di Caserta, 29-30 aprile 2011

L’amiloidosi: il danno cardiaco e le conseguenze

C. Quarta, C. Rapezzi

“.. an infiltrative CMP that looks like hypertrophic or hypertensive heart disease..”

Apo A

immunoglobulin

Lysozime

TTR

Terminology and Classification of Amyloidoses

Amyloid protein

AL

ATTR

AA

A ß2M

AApo AIIAFibAlys

….AßAPrP

Syndrome or involved tissue

Primary / Myeloma associated

Familial (PAF) Senile (wilde type TTR)

Secondary, reactive

Hemodyalisis associated

FamilialFamilialFamilial

….Alzheimer’s desease, agingSpongioform encephalopathies

Precursor

immunoglobulinlight chain

Transthyretin

Serum AA

ß2 microglobulin

Apolipoprotein AIIFibrinogen chainLysozyme

….Aß protein precursorPrion protein

Amyloid Heart Disease: Therapeutic Strategies

Heart & liver transplantation

high dose chemotherapy

autologous stem cell transplantation

Hereditary

ATTR

Liver transplantation

chemotherapy

AL

heart transplantation

“new stabilizer drugs”

SSAtreatment of heart failure

heart transplantation

AL(n=157)

ATTR(n=61)

SSA(n=15)

PValu

e

Restrictive filling pattern, n (%)

82/150 (55)

22/59 (37)

4/14 (29) 0.024

Dip-plateau morphology of RV pressure tracing, n (%)

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)

10 (66) 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) 0.02

Rapezzi et al, Circulation 2009;120:1203-1212

Log Rank p = 0.00010%

25%

50%

75%

100%

Su

rviv

al

15 7 2 1SSA61 28 9 3 1ATTR

157 69 36 15 7ALat risk

0 2 4 6 8years

ALATTRSSA

OVERALL SURVIVAL

Rapezzi et al, Circulation 2009;120:1203-1212

MACE FREE SURVIVAL

Log Rank p = 0.00480%

25%

50%

75%

100%

Su

rviv

al

14 6 1SSA57 26 10 4 1ATTR

131 53 27 10 5ALat risk

0 2 4 6 8years

ALATTRSSA

Vascular

localization AL 79%

ATTR 21% SSA 0%

p<0,0001

InflammationAL 14%ATTR 3%SSA 33% p 0,014

Rapezzi et al, Circulation 2009;120:1203-1212

•Direct toxic effect of circulating light chains

•Coronary (microvascular) involvement

•Duration/rapidity of amyloid accumulation

•………

Different prognosis and functional impairment

Sudden death?