Eleventh International Symposium HEART FAILURE & Co. MORTE IMPROVVISA SUDDEN DEATH Reggia di Caserta, aprile 2011 Lamiloidosi: 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 ß 2 M AApo AII AFib Alys …. Aß APrP Syndrome or involved tissue Primary / Myeloma associated Familial (PAF) Senile (wilde type TTR) Secondary, reactive Hemodyalisis associated Familial …. Alzheimers desease, aging Spongioform encephalopathies Precursor immunoglobulin light chain Transthyretin Serum AA ß 2 microglobulin Apolipoprotein AII Fibrinogen chain Lysozyme …. Aß protein precursor Prion 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 SSA treatment of heart failure heart transplantation

AL (n=157) ATTR (n=61) SSA (n=15) P Value 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:

CONIGLIO

Perugini et al, Heart 2006;92:

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, mV92 ± ± ± 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 ± ± ± 150< Diastolic IVS (mm)16 ± 320 ± 417 ± 4< LV ejection fraction (%)53 ± 1344 ± 1558 ± 13< Restrictive filling pattern, n (%) 82/150 (55)4/14 (29)22/59 (37)0.02 Rapezzi et al, Circulation 2009;120:

OVERALL SURVIVAL Rapezzi et al, Circulation 2009;120: MACE FREE SURVIVAL

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:

Direct toxic effect of circulating light chains Coronary (microvascular) involvement Duration/rapidity of amyloid accumulation ……… Different prognosis and functional impairment

Sudden death ?