**2. Classification of cardiac amyloidosis**

Cardiac amyloidosis is classified with regard to the origin of protein precursors in 6 types: primary (AL), secondary (reactive, AA), senile systemic, hereditary (familial), isolated atrial and hemodialysis-associated amyloidosis. Differentiation between these forms is based on immunohistochemical and genetic testing and implies the patient´s prognosis and therapeutic strategies.

Primary amyloidosis (AL) is the disease of immunoglobulin light-chain proteins produced from plasma cells in multiple myeloma and other plasma cell dyscrasias (Waldenström macroglobulinemia, B-cell lymphoma, a. o.). Its incidence is rare, estimated for 8.9 per million population (Kyle, Linos et al. 1992), however, its clinical course is aggressive with poor prognosis. The median survival without treatment is 13 months and may be prolonged to 17 months with melphalane and prednisone therapy (Kyle, Gertz et al. 1997). Predominant cardiac involvement is the cause of dim course with median life expectancy of 4 months since clinical manifestation of congestive heart failure. Death is attributed to intractable low cardiac output or fatal arrhytmia. Sudden cardiac death may be preceded by syncope (Chamarthi, Dubrey et al. 1997).

Secondary amyloidosis (AA) is caused by the accumulation of amyloid A fibrils formed from an acute-phase reactant, serum amyloid A protein, in chronic inflammatory diseases like rheumatoid arthritis, familial Mediterranean fever, chronic infections, chronic lung diseases, tuberculosis, and inflammatory bowel disease. The heart seems to be affected less frequently whereas the kidney involvement leads to proteinuria and renal failure. The treatment of the underlying inflammatory process can reverse the disease (Gillmore, Lovat et al. 2001).

Senile systemic amyloidosis is related to liver production of a wild-type transthyretin transport protein (TTR). Amyloid deposits can be found in the heart, aorta, brain, pancreas, lung, liver, kidneys, and other organs. Senile systemic amyloidosis seems to be an age related disease, affecting predominantly men above the age of 70, with age-increasing incidence. Median survival of 75 months indicates less aggressive course of the disease (Cohen 1967; Ng, Connors et al. 2005).

Hereditary (familial) amyloidosis is an autosomal dominant disease in which genetically mutated proteins, namely TTR, form the insoluble deposits. More than 80 transthyretin mutation have been identified as well as mutations in other proteins (fibrinogen Aa, lysozyme, apolipoprotein A-I, and gelsolin) have also been reported (Connors, Richardson et al. 2000). Besides cardiac involvement the other manifestations are peripheral and autonomic polyneuropathy with mainly gastrointestinal symptoms, renal impairment.

Isolated atrial amyloidosis (AANF) is caused by atrial natriuretic peptide secretion in response to atrial dilation in valvular disease and chronic atrial fibrillation as well as in correlation to increasing age. Thin atrial amyloid deposits however do not affect significantly the cardiac performance. Cardiac amyloidosis may also develop in patients receiving long-term dialysis due to accumulation of beta2-microglobulin from chronic uremia (Gorevic, Casey et al. 1985). Amyloid deposits may be found in myocardium, pericardium and valves with minimal clinical impact (Noel, Zingraff et al. 1987).
