Pondering the Prognosis and Pathology of Cardiac Amyloidosis: Answers Breed Questions.

SEE PAGE 126 C ardiac amyloidosis (CA) is part of a systemic disease characterized by the deposition of amyloid in multiple tissues. Although the heart is often the predominant organ involved in systemic amyloidosis, this is not always the case, as CA of varying severity may be present when a patient with amyloidosis presents with symptoms related to another organ. Thus, in familial amyloidosis, CA may accompany a painful neuropathy; in AL amyloidosis it may be found when a patient presents with nephrotic syndrome, whereas in senile systemic amyloidosis it is almost invariably responsible for the presenting symptom. Although the presence of CA is often the major prognostic factor, the heterogeneity of presentation makes analyses of prognostic factors that are limited to the cardiovascular system difficult because other organ system disease can affect outcome and should ideally be taken into account. The biochemical constituents of amyloid vary between the various types. All amyloid deposits have a similar structure on light and electron microscopy, and all share certain biochemical components. However, there are many individual precursor proteins that can form amyloid deposits, and these differ greatly one from another and define the nature of the disease in the individual patient (1). For example, the precursor protein transthyretin (TTR) in a mutant form is responsible for familial amyloidosis, and wildtype TTR can cause senile amyloid. These proteins are completely different from the abnormal light chain