Amyloid diseases of the heart: assessment, diagnosis, and referral

The amyloidoses are a group of diseases in which amyloid, a proteinaceous substance, deposits in one or more organs. As many as 23 different precursor proteins to the formation of amyloid have been described in man. These may deposit themselves in a fibrillar matrix within selected tissues. Fibrils are formed when normally soluble constituents undergo transformational change and misfold to become relatively insoluble. A variety of mechanisms promote these changes, which result in the final common pathway of the deposition of non-branching fibrils that can be visualised by electron microscopy and which are seen on light microscopy as a homogenous extracellular material (figure 1). Figure 1 Myocardial biopsy from a patient with congestive cardiac failure and echocardiographic appearances of amyloid deposition. The myocytes appear yellow with the amyloid staining turquoise (sulfated Alcian blue stain). Immunostaining subsequently confirmed transthyretin as the constituent protein. In the developed world, cardiologists predominantly encounter three main types of amyloidosis that affect the heart; light chain (AL) amyloidosis, senile systemic amyloidosis (SSA), and familial amyloidosis (FAP); the latter most commonly results from a mutation in transthyretin. In the developing world, secondary amyloid (AA) is more prevalent, due to chronic infections and inadequately treated inflammatory conditions. Occurring worldwide and later in life, a further amyloid type to affect the heart is isolated atrial amyloid (IAA).w1 w2 Finally, and much less common, are the non-transthyretin variants, including mutations of fibrinogen, apoprotein, and gelsolin. These rarer types can cause significant cardiac compromise. Cardiac involvement in amyloidosis is usually part of a systemic disease. The heart is frequently the predominant organ affected but, in some forms of the disease, isolated heart involvement can occur. In patients with a non-cardiac biopsy showing amyloid deposition, cardiac involvement has been defined—by a consensus opinion from the 10th International Symposium on Amyloidosis1—as …