Current therapeutic strategies in cardiac amyloidosis

Amyloidosis is a systemic disease in which clinical manifestations are caused by the replacement of normal tissue with insoluble amyloid fibrils. Cardiac involvement causes a restrictive cardiomyopathy and is associated with poor functional outcomes. Cardiac magnetic resonance imaging and measurement of B-type natriuretic peptide are particularly helpful in distinguishing restrictive cardiomyopathy from constrictive pericarditis, but a tissue biopsy is required to make the diagnosis of amyloidosis. Although standard treatment options for congestive heart failure may provide symptomatic relief in cardiac amyloidosis, prognosis remains dismal. Judicious diuretic use remains the mainstay of therapy, but achieving optimal fluid balance is difficult because patients are usually "preload dependent." Angiotensin-converting enzyme inhibitors in low doses are often helpful but may lead to orthostatic hypotension, particularly in patients who also have involvement of the autonomic nervous system. beta Blockers may be useful if given relatively early in the disease process, but should be used with caution in patients with advanced disease because they may exacerbate symptoms. Therapy aimed at the underlying disease process in primary systemic amyloidosis is based on treatment regimens used in multiple myeloma, such as melphalan and prednisone. These offer limited benefit when cardiac involvement is significant, but newer treatments, including the novel anthracycline 4'-iodo-4'-deoxydoxorubicin, potentially combined with autologous stem cell transplantation, offer some hope for the future.