Cardiac Amyloidosis

Excerpt

Amyloidosis is a systemic disease characterized by the extracellular deposition of insoluble proteins. In cardiac amyloidosis, or amyloid cardiomyopathy, amyloid fibrils accumulate in the interstitial spaces between myocytes, leading to cellular damage, reduced compliance, and increased stiffness. The condition is primarily caused by the deposition of 2 abnormally folded proteins: monoclonal immunoglobulin light chains and transthyretin, the latter also known as amyloid transthyretin (ATTR), a protein that transports thyroxine and retinol. The most common form is amyloid light-chain amyloidosis, affecting more than 10 individuals per million annually. The 2nd form, ATTR amyloidosis, results from the deposition of either normal or mutated transthyretin proteins. Other causes of amyloidosis are also discussed below (see Etiology).

Cardiac amyloidosis is the most common type of restrictive cardiomyopathy, with cardiac sarcoidosis and cardiac hemochromatosis as the other 2 variants. Infiltrative cardiomyopathies are characterized by depressed diastolic function in the presence of a nondilated left ventricle. Regardless of etiology, cardiac amyloidosis is the leading cause of mortality in patients with systemic amyloidosis.

Cardiac amyloidosis may present as a primary condition or be discovered incidentally in patients showing other signs and symptoms of systemic amyloidosis. Diagnostic and treatment delays are common. Cardiac involvement in systemic amyloidosis has prognostic significance and is the most critical determinant of survival in these patients.