AL Cardiac Amyloidosis: Classification, Diagnosis, and Treatment

Abstract

Cardiac amyloidosis is a restrictive cardiomyopathy characterized by extracellular deposition of protein fragments known as amyloid. The natural history of the disease, involvement of other organs, and treatment options vary significantly based on the protein of origin. In AL amyloidosis, amyloid protein is derived from immunoglobulin light chain, and most often involves the kidneys and the heart. Cardiac involvement is associated with symptoms of heart failure and dictates the clinical course of the disease. Cardiac amyloidosis can be diagnosed noninvasively by echocardiography and cardiac MRI, in the presence of a plasma cell dyscrasia and an extracardiac biopsy demonstrating amyloid. In the case of equivocal imaging findings or discordant data, endomyocardial biopsy may be used for diagnosing cardiac amyloid and for determining the protein of origin. Treatment is aimed at relieving congestive symptoms and targeting the underlying plasma cell dyscrasia. Modern chemotherapy regimens and autologous stem cell transplantation (ASCT) have resulted in durable hematologic response and prolonged survival, but patients with significant cardiac amyloidosis are often not candidates for ASCT. In some cases, orthotopic heart transplantation followed by ASCT is an effective treatment option, although few patients may be eligible for this course of treatment. While AL amyloidosis remains a disease with significant morbidity and mortality, newer treatment options including anti-light chain antibodies and RNA silencing drugs hold great promise.