Contemporary treatment of amyloid heart disease.

ABSTRACT

The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in ß-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied.