Diagnosis and management of the cardiac amyloidoses.

Cardiac amyloidosis is a manifestation of one of several systemic diseases known as the amyloidoses.1,2 This uncommon disease is probably underdiagnosed, and even when a diagnosis of amyloidosis of the heart is made, the fact that there are several types of amyloid, each with its unique features and treatment, is often unrecognized. This can lead to errors in management and in the information conveyed to the patient. The purpose of this review is to familiarize the reader with the clinical features of amyloidosis and to address the approach to the patient with this disease, focusing on the various types of amyloidosis, their prognosis and treatment. The common feature of this group of diseases is the extracellular deposition of a proteinaceous material that, when stained with Congo red, demonstrates apple-green birefringence under polarized light and that has a distinct color when stained with sulfated Alcian blue (Figure 1). Viewed with electron microscopy, the amyloid deposits are seen to be composed of a -sheet fibrillar material (Figure 2). These nonbranching fibrils have a diameter3 of 7.5 to 10 nm and are the result of protein misfolding.4,5 Cardiac involvement in amyloidosis may be the predominant feature or may be found on investigation of a patient presenting with another major organ involvement. The presence of cardiac amyloidosis and its relative predominance varies with the type of amyloidosis. Thus, senile systemic amyloidosis and some forms of transthyretin amyloidosis invariably affect the heart, whereas cardiac involvement ranges from absent to severe in amyloidosis derived from a light-chain precursor (AL amyloidosis). Secondary amyloidosis almost never affects the heart in any clinically significant manner.6 The specific composition of the fibrils differs in the different types of amyloid7 and are outlined in the Table. Both on the basis of common usage and for the sake of simplicity, “cardiac amyloidosis” is used here to describe involvement of the heart by amyloid deposition, whether as part of systemic amyloidosis (as is most commonly the case) or as a localized phenomenon. Regardless of the underlying pathogenesis of amyloid production, cardiac amyloidosis is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart.8 Amyloid deposits occur in the ventricles and atria, as well as perivascularly (particularly in the small vessels) and in the valves. The conduction system may also be involved. The infiltrative process results in biventricular wall thickening with nondilated ventricles. The ensuing elevation of pressure in the thin-walled atria is associated with atrial dilation, despite thickening of the atrial walls by amyloid deposition. Because cardiac involvement very frequently coexists with significant dysfunction of other major organs, the initial suspicion of cardiac amyloidosis is often triggered by the recognition that the heart disease is part of a multiorgan disorder. Conversely, if other organ dysfunction such as nephrotic syndrome predominates, recognition of a cardiac problem may be delayed because of the focus on these organ systems. Because the clinical manifestations and progression of the disease may vary considerably on the basis of the amyloid fibril precursor, the various types of amyloid heart disease are dealt with individually in this review.