Isolated atrial amyloidosis from atrial natriuretic peptide - a common but overlooked cardiac condition

Interest in the misfolding and aggregation of human proteins into amyloid fibrils has increased dramatically in recent years. The systemic amyloidoses constitute a group of serious disorders that often affect the heart. Each systemic amyloid type is derived from one of several plasma proteins, most commonly immunoglobulin light chains or transthyretin. Rapid progress has been made in developing effective treatments for several systemic forms. There is also growing evidence that localized amyloids - such as those found in the brain or in the islets of Langerhans - or their smaller prefibrillar aggregates can exert toxic effects on nearby cells. However, other localized amyloids remain insufficiently understood. Isolated atrial amyloid (IAA) is derived from the polypeptide hormone atrial natriuretic peptide (ANP), which is expressed by atrial cardiomyocytes. IAA is a common age-related amyloidosis, affecting the left atrium more frequently than the right, with highly variable prevalence reported across studies. The pathogenesis of IAA is unknown, although increased local concentrations of the precursor polypeptide are typically important in other hormone-derived amyloid disorders. IAA is suspected to contribute to the development of atrial fibrillation, but its potential mechanisms remain unclear and have been difficult to investigate due to the lack of methods for visualizing deposits in vivo. This paper, which provides an overview of the current research on IAA, highlights key gaps in knowledge and proposes approaches for studying IAA in vivo.