Biomarkers in Subclinical Transthyretin Cardiac Amyloidosis

The most common type of cardiac amyloidosis is transthyretin amyloidosis (ATTR-CM). Early forms of the disease can often go undetected. Effective pharmacological treatments are available for ATTR-CM. However, current treatment options may be more effective when used earlier in the disease, making early detection paramount. Below, we discuss updates with regards to the role that blood-based biomarkers play in detecting subclinical cardiac amyloidosis.

Carriers of amyloidogenic mutations in the TTR gene are at a heightened risk of developing heart failure and have higher mortality rates compared with noncarrier counterparts. Conventional biomarkers, such as the cardiac troponins and natriuretic peptides, may be useful to monitor subclinical cardiac amyloidosis. In addition, recent studies have demonstrated links between amyloidogenic TTR carrier status and low levels of circulating transthyretin (TTR) and retinol-binding protein 4 (RBP4). Laboratory advances have also allowed for the development of peptide-based detection methods. Probes targeting transthyretin aggregates and nonnative TTR peptides have shown promise in differentiating ATTR from non-ATTR amyloidosis populations. Finally, recent studies have identified neurofilament light chains as potential biomarkers for detecting polyneuropathy-predominant amyloidosis. Conventional biomarkers, such as cardiac troponin and natriuretic peptides may indicate evolving amyloid deposition in early ATTR-CM. However, they are non-specific and emerging biomarkers such as serum transthyretin levels, retinol-binding protein 4, transthyretin aggregates, nonnative TTR, and neurofilament light chains may hold promise in characterizing subclinical ATTR.