Hearts are NOT Made to Be Broken: Expert Opinion on Amyloid Light-Chain Cardiac Amyloidosis

Abstract

Amyloid light-chain (AL) amyloidosis is a rare systemic disease caused by plasma cell dyscrasia. These plasma cells produce excess Ig light chains, which can misfold, aggregate, and deposit in tissues, resulting in toxicity and organ dysfunction. The heart is among the most commonly affected organs and cardiac involvement is associated with significantly worse outcomes. Despite advances in the treatment of the underlying plasma cell dyscrasia, the survival of patients with advanced heart involvement is extremely poor. The median survival of patients with cardiac AL can be as short as 6 months from diagnosis, depending on severity of cardiac involvement. It is a condition of high unmet medical need. Timely diagnosis is essential, yet detecting the disease is fraught with challenges, not least a lack of recognition among clinicians. In addition, the treatments that are currently available, which include anti-plasma cell dyscrasia chemotherapy and immunotherapy, are far from ideal, offering complete response rates of around 50% and organ response rates of between 40–50%. However, new antibodies with the potential to target the amyloid deposits have demonstrated encouraging results in early phase studies and are now moving into late-stage development. Giovanni Palladini, Amyloidosis Research and Treatment Centre Foundation, San Matteo, Italy, and Department of Molecular Medicine, University of Pavia, Italy, explained how these new agents have the potential to change the AL amyloidosis treatment landscape and calls on cardiologists everywhere to consider AL amyloidosis when assessing patients with heart failure (HF).