Transthyretin amyloid cardiomyopathy: Evolving therapies, expanding hope

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and life-threatening condition characterized by the deposition of misfolded transthyretin (TTR) protein in the myocardium, leading to restrictive cardiomyopathy and heart failure. Given its high mortality rate and historically limited therapeutic options, there is a growing need for effective treatments. Current therapeutic strategies focus on reducing the production of TTR using RNA-targeted therapies and stabilizing the native TTR tetramer to prevent misfolding and aggregation. In recent years, emerging therapies-including monoclonal antibodies aimed at promoting amyloid clearance and gene-editing techniques designed to eliminate pathogenic TTR expression-have demonstrated encouraging results in early-phase studies. However, several challenges persist, including delays in diagnosis, variability in clinical response, and limited long-term outcome data. Early detection, timely initiation of treatment, and a personalized approach based on disease stage and genotype are critical to improving prognosis. Ongoing clinical trials are expected to provide further insight into the durability, safety, and broader applicability of these novel therapies, potentially reshaping the treatment landscape for ATTR-CM.

Keywords: Amyloid cardiomyopathy; Amyloidosis; Cardiomyopathy; Heart failure; Transthyretin.