Transthyretin Amyloid Cardiomyopathy: The Plot Thickens as Novel Therapies Emerge

Transthyretin amyloid cardiomyopathy (ATTR-CM) has transitioned from an underdiagnosed condition to a rapidly evolving therapeutic frontier. This review highlights the expanding treatment landscape, beginning with evidence from key clinical trials for transthyretin tetramer stabilizers and RNA silencers, and extending to novel therapies including gene-editing agents and monoclonal antibody-based fibril depleters. We summarize pivotal trial data - including the ATTR-ACT, HELIOS-B, and APOLLO-B trials - and describe ongoing investigations aimed at broadening therapeutic options. Practical considerations such as route and frequency of administration, tolerability, and regulatory status are outlined to support clinical decision-making. A dedicated section on limitations and special populations addresses the generalizability of trial findings to the diverse patients encountered in practice. Finally, we explore key unresolved questions, including the need for head-to-head comparative trials, the potential role of combination therapy, and the optimal timing for initiating treatment as earlier recognition becomes more common. As novel therapies gain approval this review serves as a timely, focused resource to support clinicians managing ATTR-CM.