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Review
. 2025 Sep;14(3):385-401.
doi: 10.1007/s40119-025-00424-6. Epub 2025 Jul 19.

Current and Future Treatment Landscape of Transthyretin Amyloid Cardiomyopathy

Emily Margolin  1 , Lily K Stern  2 , Alessia Argiro  3 , Julie L Rosenthal  4 , Marcus A Urey  1 , Kevin M Alexander  5
Affiliations
Review

Current and Future Treatment Landscape of Transthyretin Amyloid Cardiomyopathy

Emily Margolin et al. Cardiol Ther. 2025 Sep.

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease caused by the deposition of insoluble amyloid fibrils derived from misfolded transthyretin (TTR). The treatment landscape is rapidly evolving, with disease-modifying therapies now targeting distinct steps in disease progression. Management requires both disease-modifying treatment and symptom-guided treatment of heart failure and arrhythmias, along with device therapy and consideration of advanced heart failure interventions (i.e., heart transplantation) in select patients. Therapeutic advances have significantly increased treatment possibilities, selection of appropriate therapy, switching between therapies, combination strategies, and how to monitor treatment response over time. This review summarizes available and investigational therapies for ATTR-CM and considers practical questions that guide clinical decision-making, with the goal of helping clinicians navigate the evolving therapeutic landscape.

Keywords: Acoramidis; Disease-modifying therapy; Heart failure; Tafamidis; Transthyretin amyloid cardiomyopathy (ATTR-CM); Treatment; Vutrisiran.

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Conflict of interest statement

Declarations. Conflict of interest: Emily Margolin, MD, and Alessia Argiro, MD, have nothing to disclose. Lily Stern, MD, has received research grants from Intellia Therapeutics and Pfizer. Julie Rosenthal, MD, has received consulting fees from BridgeBio and Novo Nordisk, and research funding for clinical studies from Novo Nordisk, Ionis, and Alnylam. Marcus Urey, MD, has received consulting fees from Alnylam, AstraZeneca, BridgeBio, Pfizer, and research funding for clinical studies from Alexion, Intellia, and Ionis. Kevin Alexander, MD, has received consulting fees from Alexion, Alnylam, Arbor Biotechnologies, Bridgebio, Novo Nordisk, and Pfizer. Kevin Alexander, MD, is an Editorial Board member of Cardiology and Therapy. Kevin Alexander was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions. Ethical Approval: This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

Figures

Fig. 1
Fig. 1
The evolving treatment landscape of transthyretin amyloid cardiomyopathy. Created in BioRender. Margolin, E. (2025) https://BioRender.com/ mz5wyr4. Dates reflect projected FDA approval for treatment of transthyretin amyloid cardiomyopathy, including therapies that were not approved. *FDA-approved for the treatment of transthyretin amyloid cardiomyopathy. †FDA-approved for the treatment of transthyretin amyloid polyneuropathy. *†FDA-approved for the treatment of transthyretin amyloid cardiomyopathy and transthyretin amyloid polyneuropathy. Pink: transthyretin stabilized. Green: transthyretin silencer. Yellow: gene-editing therapy. Purple: degrader/depleter. siRNA small interfering ribonucleic acid, ASO antisense oligonucleotide, TBD to be determined
See this image and copyright information in PMC

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