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Review
. 2025 May;13(5):685-694.
doi: 10.1016/j.jchf.2025.03.017.

Current Landscape of Therapies for Transthyretin Amyloid Cardiomyopathy

Jan M Griffin  1 , Justin L Grodin  2 , Frederick L Ruberg  3 , Ahmad Masri  4 , Mazen Hanna  5 , Mathew S Maurer  6
Affiliations
Review

Current Landscape of Therapies for Transthyretin Amyloid Cardiomyopathy

Jan M Griffin et al. JACC Heart Fail. 2025 May.

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative cardiomyopathy that results from myocardial deposition of misfolded transthyretin (TTR) protein. The biology of amyloid formation has been elucidated resulting in several effective therapeutic strategies. Accordingly, the therapeutic landscape for ATTR-CM is rapidly evolving, with multiple disease-modifying therapies (DMTs) approved and others anticipated to be imminently available. Currently, DMT strategies involve either stabilization of TTR, thereby inhibiting misfolding, or reduction of hepatic TTR production, and antibodies ("depleters") that facilitate amyloid fibril removal are under development. In this review, available evidence is synthesized and expert experience provided to assist clinicians in the complex navigation of treatment selection and the role of advanced therapies (heart transplantation and left ventricular assist device), as well as to identify key areas for future research.

Keywords: amyloid; cardiomyopathy; therapy; transthyretin.

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Conflict of interest statement

Funding Support and Author Disclosures Dr Griffin has received grants from Pfizer and BridgeBio and consulting fees from Pfizer, BridgeBio, and AstraZeneca. Dr Grodin has received personal fees from Pfizer, Alnylam, Eidos/BridgeBio, AstraZeneca, Alexion, Lumanity, Novo Nordisk, Ultromics, Intellia, and Tenax Therapeutics; and grant support from National Heart, Lung, and Blood Institute (R01HL160892), Pfizer (67656485), Eidos/BridgeBio, and Texas Health Resources Clinical Scholars Fund. Dr Ruberg is supported by National Institutes of Health (NIH) R01 HL139671; has received institutional research grant support from Akcea/Ionis Therapeutics, Anumana, Alnylam Pharmaceuticals, TriNetX, and Pfizer; and has received consulting fees from AstraZeneca and Attralus. Dr Masri has received research grants from Pfizer, Ionis, Attralus, and Cytokinetics; and consulting fees from Cytokinetics, BMS, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Prothena, BioMarin, Edgewise, AstraZeneca, and Tenaya. Dr Hanna has served on advisory boards for Pfizer, Alnylam, Ionis, BridgeBio, Attralus, Alexion Pharmaceuticals, and Novo Nordisk. Dr Maurer has received grant support from National Institutes of Health R01HL139671 and AG081582; grants from Alnylam, BridgeBio, Intellia, and Ionis; and personal fees from Alnylam, Novo Nordisk, Roche, Prothena AstraZeneca, Ionis, and Intellia.

References

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    1. Maurer MS, Schwartz JH, Gundapaneni B et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 2018;379:1007–1016. - PubMed

MeSH terms

Supplementary concepts