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Shah et al. Vessel Plus 2021;5:53 Vessel Plus
DOI: 10.20517/2574-1209.2021.76

Review Open Access

Recent advances in the pharmacotherapy of TTR

amyloidosis of the heart

Ravi J. Shah, Stephen Pan, Gregg M. Lanier, Leanne Mellela, Wilbert S. Aronow, Diwakar Jain
Department of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY 10595, USA.

Correspondence to: Prof. Wilbert S. Aronow, Department of Cardiology, Westchester Medical Center and New York Medical
College, 100 Woods Road, Valhalla, NY 10595, USA. E-mail: wsaronow@aol.com

How to cite this article: Shah RJ, Pan S, Lanier GM, Mellela L, Aronow WS, Jain D. Recent advances in the pharmacotherapy of
TTR amyloidosis of the heart. Vessel Plus 2021;5:53. https://dx.doi.org/10.20517/2574-1209.2021.76

Received: 24 May 2021 First Decision: 7 Jul 2021 Revised: 29 Jul 2021 Accepted: 11 Aug 2021 Published: 25 Oct 2021

Academic Editors: Ugolino Livi, Alexander D. Verin Copy Editor: Yue-Yue Zhang Production Editor: Yue-Yue Zhang

Abstract
Transthyretin amyloidosis of the heart, or transthyretin amyloid cardiomyopathy (ATTR-CM), once thought to be a
rare disease, is now increasingly recognized as a common causing of restrictive cardiomyopathy, particularly in
elderly patients and patients with heart failure with preserved ejection fraction. ATTR-CM is caused by an
aggregation of misfolded transthyretin (TTR) protein amyloid fibrils in the myocardium. The TTR protein itself can
be either wild-type (ATTRwt) or one of many pathologic variants (ATTRv). Recognition of ATTR-CM has been
aided by rapid advances in technologies to diagnose the disease more accurately. Several advances in
pharmacotherapeutic treatments have significantly reduced the morbidity and mortality of the disease. Treatments
broadly fall into three categories: (1) TTR silencing through mRNA knockdown or silencing; (2) TTR stabilization;
and (3) TTR resorption or extraction. This review article provides a survey of the pharmacokinetic and clinical data
on all currently available treatments.

Keywords: Transthyretin amyloid cardiomyopathy, TTR silencing, TTR stabilization, TTR resorption, small
interfering RNA, antisense oligonucleotides, carboxylic acid derivate, salicylic acid derivative

INTRODUCTION
Transthyretin amyloid cardiomyopathy (ATTR-CM) is restrictive cardiomyopathy caused by an abnormal
extracellular deposition of amyloid fibrils in the myocardium. Transthyretin (TTR), also known as
prealbumin, is a protein synthesized primarily by the liver and is responsible for the transportation of

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
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