Transthyretin cardiac amyloidosis: A treatable form of heart failure with a preserved ejection fraction

Abstract

Cardiac amyloidosis (CA) is considered a rare disease with poor prognosis and limited therapeutic options. However, non-biopsy diagnostic modalities as well as emerging therapies are challenging this long-held belief. Radionuclide bone scintigraphy is increasingly being used in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). As such, it is expected that the number of patients diagnosed with ATTR-CA will continue to rise. Emerging therapies decrease the progressive morbidity and mortality associated with ATTR-CA. The importance of early recognition of ATTR-CA is imperative as prompt initiation of these novel agents is essential to maximize their therapeutic potential. Herein, we outline the current approach to diagnosis of ATTR-CA and review the therapeutic management of the disease.

Keywords: Amyloidosis; Cardiomyopathy; Heart failure; Inotersen; Patisiran; Tafamidis; Transthyretin.

Copyright © 2019. Published by Elsevier Inc.

Figures

Figure 1:

Phenotypic Heterogeneity of Hereditary ATTR Amyloidosis (nomenclature includes mature protein (italics) and pro-protein).

Figure 2:

Diagnostic approach to ATTR-CA. Adapted from Ruberg FL, et al. Transthyretin Amyloid Cardiomyopathy. J Am Coll Cardiol. 2019;73:2872–91. Figure 6, Diagnostic algorithm for evaluation of suspected ATTR-CM; p. 2883. AL-CA, immunoglobulin light chain cardiac amyloidosis; ATTRwt, wild type transthyretin amyloid; ATTRv, variant transthyretin amyloid; ATTR-CA, transthyretin cardiac amyloid; AV, atrioventricular; CTS, carpal tunnel syndrome; DPD, 3,3-diphosphono-1,2-propanodicarboxylic acid; eGFR, estimated glomerular filtrate rate; FLC, free light chains; GI, gastrointestinal; HMDP, 99mTc-labeled hydroxymethylene diphosphonate; LVWT, left ventricular wall thickness; LVM, LV mass; NT-proBNP, N-terminal pro-B-type natriuretic peptide; PYP, 99mTc pyrophosphate; STE, speckle tracking echocardiography; Tn, troponin. *If biopsy of the affected organ is negative and there is high clinical suspicion for CA, endomyocardial biopsy should be pursued.

Figure 3:

Target Sites of Therapy in ATTR-CA

Figure 4:

Model for Progression of ATTR-CA. Grodin JL, Maurer MS. The Truth is Unfolding About Transthyretin Cardiac Amyloidosis. Circulation. 2019;140:27–30. Figure, Conceptual model of ATTR-CA progression over time; p.28.