Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: State of the art review and focus on emerging nuclear techniques

Abstract

Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with 99m Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly 99m Tc-DPD and 99m Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook.

Prognostic implication of relative regional strain ratio in cardiac amyloidosis

“…Amyloidosis is a systemic disease characterised by extracellular deposition of misfolded protein into various organs 1. Amyloid infiltration of the heart typically leads to a restrictive cardiomyopathy and progressive congestive heart failure.…”

Nuclear imaging of cardiac amyloidosis. ‘We’ve only just begun’

“…3 This differentiation may gain additional importance in the near future with the introduction of novel therapies that target the transthyretin protein and therefore would be specific for the treatment of the ATTR subtype. 4 The diagnosis is often confirmed either by demonstrating amyloid deposits on endomyocardial biopsy or by demonstrating histologic amyloid deposits on biopsy from extracardiac tissues (e.g., abdominal fat pad, rectum, etc.) in patients with clinical/imaging suspicion of cardiac involvement.…”

Transthyretin Cardiac Amyloidosis in Older Adults: Optimizing Cardiac Imaging to the Corresponding Diagnostic and Management Goal

“…Furthermore, TTE typically signals the possibility of ATTR-CA only after lifelong myocardial infiltration of amyloid fibrils [19] as it lacks sensitivity for detection of early myocardial infiltration. Therefore, TTE is a tool best applied in older adults for raising suspicion of late-stage, but usually not early disease [12, 13, 15]. …”