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Page 2 of 11 Mattana et al. Vessel Plus 2022;6:13 https://dx.doi.org/10.20517/2574-1209.2021.87

nuclear physicians to have the most specific approaches in acquiring and interpreting bone scintigraphy for
transthyretin cardiac amyloidosis.

Keywords: Cardiac amyloidosis, 99m Tc-PYP, 99m Tc-DPD, bone scintigraphy, nuclear medicine

INTRODUCTION
Amyloidosis is a systemic disease with different clinical presentation depending on the tissues and organs
involved. Cardiac amyloidosis (CA) is a restrictive infiltrative cardiomyopathy and is associated with the
worst prognosis among the amyloidotic pathologies. CA remains underdiagnosed and underestimated
[1]
because it can occur with non-specific symptoms and is correlated with considerable mortality . CA is
caused by extracellular deposition of amyloidogenic proteins in the heart tissue; the most common amyloid
proteins involved are amyloid light-chain (in AL amyloidosis) and transthyretin (TTR) in TTR amyloidosis
(ATTR). While the AL form is most frequently associated with hematologic disease (myeloma and
monoclonal gammopathies), the TTR forms can be due to a mutated form of TTR (TTRv) or a wild-type
[2]
form (TTRwt), the latter responsible for senile amyloidosis . Another systemic form of amyloidosis is the
AA type, which is related to the deposition of the Serum Amyloid A protein in the organs involved ; the
[3]
most frequent clinical presentation is a chronic inflammatory condition associated with renal insufficiency.
The liver and gastrointestinal tract can also be involved, while myocardial, skin, and soft tissue involvement
is extremely uncommon. The AA form can be evaluated with labeled-SAP scintigraphy, while bone tracer
scintigraphy is useless in this type of amyloidosis.

In 50%-80% of patients with clinically suspected AL amyloidosis, a biopsy of subcutaneous fat, salivary
[4,5]
gland, or rectum is needed to confirm the diagnosis ; in patients with suspected TTR cardiac amyloidosis
(TTR-CA), an endomyocardial biopsy (EMB) is frequently necessary to confirm the diagnosis , but
[5]
myocardial perforation and tamponade are among the risks of complications associated with EMB and
require a good level of expertise to avoid diagnostic delay and procedure-related complications.
[6]

Nowadays, it is widely recognized that EMB could be avoided thanks to a diagnostic algorithm derived from
a multicenter consensus paper that underlines the role of bone scintigraphy for the evaluation of the TTR-
[7]
CA . Even if echocardiography is a valuable and widely accessible tool for investigating heart failure, it is
neither sensitive nor specific for CA . Cardiac magnetic resonance (CMR) imaging can offer a much
[8]
greater diagnostic value in CA, but it is costly, contraindicated in a substantial proportion of patients. and
suffers from false-positive and -negative results. Furthermore, both echocardiography and CMR have the
limit to not allow distinguishing different types of amyloid. During the last years, radionuclide imaging has
increasingly been used to facilitate the diagnosis of CA, avoiding EMB and overcoming the limitation of
echocardiography and CMR because it can be considered a non-invasive diagnostic tool for the presence
[7]
of amyloid with the advantage of accurately differentiating the two main forms (AL and TTR, which have
completely different therapies, clinical evolution, and prognosis). In comparison to CMR and
echocardiography, another potential role of radionuclide imaging could be the ability to early diagnose CA
[Figure 1], especially in patients with proved genetic mutation without symptoms (carriers) since new
specific drugs have been developed.

Technetium-99m pyrophosphate ( Tc-PYP) and technetium-99m 3,3-diphosphono-1,2-
99m
propanodicarboxylic acid ( Tc-DPD) tracers, initially developed for bone nuclear imaging, have been
99m
increasingly used to evaluate the presence of CA. For both tracers [Figures 2 and 3], a visual evaluation
following the scoring system proposed by Perugini can be performed . This score compares the heart tracer
[9]