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Genovesi et al. Vessel Plus 2021;5:50 https://dx.doi.org/10.20517/2574-1209.2021.67 Page 3 of 11

function, which is often compromised earlier than systolic function in patients with CA. However,
radiation-free morphological imaging, such as cardiac echocardiography and magnetic resonance, is to be
preferred in defining ventricular function of patient with known or suspected AC.

METABOLISM
The study of cellular metabolism with conventional nuclear medicine techniques using
radiopharmaceuticals such as 123I-β-methyl-iodophenyl-pentadecanoic acid (123I-BMIPP) and 99mTc-
pentavalent dimercaptosuccinic acid (99mTc-V-DMSA) has also been evaluated for the diagnosis of
CA [9,10] . Despite the promising results of these methods, the use of these radiopharmaceuticals in clinical
practice has not become common due to their limited availability and the non-optimal quality of the images
obtained.

In nuclear medicine, the predominant role in the study of cellular metabolism is certainly played by PET
with 18F-FluoroDeoxyGlucose (FDG); this radiopharmaceutical is widely used for PET studies in oncology,
as the degree of tissue uptake of the radiopharmaceutical is directly related to the cellular glycolytic activity
and, consequently, the degree of disease activity and its degree of de-differentiation.

Despite the widespread availability of PET/CT scanners and FDG, there is little evidence in the literature on
the usefulness of the study of glucose metabolism in CA, which is limited to case reports [11,12] .

Since the vital myocardium physiologically metabolizes glucose as an energy substrate, PET studies for the
evaluation of CA should require a specific preparation by means of a low-carbohydrate and high-fat diet in
the 12 h preceding the examination to obtain a shift of the myocardial metabolism towards fatty acids: in
this way, areas of FDG uptake could be referred to pathologic processes related to the presence of amyloid
[13]
similarly to what is described for cardiac sarcoidosis .

In any case, the presence of FDG uptake areas would not be a direct sign of the presence of amyloid
substance but possibly an indirect sign linked to the presence of inflammation; due to its reduced specificity,
this technique has not found wide use in the diagnostic process of CA.

MYOCARDIAL INNERVATION
Patients with amyloidosis often develop degeneration of cardiac autonomic innervation, which leads to
cardiac rhythm alterations; this occurrence is frequent in patients with ATTR, particularly in hereditary
forms, and with AL.

123I-metaiodobenzylguanidine (123I-MIBG) is a chemically modified analog of noradrenaline which is
stored within the presynaptic vesicles of the sympathetic terminations which allows a non-invasive
assessment of myocardial innervation. Tanaka et al. demonstrated that, in patients with a familial form of
[14]
amyloidosis, myocardial sympathetic denervation could occur even before the development of
pseudohypertrophy or left ventricular dysfunction. Patients suffering from AL amyloidosis with cardiac
involvement also have a reduction in cardiac uptake, but it is less than that of healthy controls or those of
transthyretin forms [15-17] ; however, since the degree of denervation presents an extensive overlap between AL
and ATTR forms, it is not possible to use 123-MIBG scintigraphy to formulate a differential diagnosis
between the two types of CA . However, the presence of impaired cardiac sympathetic innervation is a
[17]
worsening prognostic factor and 123I-MIBG scintigraphy can provide important information on patient’s
outcome; in fact, the reduction of the heart/mediastinal uptake ratio has been shown to be an independent
prognostic indicator with a 42% increased mortality in patients with H/R < 1.6 . Despite these interesting
[18]