Lights and Shadows of Clinical Applications of Cardiac Scintigraphy with Bone Tracers in Suspected Amyloidosis

Radionuclide bone scintigraphy is the cornerstone of an imaging-based algorithm for accurate non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA). In patients with heart failure and suggestive echocardiographic and/or cardiac magnetic resonance imaging findings, the positive predictive value of Perugini grade 2 or 3 myocardial uptake on a radionuclide bone scan approaches 100% for the diagnosis of ATTR-CA as long as there is no biochemical evidence of a clonal dyscrasia. The technetium-labelled tracers that are currently validated for non-invasive diagnosis of ATTR-CA include pyrophosphate (99mTc-PYP); hydroxymethylene diphosphonate (99mTc-HMDP); and 3,3-diphosphono-1,2-propanodicarboxylate (99mTc-DPD). Although nuclear scintigraphy has transformed the contemporary diagnostic approach to ATTR-CA, a number of grey areas remains, including the mechanism for binding tracers to the infiltrated heart, differences in the kinetics and distribution of these radiotracers, differences in protocols of image acquisition worldwide, the clinical significance of extra-cardiac uptake, and the use of this technique for prognostic stratification, monitoring disease progression and assessing the response to disease-modifying treatments. This review will deal with the most relevant unmet needs and clinical questions concerning scintigraphy with bone tracers in ATTR-CA, providing expert opinions on possible future developments in the clinical application of these radiotracers in order to offer practical information for the interpretation of nuclear images by physicians involved in the care of patients with this ATTR-CA.