How to perform and interpret cardiac amyloidosis radionuclide imaging (CARI)

Cardiac amyloidosis radionuclide imaging (CARI) has transformed the diagnostic approach to suspected transthyretin cardiomyopathy (ATTR-CM), enabling non-invasive diagnosis and reducing the need for biopsy. This review provides practical guidance for performing and interpreting CARI, illustrated by a clinical case. Exclusion of monoclonal gammopathy is essential to preserve specificity. When absent, Perugini grade 2–3 uptake on single-photon emission computed tomography (SPECT) is diagnostic; planar imaging or heart-to-contralateral ratios alone are insufficient. Optimal practice includes validated tracers (99mTc-DPD, -PYP, -HMDP), correct timing to avoid blood pool activity, and SPECT - preferably with CT - for accurate localization. Interpretation should account for pitfalls such as non-diffuse uptake, artifacts, and alternative causes (e.g., AL amyloidosis, infarction, drug toxicity). Emerging applications include quantitative SPECT/CT for staging, prognosis, and therapy monitoring, though standardization is needed. Adherence to expert consensus and technical standards maximizes diagnostic accuracy and safe integration of CARI into the management of cardiac amyloidosis.