Semi-Quantification of Myocardial Uptake of Bone-Seeking Agents in Suspected Cardiac Amyloidosis

Bone scintigraphy has emerged as a key tool for non-invasive etiologic diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). We focused on a new semi-quantification method (on planar imaging) that could complement the qualitative/visual Perugini scoring system, especially when SPET/CT is not available.

We retrospectively/qualitatively evaluated 8674 consecutive, planar 99mTc-biphosphonate scintigraphies (performed for non-cardiac reasons), identifying 68 (0.78%) individuals (mean age 79 ± 7 years, range 62-100 years; female/male ratio 16/52) presenting myocardial uptake. Due to the retrospective nature of the study, no SPET/CT, pathologic or genetic confirmation was obtained. The Perugini scoring system was determined (in patients presenting cardiac uptake) and compared with three newly proposed semi-quantitative indices. We took 349 consecutive bone scintigraphies, qualitatively absent of any cardiac/pulmonary uptake, as "healthy controls" (HC).

The heart-to-thigh ratio (RHT) and lung-to-thigh ratio (RLT) indices were significantly higher in patients than in HCs (p ≤ 0.0001). There were statistically significant differences for RHT in HCs vs. patients with qualitative Perugini scores of 1 or >1 (with p ranging from ≤0.001 to ≤0.0001). ROC curves showed that RHT outperformed the other indices and was more accurate in both male and female groups. Furthermore, in the male population, RHT accurately distinguished HCs and patients with scores of 1 (less likely affected by ATTR) from patients with qualitative scores >1 (more likely affected by ATTR) with an AUC of 99% (sensitivity: 95%; specificity: 97%).

The proposed semi-quantitative RHT index can accurately/semi-quantitatively distinguish between HCs and subjects probably affected by CA (Perugini scores from 1 to 3), and could be particularly useful when no SPET/CT data are available (such as in retrospective studies and data mining). Furthermore, RHT can semi-quantitatively predict, with very high accuracy, subjects in the male population more likely to be affected by ATTR. The present study, although using a very large sample, is however retrospective, monocentric, and therefore the generalizability of the results should be proved by an accurate external validation.

The proposed heart-to-thigh ratio (RHT) can distinguish healthy controls and subjects that are probably affected by cardiac amyloidosis in a simple and more reproducible way, as compared to standard qualitative/visual evaluation.