Usefulness and limitations of ^99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy

Purpose We previously reported in a small series of patients that ^99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid ( ^99mTc-DPD) scintigraphy tested positive in transthyretin-related (TTR) (both mutant and wild-type) but not in primary (AL) amyloidotic cardiomyopathy (AC). We extended our study to a larger cohort of patients with AC. Methods We evaluated (1) 45 patients with TTR-related AC (28 mutant and 17 wild-type), (2) 34 with AL-related AC and (3) 15 non-affected controls. Myocardial uptake of ^99mTc-DPD (740 MBq i.v.) was semiquantitatively and visually assessed at 5 min and at 3 h. Results Heart retention (HR) and heart to whole-body retention ratio (H/WB) of late ^99mTc-DPD uptake were higher among TTR-related AC (HR 7.8%; H/WB 10.4) compared with both unaffected controls (HR 3.5%; H/WB 5.7; p<0.0001) and AL-related AC (HR 4.0%; H/WB 6.1; p<0.0001). For the diagnosis of TTR-related AC, positive and negative predictive accuracy of visual scoring of cardiac retention were: 80 and 100% (visual score ≥1); 88 and 100% (visual score ≥2); and 100 and 68% (visual score = 3). At adjusted linear regression analysis, TTR aetiology turned out to be the only positive predictor of increasing ^99mTc-DPD uptake in terms of both HR [β 2.5, 95% confidence interval (CI) 1.5-3.5; p99mTc-DPD scintigraphy was confirmed to be useful for differentiating TTR from AL-related AC, diagnostic accuracy was lower than previously reported due to a mild degree of tracer uptake in about one third of AL patients. ^99mTc-DPD scintigraphy can provide an accurate differential diagnosis in cases of absent or intense uptake evaluated by visual score.