Understanding the [99mTc]Tc-DPD-positive spectrum in cardiac amyloidosis: Clinical and prognostic insights

Background Bone scintigraphy with [ 99m Tc]Tc-DPD is central to the non-invasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), but [ 99m Tc]Tc-DPD-positive studies encompass heterogeneous scintigraphic patterns whose clinical significance remains uncertain. This study compared the clinical, laboratory, and imaging characteristics of patients with ATTR-CM according to scintigraphic pattern and ATTR subtype, evaluated long-term outcomes, and assessed interpretation of the Perugini grading system among Portuguese Nuclear Medicine physicians. Methods This retrospective study included patients with confirmed wild-type ATTR (ATTRwt) or Val30Met hereditary ATTR (ATTRv) who underwent [ 99m Tc]Tc-DPD scintigraphy. Studies were classified as DPD-negative (Perugini grades 0–1), Pattern A (grade 2), or Patterns B and C (grade 3 with preserved or reduced bone-to-soft-tissue [B/ST] ratio, respectively). Pattern assignment was based on visual assessment, while semiquantitative indices were analysed descriptively. Clinical, laboratory, echocardiographic, and outcome data were collected. Outcomes included major adverse cardiovascular events (MACE) and all-cause mortality. Results Among 180 patients with confirmed ATTR-CM, 77% were male, mean age was 66 years, and 38% had ATTRwt. [ 99m Tc]Tc-DPD-positive patients were predominantly ATTRwt (76%) or late-onset ATTRv (21%) and showed a more advanced cardiac phenotype, whereas early-onset ATTRv was mainly [ 99m Tc]Tc-DPD-negative (82%) and associated with greater neurological involvement. Within [ 99m Tc]Tc-DPD-positive ATTRwt, the B/ST ratio was significantly lower in Pattern C (p < 0.001). [ 99m Tc]Tc-DPD-positive patients experienced more MACE (25% vs. 5%; p < 0.001) and higher all-cause mortality (30% vs. 14%; p = 0.008), although overall survival did not differ significantly. Pattern C was associated with the shortest survival within DPD-positive ATTRwt. Interobserver agreement was excellent for [ 99m Tc]Tc-DPD-positive versus [ 99m Tc]Tc-DPD-negative classification (κ = 1.00) and good for Perugini grading (weighted κ = 0.93). Conclusions [ 99m Tc]Tc-DPD-positive ATTR represents a heterogeneous imaging phenotype. In ATTRwt, a reduced B/ST ratio identified an exploratory subgroup with poorer outcomes. These findings suggest that semiquantitative assessment may complement conventional visual interpretation, although prospective multicentre studies incorporating standardized SPECT/CT are required.