Segmental and global amyloid burden and myocardial mechanics: a multimodality imaging comparison

Bone scintigraphy with bisphosphonate tracers is a cornerstone of noninvasive diagnosis in transthyretin amyloid cardiomyopathy (ATTR-CM). However, methods for estimating the extent and regional distribution of myocardial amyloid burden using single-photon emission computed tomography (SPECT) remain insufficiently validated. This study aimed to evaluate whether global and segmental myocardial radiotracer uptake, assessed by bisphosphonate SPECT, correlates with myocardial amyloid infiltration measured by cardiac magnetic resonance (cMRI)-derived extracellular volume (ECV), and to explore the relationship between these imaging markers and myocardial mechanics. Twenty-seven patients with ATTR-CM who underwent multimodality imaging with bisphosphonate SPECT, cMRI, and transthoracic echocardiography (TTE) between 2017 and 2025 were retrospectively screened. Sixteen patients with complete segmental datasets across all imaging modalities were included in the final analysis. Segmental mixed-effects models were used to account for clustering of myocardial segments within patients. Segmental extent of amyloid burden assessed by SPECT was significantly associated with segmental ECV (β = 0.042, SE = 0.010, t = 4.22), indicating higher radiotracer retention in segments with greater myocardial infiltration. Segmental ECV demonstrated a strong association with impaired longitudinal strain (β = 0.269, SE = 0.043, t = 6.22). In contrast, the direct relationship between radiotracer uptake and longitudinal strain was weaker and not statistically significant (β = 0.016, SE = 0.010, t = 1.60). In combined models, ECV remained independently associated with strain (β = 0.266, SE = 0.045, t = 5.96), whereas radiotracer uptake lost significance (β = 0.003, SE = 0.010, t = 0.29). At the global level, global extent amyloid burden (GEAB) correlated significantly with ECV (β = 0.435, P = 0.018), while the association between GEAB and global longitudinal strain was weaker and nonsignificant (β = 0.092, P = 0.10). Semiquantitative myocardial uptake on bisphosphonate SPECT demonstrates significant concordance with cMRI-derived extracellular volume, supporting its role as a surrogate marker of myocardial amyloid burden. However, myocardial mechanics appear to be more closely associated with extracellular expansion than with radiotracer uptake itself. These findings suggest that current SPECT techniques can estimate myocardial amyloid distribution but remain limited in segmental precision compared with cMRI, likely due to the spatial resolution of conventional SPECT systems and the lack of dedicated processing algorithms for cardiac amyloidosis.