Gated SPECT/CT uptake patterns in ATTR-CA: Association with myocardial burden, function and prognosis

Background Gated SPECT/CT (gSPECT/CT) offers detailed myocardial radiotracer distribution imaging in cardiac transthyretin amyloidosis (ATTR-CA), but lacks a standardized classification. We aimed to develop and validate a gSPECT/CT-based classification system for ATTR-CA and to explore its correlation with clinical profile, cardiac function, and outcomes. Methods We conducted an observational study in 130 patients (76.2% male) with confirmed ATTR-CA who underwent planar [99mTc]Tc-DPD scintigraphy and thoracic gSPECT/CT. Myocardial polar maps were constructed and uptake patterns were classified as septal, waning moon, vault, waxing moon, diffuse, or doughnut. Clinical, echocardiographic and genetic data were compared across patterns. A quantitative parameter—the percentage of affected myocardium—was derived from SPECT segmentation. Statistical analyses included Kruskal–Wallis and Fisher’s exact tests (Monte Carlo simulation). Results The proportion of female patients differed significantly among patterns (p = 0.041). Diffuse and doughnut patterns predominated in patients with Perugini grade 3 uptake. Myocardial involvement increased progressively across patterns (47% in septal to 85% in diffuse; p < 0.001). LVEF distribution varied: preserved LVEF was more frequent in the waning moon group, while reduced LVEF predominated in septal and doughnut patterns. Heart failure was more common in diffuse and doughnut groups (p = 0.040), and mortality was highest in waxing moon and diffuse groups (p = 0.047). Genetic variants were detected exclusively in vault, waxing moon and diffuse patterns (p = 0.021). Conclusions We propose a novel gSPECT/CT-based classification for ATTR-CA that combines qualitative uptake patterns with quantitative myocardial involvement. This system correlates strongly with sex, LVEF, heart failure, genetic findings and mortality, improving phenotypic characterization and potentially aiding risk stratification.