Quantitative single photon emission computed tomography/computed tomography of Tc-99m-pyrophosphate scans: metrics for short-term risk stratification in transthyretin cardiac amyloidosis

BACKGROUND: Radionuclide SPECT/computed tomography (CT) is standard for diagnosing transthyretin cardiac amyloidosis (ATTR-CM), but the prognostic value of quantitative metrics remains incompletely defined. We investigated their prognostic utility and additive value beyond existing staging systems. METHODS: Retrospective study of patients undergoing technetium-99m-pyrophosphate (PYP) SPECT/CT, including consecutive clinically referred patients (October 2023 to 2024) and trial participants with positive scans from January 2022. Myocardial PYP was quantified using standardized uptake values (SUVmean and SUVmax) and volumetric measures [percent injected dose (%ID), cardiac amyloid activity (CAA)]. Major adverse cardiovascular events (MACEs) comprised heart failure hospitalization or death. Cox and Kaplan-Meier analyses assessed associations; likelihood ratio testing and change in area under the curve (AUC) evaluated the additive prognostic value to existing staging systems. RESULTS: Among 43 patients with ATTR-CM, 16 experienced MACE over a median 518 days. AUCs ranged from 0.74 to 0.88 at 3 months and 0.56-0.62 at 12 months. All variables trended toward association with MACE: SUVmean (P = 0.02), SUVmax (P = 0.03), %ID (P = 0.06), and CAA (P = 0.06). After age adjustment, cut-points for SUVmax (5.8) and SUVmean (3.5) remained associated with MACE. Adding imaging variables to the National Amyloidosis Centre and Columbia staging systems did not significantly improve prognostic accuracy (Δχ2: 0.40-2.48, P = 0.11-0.53). Interobserver reproducibility was high (intraclass correlation coefficients = 0.89-0.99). CONCLUSION: Quantitative Tc-99m-PYP SPECT/CT metrics were associated with short-term outcomes in ATTR-CM, but did not improve established staging systems. Findings are hypothesis-generating and require validation in larger cohorts.