Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis

Aims: Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

Methods and results: Consecutive ATTR-CA patients (n=100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD SPECT/CT imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n=50; high DPD uptake: >5.4, n=50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r=0.366,p<0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r=0.316,p=0.002), LV diastolic function (E/e' average: r=0.304, p=0.013), NT-proBNP (r=0.332,p<0.001), troponin T (r=0.233,p=0.022), 6-minute walk distance (6MWD: r=-0.222,p=0.033) and National Amyloidosis Centre (NAC) stage (r=0.294,p=0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: p=0.012, RV-FW-LS: p=0.036), LV diastolic function (E/e' average: p=0.035), cardiac biomarkers (NT-proBNP: p=0.012, troponin T: p=0.044), exercise capacity (6MWD: p=0.035) and disease stage (NAC stage I: p=0.045, III: p=0.006), and experienced adverse outcomes compared to the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95%CI:1.439-5.737), p=0.003; DPD retention index: adjusted HR 1.221 (95%CI: 1.078-1.383), p=0.002].

Conclusion: In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA.