Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis

Abstract

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. Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography 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 min 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 with 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]. 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.