Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis
René Rettl, Franz Duca, Christina Kronberger, Christina Binder, Robin Willixhofer, Nikita Ermolaev, Michael Poledniczek, Felix Hofer, Christian Nitsche, Christian Hengstenberg, Roza Badr Eslam, Johannes Kästner, Jutta Bergler‐Klein, Marcus Hacker, Raffaella Calabretta, Andreas A. Kammerlander
Abstract
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 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]. 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.