DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis

Background: The pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium.

Objectives: This study aimed to investigate associations between quantitative cardiac Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM.

Methods: Forty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups.

Results: ATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, β = 0.139,  < 0.001), native T1 time (r = 0.432, β = 0.020,  = 0.005), RV-LS (r = 0.445, β = 0.204,  = 0.004), NT-proBNP (log) (r = 0.458, β = 2.842,  = 0.003), troponin T (r = 0.422, β = 0.048,  = 0.007), 6MWD (r = 0.385, β = -0.007,  = 0.017), and NAC stage (r = 0.490, β = 1.785,  = 0.001). Cohort comparison demonstrated differences in ECV ( = 0.001), native T1 time ( = 0.013), RV-LS ( = 0.003), NT-proBNP ( < 0.001), troponin T ( = 0.046), 6MWD ( = 0.002), and NAC stage (I:  < 0.001, II:  = 0.030, III:  = 0.021).

Conclusions: In ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.