Novel SPECT/CT biomarker in transthyretin cardiac amyloidosis: correlation with myocardial amyloid load and cardiac structure and function

Abstract Background Single photon emission computed tomography/computed tomography (SPECT/CT) with determination of standardized uptake value (SUV) allows quantification of cardiac amyloid deposition. Purpose We aimed to investigate the relationship between quantitative cardiac tracer uptake determined by SPECT/CT and myocardial amyloid load, as well as cardiac structure and function in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), and to identify nuclear imaging biomarkers for monitoring disease progression. Methods ATTR-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid ([99mTc]-DPD) scintigraphy and SPECT/CT imaging (n=40) with determination of SUV, as well as cardiac magnetic resonance imaging (CMR, n=25) and transthoracic echocardiography (TTE, n=40). Results We observed significant correlations (r, Pearson's correlation coefficient) between SUV retention index and myocardial amyloid load [CMR extracellular volume (ECV): r=0.565, p=0.004, Figure 1A], cardiac structure [CMR interventricular septum: r=0.409, p=0.042, Figure 1B; CMR left ventricular mass index: r=0.508, p=0.010, Figure 1C], longitudinal cardiac function [TTE left ventricular global longitudinal strain (LV GLS): r=0.531, p=0.003, Figure 1D; TTE right ventricular free wall longitudinal strain: r=0.470, p=0.024, Figure 1E; TTE left atrial reservoir strain (LASr): r=-0.434, p=0.038, Figure 1F] and cardiac biomarkers [N-terminal prohormone of brain natriuretic peptide (NT-proBNP): r=0.475, p=0.004; high-sensitive troponin T (hs-TnT): r=0.358, p=0.027]. ATTR-CM patients were divided into two cohorts based on the median (4.32 mg/dL) of SUV retention index (low SUV uptake cohort: ≤4.32 mg/dL, n=20; high SUV uptake cohort: >4.32 mg/dL, n=20). We observed significant between-cohort differences with respect to LV ejection fraction (low SUV uptake: 51.8% vs. high SUV uptake: 46.2%, p=0.045), LV GLS (-14.5% vs. -11.1%, p=0.001), LASr (11.6% vs. 7.1%, p=0.023), NT-proBNP (1300 pg/mL vs. 2786 pg/mL, p<0.001), hs-TnT (42.9 ng/L vs. 62.2 ng/L, p=0.016) and 6-min walk distance (440.1 m vs. 330.1 m, p=0.022). Conclusions Using quantitative SPECT/CT imaging, we demonstrated that SUV retention index correlates with myocardial amyloid load, cardiac structure and function, and cardiac biomarkers. Our data suggest that quantitative SPECT/CT imaging with determination of SUV retention index may be a valid tool to monitor disease progression in ATTR-CM patients.Figure 1