Abstract 16785: 99mtc-pyp Scintigraphy for Differentiating Light-Chain Cardiac Amyloidosis (AL) from the Transthyretin-Related Familial and Senile Cardiac Amyloidoses

Abstract

Background: Differentiating immunoglobulin light-chain (AL) from transthyretin-related (ATTR) cardiac amyloidoses is imperative given implications for prognosis, therapy, and genetic counseling. We validated the discriminatory ability of 99mTc-pyrophosphate scintigraphy (99mTc-PYP) in AL vs. TTR-related cardiac amyloidoses.

Methods: 43 subjects with biopsy proven cardiac amyloidosis (12 AL, 15 ATTR wild-type, and 16 ATTR mutants) and 4 heart failure with preserved ejection fraction (HFpEF) controls, underwent 99mTc-PYP single-photon positive emission computed tomography (SPECT) cardiac imaging. Patients received 15-25 mCi of 99mTc-PYP intravenously and anterior, lateral, and left anterior oblique views were obtained at one hour over 8 minutes duration. Scans were performed by experienced nuclear cardiologists blinded to the subjects’ cohort assignment. Cardiac retention was assessed with a semiquantitative visual score (0=no cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=strong uptake greater than bone) and by quantitative analysis by drawing region of interest (ROI) over the heart corrected for background counts and calculating an ROI-to-background ratio.

Results: Subjects with ATTR cardiac amyloid had a significantly higher semiquantitative cardiac visual score than other cohorts (2.9+0.1 vs. 0.6+0.2, p<0.0001) as well as a higher quantitative score (1.80±0.04 vs. 1.15±0.04, p<0.0001). Using a ROI-to-background ratio > 1.5 consistent with intensely diffuse myocardial tracer retention had a 97% sensitivity and 100% specificity with area under the curve 0.994, p=0.001 for identifying ATTR cardiac amyloidosis. One ATTR patient with the Thr59Lys mutation but who did not have a thickened myocardium relative to other ATTR patients had mild cardiac uptake.

Conclusions: 99mTc-PYP SPECT is able to distinguish AL from ATTR cardiac amyloidosis. This has important diagnostic implications.