^99m Tc-Pyrophosphate Scintigraphy for Differentiating Light-Chain Cardiac Amyloidosis From the Transthyretin-Related Familial and Senile Cardiac Amyloidoses

TLDR

Differentiating immunoglobulin light‑chain (AL) from transthyretin‑related cardiac amyloidoses (ATTR) is imperative given implications for prognosis, therapy, and genetic counseling. The study validated the discriminatory ability of (99m)Tc‑PYP scintigraphy to differentiate AL from ATTR cardiac amyloidosis in 45 subjects. Scans were performed by blinded nuclear cardiologists, and cardiac uptake was quantified using a visual score and a heart‑to‑contralateral ratio. ATTR patients showed markedly higher visual and quantitative uptake scores, and a heart‑to‑contralateral ratio >1.5 yielded 97 % sensitivity and 100 % specificity (AUC 0.992), demonstrating that (99m)Tc‑PYP scintigraphy reliably distinguishes AL from ATTR cardiac amyloidosis and could serve as a simple, widely available diagnostic tool.

Abstract

Differentiating immunoglobulin light-chain (AL) from transthyretin-related cardiac amyloidoses (ATTR) is imperative given implications for prognosis, therapy, and genetic counseling. We validated the discriminatory ability of (99m)Tc-pyrophosphate ((99m)Tc-PYP) scintigraphy in AL versus ATTR.Forty-five subjects (12 AL, 16 ATTR wild type, and 17 ATTR mutants) underwent (99m)Tc-PYP planar and single-photon positive emission computed tomography cardiac imaging. Scans were performed by experienced nuclear cardiologists blinded to the subjects' cohort assignment. Cardiac retention was assessed with both a semiquantitative visual score (range, 0; no uptake to 3, diffuse uptake) and by quantitative analysis by drawing a region of interest over the heart corrected for contralateral counts and calculating a heart-to-contralateral ratio. Subjects with ATTR cardiac amyloid had a significantly higher semiquantitative cardiac visual score than the AL cohort (2.9±0.06 versus 0.8±0.27; P<0.0001) as well as a higher quantitative score (1.80±0.04 versus 1.21±0.04; P<0.0001). Using a heart-to-contralateral ratio >1.5 consistent with intensely diffuse myocardial tracer retention had a 97% sensitivity and 100% specificity with area under the curve 0.992, P<0.0001 for identifying ATTR cardiac amyloidosis. (99m)Tc-PYP cardiac imaging distinguishes AL from ATTR cardiac amyloidosis and may be a simple, widely available method for identifying subjects with ATTR cardiac amyloidosis, which should be studied in a larger prospective manner.