(99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses

Abstract

Background: 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.

Methods and results: 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.

Conclusions: (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.

Figures

Figure 1. (A–B). Semi-quantitative method of calculating the distribution of 99mTc-PYP uptake

Raw images of a representative negative (A) and positive subject (B) are shown 1 hour after radiotracer infusion. ROI circles are depicted in red and the contralateral comparison circle is depicted in blue. ROI = region of interest; C/L = contralateral; Cts = counts; Std Dev = standard deviation.

Figure 2. Mean heart to contralateral ratio according to amyloid subtype

Comparison of 99mTc-PYP mean H/CL ratio between patients with AL, ATTRwt, and ATTRm cardiac amyloidosis. AL and transthyretin-related amyloidoses are differentiated by mean H/CL ratio of 1.5. The outlier with H/CL 1.3 is an ATTRm patient with the unusual Thr59Lys mutation. AL = amyloid light-chain; ATTRwt = wild-type transthyretin amyloidosis; ATTRm = mutant transthyretin amyloidosis.