99mTc-DPD scintigraphy in immunoglobulin light chain (AL) cardiac amyloidosis

Abstract

Aims: Technetium-99m-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD scintigraphy) is recognized as highly accurate for the non-invasive diagnosis of transthyretin (ATTR) cardiac amyloidosis (CA). A proportion of patients with immunoglobulin light chain (AL) CA have also been reported to show cardiac 99mTc-DPD uptake. Herein, we assessed the frequency and degree of cardiac 99mTc-DPD uptake and its clinical significance among patients with AL CA.

Methods and results: Between 2010 and 2017, 292 consecutive patients with AL CA underwent 99mTc-DPD scintigraphy and were included in this study: 114 (39%) had cardiac 99mTc-DPD uptake: grade 1 in 75%, grade 2 in 17%, and grade 3 in 8% of cases. Patients with cardiac 99mTc-DPD uptake had poorer cardiac systolic function and higher N-terminal pro-brain natriuretic peptide. No differences were noted in cardiac magnetic resonance parameters between patients with and without cardiac 99mTc-DPD uptake (N = 19 and 42, respectively). Patients with cardiac 99mTc-DPD uptake showed a trend to worse survival than those with no uptake (log-rank P = 0.056). Among 22 patients who underwent serial 99mTc-DPD scintigraphy, 5 (23%) showed reduction in the grade of cardiac uptake.

Conclusions: In this large cohort of patients with AL CA, 99mTc-DPD scintigraphy ∼40% of cases showed cardiac uptake, including grade 2-3 in 10% of all patients (25% of those with cardiac 99mTc-DPD uptake). Cardiac 99mTc-DPD uptake was associated with poorer cardiac function and outcomes. These data highlight the critical importance of ruling out AL amyloidosis in all patients with cardiac 99mTc-DPD uptake to ensure such patients are not assumed to have ATTR CA.

Keywords: 99mTc-DPD scintigraphy; amyloidosis; cardiomyopathy; diagnosis; light chain; prognosis.

Figure 1

^99mTcDPD scintigraphy (3 hours’ image acquisition) in a patient with stage 3a light chain (AL) cardiac amyloidosis. While at diagnosis (left) the cardiac and bone uptake were, respectively, intense and attenuated (visual score = 2), after 2 years (right) the degree of cardiac uptake has substantially reduced, while the bone uptake has increased (visual score = 1).

Figure 2

Overall survival in patients with AL cardiac amyloidosis according to the presence or absence of cardiac ^99mTc-DPD uptake.

Figure 3

Diagnostic algorithm in patients with suspect cardiac amyloidosis and evidence of cardiac uptake on 99mTc-DPD scintigraphy (or equivalent bone scanning). While with a ^99mTcDPD grade 2 or 3 the absence of a monoclonal protein in serum/urine is diagnostic of ATTR cardiomyopathy, its presence requires more investigations, and in particular the differential diagnosis between ATTR and AL amyloidosis via endomyocardial biopsy in patients older than 50 years, that are at higher risk of ATTR. A ^99mTcDPD grade 1 in absence of a monoclonal protein in serum/urine still requires an endomyocardial biopsy to understand the nature of the underlying cardiomyopathy/amyloidosis.