Prognostic utility of the Perugini grading of 99mTc-DPD scintigraphy in transthyretin (ATTR) amyloidosis and its relationship with skeletal muscle and soft tissue amyloid

Abstract

High-grade (Perugini grade 2 or 3) cardiac uptake on bone scintigraphy with 99m Technetium labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99m Tc-DPD) has lately been confirmed to have high diagnostic sensitivity and specificity for cardiac transthyretin (ATTR) amyloidosis. We sought to determine whether patient stratification by Perugini grade on 99m Tc-DPD scintigraphy has prognostic significance in ATTR amyloidosis. Methods and Results Patient survival from time of 99m Tc-DPD scintigraphy was determined in 602 patients with ATTR amyloidosis, including 377 with wild-type ATTR and 225 with mutant ATTR amyloidosis (ATTRm). Patients were stratified according to Perugini grade (0-3) on 99m Tc-DPD scan. The prognostic significance of additional patient and disease-related factors at baseline were determined. In the whole cohort, the finding of a Perugini grade 0 99m Tc-DPD scan (n=28) was invariably associated with absence of cardiac amyloid according to consensus criteria as well as significantly better patient survival compared to a Perugini grade 1 (n=28), 2 (n=436) or 3 (n=110) 99m Tc-DPD scan (p<0.005). There were no differences in survival between patients with a grade 1, grade 2 or grade 3 99m Tc-DPD scan in wild-type ATTR (n=369), V122I-associated ATTRm (n=92) or T60A-associated ATTRm (n=59) amyloidosis. Cardiac amyloid burden, determined by equilibrium contrast cardiac magnetic resonance imaging, was similar between patients with Perugini grade 2 and Perugini grade 3 99m Tc-DPD scans but skeletal muscle/soft tissue to femur ratio was substantially higher in the latter group (p<0.001). Conclusion 3 99m Tc-DPD scintigraphy is exquisitely sensitive for identification of cardiac ATTR amyloid, but stratification by Perugini grade of positivity at diagnosis has no prognostic significance.

Magnetic Resonance in Transthyretin Cardiac Amyloidosis

“…Bone tracer scintigraphy, using as a sensitive tool for the identification of cardiac ATTR (7)(8)(9). However, this nuclear medicine method is typically only performed to confirm ATTR when a clinical suspicion exists, as it does not provide information on any of the other differentials of LVH, cardiac morphology, or function, and is semi-quantitative only (10), a limitation given the development of therapies able to stop or remove cardiac amyloid deposits (9,11).…”

Quantification of myocardial 99mTc-labeled bisphosphonate uptake with cadmium zinc telluride camera in patients with transthyretin-related cardiac amyloidosis

“…Consequently, bisphosphonate ([ 99m Tc]TcDPD, [ 99m Tc]PyP or [ 99m Tc]TcHMDP) scintigraphy is now a key feature in the diagnostic algorithm in patients with suspected cardiac ATTR [5,22]. However, the visual assessment of cardiac uptake according to the widely used Perugini grading failed to predict patient prognosis [23]. Recent data pointed out that the intensity of cardiac uptake is a powerful predictor of poor cardiac outcome [10,11].…”

“…The count statistics in heart and background regions in the planograms take into account the projection of every anatomic structure that binds the bone radiopharmaceutical, including the rib cage, the sternum, and the soft tissues [25]. Extracardiac uptake, including soft tissue involvement, is not constant and varies according to the stage of the disease [23]. On the other hand, the H:B ratio obtained from 3D reconstructed images reflect the heart retention normalized to the lung uptake, a metric that is not influenced by sternum, rib cage, or muscle uptake that are not included in VOIs.…”

Diagnostic approach to light-chain cardiac amyloidosis and its differential diagnosis

“…Several nuclear medicine imaging techniques have become available for the diagnosis and prognostic stratification of cardiac amyloidosis [42]. Bone scintigraphy using radiolabeled 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid tracer is useful in differentiating between ATTR and AL cardiac amyloidoses, revealing a positive uptake in ATTR cardiac amyloidosis [43] and false-positive results in AL cardiac amyloidosis [44].…”