Noninvasive etiologic diagnosis of cardiac amyloidosis using ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy

OBJECTIVES: We investigated the diagnostic accuracy of ^99mTc-3, 3-diphosphono-1,2-propanodicarboxylic acid (^99mTc-DPD) scintigraphy for differentiation of monoclonal immunoglobulin light-chain (AL) and transthyretin (TTR)-related cardiac amyloidosis. BACKGROUND: Differential diagnosis between TTR-related and AL amyloidosis is often complex and time-consuming. METHODS: Patients under routine observation with TTR-related/AL systemic amyloidosis and echocardiographic evidence of cardiac involvement were studied with ^99mTc-DPD scintigraphy. RESULTS: Patients with cardiac involvement of TTR-related (group A; n = 15) and AL (group B; n = 10) etiology were comparable for left ventricular mass and renal function. Heart and heart/whole-body tracer retention were significantly higher (p <0.05) in group A as compared with group B and with 10 unaffected controls. At visual scoring, cardiac ^99mTc-DPD uptake was present in all group A patients and absent in all group B patients; thus, using genotyping/immunohistochemistry as the reference technique, the accuracy of ^99mTc-DPD scintigraphy for distinction of TTR-related and AL etiology was 100%. Cardiac ^99mTc-DPD uptake was also absent among unaffected controls. Using echocardiography as the reference standard for recognition of cardiac involvement, sensitivity and specificity of scintigraphy were both 100% for group A patients; in group B, sensitivity was 0% and specificity was 100% (accuracy, 50%). Eleven patients with myocardial ^99mTc-DPD uptake underwent ^99mTc-methylene diphosphonate (^99mTc-MDP) scintigraphy; all patients showed a ^99mTc-MDP myocardial visual score of 0. CONCLUSIONS: Etiology is a third major cause -in addition to type of organ-involved (soft-tissue/heart) and tracer type -of scintigraphic variability in cardiac amyloidosis. This is a highly relevant consideration for future studies. We conclude that ^99mTc-DPD scintigraphy is a useful step in the workup of the differential diagnosis of TTR versus AL etiology in patients with documented cardiac amyloidosis.