Role of 99mTc-DPD Scintigraphy in Diagnosis and Prognosis of Hereditary Transthyretin-Related Cardiac Amyloidosis

Study Questions:

What is the role of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) in detecting myocardial amyloid infiltration across a wide spectrum of cardiac involvement and in predicting major adverse cardiac events (MACE)?

Methods:

The investigators evaluated 63 patients with transthyretin-related amyloidosis (ATTR): 40 with and 23 without echocardiographically diagnosed amyloidotic cardiomyopathy (AC). Myocardial uptake of 99mTc-DPD scintigraphy was semiquantitatively and visually assessed at 5 minutes and 3 hours. To explore possible associations with MACE-free survival, univariate Cox regression analysis was initially performed with clinical, echocardiographic, electrocardiographic, and scintigraphic variables. Multivariate analysis was then performed by entering into the model the variables that were significant (p < 0.05) on univariate analysis, but unrelated to each other.

Results:

All patients with AC showed moderate-to-severe myocardial tracer uptake (i.e., visual score 2). Within the subgroup without AC, only four patients (with Ala36Pro, Gly47Ala, Thr49Ala, and Glu89Gln transthyretin mutations) showed myocardial tracer uptake and abnormal heart/whole body retention (H/WB) values: in all these cases, endomyocardial biopsies showed amyloidotic infiltration. The H/WB was positively correlated with left ventricular (LV) mean wall thickness (Pearson’s r = 0.695, p < 0.001) and negatively with LV ejection fraction (r = –0.368, p = 0.004). The H/WB was an unfavorable predictor of MACE-free survival at Cox univariate analysis and contributed to the multivariate model. Notably, LV wall thickness >12 mm in combination with H/WB >7.5 was associated with the highest event rate.

Conclusions:

The authors concluded that 99mTc-DPD scintigraphy can identify myocardial infiltration across a wide spectrum of morphologic/functional cardiac involvement, allowing an early diagnosis of the disease.

Perspective:

The study suggests that in patients with hereditary ATTR, 99mTc-DPD scintigraphy can identify myocardial infiltration across a wide spectrum of morphologic and functional cardiac involvement, increasing the accuracy of echocardiographic diagnosis of AC and allowing early diagnosis of the disease, and 99mTc-DPD myocardial uptake is a prognostic determinant of ‘cardiac’ outcome in ATTR. It should be noted that the prognostic contribution may be quite different in patients with Val30Met TTR mutation, where myocardial involvement is infrequent (and age-dependent) and neurologic progression is generally the main prognostic determinant. Furthermore, given the small study sample, the role of 99mTc-DPD scintigraphy in the early diagnosis of ATTR-related myocardial disease needs to be confirmed by additional studies.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Early Diagnosis, Cardiomyopathies, Biopsy, Heart Failure, Amyloid Neuropathies, Familial, Electrocardiography


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