Imaging of cardiac amyloidosis by (99m)Tc-PYP scintigraphy.

OBJECTIVE: Cardiac amyloidosis (CA) is an underestimated and underdiagnosed cause of cardiac insufficiency. Despite being often considered as a solitary entity attributable to extracellular deposition of fibrillary proteins, there exist at least two different pathophysiologic backgrounds, with different clinical course and treatment. a) In light-chain cardiac amyloidosis (immunoglobulin light-chain amyloidosis-AL) the fibrils consist of light-chain immunoglobulins produced by a clonal plasma cell population in bone marrow. b) In CA related to transthyretin (transthyretin-related amyloidosis - ATTR), whether familial amyloid cardiomyopathy or senile systemic amyloidosis, monomers or dimers of the normally tetrameric protein of transthyretin are deposited in the myocardium. Today, definitive diagnosis of cardiac amyloid disease is based on endomyocardial biopsy in conjunction with immunohistochemical parameters or, in ambiguous cases, with mass spectroscopy. Several radiotracers have been hitherto tried in the detection of CA. SUBJECTS AND METHODS: In this pilot study technetium-99m pyrophosphate ((99m)Tc-PYP) was administered to patients suffering from CA, aiming to differentiate scintigraphically between AL and ATTR. Twelve patients (8 males, aged [mean±SD] 70,6±13,2y; 4 females, aged 65,7±9,9y) were enrolled for the discrimination between AL and ATTR. Diagnosis was confirmed by biopsy combined with the clinical and laboratory evaluation of the patients. Myocardial scintigraphy (planar and tomographic imaging) was conducted at 1, 2 and/or 3h after intravenous administration of 555-925MBq (99m)Tc-PYP. Myocardial radiotracer uptake was evaluated optically and also by a semiquantitative method. Two regions of interest (ROI) were drawn: one over the heart and another over the contralateral hemithorax, to calculate the corresponding heart-to-contralateral (H/CL) count ratio. According to established reference standards, a cut-off H/CL value of 1.5 best discriminates between the two conditions. (99m)Tc-PYP scintigraphy revealed diffuse intense myocardial uptake upon visual evaluation that was also verified semi-quantitatively in 6 patients, all of which had ATTR. Faint or no myocardial tracer uptake was found in 4 patients who were diagnosed with AL. Two AL patients had a borderline positive scan on visual evaluation but their H/CL ratios did not exceed the value of 1.5. In three patients, we also attempted scintigraphy with the tracer pentavalent (99m)Tc-dimercaptosuccinic acid. Results and possible mechanisms of uptake are discussed. The sensitivity and specificity of scintigraphy with (99m)Tc-PYP was high, albeit the small number of patients. IN
CONCLUSION: These preliminary results are compatible with current international literature, and demonstrate that scintigraphy with (99m)Tc-PYP may prove a simple, non-invasive and widely available method in the identification of patients with the ATTR subtype, thus optimizing therapeutic decisions.