Non-Biopsy Diagnosis of Cardiac Transthyretin Amyloidosis

Study Questions:

What is the diagnostic value of bone scintigraphy as a noninvasive test for transthyretin type (ATTR) cardiac amyloidosis?


The authors conducted a retrospective analysis of multicenter data of bone scintigraphy using one of three tracers (99mTc-DPD [n = 877], 99mTc-PYP [n = 199], or 99mTc-HMDP [n = 141]) for the evaluation of known or suspected ATTR cardiac amyloidosis. Images were qualitatively rated by comparison to bone uptake (grade 0 – no cardiac uptake; grade 1 – mild uptake less than bone; grade 2 – moderate uptake equal to bone; grade 3 – high uptake greater than bone). Results were compared to biopsy, echocardiographic, cardiac magnetic resonance imaging, as well as serum and urine chemistry data.


Out of a total of 1,498 patients, 1,217 were included in the analysis (281 were excluded due to diagnostic uncertainty). A total of 857 were determined to have amyloidosis on the basis of biopsy and imaging data. The overall sensitivity of grade 1 or higher cardiac uptake was >99% (positive scan in 259 of 261 patients with cardiac ATTR amyloid), and specificity was 68% (negative scan in 77 of 113 patients without cardiac ATTR amyloid). The primary reason for low specificity was low-level uptake in patients with non-ATTR forms of amyloidosis. When only grade 2 or 3 uptake was considered, sensitivity and specificity were 91% and 87%, respectively. When grade 2 or 3 uptake was combined with the absence of a monoclonal protein in the serum and urine, the specificity and positive predictive value were 100%.


The authors concluded that bone scintigraphy has high diagnostic accuracy for cardiac ATTR amyloidosis.


There has been a resurgence of interest in bone scintigraphy for the diagnosis of ATTR amyloidosis. This finding had initially been reported several decades ago, but has been rediscovered as specific treatments for this disease are on the horizon. Overall, this study adds to the body of literature suggesting that this noninvasive test is highly sensitive and specific. However, caution should be used before extrapolating these data to general clinical practice. First, all of these patients were referred to an amyloidosis center and thus had at least a moderate to high pretest suspicion of cardiac amyloidosis, as evidenced by the very high rate of amyloidosis in general (70% of patients had biopsy evidence of cardiac or extracardiac amyloidosis). Whether these data can be extended to all patients with unexplained left ventricular hypertrophy remains uncertain. This is particularly important, as acute or chronic ischemia can also lead to uptake of bone tracers. Indeed, 99mTc-PYP was used decades ago for early identification of myocardial infarction. Consequently, further validation is needed to extend these data to patients without high suspicion for amyloidosis who may have chronic subendocardial ischemia due to left ventricular hypertrophy. Last, it will also be important to further validate and compare the three individual tracers used in this study.

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