Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis

Background—Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal cardiomyopathy for which several
promising therapies are in development. The diagnosis is frequently delayed or missed because of the limited specificity
of echocardiography and the traditional requirement for histological confirmation. It has long been recognized that
technetium-labeled bone scintigraphy tracers can localize to myocardial amyloid deposits, and use of this imaging
modality for the diagnosis of cardiac ATTR amyloidosis has lately been revisited. We conducted a multicenter study to
ascertain the diagnostic value of bone scintigraphy in this disease.
Methods and Results—Results of bone scintigraphy and biochemical investigations were analyzed from 1217 patients
with suspected cardiac amyloidosis referred for evaluation in specialist centers. Of 857 patients with histologically
proven amyloid (374 with endomyocardial biopsies) and 360 patients subsequently confirmed to have nonamyloid
cardiomyopathies, myocardial radiotracer uptake on bone scintigraphy was >99% sensitive and 86% specific for cardiac
ATTR amyloid, with false positives almost exclusively from uptake in patients with cardiac AL amyloidosis. Importantly,
the combined findings of grade 2 or 3 myocardial radiotracer uptake on bone scintigraphy and the absence of a monoclonal
protein in serum or urine had a specificity and positive predictive value for cardiac ATTR amyloidosis of 100% (positive
predictive value confidence interval, 98.0–100).
Conclusions—Bone scintigraphy enables the diagnosis of cardiac ATTR amyloidosis to be made reliably without the need for
histology in patients who do not have a monoclonal gammopathy. We propose noninvasive diagnostic criteria for cardiac
ATTR amyloidosis that are applicable to the majority of patients with this disease. (Circulation. 2016;133:2404-2412.
DOI: 10.1161/CIRCULATIONAHA.116.021612.)