Application and Pitfalls of 99mTechnetium Pyrophosphate Scintigraphy in the Diagnosis of Transthyretin Amyloid Cardiomyopathy

Bone scintigraphy with radiolabeled tracers is a highly sensitive and specific technique for the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) when considered in the context of other biochemical and imaging findings. However, bone scintigraphy has been underused for early diagnosis, and technical procedures have not been standardized. Researchers outlined clinical characteristics that would suggest the use of this technique and potential pitfalls in the interpretation of findings.

A common radiotracer used for scintigraphy for ATTR-CM is 99mtechnetium pyrophosphate (99mTC-PYP). Laboratory tests for serum-free light chain levels and serum and urine protein electrophoresis with immunofixation must be performed to interpret 99mTC-PYP scintigraphy results because amyloid light chain cardiac amyloidosis is also detected by 99mTC-PYP scintigraphy.

When to Consider PYP Scintigraphy

Clinicians may suspect ATTR-CM and consider using 99mTC-PYP scintigraphy with the following clinical presentations: a family history of hereditary ATTR; age ≥60 years with unexplained cardiac findings; progressive heart failure; heart failure with preserved ejection fraction associated with left ventricular hypertrophy; heart failure with reduced ejection fraction associated with left ventricular hypertrophy and atrial fibrillation; abnormal echocardiographic findings, such as low QRS voltage or conduction disturbance; cardiac hypertrophy with diastolic dysfunction or apical sparing on echocardiography; suspicious cardiac magnetic resonance imaging findings, such as increased native T1, diffuse subendocardial late gadolinium enhancement, and increased extracellular volume; or persistently elevated cardiac troponin or NT-pro-BNP.

ATTR may also cause neurologic symptoms. Bilateral carpal tunnel syndrome in older patients with cardiac hypertrophy is a common feature of ATTR-CM.

False Positives

False positives with 99mTC-PYP scintigraphy for ATTR-CM may occur in patients with acute myocardial infarction, hypertrophic cardiomyopathy, or hydroxychloroquine toxicity. Other types of cardiac amyloidosis also cause radiotracer uptake.

When 99mTC-PYP uptake is grade 1, or mild, and the light chain laboratory tests are negative, the researchers recommended other tests. 99mTC-PYP uptake in these cases may occur when uptake is by the cardiac blood pool rather than the myocardium. Blood pool uptake can be excluded by examining single photon-emission computed tomography images. They then recommended reviewing cardiac magnetic resonance and echocardiography results and performing a biopsy if ATTR-CM is still suspected. In patients for whom the suspicion of ATTR-CM is weak, 99mTC-PYP scintigraphy could also be repeated in 6 months to 1 year when uptake may be stronger as the disease progresses.

False Negatives

False negatives with 99mTC-PYP scintigraphy can occur with low levels of amyloid deposition, rib fractures, valvular or annular calcifications, myocardial infarction within the previous month, and certain hereditary ATTR mutations.

The researchers suggested that future studies are needed to understand the mechanisms of radiotracer uptake in amyloidosis and the cost-effectiveness of 99mTC-PYP scintigraphy.

Source: Tahara N, Lairez O, Endo J, et al. 99mTechnetium-pyrophosphate scintigraphy: a practical guide for early diagnosis of transthyretin amyloid cardiomyopathy. ESC Heart Fail. 2022;9:251-262.

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