Pyrophosphate imaging aids in diagnosing cardiac amyloidosis
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Utilization of pyrophosphate imaging to identify patients with cardiac amyloidosis has increased, although questions remain regarding its use for screening and to assess responses to therapy, according to a presentation.
Although pyrophosphate imaging has been used and researched for decades, data on its use in differentiating light-chain (AL) amyloidosis from transthyretin (ATTR) amyloidosis started around 2013, Frederick L. Ruberg, MD, associate professor of medicine and radiology and associate chief of cardiovascular medicine at Boston University School of Medicine and Boston Medical Center, said during the presentation at the Scientific Session and Exhibition of the American Society of Nuclear Cardiology.
“That really accelerated the pathway of [pyrophosphate] adaptation in the United States,” Ruberg added.
The American Society of Nuclear Cardiology has published practice points on the use of pyrophosphate imaging in cardiac amyloidosis, the first of which was released in 2016. The organization also published expert consensus recommendations in 2019 on multimodality imaging in cardiac amyloidosis including nuclear imaging, cardiac MRI and echocardiography.
“This document really served the purpose to standardize how the imaging is done, and that standardization has led to a significant uptick in community adaptation,” Ruberg said in the presentation. “Now, physicians who are practicing around the world, particularly in the United States for [pyrophosphate] imaging, have a document they can look to that can tell them exactly how to perform the imaging correctly and exactly how to report it. Given heterogeneity that existed prior to publication of these guidelines, the document created some conformity that really wasn’t present from reviewing methods in the literature.”
In 2020, the American Heart Association also published a scientific statement on the diagnosis and management of patients with cardiac amyloidosis. This document describes how pyrophosphate imaging can be essential to diagnose amyloidosis, particularly ATTR amyloidosis, once a plasma cell abnormality is excluded by blood test.
“ATTR amyloidosis is, by far the more important disease in terms of frequency in population,” Ruberg said in the presentation. “AL is critical and cannot be missed ... but [pyrophosphate] imaging can be used to diagnose ATTR in the right context, and that’s why it figures so centrally in the guidelines.”
The diagnosis of ATTR amyloidosis has increased over the past few years due to the increase in utilization of pyrophosphate imaging, according to the presentation. Despite this increased use, Ruberg observed several unfavorable trends related to common but avoidable errors in pyrophosphate imaging. These include the failure to perform or properly interpret light-chain testing, using pyrophosphate imaging in inappropriate clinical scenarios and failure to obtain single-photon emission CT to differentiate blood pool from cardiac uptake.
Pyrophosphate imaging cannot be interpreted without light-chain assessment, which is done through serum-free light chains and serum and urine immunofixation electrophoresis.
“When one looks at these results, one can then appropriately determine whether or not [pyrophosphate] imaging can be diagnostic for TTR amyloidosis,” Ruberg said during the presentation. “Cardiologists are not comfortable nor should they be necessarily with these light-chain assay ranges. ... Basically, the concept here is that when the free light-chain ratio is abnormal or when the serum immunofixation is abnormal, you must refer to hematology for further evaluation. A multidisciplinary approach is essential in this context."
It is important to obtain scans in the right clinical scenario and to recognize AL amyloidosis because it is life-threatening, according to the presentation. In addition, incorrectly diagnosing ATTR amyloidosis may lead to treating inappropriate patients with tafamidis (Vyndamax and Vyndaqel, FoldRx/Pfizer). Although the drug is an effective treatment for ATTR amyloidosis, it is expensive. Even after financial assistance, some patients prescribed this drug may have copays of up to $1,700 per month, according to the presentation.
“If patients are basically being asked to shoulder the burden of a very expensive drug, you really want to make sure they actually have the disease for which they’re being treated,” Ruberg said in the presentation.
Future trends in the use of pyrophosphate imaging may be shaped by several unanswered questions regarding the use of bone scintigraphy as a screening test, cost-effectiveness of screening, follow-up in asymptomatic allele carriers of TTR mutations and the role of imaging for prognostication or following disease response.
“We’ve reached a perfect storm for ATTR amyloidosis,” Ruberg said during the presentation. “We have an understanding that the epidemiology of ATTR amyloidosis is much more prevalent than we thought before and this understanding, in large part, has been shaped by the access to [pyrophosphate] imaging, affording a means to an easy diagnosis in scenarios where we didn’t think about it before.”
References:
- Dorbala S, et al. J Nucl Cardiol. 2020;doi:10.1007/s12350-019-01761-5.
- Kittleson MM, et al. Circulation. 2020;doi:10.1161/CIR.0000000000000792.
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Ruberg FL. Amyloid-Best Practices. Presented at: Scientific Session and Exhibition of the American Society of Nuclear Cardiology; Sept. 25-26, 2020 (virtual meeting).
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