Clinical application of cardiac scintigraphy with bone tracers: controversies and pitfalls in cardiac amyloidosis

Abstract

Cardiac amyloidosis (CA) is a life-threatening disease caused by extracellular deposition of amyloidogenic proteins in the heart tissue; it could be associated with a poor prognosis and remains underdiagnosed and underestimated. During the last years, bone scintigraphy has been widely used to facilitate the diagnosis of CA, avoid endomyocardial biopsy, and differentiate amyloid light-chain amyloidosis from transthyretin amyloidosis. Technetium-99m pyrophosphate (99mTc-PYP) is the most used tracer in the United States, but a standardized and shared acquisition protocol is still lacking; technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) is widely used in Europe and can count on a more grounded data than 99mTc-PYP. Both tracers suffer from some diagnostic limitations (due to their biochemical characteristics) and pitfalls that can lead to a misdiagnosis of CA. We aim to briefly describe the main differences between 99mTc-PYP and 99mTc-DPD, analyzing the data available in the literature and highlighting the most frequent causes of misdiagnosis and pitfalls. Both 99mTc-DPD and 99mTc-PYP show good accuracy for the diagnosis of CA with high specificity and sensibility. Nevertheless, to achieve this accuracy, the correct acquisition protocols must be followed for each tracer, as suggested in the latest recommendation. Proper diagnosis of CA has a crucial role in patient management; therefore, it is important for nuclear physicians to have the most specific approaches in acquiring and interpreting bone scintigraphy for transthyretin cardiac amyloidosis.

Imaging findings of right cardiac amyloidosis: impact on prognosis and clinical course

“…The exam consists of a static image one or 3 h after the bone-tracer injection and the interpretation is usually performed by quantitative or semi-quantitative analysis (absent, local, or diffuse uptake) [ 59 ].…”

“…The prognostic value of 99mTc-bisphosphonate bone scintigraphy is given by its ability to distinguish the ATTR-CA the AL-CA which is characterized by a worse prognosis [ 59 ]. Furthermore major adverse cardiac events, acute heart failure, and higher mortality are all linked to greater myocardial retention of the various bone tracers [ 60 ].…”

Re-Definition of the Epidemiology of Cardiac Amyloidosis

“…The careful evaluation of the clinical presentation of patients is essential for an operational interpretation of the scintigraphy image and to assess the need for further investigations such as CMR, tissue sampling for histological analysis or genetic investigation for TTR mutations. In case of complex clinical cases or unexpected results, multidisciplinary management and discussions are valuable resources for optimizing patient care [ 18 , 19 ].…”

The changing perspective on cardiac amyloidosis in the modern era

“…A cutting-edge step forward for diagnosis was the possibility in achieving a non-invasive confirmation of ATTR-CA in the presence of high-grade cardiac retention (Perugini grade 2-3) in patients without monoclonal components (99% accuracy, 100% specificity) [9,10] . However, controversies and pitfalls of bone tracer scintigraphy exist, as critically pointed out by Mattana et al [11] .…”

“…Although this approach has increased the diagnostic yield and the chance of earlier disease recognition, a consistent diagnostic delay still remains (≈ 34 months from symptoms onset to diagnosis) [12] . In addition, the non-invasive algorithm suffers from some limitations in real-world applications, as in patients with intense cardiac retention at scintigraphy and monoclonal gammopathy of undetermined significance requiring histological evidence of amyloid deposits or in the presence of false-negative scintigraphy results due to peculiar TTR mutations (i.e., Phe84Leu and Ser97Tyr) [9,10] . In this scenario, cardiac magnetic resonance and positron emission tomography can aid clinicians in the diagnosis and management of the disease, as discussed by Pica et al [13] and Genovesi et al [14] .…”