Elsevier

Journal of Nuclear Cardiology

Volume 29, Issue 6, December 2022, Pages 3126-3136
Journal of Nuclear Cardiology

Original Article
Amyloid deposit corresponds to technetium-99m-pyrophosphate accumulation in abdominal fat of patients with transthyretin cardiac amyloidosis

https://doi.org/10.1007/s12350-021-02890-6Get rights and content

Abstract

Background

Radionuclide imaging using bone-avid tracers plays a critical role in diagnosing transthyretin cardiac amyloidosis (ATTR-CA), but technetium-99m-pyrophosphate (PYP) rarely allows the detection of extracardiac amyloid infiltration. We retrospectively investigated the frequency of PYP uptake in the subcutaneous abdominal fat of patients with ATTR-CA and its relevance to the results of fine-needle aspiration biopsy (FNAB) of this tissue.

Methods

Chest-centered images of PYP scintigraphy were obtained 2 h after the intravenous injection of the tracer (20 mCi), and the frequency of PYP uptake in the subcutaneous abdominal fat was evaluated. Amyloid deposits of fat smears taken by subcutaneous abdominal fat FNAB were assessed by Congo red staining.

Results

Twenty-four patients with ATTR-CA were included. Ten (41.7%) patients showed some PYP uptake in the subcutaneous abdominal fat (positive PYP group), and 14 patients did not (negative PYP group). Amyloid deposits were detected by subcutaneous abdominal fat FNAB in 7/10 patients (70.0%) of the positive PYP group versus 0/14 patients (0%) of the negative PYP group, and the difference was significant.

Conclusions

In patients with ATTR-CA, abnormal PYP uptake in the subcutaneous abdominal fat could reflect the regional amyloid deposition confirmed by FNAB of this tissue.

Introduction

Cardiac amyloidosis (CA) has two main subtypes—transthyretin (ATTR)-CA and immunoglobulin light chain (AL)-CA—characterized by the infiltration of amyloid fibril proteins.1 ATTR-CA is further subdivided into wild-type (ATTRwt)-CA and variant-type (ATTRv)-CA based on the presence of a transthyretin gene mutation. Radionuclide imaging with bone-avid tracers has emerged as an important non-invasive tool in diagnosing suspected ATTR-CA, particularly owing to its capacity to differentiate with high sensitivity and specificity from other cardiomyopathies, including AL-CA.1,2 Cardiac uptake on a bone-avid tracer scan in the absence of a monoclonal protein confirmed by serum and urine immunofixation electrophoresis or abnormal serum-free light chain assay is a diagnostic predictor of ATTR-CA.3 For this, three bone-avid tracers, namely, technetium-99m-pyrophosphate (PYP), -3,3-diphosphono-1,2-propanedicarboxylic acid (DPD), and -hydroxymethylene diphosphonate (HMDP), are used, although they are not universally available. Τechnetium-99m-DPD/-HMDP, predominantly used for whole-body imaging, allows the detection of extracardiac amyloid infiltration, whereas whole-body PYP imaging does not provide any additional diagnostic value, and PYP has been used only in chest/cardiac planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging.2,4

Confirmation of amyloid deposits and typing by immunohistochemistry are needed in cases wherein both bone scintigraphy and monoclonal protein tests are abnormal.1 In Japan, the dosing requirements for tafamidis meglumine are strict because of the high cost of this drug under the National Health Insurance scheme (5 million Japanese Yen a month). For the drug to be prescribed, the genetic testing to differentiate between the ATTRwt amyloidosis and ATTRv amyloidosis after determining ATTR amyloidosis by immunohistochemical analysis is a prerequisite. The precise diagnosis of ATTR-CA requires an endomyocardial biopsy to demonstrate amyloid deposition. However, this procedure is relatively invasive and cannot be routinely performed. A sampling of an alternative tissue for screening biopsy minimizes the need for an endomyocardial biopsy. For example, fine-needle aspiration biopsy (FNAB) for subcutaneous abdominal fat is a safe and reliable screening procedure, although it has very low sensitivity in ATTRwt-CA.5 We encountered a case of ATTR-CA with marked accumulation of PYP in the subcutaneous abdominal fat as well as in the myocardium, in which subcutaneous abdominal fat FNAB demonstrated positive results for transthyretin amyloid deposits.6 Therefore, this study retrospectively investigated the frequency of PYP uptake in the subcutaneous abdominal fat and determined its relevance to the results of fine-needle aspiration biopsy (FNAB) of this tissue in patients with ATTRwt-CA.

Section snippets

Study Patients

A total of 32 consecutive patients with myocardial accumulation of radiotracers, as revealed by PYP scintigraphy performed as part of their routine clinical care at Yawatahama City General Hospital from 04/2017 to 03/2021, were retrospectively evaluated. Patients underwent comprehensive evaluation comprising electrocardiography, echocardiography, and biochemical tests, including cardiac biomarkers, serum and urine immunofixation electrophoresis, and serum-free light chain assay. As needed,

Study Patients

Among the 32 patients, 5 in whom subcutaneous abdominal fat FNAB was not done were excluded from this study. In addition, 4 suspected ATTR-CA patients were also excluded from the analysis. Thus, 24 patients with ATTR-CA (ATTRwt-CA, 16; ATTR-CA, 8) were included in this study. Seven (29.2%) were female, and the mean age of the patients was 85.3 years (range, 70-96 years). The background and clinical characteristics of the 24 patients are summarized in Table 1. The clinical profile leading to the

Discussion

This study demonstrated that the abnormal uptake of PYP in the subcutaneous abdominal fat could be proportional to the regional amyloid deposition confirmed by FNAB of this tissue in patients with ATTRwt-CA. However, cardiac amyloid burden based on electrocardiographic, echocardiographic, and PYP scintigraphy parameters were not different between the positive and negative PYP groups. The positive PYP group patients tended to be older females, although the reason for this is unknown.

As ATTRwt

New Knowledge Gained

Patients with abnormal uptake of PYP in both myocardium and subcutaneous abdominal fat, although infrequent, had a high yield of subcutaneous abdominal fat FNAB. When confirmation of amyloid deposits by Congo red staining and typing by immunohistochemistry is needed, subcutaneous abdominal fat FNAB may be selected as the first screening biopsy method in these patients. Positive results in screening biopsy minimize the requirement for high-risk and more invasive target organ biopsies, such as

Conclusion

Our study suggests that in ATTRwt-CA patients, PYP imaging could demonstrate the amyloid burden in the subcutaneous abdominal fat, which was not associated with the volume of myocardial amyloid deposits; thus, the amyloid would deposit according to pre-set regional predilection. The predilection for older female patients with a positive radiotracer uptake in the subcutaneous abdominal fat should be determined in further studies involving larger case numbers.

Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

Disclosures

The authors have no conflicts of interest to disclose.

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