Original ArticleAmyloid deposit corresponds to technetium-99m-pyrophosphate accumulation in abdominal fat of patients with transthyretin cardiac amyloidosis
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.
References (22)
- et al.
ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2-evidence base and standardized methods of imaging
J Nucl Cardiol
(2019) - et al.
State-of-the-art radionuclide imaging in cardiac transthyretin amyloidosis
J Nucl Cardiol
(2019) - et al.
Non-cardiac uptake of technetium-99m pyrophosphate in transthyretin cardiac amyloidosis
J Nucl Cardiol
(2019) - et al.
Extracardiac accumulation of technetium-99m-pyrophosphate in transthyretin cardiac amyloidosis
JACC Case Rep
(2021) - et al.
AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: Part III: Intraventricular conduction disturbances: A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: Endorsed by the International Society for Computerized Electrocardiology
J Am Coll Cardiol
(2009) - et al.
Amyloid cardiomyopathy: Characterization by a distinctive voltage/mass relation
Am J Cardiol
(1982) - et al.
Recommendations for the evaluation of left ventricular diastolic function by echocardiography: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging
J Am Soc Echocardiogr
(2016) - et al.
Definitions for a common standard for 2D speckle tracking echocardiography: Consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging
J Am Soc Echocardiogr
(2015) - et al.
Tc-99m-PYP imaging for cardiac amyloidosis: Defining the best protocol before the flood gates burst
J Nucl Cardiol
(2020) - et al.
National patterns in imaging utilization for diagnosis of cardiac amyloidosis: A focus on Tc99m-pyrophosphate scintigraphy
J Nucl Cardiol
(2017)
Nonbiopsy diagnosis of cardiac transthyretin amyloidosis
Circulation
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