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

Takahashi, Koji; Sasaki, Daisuke; Yamashita, Mina; Sakaue, Tomoki; Enomoto, Daijiro; Morioka, Hiroshi; Uemura, Shigeki; Okura, Takafumi; Ikeda, Shuntaro; Kono, Taizo; Hiratsuka, Yoshiyasu; Saijo, Akira; Yamamura, Nobuhisa; Kitazawa, Sohei; Yamashita, Taro; Ueda, Mitsuharu

doi:10.1007/s12350-021-02890-6

Cited by 14 publications

(24 citation statements)

References 21 publications

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“…Rokke et al observed that patients with merely neuropathic symptoms display higher sensitivity for the diagnosis of hereditary ATTR based on abdominal fat pad biopsies compared to patients with pure cardiomyopathy (CM). 35,36 Interestingly, in our analysis of wtATTR patients with additional quantitative SPECT/CT SUVpeak of the subcutaneous fat showed only a trend to be significantly increased in patients with PNP. It may be noticeable that these results appear somewhat worse than for the entire group with hATTR patients combined.…”

Section: Discussionmentioning

confidence: 69%

Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

Wollenweber

Kretschmer-Chott

Wurm

et al. 2023

Journal of Nuclear Cardiology

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Background With the introduction of several drugs for the therapy of transthyretin-related amyloidosis (ATTR) which slow down the disease, early detection of polyneuropathy (PNP) is becoming increasingly of interest. [99mTc]-3,3-Diphosphono-1,2-Propanodicarboxylic Acid (DPD) bone scintigraphy, which is used for the diagnosis of cardiac (c)ATTR, can possibly make an important contribution in the identification of patients at risk for PNP. Methods Fifty patients with cATTR, who underwent both planar whole-body DPD scintigraphy and nerve conduction studies (NCS) were retrospectively evaluated. A subgroup of 22 patients also underwent quantitative SPECT/CT of the thorax from which Standardized Uptake Values (SUVpeak) in the subcutaneous fat tissue of the left axillar region were evaluated. Results The Perugini score was significantly increased in patients with cATTR and additional diagnosis of PNP compared to patients without (2.51 ± 0.51 vs 2.13 ± 0.52; P = 0.03). Quantitative SPECT/CT revealed that DPD uptake in the subcutaneous fat of the left axillar region was significantly increased in cATTR patients with compared to patients without (1.36 ± 0.60 vs 0.74 ± 0.52; P = 0.04). Conclusion This study suggests that DPD bone scintigraphy is a useful tool for identification of patients with cATTR and a risk for PNP due to increased DPD soft tissue uptake.

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Section: Discussionmentioning

confidence: 69%

Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

Wollenweber

Kretschmer-Chott

Wurm

et al. 2023

Journal of Nuclear Cardiology

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“…Two reports from Japan 19,20 revealed that female patients with ATTRwt amyloidosis were older and had a higher yield of ATTR deposition, confirmed using specimens from abdominal fat, than male patients. We previously reported that patients who showed some 99m Tc-PYP uptake in subcutaneous abdominal fat were usually older female patients 13 . Stats and Stone 21 reported that the density of microcalcifications, considered to be binding sites of bone-avid radiotracers, in endomyocardial biopsy specimens was not related to patient age.…”

Section: Discussionmentioning

confidence: 98%

“…Thirty-six consecutive patients with ATTR-CA, diagnosed at Yawatahama City General Hospital between June 2020 and May 2022, were included in the study. All patients underwent a comprehensive evaluation, including electrocardiography, echocardiography, and biochemical tests, such as the analysis of cardiac biomarkers (high-sensitivity cardiac troponin I and brain natriuretic peptide levels), serum and urine immunofixation electrophoresis, and serum-free light chain assay, as part of routine clinical care, as reported previously 13 . 99m Tc-pyrophosphate scintigraphy was performed if ATTR amyloidosis was suspected based on symptoms and the aforementioned findings.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, biopsies to definitively diagnose ATTR amyloidosis and genetic testing using TTR gene sequencing were performed as needed. Biopsy specimen evaluation was performed using Congo red staining and immunohistochemical analysis as reported previously 13,14 …”

Section: Methodsmentioning

confidence: 99%

“…Definition of ATTRwt-CA, ATTR-CA, and Suspected ATTR-CA Transthyretin CA was defined as the positive myocardial uptake of tracer detected using 99m Tc-PYP scintigraphy with or without an ATTR-positive biopsy in the absence of plasma cell dyscrasia or with an ATTR-positive biopsy in the presence of plasma cell dyscrasia. 5,13 Suspected ATTR-CA was defined as positive myocardial uptake of the tracer detected using PYP scintigraphy without an ATTR-positive biopsy in the presence of plasma cell dyscrasia. Wild-type transthyretin CA was defined as ATTR-CA with a normal TTR genetic sequence.…”

Section: Ethical Approvalmentioning

confidence: 99%

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99mTc-Pyrophosphate Scintigraphy Can Image Tracer Uptake in Skeletal Trunk Muscles of Transthyretin Cardiac Amyloidosis

Takahashi

Hiratsuka²,

Sasaki³

et al. 2022

Clin Nucl Med

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Purpose: 99m Tc-pyrophosphate ( 99m Tc-PYP) uptake in the skeletal muscles is minimal in patients with transthyretin cardiac amyloidosis (ATTR-CA) when assessed qualitatively and quantitatively. We previously demonstrated moderate-to high-grade 99m Tc-PYP uptake in the subcutaneous abdominal fat of some patients with ATTR-CA and showed that this abnormal finding could reflect the regional amyloid burden of this tissue. We aimed to investigate the frequency of 99m Tc-PYP uptake in skeletal trunk muscles of patients with ATTR-CA. Methods: Chest-and abdomen-centered 99m Tc-PYP scintigraphy images were obtained 2 hours after IV injections of the tracer (20 mCi) in 36 patients with ATTR-CA. The frequency of 99m Tc-PYP uptake in the following 11 skeletal trunk muscles was investigated: pectoralis major, deltoid, subscapularis, infraspinatus, trapezius, latissimus dorsi, erector spinae, psoas major, abdominal oblique, rectus abdominis, and the gluteus muscles. Results: Ten of the 11 muscles were involved in patients with the highest number of 99m Tc-PYP uptake in the skeletal trunk muscles examined, whereas no muscle was involved in a patient with the least uptake. The muscle with the highest rate of 99m Tc-PYP uptake, observed in 34 of 36 patients (94.4%), was the abdominal oblique. No tracer uptake was observed in the psoas major. The frequency of radiotracer uptake in the remaining examined muscles was between those of abdominal oblique and psoas major muscles. Conclusions: Radiotracer uptake was often detectable in some skeletal trunk muscles of ATTR-CA, although the muscles of patients examined and the skeletal trunk muscles of 1 patient showed heterogeneity in the uptake of 99m Tc-PYP.

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[99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients

Tingen,

Groothof,

Tubben

et al. 2024

Eur J Nucl Med Mol Imaging

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Purpose Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality. Methods This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied. Results ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality. Conclusion Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

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

Cited by 14 publications

References 21 publications

Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

Does [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) soft tissue uptake allow the identification of patients with the diagnosis of cardiac transthyretin-related (ATTR) amyloidosis with higher risk for polyneuropathy?

99mTc-Pyrophosphate Scintigraphy Can Image Tracer Uptake in Skeletal Trunk Muscles of Transthyretin Cardiac Amyloidosis

[99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients

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