Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Annals of Nuclear Medicine
Published in: Annals of Nuclear Medicine 4/2024

22-01-2024 | Scintigraphy | Original Article

Performance of 99mTc-PYP scintigraphy in the diagnosis of hereditary transthyretin cardiac amyloidosis

Authors: Honghui Guo, Sha Wu, Xin Xiang, Shuai Wang, Zhihui Fang, Qianchun Ye, Yao Zou, Yunhua Wang, Daoquan Peng, Xiaowei Ma

Published in: Annals of Nuclear Medicine | Issue 4/2024

Login to get access

Abstract

Objective

Most reported research has primarily investigated wild-type transthyretin cardiac amyloidosis (ATTRwt-CA). However, the application of bone scintigraphy for hereditary transthyretin cardiac amyloidosis (ATTRv-CA) has not been systematically investigated. Therefore, in this study, we aimed to evaluate the diagnostic value of 99mTc-PYP scintigraphy in ATTRv-CA.

Methods

Fifty-four patients were enrolled in a highly suspected cardiac amyloidosis cohort. Transthyretin (TTR) gene characteristics were summarized in the ATTRv-CA group. In 99mTc-PYP scintigraphy, the diagnostic efficiency of the visual score (VGS) and heart-to-contralateral chest (H/CL) ratio were evaluated. Furthermore, the interobserver consistency among the diagnosticians was investigated.

Results

Twenty-eight patients were diagnosed with ATTRv-CA with eight genotypes. The Ala97Ser genotype accounts for 46% (n = 13) with a mean age of disease onset, definite diagnosis, and interval of 61.6 ± 1.9, 66.5 ± 1.3, and 4.0 (3.0, 6.2) years, respectively. Their VGS is Grade 3, and their H/CL ratio is higher than that of the non-Ala97Ser group, but no statistical significance exists (mean H/CL: 1.95 ± 0.06 vs. 1.87 ± 0.02, p = 0.844). Additionally, ATTRv-CA patients showed VGS ≥ 2, and mean H/CL ratio of 2.09 ± 0.06. The sensitivity and specificity of VGS were 100% and 65%, respectively. And the interobserver consistency analysis of VGS showed the intraclass correlation coefficient is 0.522. The best cutoff value of H/CL ratio was 1.51 (AUC = 0.996), and the diagnostic consistency of H/CL (bias: 0.018) was high.

Conclusions

Ala97Ser is the most common genotype in ATTRv-CA in our cohort, with characteristics of later onset and rapid progression, but delayed diagnosis and extensive 99mTc-PYP uptake. Overall, ATTRv-CA patients showed moderate-to-extensive myocardial 99mTc-PYP uptake. Additionally, VGS carries subjectivity, low specialty and interobserver consistency. But H/CL exhibit high diagnostic efficacy and interobserver consistency. The H/CL ratio is more useful than VGS.
Appendix
Available only for authorised users
Literature
1.
Alexander KM, Masri A. Recipe for success in transthyretin cardiomyopathy: monoclonal protein rule out, SPECT imaging, and genetic testing. JACC Cardiovasc Imaging. 2021;14:1232–4.CrossRefPubMed
2.
Castaño A, Narotsky DL, Hamid N, Khalique OK, Morgenstern R, DeLuca A, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017;38:2879–87.CrossRefPubMedPubMedCentral
3.
4.
Benson MD, Buxbaum JN, Eisenberg DS, Merlini G, Saraiva MJM, Sekijima Y, et al. Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2020;27:217–22.CrossRefPubMed
5.
Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86:1036–43.CrossRefPubMed
6.
Haq M, Pawar S, Berk JL, Miller EJ, Ruberg FL. Can 99mTc-pyrophosphate aid in early detection of cardiac involvement in asymptomatic variant TTR amyloidosis? JACC Cardiovasc Imaging. 2017;10:713–4.CrossRefPubMed
7.
Hsueh H-W, Chao C-C, Chang K, Jeng Y-M, Katsuno M, Koike H, et al. Unique phenotypes with corresponding pathology in late-onset hereditary transthyretin amyloidosis of A97S vs. V30M. Front Aging Neurosci. 2021;13:786322.CrossRefPubMed
8.
Poterucha TJ, Elias P, Bokhari S, Einstein AJ, DeLuca A, Kinkhabwala M, et al. Diagnosing transthyretin cardiac amyloidosis by technetium Tc 99m pyrophosphate: a test in evolution. JACC Cardiovasc Imaging. 2021;14:1221–31.CrossRefPubMed
9.
Merlo M, Porcari A, Pagura L, Cameli M, Vergaro G, Musumeci B, et al. A national survey on prevalence of possible echocardiographic red flags of amyloid cardiomyopathy in consecutive patients undergoing routine echocardiography: study design and patients characterization - the first insight from the AC-TIVE Study. Eur J Prev Cardiol. 2022;29:e173–7.CrossRefPubMed
10.
Merlo M, Pagura L, Porcari A, Cameli M, Vergaro G, Musumeci B, et al. Unmasking the prevalence of amyloid cardiomyopathy in the real world: results from phase 2 of AC-TIVE study, an Italian Nationwide survey. Eur J Heart Fail. 2022;24(8):1377–86.CrossRefPubMed
11.
Ayers MP, Peruri AV, Bourque JM. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. J Nucl Cardiol. 2021;28:1846–50.CrossRefPubMed
12.
Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circulation. 2016;133:2404–12.CrossRefPubMed
13.
Garcia-Pavia P, Rapezzi C, Adler Y, Arad M, Basso C, Brucato A, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42:1554–68.CrossRefPubMedPubMedCentral
14.
Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, 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. Circ Cardiovasc Imaging. 2021;14: e000029.PubMed
15.
16.
Carroll A, Dyck PJ, de Carvalho M, Kennerson M, Reilly MM, Kiernan MC, et al. Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis. J Neurol Neurosurg Psychiatry. 2022;93:668–78.CrossRefPubMed
17.
Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 2 of 2-diagnostic criteria and appropriate utilization. Circ Cardiovasc Imaging. 2021;14: e000030.PubMed
18.
Bokhari S, Morgenstern R, Weinberg R, Kinkhabwala M, Panagiotou D, Castano A, et al. Standardization of 99mTechnetium pyrophosphate imaging methodology to diagnose TTR cardiac amyloidosis. J Nucl Cardiol. 2018;25:181–90.CrossRefPubMed
19.
Sperry BW, Bateman TM, Akin EA, Bravo PE, Chen W, Dilsizian V, et al. Hot Spot Imaging in Cardiovascular Diseases: An Information Statement from SNMMI, ASNC, and EANM. J Nucl Med. 2022;jnumed.122.264311.CrossRefPubMed
20.
Sperry BW, Burgett E, Bybee KA, McGhie AI, O’Keefe JH, Saeed IM, et al. Technetium pyrophosphate nuclear scintigraphy for cardiac amyloidosis: Imaging at 1 vs 3 hours and planar vs SPECT/CT. J Nucl Cardiol. 2020;27:1802–7.CrossRefPubMed
21.
Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6:195–201.CrossRefPubMedPubMedCentral
22.
Law S, Bezard M, Petrie A, Chacko L, Cohen OC, Ravichandran S, et al. Characteristics and natural history of early-stage cardiac transthyretin amyloidosis. Eur Heart J. 2022;43:2622–32.CrossRefPubMedPubMedCentral
23.
Rowczenio DM, Noor I, Gillmore JD, Lachmann HJ, Whelan C, Hawkins PN, et al. Online registry for mutations in hereditary amyloidosis including nomenclature recommendations. Hum Mutat. 2014;35:E2403–12.CrossRefPubMed
24.
Russo M, Obici L, Bartolomei I, Cappelli F, Luigetti M, Fenu S, et al. ATTRv amyloidosis Italian registry: clinical and epidemiological data. Amyloid. 2020;27:259–65.CrossRefPubMed
25.
Rapezzi C, Longhi S, Milandri A, Lorenzini M, Gagliardi C, Gallelli I, et al. Cardiac involvement in hereditary-transthyretin related amyloidosis. Amyloid. 2012;19(Suppl 1):16–21.CrossRefPubMed
26.
Musumeci MB, Cappelli F, Russo D, Tini G, Canepa M, Milandri A, et al. Low sensitivity of bone scintigraphy in detecting Phe64Leu mutation-related transthyretin cardiac amyloidosis. JACC Cardiovasc Imaging. 2020;13:1314–21.CrossRefPubMed
27.
Chou CT, Lee CC, Chang DM, Buxbaum JN, Jacobson DR. Familial amyloidosis in one Chinese family: clinical, immunological, and molecular genetic analysis. J Intern Med. 1997;241:327–31.CrossRefPubMed
28.
Chou CT, Lee CC, Chang DM, Buxbaum JN, Jacobson DR. Transthyretin Ala97Ser is associated with familial amyloidotic polyneuropathy in a Chinese-Taiwanese family. J Intern Med. 1997;241:327–31.CrossRefPubMed
29.
Yu A-L, Chen Y-C, Tsai C-H, Chao C-C, Su M-Y, Juang JJ-M, et al. Tafamidis treatment decreases 99mTc-pyrophosphate uptake in patients with hereditary Ala97Ser transthyretin amyloid cardiomyopathy. JACC Cardiovasc Imaging. 2023;16:866–7.
30.
Ungerer MN, Hund E, Purrucker JC, Huber L, Kimmich C, Aus dem Siepen F, et al. Real-world outcomes in non-endemic hereditary transthyretin amyloidosis with polyneuropathy: a 20-year German single-referral centre experience. Amyloid. 2021;28:91–9.
31.
Ayers MP, Peruri AV, Bourque JM. Transforming ATTR cardiac amyloidosis into a chronic disease: The enormous potential of quantitative SPECT to improve diagnosis, prognosis, and monitoring of disease progression. J Nucl Cardiol. 2021;28:1846–50.CrossRefPubMed
32.
Masri A, Bukhari S, Ahmad S, Nieves R, Eisele YS, Follansbee W, et al. Efficient 1-hour technetium-99 m pyrophosphate imaging protocol for the diagnosis of transthyretin cardiac amyloidosis. Circ Cardiovasc Imaging. 2020;13: e010249.CrossRefPubMedPubMedCentral
33.
Sperry BW, Vranian MN, Tower-Rader A, Hachamovitch R, Hanna M, Brunken R, et al. Regional variation in technetium pyrophosphate uptake in transthyretin cardiac amyloidosis and impact on mortality. JACC Cardiovasc Imaging. 2018;11:234–42.CrossRefPubMed
34.
Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1:880–9.CrossRefPubMed
Metadata
Title
Performance of 99mTc-PYP scintigraphy in the diagnosis of hereditary transthyretin cardiac amyloidosis
Authors
Honghui Guo
Sha Wu
Xin Xiang
Shuai Wang
Zhihui Fang
Qianchun Ye
Yao Zou
Yunhua Wang
Daoquan Peng
Xiaowei Ma
Publication date
22-01-2024
Publisher
Springer Nature Singapore
Published in
Annals of Nuclear Medicine / Issue 4/2024
Print ISSN: 0914-7187
Electronic ISSN: 1864-6433
DOI
https://doi.org/10.1007/s12149-023-01898-x

Other articles of this Issue 4/2024

Annals of Nuclear Medicine 4/2024 Go to the issue

Original Article

Simultaneous evaluation of brain metastasis and thoracic cancer using semiconductor 11C-methionine PET/CT imaging

Original Article

Development and application of a fully automatic multi-function cassette module Mortenon M1 for radiopharmaceutical synthesis

Correction

Correction: Radiation dosimetry and pharmacokinetics of the tau PET tracer florzolotau (18F) in healthy Japanese subjects

Original Article

Left ventricular mechanical dyssynchrony after chemotherapy in breast cancer patients with normal rest gated SPECT-MPI

Original Article

Visual and whole-body quantitative analyses of 68 Ga-DOTATATE PET/CT for prognosis of outcome after PRRT with 177Lu-DOTATATE

Original Article

A first-in-man study of [18F] FEDAC: a novel PET tracer for the 18-kDa translocator protein