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Diagnostic efficacy of bone scintigraphy in transthyretin cardiac amyloidosis: an updated systematic review and Bayesian bivariate meta-analysis

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Abstract

Purpose

Radionuclide bone scintigraphy is increasingly attracting the attention of clinicians as a tool for the specific diagnosis of transthyretin (ATTR) cardiac amyloidosis. We aimed to describe the diagnostic value of bone scintigraphy in ATTR amyloid cardiomyopathy (ATTR-CA) by performing a meta-analysis of multiple studies.

Methods

We searched all literature included in PubMed and EMBASE until August 10, 2021. A Bayesian bivariate meta-analysis was used for all included studies. Diagnostic performance of bone scan for the diagnosis of ATTR-CA was assessed by calculating pooled sensitivity, specificity, LLR  +  (Log positive likelihood ratio), LLR − (Log negative likelihood ratio), LDOR (Log diagnostic odds ratio), and plotting forest maps. Summary receiver operating characteristic curves (SROC) were fitted based on a Bayesian bivariate hierarchical model to assess the overall diagnostic efficacy of bone scan for the diagnosis of ATTR-CA. A meta-analysis with subgroups based on imaging time, diagnostic criteria, and different radiotracers was performed to compare the differences in diagnostic efficacy.

Results

We included a total of 39 publications with a total of 3636 patients. The pooled sensitivity, specificity, LLR  +, LLR −, and LDOR of bone scan for diagnosing ATTR-CA were 0.97, 0.96, 3.22, − 3.59, and 6.81, respectively; the SROC curve showed excellent diagnostic performance with an area under the curve of 0.99. The semi-quantitative visual score method, quantitative ratio (i.e., H/CL, H/WB, H/M) analysis, and quantitative cardiac SUVmax/peak analysis all had higher pooled sensitivity (0.97 vs. 0.98 vs. 1.00); the pooled specificity of cardiac SUVmax analysis was lower than that of visual scoring and quantitative ratio analysis (0.87 vs. 0.96 vs. 0.96). Regarding imaging time, the pooled sensitivity, specificity, LLR  +, LLR − and LDOR were better for 3-h imaging than 1-h (0.98 vs. 0.97; 0.97 vs. 0.95; 3.49 vs. 3.03; − 3.91 vs. − 3.72; 7.40 vs. 6.75). Among the different bone-seeking tracers, the pooled sensitivities of 99mTc-DPD, 99mTc-PYP, and 99mTc-HMDP were 0.98, 0.95, and 1.00, respectively, and the pooled specificities were 0.94, 0.95, and 0.98, respectively.

Conclusions

Bone scintigraphy has an excellent diagnostic performance in ATTR-CA. An accurate diagnosis of ATTR-CA can be made based on the semi-quantitative visual score, quantitative ratios of planar imaging, and cardiac bone-tracer uptake values of SPECT images.

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Data availability

All analytical data are included in this article. If the original data tables are required, they can be obtained by contacting the corresponding author.

Code availability

When we use the R language, we use the related code of the INLA package and the meta4diag package. Detailed code is available by contacting the corresponding author.

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Funding

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Authors and Affiliations

  1. Department of Nuclear Medicine, Zhongshan Hospital, Fudan University (Xiamen Branch), Xiamen, China

    Dan Ruan

  2. Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Rd., Xiamen, 361003, China

    Long Sun

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  1. Dan Ruan
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  2. Long Sun
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LS provided the ideas for this review, and DR completed the analysis of the data and the writing of the manuscript. The search and inclusion of the literature were done by both authors.

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Correspondence to Long Sun.

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Ruan, D., Sun, L. Diagnostic efficacy of bone scintigraphy in transthyretin cardiac amyloidosis: an updated systematic review and Bayesian bivariate meta-analysis. Clin Transl Imaging 10, 85–98 (2022). https://doi.org/10.1007/s40336-021-00471-8

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