Diagnostic Test Accuracy of Bone Scintigraphy in the Diagnosis of Attr Amyloidosis: A Systematic Review and Meta-Analysis
Authors: Azzam Muayad , Kawtharany Hassan , Nazzal Jamil , Kukreti Vishal , Seftel Matthew D. , Alkhader Aseel , Hamarsha Qais , Khraise Tala , AlMasri Mohammad Mahmoud , Abou Zeid Hadi Khaled , Alwan Iktimal , Jaber Noor , Fraitekh Mohammad , Dasgupta Noel , Comenzo Raymond , Jamal Faizi , Aguirre Maria Adela , Boedicker Deborah , Bumma Naresh , Carroll Antonia , Cook Joselle , De La Torre Alfredo H. , Dispenzieri Angela , Khouri Jack , Leung Nelson , Picken Maria M. , Raza Shahzad , Sanchorawala Vaishali , Shaikh Hira , Sarswat Nitasha , Singh Daulath , Mustafa Reem A 
Published: December 2024

Introduction:
For cardiac transthyretin (ATTR) amyloidosis, bone scintigraphy has emerged as a noninvasive diagnostic tool. The use of different tracers, namely Pyrophosphate (PYP), 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD), HydroxymethyleneDiphosphonate (HMDP), allow for the detection of amyloid deposits in the heart. The aim of this systematic review is to evaluate the diagnostic test accuracy of bone scintigraphy in ATTR and light chain (AL) amyloidosis.
Methods:
As part of the ASH AL Amyloidosis Diagnostic Guideline, we performed systematic reviews for 7 prioritized PICO questions related to the screening, diagnosis and organ involvement evaluation of AL amyloidosis. Electronic searches were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception till January 2024. Two reviewers independently and in duplicate performed title and abstract screening and full text article screening on LASER AI, with conflicts resolved by a third reviewer.
Studies were eligible if they included patients that performed both a bone scintigraphy scan and an endomyocardial biopsy for suspicion of ATTR amyloidosis. Test positivity for the visual score was defined to be ≥2, for the heart over contralateral (H/CL) ratio it was &gt; 1.5 at one hour and &gt;1.3 at 3 hours. Diagnostic test accuracy measures of interest were sensitivity, specificity, positive and negative predictive value. Statistical analysis was performed on STATA 18.0. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence.
Results:
After deduplication, we retrieved 29,237 studies from electronic databases. 12 studies with 1127 patients reported on visual score in patients suspected to have ATTR amyloidosis. The pooled sensitivity for visual score was 96% (95% CI 92.0-98.0) while specificity was 90% (95% CI 84.0-95.0) (Certainty of evidence (COE): Moderate ⨁⨁⨁◯). 3 studies reported on ATTR visual score in combination with evaluating for monoclonal gammopathy, the pooled sensitivity was decreased to 93% (95% CI 65-99) and while specificity increased to 99% (95% CI 80-100) (COE: Moderate ⨁⨁⨁◯). H/CL was evaluated in 5 studies with 189 patients; pooled sensitivity was 97% (95% CI 89.0-99.0) and specificity was 88% (95% CI 64-97) (COE: Low ⨁⨁◯◯).
We also performed subgroup analyses for the diagnostic test accuracy of visual score for the different tracers (PYP, DPD, HMDP) in patients suspected to have ATTR amyloidosis. DPD was found to have the highest sensitivity which was found to be 97% (95% CI 91.0-99.0) and a specificity of 95 (95% CI 86.0-98.0) (4 studies, n = 297 COE: Moderate ⨁⨁⨁◯). The sensitivity and specificity for PYP was 95% (95% CI 87.0-98.0) and 90% (95% CI 79.0-96.0) (7 studies, n = 377 COE: Moderate ⨁⨁⨁◯). 1 study reported on HMDP with a sensitivity and specificity of 79% (95% CI 49.0-95.0) and 100% (95% CI 59.0-100.0) (COE: Low ⨁⨁◯◯).
Conclusion:
Bone scintigraphy has a high sensitivity and specificity for the diagnosis of ATTR amyloidosis, particularly in patients without a monoclonal gammopathy.