Yield of bone scintigraphy screening for transthyretin‐related cardiac amyloidosis in different conditions: Methodological issues and clinical implications

Abstract Background Transthyretin‐related cardiac amyloidosis (TTR‐CA) is thought to be particularly common in specific at‐risk conditions, including aortic stenosis (AS), heart failure with preserved ejection fraction (HFpEF), carpal tunnel syndrome (CTS) and left ventricular hypertrophy or hypertrophic cardiomyopathy (LVH/HCM). Methods We performed a systematic revision of the literature, including only prospective studies performing TTR‐CA screening with bone scintigraphy in the above‐mentioned conditions. Assessment of other forms of CA was also evaluated. For selected items, pooled estimates of proportions or means were obtained using a meta‐analytic approach. Results Nine studies (3 AS, 2 HFpEF, 2 CTS and 2 LVH/HCM) accounting for 1375 screened patients were included. One hundred fifty‐six (11.3%) TTR‐CA patients were identified (11.4% in AS, 14.8% in HFpEF, 2.6% in CTS and 12.9% in LVH/HCM). Exclusion of other forms of CA and use of genetic testing was overall puzzled. Age at TTR‐CA recognition was significantly older than that of the overall screened population in AS (86 vs. 83 years, p = .04), LVH/HCM (75 vs. 63, p < .01) and CTS (82 vs. 71), but not in HFpEF (83 vs. 79, p = .35). In terms of comorbidities, hypertension, diabetes and atrial fibrillation were highly prevalent in TTR‐CA‐diagnosed patients, as well as in those with an implanted pacemaker. Conclusions Screening with bone scintigraphy found an 11–15% TTR‐CA prevalence in patients with AS, HFpEF and LVH/HCM. AS and HFpEF patients were typically older than 80 years at TTR‐CA diagnosis and frequently accompanied by comorbidities. Several studies showed limitations in the application of recommended TTR‐CA diagnostic algorithm, which should be addressed in future prospective studies.


Introduction
Objectives 4 Provide an explicit statement of the objective(s) or question(s) the review addresses. Introduction

METHODS
Eligibility criteria 5 Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses.

Methods, Supplementary materials
Information sources 6 Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted.

Methods
Search strategy 7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.

Methods, Supplementary materials
Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

Supplementary materials
Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

Methods
Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

Methods
10b List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.

Methods
Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

Methods
Effect measures 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results. NA

Synthesis methods
13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

Supplementary materials
13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data Methods

Item # Checklist item
Location where item is reported conversions.
13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. Methods 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

Methods
13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression). NA 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. NA

Reporting bias assessment
14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). Methods

Certainty assessment
15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. NA

Study selection
16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.

Supplementary materials
16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. For more information, visit: http://www.prisma-statement.org/