Diagnostic accuracy of alternative biomarkers for acute aortic syndrome: a systematic review

Background: D-dimer is the only biomarker currently recommended in guidelines for the diagnosis of acute aortic syndrome (AAS). We undertook a systematic review to determine whether any alternative biomarkers could be useful in AAS diagnosis.

Methods: We searched electronic databases (including MEDLINE, EMBASE and the Cochrane Library) from inception to February 2024. Diagnostic studies were eligible if they examined biomarkers other than D-dimer for diagnosing AAS compared with a reference standard test in people presenting to the ED with symptoms of AAS. Case-control studies were identified but excluded due to high risk of bias. Selection of studies, data extraction and risk of bias assessments using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool were undertaken independently by at least two reviewers. We used narrative synthesis to summarise the findings.

Results: We identified 2017 citations, included 13 cohort studies (n=76–999), and excluded 38 case-control studies. Methodological quality was variable, with most included studies having unclear or high risk of bias and applicability concerns in at least one item of the QUADAS‐2 tool. Only two studies reported biomarkers with sensitivity and specificity comparable to D-dimer (ie, >90% and >50%, respectively). Wang et al reported 99.1% sensitivity and 84.9% specificity for soluble ST2; however, these findings conflicted with estimates of 58% sensitivity and 70.8% specificity reported in another study. Chun and Siu reported 95.6% sensitivity and 56.1% specificity for neutrophil count, but this has not been confirmed elsewhere.

Conclusion: There are many potential alternative biomarkers for AAS but few have been evaluated in more than one study, study designs are often weak and reported biomarker accuracy is modest or inconsistent between studies. Alternative biomarkers to D-dimer are not ready for routine clinical use.

PROSPERO registration number: CRD42022252121.