Molecular biomarkers predicting newly detected atrial fibrillation after ischaemic stroke or TIA: A systematic review

Abstract

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance. Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included. Results: Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69–0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68–0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75–0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF. Conclusion: Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays.

Diagnostic Utility of N-Terminal Pro-B-Type Natriuretic Peptide in Identifying Atrial Fibrillation Post-Cryptogenic Stroke: A Systematic Review and Meta-Analysis

“…Our study contributes to the expanding body of evidence suggesting NT-proBNP holds potential as a biomarker for AF following cryptogenic stroke [ 16 , 19 , 30 ]. Offering a straightforward test, NT-proBNP empowers clinicians to evaluate each cryptogenic stroke patient’s likelihood of having underlying AF more precisely [ 21 ].…”

“…This dynamic pattern reduces the effectiveness of NT-proBNP in cryptogenic stroke, where its primary potential lies in the risk stratification of patients with paroxysmal AF. A clinically significant entity is atrial cardiopathy, characterized by an elevated NT-proBNP and an increased stroke risk, often in the absence of AF [ 30 , 39 ]. In our study, these patients may have appeared as false positives, leading to an underestimation of specificity.…”

“…In our study, these patients may have appeared as false positives, leading to an underestimation of specificity. Given that atrial cardiopathy frequently precedes AF, there remains uncertainty regarding the potential benefits of anticoagulation in these patients [ 30 , 39 ].…”

“…To improve the accuracy of NT-proBNP in clinical practice, researchers have explored several other biomarkers and clinical factors that can complement its diagnostic potential [ 30 ]. For instance, Kneihsl et al [ 20 ] demonstrated that while NT-proBNP alone had a sensitivity of 58.3% in detecting AF following cryptogenic stroke, this sensitivity increased to 92% when integrating a risk score combining NT-proBNP with age and various indicators from brain imaging and echocardiography.…”

“…Another limitation is that our study only utilized a single measurement of NT-proBNP rather than tracking changes over time. This is crucial, as the stroke itself may influence NT-proBNP levels due to the release of pro-inflammatory cytokines [ 30 ]. Lastly, our analysis focused on diagnostic accuracy.…”