Association between different biomarkers and mortality in moderate or asymptomatic severe aortic stenosis: a systematic review

Abstract

Background: Moderate and asymptomatic severe aortic stenosis (AS) are diseases with heterogeneous prognosis, making clinical decision-making complex. Traditional strategies that rely solely on symptomatology may miss the optimal window for intervention. Circulating biomarkers have the potential to enhance risk stratification and help to guide the timing of aortic valve replacement (AVR). Objective: To assess the association between biomarkers and mortality in patients diagnosed with moderate AS (both symptomatic and asymptomatic) or asymptomatic severe AS, through a systematic review. Methods: MEDLINE (via Pubmed), Web of Science, and Scopus were searched from inception up to January 27, 2025. Cohort studies evaluating BNP, NT-proBNP, Troponin, galectin-3, or ST2 prior to AVR, and reporting mortality outcomes were eligible. Two independent reviewers performed screening, data extraction and quality assessment. Given the heterogeneity in exposure and outcome definitions, a narrative synthesis was performed. Results: A total of ten studies met the inclusion criteria. Five studies were focused on BNP, and other five on NT-proBNP. No other biomarker was evaluated in this setting. Despite some heterogeneity in biomarkers cut-points, most of the studies have shown a positive association between high levels of BNP and NT-proBNP and all-cause or cardiovascular mortality. Conclusions: These findings support the use of BNP and NT-proBNP in patients with moderate or asymptomatic severe AS patients, according to the positive association with mortality. While they may potentially help to guide earlier AVR decisions, standardized thresholds and prospective validation are needed, along with further research on the prognostic role of additional biomarkers in this population.