Galectin-3 Is Independently Associated With Short-Term Mortality and Identifies Low-Risk Patients With Acute Dyspnea in the Emergency Department: A Retrospective Cohort Study.

Background: Dyspnea is a common and diagnostically challenging symptom in the emergency department (ED), particularly among older adults with multimorbidity. Traditional risk stratification tools often perform poorly in this population. Galectin-3 (Gal-3), a biomarker of inflammation and fibrosis, may reflect biological aging and resilience, potentially improving early mortality risk assessment. Objectives: To evaluate the independent association between Gal-3 and 30-day mortality in patients presenting with acute dyspnea; to assess its utility for identifying patients at low risk of short-term mortality; and to determine its incremental value in improving prediction of 30-day mortality when added to clinical risk models. Design: Retrospective observational study based on the Acute Dyspnea Study (ADYS). Methods: The study included 763 adult ED patients with acute dyspnea. Gal-3 was measured as NPX (Normalized Protein Expression) values using the Olink proximity extension assay, and NT-proBNP was measured using standard laboratory methods. The primary outcome was 30-day all-cause mortality. Multivariable logistic regression and Cox regression analyses were performed, with internal validation by bootstrap resampling. Predictive performance was evaluated using ROC curves, AUC, and the Youden index, and incremental value was assessed by AUC comparison and net reclassification improvement (NRI). Results: Among the 763 patients, 49 (6.4%) died within 30 days. Gal-3 NPX was independently associated with 30-day mortality (OR 1.97; 95% CI: 1.16-3.36; p = 0.013). Although Gal-3 NPX alone demonstrated moderate discrimination (AUC 0.69), relatively low Gal-3 NPX levels within the cohort effectively ruled out short-term mortality, with a negative predictive value of 96%. Adding Gal-3 NPX to the clinical model modestly improved predictive performance (AUC increased from 0.803 to 0.819; NRI 0.028), primarily by enhancing identification of low-risk patients. Conclusion: Gal-3 NPX was independently associated with 30-day mortality in patients with acute dyspnea. Although its addition yielded only a modest, non-significant improvement in overall risk prediction, Gal-3 may be useful for ruling out short-term mortality, supporting its potential role as a negative prognostic marker in the ED setting.