Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL): A Novel Biomarker for Prognostic Assessment and Risk Stratification of Acute Pulmonary Embolism

Background: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with poor prognosis in cardiovascular diseases. However, the predictive value of TRAIL for the short-term outcome and risk stratification of acute pulmonary embolism (PE) remains unknown. Methods: This study prospectively included 151 normotensive patients with acute PE. The study outcome was a composite of 30-day adverse events, defined as PE-related death, shock, mechanical ventilation, cardiopulmonary resuscitation, and major bleeding. Results: Overall, nine of 151 (6.0%) patients experienced 30-day adverse composite events. Multivariable logistic regression showed that TRAIL was an independent predictor of study outcome (OR 0.19 per SD; 95% CI 0.04-0.90). An ROC curve revealed that TRAIL's area under the curve (AUC) was 0.83 (95% CI 0.76-0.88). The optimal cut-off value for TRAIL was 18 pg/mL, with a sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, and negative likelihood ratio of 89%, 69%, 99%, 15%, 2.87, and 0.16, respectively. Compared with the risk stratification algorithm outlined in the 2019 ESC guidelines, our biomarker-based risk stratification strategy (combining TRAIL and hs-cTnI) has a similar risk classification effect. Conclusion: Reduced plasma TRAIL levels predict short-term adverse events in normotensive patients with acute PE. The combination of the 2019 ESC algorithm and TRAIL aids risk stratification in normotensive patients with acute PE.