Risk Stratification in Pulmonary Embolism: The Expanding Role of Biomarkers

Pulmonary embolism (PE) remains a frequent and potentially fatal condition, with early mortality largely driven by (RV) failure and hemodynamic collapse. Rapid and accurate prognostic assessment is therefore central to management. Current European Society of Cardiology (ESC) strategies rely first on hemodynamic status to identify high-risk patients requiring urgent reperfusion consideration, and then-when patients are normotensive-on a stepwise approach combining clinical risk scores, RV imaging, and circulating biomarkers. Clinical tools such as HESTIA and the Pulmonary Embolism Severity Index (PESI)/simplified PESI (sPESI) enable early identification of low-risk patients suitable for outpatient pathways and stratify 30-day mortality risk, but do not integrate biological data. Consequently, biomarkers have an expanding role in refining prognosis, particularly within the heterogeneous intermediate-risk group. This review provides a practical overview of established and emerging biomarkers for PE risk stratification. Conventional cardiac biomarkers-troponins and natriuretic peptides (BNP/NT-proBNP)-reflect RV myocardial injury and strain and, when combined with imaging evidence of RV dysfunction, allow discrimination between intermediate-low- and intermediate-high-risk PE, guiding monitoring intensity and escalation strategies. D-dimer, while essential in diagnostic algorithms because of its high negative predictive value, has only an adjunctive and indirect prognostic role. Beyond these markers, growing evidence supports additional biomarkers capturing complementary pathways: neurohormonal stress (copeptin), early myocardial injury (H-FABP), inflammation and hypoxia (GDF-15), tissue hypoperfusion (lactate), and molecular regulation (circulating microRNAs). Readily available inflammatory indices derived from blood counts (NLR, PLR, LMR), red cell distribution width, and hs-CRP may further contribute within multimarker models, although specificity and validation remain limitations. Future directions include multimodal and omics-driven biomarker profiling integrated with advanced imaging to enable more precise, dynamic, and personalized PE care, from acute risk prediction to long-term follow-up and prevention of chronic thromboembolic complications.