Syncope as a predictor of high-risk phenotype in acute pulmonary embolism: insights from objective clinical markers and a modified sPESI score

Background Early risk stratification is crucial for managing acute pulmonary embolism (APE). Syncope, although not a typical symptom of APE, is associated with high-risk APE patients. However, its role in early risk stratification and the objective markers defining high-risk syncope patients remain inadequately defined. Purpose To identify objective clinical predictors of syncope in APE and evaluate the impact of syncope on early risk stratification and clinical prognosis. Methods A retrospective study was conducted on 261 APE patients in our center between 2015 and 2022. The diagnosis of pulmonary embolism was based on the 2019 ESC Guidelines for PE. Patients were divided into the syncope (n=46, 17.6%) and non-syncope groups based on the presence of syncope within 14 days after the APE onset, defined as a sudden and transient loss of consciousness characterized by rapid onset, brief duration, and complete spontaneous recovery. Exclusion criteria included recurrent pulmonary embolism, chronic thromboembolic pulmonary disease, and the presence of moderate or severe valvular disease or cardiomyopathy. Multivariate logistic regression and restricted cubic splines (RCS) identified independent predictors and threshold effects for syncope. A "Modified sPESI score" was developed by incorporating syncope into the standard sPESI framework. The primary composite outcome was defined as all-cause death, fatal PE, or major bleeding. Results The syncope group showed a higher central clot burden (91.4% vs. 49.5%, P<0.001) and significantly elevated cardiac markers, including cTnI (0.17 vs. 0.03 ng/mL, P<0.001) and NT-proBNP (2105.95 vs. 567.40 ng/L, P<0.001).Multivariate analysis identified precordial T-wave inversion (TWI) as the strongest independent predictor of syncope (aOR 6.83; 95% CI: 2.35-19.88, P<0.001), remaining significant even after adjusting for RV dysfunction, cTnI and NT-proBNP. RCS analysis demonstrated linear risk increases for syncope when D-dimer >4000 ng/mL(Figure 1A) and RVD/LVD ratio ≥0.7 (Figure 1B). Importantly, the Modified sPESI score demonstrated superior prognostic accuracy for the primary composite outcome compared to the standard sPESI (AUC: 0.768 vs. 0.734; 95% CI: 0.646–0.891, P=0.004). Although syncope patients received more aggressive anticoagulation and thrombolysis, they exhibited a trend toward higher PE-specific mortality (6.52% vs. 1.40%) (Figure 1C). Conclusion Syncope identifies a high-risk PE phenotype characterized by central embolism and RV strain. Precordial TWI, D-dimer >4000 ng/mL, and RVD/LVD ≥0.7 are critical objective indicators. Integrating syncope into the sPESI score significantly improves the prediction of the clinical outcomes, enhancing early risk stratification in clinical practice.