Clinical Characteristics and Early Outcomes of Acute Pulmonary Embolism Presenting with Syncope

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Background: The prognostic significance of syncope in patients with acute pulmonary embolism (PE) remains uncertain. We assessed its association with early outcomes and explored whether distinct clinical phenotypes could be identified within this group. Methods: We analyzed a prospectively collected single-center cohort of patients with confirmed symptomatic PE diagnosed between 2010 and 2025, grouped by syncope at presentation. The primary outcome was a 30-day composite of all-cause mortality, major bleeding, and recurrent venous thromboembolism. Associations were estimated using inverse probability of exposure weighting. Estimand A balanced baseline confounders, whereas Estimand B additionally balanced measured markers of acute severity. Within the syncope subgroup, exploratory clustering used 13 baseline clinical variables. Results: Among 2,331 patients with PE, 329 (14.1%) presented with syncope. Under Estimand A, syncope was associated with a 14.0-percentage-point higher risk of the composite outcome (95% confidence interval [CI]: 9.0-19.6; risk ratio [RR]: 2.71, 95% CI: 2.02-3.52). Under Estimand B, the association was substantially attenuated, with a risk difference of 5.2 percentage points (95% CI: - 0.2 to 10.6; RR: 1.54, 95% CI: 0.98-2.19). A similar attenuation was observed for all-cause mortality and major bleeding. Exploratory clustering identified four phenotypes, none of which met the prespecified criteria for internal stability. Conclusion: In acute PE, syncope identifies patients at higher risk of early adverse outcomes. This association was substantially attenuated after accounting for measured acute severity, suggesting that syncope mainly marks a more severe initial presentation rather than carrying prognostic information independent of severity.

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