“Prevalence of pulmonary embolism among patients hospitalized for syncope,” NEJM, 2016, Italy
Question: What is the prevalence of pulmonary embolism in patients hospitalized for a first episode of syncope?
Study Type: Multicenter cross-sectional study at 11 hospitals in Italy
Study Population: Patients admitted for syncope were eligible. Exclusion criteria included pregnancy, previous episodes of syncope, and use of anticoagulation.
Study Groups: Enrolled patients had a simplified dichotomized Wells score calculated and a D-dimer drawn. Patients with a Wells score ≤4 and a negative D-dimer were considered to have PE excluded. Patients with a Wells score >4, a positive D-dimer, or both underwent further evaluation for PE with either a PE-CT or V/Q scan
Primary Outcome: Presence of a pulmonary embolism on either PE-CT or V/Q scan.
Results: Of 2,584 patients who visited the ED for syncope, 717 were admitted, and 560 (22% of all patients) were included in the study. The median age of the cohort was 80. 330 patients (60%) had a PE excluded by a low-risk Wells score and a negative D-dimer. PE was identified in 97 of the remaining 230 patients (17% of the study cohort). Of patients diagnosed with a PE, 45% had a RR>20, 33% had a HR >100, 40% had clinical signs of DVT, and 20% had active cancer. 17 patients with a PE (18%) had a small thrombus burden identified by either a subsegmental PE on CT-PE or a perfusion defect of 1-25% on V/Q scan.
Caveats: No information on outcomes of patients discharged from the ED, normal diagnostic testing for PE risk stratification (troponin, BNP, echo) not included, age-adjusted D-dimer not used, no outcomes information for patients diagnosed with a PE, concern regarding generalizability (the study cohort was elderly and the prevalence of PE in Europe is different than in the United States).
Take-home Point: A diagnosis of pulmonary embolism should be considered in patients admitted to the hospital with a first episode of syncope.
Commentary: There is concern that this article will be used to justify indiscriminate testing for PE in patients with syncope (one educational blog review of this article is entitled “The Impending Pulmonary Embolism Apocalypse”). My thoughts on what this trial should and should not do:
- This trial should remind clinicians of the important Christopher study (JAMA 2006) which showed that a clinical decision score (a dichotomized Wells score) combined with D-dimer testing can exclude PE and avoid unnecessary CT scans with a low miss rate (<0.5%) in a large number of patients. Interns and residents not familiar with this article should give it a read.
- This trial should also remind clinicians that pulmonary embolism is a potential cause of syncope and that especially in older patients with concerning signs/symptoms, a diagnostic evaluation for VTE should be considered. Of patients diagnosed with PE in this trial, 45% were tachypneic, 33% were tachycardic, 40% had signs of DVT, and 40% had a high risk Wells score on presentation all in a cohort in which 20% had active cancer. Considering the diagnosis of VTE in this group seems like a reasonable thing to do. It is notable that 25% of patients who were diagnosed with a PE did not have clinical manifestations of VTE.
- The prevalence of 17% found in this study should not be generalized to practice in theUS. Multiple studies have found the prevalence of PE in Europe to be consistently higher than in the United States (around 25-30% for Europe vs. <10% in the US). The patients in this trial were also elderly and likely a higher risk cohort than other syncope populations. The striking difference between the prevalence of 17% found in this trial and the very low prevalence found in the studies they cite (<3%) likely in part reflect their rigorous testing and unique patient cohort.
- Identification should not be conflated with causation. 18% of patients had a small thrombus burden identified on either CT or V/Q scanning. It is not clear from the trial if these small clots were the cause of syncope or if identifying and treating them impacts patient outcomes.