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Prandoni P, et al. "Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope". The New England Journal of Medicine. 2016. 375(16):1524-31.
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Clinical Question

In patients admitted for first episode of syncope, what is the prevalence of pulmonary embolism?

Bottom Line

In patients admitted for first episode of syncope, 17% were found to have pulmonary embolism after a standardized, guideline-based inpatient evaluation. Pulmonary embolism was identified in 12.7% of patients with an alternative etiology for syncope and 25.4% of patients who did not. Pulmonary embolism was identified in 25% of patients without typical signs or symptoms.

Major Points

Syncope, or a transient loss of consciousness with rapid onset, short duration, and spontaneous resolution due to transient cerebral hypoperfusion is a common cause for admission to the hospital. Although pulmonary embolism (PE) is commonly invoked as a potential cause of syncope, its actual prevalence among patients admitted to the hospital for syncope is unknown. Furthermore, it is unclear whether patients presenting with syncope due to PE can present without the classic signs and symptoms of PE such as hypoxia and tachycardia. A rigorous study designed to characterize the incidence of PE among patients presenting with syncope was needed in order to determine the appropriate index of suspicion for PE in these patients.

The 2016 Pulmonary Embolism in Syncope Italian Trial (PESIT) was an uncontrolled trial enrolling consecutive patients admitted to the hospital with syncope and subjecting them to a protocolized workup for PE regardless of clinical suspicion for the purposes of better defining the prevalence of PE in this population. Patients with low pretest probability for PE and negative d-dimer assay were determined to be PE negative, while patients with either high pretest probability or positive d-dimer assay underwent CTA chest or VQ scan to determine the presence of PE. Of 560 patients included in the study, 97 patients were ultimately diagnosed with PE (17.3% prevalence). In patients with syncope of undetermined origin, prevalence of PE was 25.4%. In patients with a potential alternative explanation of syncope, prevalence of PE was 12.7%. Although the prevalence of PE signs and symptoms (tachycardia, tachypnea, hypotension, signs and symptoms of DVT) were higher in the patients diagnosed with PE, 24 of the 97 patients with PE (24.7%) had no clinical signs or symptoms. The majority of PEs diagnosed were in a clinically significant location (93.1% segmental or greater on CTA).

Although limited in its generalizability (81% of initially eligible patients excluded, primarily due to discharge from the ED), the results of PESIT suggest that prevalence of PE is substantial (1 in 6) among patients admitted to the hospital for a first episode of syncope. Importantly, in this group the lack of signs or symptoms suggestive of PE or an alternative explanation for syncope seem insufficient to rule out the diagnosis of PE on clinical grounds as the prevalence of PE remained significant in both of these groups (25% prevalence of PE in patients without signs or symptoms and 13% prevalence of PE in patients with an alternative explanation for syncope). Further study, ideally with a randomized-controlled trial, will be required to establish whether routine diagnostic workup for PE in these patients results in improved outcomes and cost effectiveness.


No guidelines have been published reflecting the results of this study.


  • Multicenter, non-randomized, uncontrolled trial
  • N=560
  • Setting: 11 hospitals in Italy
  • Period: March 2012 - October 2014
  • Analysis: Cross-sectional
  • Primary outcome: Pulmonary embolism


Inclusion Criteria

  • Age 18 or greater
  • Presentation with first lifetime syncope
  • Admission to the medical ward

Exclusion Criteria

  • Epileptic seizure
  • Stroke
  • Head trauma
  • On anticoagulation therapy for another indication
  • Pregnant

Baseline Characteristics

  • Demographics: Age 76 years, male 40%
  • Co-morbidities: Obese 6%,
  • Suspected syncope: Neural 27%, orthostatic 20%, cardiac 17%, unknown 37%
  • Clinical features: Prodrome 41%, tachypnea 14%, tachycardia 19%, SBP < 110 25%, clinical signs or symptoms of DVT 11%
  • Thrombotic risk: Immobile 7%, trauma/surgery 5%, cancer 12%, infectious disease 9%


  • Patients subjected to protocolized workup for syncope
    • A medical history was obtained including the presence of prodromal symptoms, presence of known cardiac disease, recent bleeding, causes of volume depletion or venous pooling, recent exposure to new or stronger hypotensive drugs or drugs causing bradycardia or tachycardia, symptoms or risk factors for venous thromboembolism
    • Patients were evaluated for presence of arrhythmias, tachycardia, valvular heart disease, hypotension, autonomic dysfunction, tachypnea, and leg swelling/redness
    • All patients underwent chest radiography, arterial blood gas analysis, and routine blood testing including d-dimer assay
    • Further diagnostic workup included carotid sinus massage, tilt testing, echocardiography, and 24-hour electrocardiography if applicable
  • Syncope was defined as a transient loss of consciousness with rapid onset, short duration, and spontaneous resolution with no other clear etiology
  • Reason for admission included trauma related to fall, severe coexisting conditions, failure to identify cause of syncope, high probability of cardiac syncope
  • Presence or absence of pulmonary embolism was determined by the use of a validated algorithm based on pretest probability and d-dimer results
    • Pretest probability of PE was determined using the modified Wells score (>4 = "likely" and ≤4 = "unlikely")
    • In patients with "unlikely" pretest probability and negative d-dimer assay, diagnosis of PE was not made
    • Patients with "likely" pretest probability and/or positive d-dimer assay underwent CTA chest or VQ scan to assess for PE. A positive scan was defined as an intraluminal filling defect (CTA) or a segment with at least 75% perfusion defect with normal ventilation (VQ)
  • All study assessments were completed within 48 hours of admission
  • In patients with PE, thrombotic burden was assessed by a central adjudication committee through identification of the most proximal location of the embolus on CT or measurement of the severity of the perfusion defect on VQ scan


'Comparisons when present are PE present vs. PE absent'

Primary Outcome

Pulmonary Embolism
97/560 (17.3%) [95% CI 14.2-20.5]

Secondary Outcomes

33.0% vs. 16.2%
36.1% vs. 22.9%
Clinical signs or symptoms of DVT
40.2% vs. 4.5%
Previous thromboembolic disease
11.3% vs. 4.3%
Active cancer
19.6% vs. 9.9%
Thrombotic Burden
Main PA: 30 (41.7%)
Lobar: 18 (25.0%)
Segmental: 19 (26.4%)
Subsegmental: 5 (6.9%)

Subgroup Analysis

Explanation for Syncope

Undetermined: 25.4% [95% CI 19.4-31.3]
Alternative Etiology: 12.7% [95% CI 9.2-16.1]


  • Only 560 out of 2584 eligible patients were included in the study (1867 excluded due to discharge from the ED), allowing for selection bias and limiting generalizability to patients who are not admitted, treated in the outpatient setting, or have a known history of syncope.
  • Only 50% of patients diagnosed with PE using VQ scan had a perfusion defect larger than 25% of total lung area and only 67% of patients diagnosed with PE using CTA had main PA or lobar artery pulmonary embolism, making it possible that PE was incidentally diagnosed (i.e., not actually the cause of syncope) in a sizable group of patients.


  • Study supported by research funding from the University of Padua

Further Reading