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Nearly One in Six Patients Hospitalized for First-Time Syncope Have Pulmonary Embolism

December 30, 2021

The prevalence of pulmonary embolism (PE) among hospitalized patients with syncope is not well understood, and international guidelines – such as the European Society of Cardiology and the American Heart Association – do not recommend a diagnostic workup for PE in this patient population. According to a cross-sectional study led by Paolo Prandoni, MD, PhD, of the Department of Cardiovascular Sciences in the Vascular Medicine Unit at the University of Padua in Italy, and researchers, which was published in the New England Journal of Medicine, the prevalence of PE in patients hospitalized for first-time syncope was 17.3 percent (95% CI 14.2-20.5), or approximately one in six patients.

"A diagnostic workup for PE should be strongly encouraged in all patients admitted with a first episode of syncope (provided they are not anticoagulated), including those in whom there is an apparent explanation for the episode of syncope," Dr. Prandoni told ASH Clinical News. "As PE is a serious and potentially lethal complication that can be treated effectively and safely with the available antithrombotic drugs, its prompt detection is crucial."

The study included adult patients who were hospitalized for a first episode of syncope (defined as a transient loss of consciousness with rapid onset, short duration [i.e., <1 minute], and spontaneous resolution, after obvious causes such as epileptic seizure, stroke, and head trauma have been ruled out).

All patients who were admitted to a medical ward after visiting the emergency department at one of 11 participating general hospitals in Italy (2 academic and 9 non-academic) were eligible for inclusion, provided they did not have a previous episode of syncope, were not receiving anticoagulation therapy, and were not pregnant. Patients visited the hospital for the following reasons:

  • trauma related to falls
  • severe coexisting conditions
  • failure to identify an explanation for the syncope
  • high probability of cardiac syncope on the basis of the Evaluation of Guidelines in Syncope Study score

Between March 2012 and October 2014, 2,584 patients were admitted to the emergency department for syncope. The final patient cohort was 560, with a median age of 80 years (range = 72-85 years). All patients underwent an assessment within 48 hours of being admitted to the hospital, regardless of alternate explanations for syncope. Assessment included a medical history, including the presence of prodromal symptoms of autonomic activation, presence of known cardiac disease, recent bleeding, causes of volume depletion or venous pooling, and recent exposure to new or stronger hypotensive drugs or drugs that could cause bradycardia or tachycardia. Patient were interviewed about symptoms (pain and swelling) in the legs and presence of risk factors for venous thromboembolism (VTE), ongoing hormonal treatment, prolonged immobilization of ≥1 week, active cancer, and history of VTE. Patients were evaluated for the presence of arrhythmias, tachycardia (i.e., heart rate >100 beats/min), valvular heart disease, hypotension (i.e., systolic blood pressure <110 mm Hg), autonomic dysfunction, tachypnea (i.e., respiratory rate >20 breaths/min), and swelling or redness of the legs.

Patients also underwent chest radiography, electrocardiography, arterial blood gas testing, and routine blood testing that included a D-dimer assay.

Patients considered at low risk for PE based on a low pretest clinical probability score and a negative D-dimer assay received no further diagnostic screening, and PE was not assumed. The remaining patients received a CT pulmonary angiography or ventilation–perfusion lung scan.

Clinical evidence suggested that PE was not the reason for syncope in 63.4 percent of patients (n=355/560), and PE diagnosis was ruled out due to low pretest probability scores and a negative D-dimer assay in 58.9 percent of patients (n=330/560).

Among the 230 remaining patients, 58.7 percent (n=135) had a positive D-dimer assay, 1.3 percent (n=3) had a high pretest probability, and 40 percent (n=92) had both.

A total of 229 patients underwent further diagnostic screening with CT (n=180) or ventilation–perfusion lung scans (n=49).

Ninety-six of these patients were diagnosed with PE: 72 patients underwent CT scans and 24 underwent ventilation–perfusion lung scan. PE was identified as the cause of death in one patient (confirmed by autopsy).

"The unexpectedly high prevalence of PE among our patients with syncope contrasts with that reported elsewhere," Dr. Prandoni and authors wrote. "Among patients who were hospitalized for a first episode of syncope and who were not receiving anticoagulation therapy, PE was confirmed in 17.3 percent [of the entire cohort], or approximately one in every six patients." Prevalence of PE among screened patients was 42.2 percent (95% CI 35.8-48.6).

"Although the prevalence of PE was highest among patients who presented with syncope of undetermined origin (25.4% of patients), almost 13 percent of patients diagnosed with PE had potential alternative explanations for syncope," the authors wrote.

Dr. Prandoni and authors also observed that patients with PE had a higher prevalence of the following conditions, compared with those without PE: tachypnea (45.4% vs. 7.1%), tachycardia (33% vs. 16.2%), hypotension (36.1% vs. 22.9%), clinical signs or symptoms of deep-vein thrombosis (40.2% vs. 4.5%), previous VTE (11.3% vs. 4.3%), and active cancer (19.6% vs. 9.9%). In addition, 24.7 percent of patients with PE (n=24/97) had no clinical manifestation of the diagnosis.

"Whenever PE cannot be excluded, therapeutic doses of either low-molecular-weight heparin or fondaparinux should be promptly given while awaiting the results of objective instrumental tests unless they are contraindicated," Dr. Prandoni advised. "This approach is potentially life-saving."

Limitations of the study include its restriction to only include patients in the hospital setting. In addition, diagnostic imaging for PE was only performed in patients who had an elevated D-dimer or high pretest clinical probability of PE. The study also did not require a specific workup for syncope diagnosis, so diagnostic variations may have influenced the findings.


Prandoni P, Lensing AWA, Prins MH, et al. Prevalence of pulmonary embolism among patients hospitalized for syncope. N Engl J Med. 2016;375:1524-31.


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