Our study used a systematic workup for pulmonary embolism in a large series of patients who were hospitalized for a first episode of syncope and showed a high prevalence of pulmonary embolism among these patients; pulmonary embolism was confirmed in approximately one of every six patients (17.3%). Although the prevalence of pulmonary embolism was highest among patients who presented with syncope of undetermined origin (25% of patients), almost 13% of patients with potential alternative explanations for syncope had pulmonary embolism. Not surprisingly, patients with dyspnea, tachycardia, hypotension, or clinical signs or symptoms of deep-vein thrombosis were more likely to have pulmonary embolism, as were those with active cancer. However, the proportion of patients who did not have these features yet had an objective confirmation of pulmonary embolism was not negligible.

The unexpectedly high prevalence of pulmonary embolism among our patients with syncope contrasts with that reported elsewhere.12-17 It should be noted, however, that in the few contemporary studies that involved patients presenting with syncope, diagnostic testing for pulmonary embolism was performed only in selected subgroups, which may have resulted in a potential underestimation of the prevalence of this vascular disorder. In contrast, our study involved consecutive patients, all of whom underwent a guidelines-based workup for pulmonary embolism,5 regardless of whether another explanation was suggested clinically. Our study also involved multiple centers, and the results across the centers were consistent, with the prevalence of pulmonary embolism ranging from 15 to 20% across centers.

Some methodologic issues in our study require comment. First, patients were included in the study if they were admitted to a medical ward after being examined in the emergency department for syncope, which was defined as full loss of consciousness for less than 1 minute, followed by spontaneous, complete resolution. As a consequence, this study did not include patients who were cared for on an ambulatory basis or patients who visited the emergency department but for whom hospitalization was not considered necessary. Second, syncope is a diagnostic challenge, because the diagnosis is based largely on the history of the patient, which could be supported by observations of bystanders who are usually not medically trained. In addition, there is often uncertainty about the causal relationship between an identified disorder (such as a self-terminating arrhythmia) and the episode of syncope. Third, all participating hospitals used a standardized protocol for the diagnostic workup of syncope that was based on international guidelines,1,2 but a specific workup was not mandated by the study protocol. In addition, the study protocol specified that a diagnosis of pulmonary embolism should not affect the usual workup for syncope. Fourth, diagnostic imaging for pulmonary embolism was performed only in patients who had an elevated d-dimer level or a high pretest clinical probability of pulmonary embolism. Nevertheless, well-conducted clinical studies have shown conclusively that pulmonary embolism is highly unlikely in patients who have a low pretest clinical probability and a negative d-dimer assay.7,8,18-22 Fifth, the study protocol did not mandate objective confirmation of deep-vein thrombosis in symptomatic patients; thus, we are not aware of the rate of this complication among patients who reported pain or swelling in their legs. However, none of the patients who were included in the study spontaneously reported these symptoms or visited the emergency department because of these symptoms. Sixth, the search for other causes of syncope was left to the discretion of the attending physicians. Hence, other causes of syncope may have been underreported. This may have been partly responsible for the fact that a definite cause of the syncope could not be determined in 205 patients. Seventh, pulmonary embolism is unlikely in patients who have had multiple episodes of syncope and in patients who are receiving anticoagulation therapy; therefore, these patients were excluded from our study, and accordingly, our study results are not applicable to such patients. Finally, we did not collect information on treatment decisions and patient follow-up after completion of the diagnostic algorithm for pulmonary embolism because this was not a study objective.

Syncope is generally expected to occur in patients with pulmonary embolism if they have a sudden obstruction of the most proximal pulmonary arteries that leads to a transient depression in cardiac output.23-25 In 49 of the 73 patients (67.1%) in our cohort who had pulmonary embolism that was diagnosed according to findings from computed tomography or autopsy, the most proximal location of the embolus was a main pulmonary artery or a lobar artery. Similarly, among the 24 patients who were assessed with ventilation–perfusion scanning, the perfusion defect was larger than 25% of the total lung area in 12 patients (50.0%). These findings suggest that, in at least half of the patients with pulmonary embolism in our study, the extent of thrombosis was large enough to produce an abrupt obstruction of the blood flow that would be likely to result in a sudden loss of consciousness.

However, in approximately 40% of the patients, the extent of pulmonary vascular obstruction was smaller. Because there was no standard approach to the evaluation of syncope, a number of patients with small pulmonary emboli may have had syncope that was associated with another condition that was missed. However, other mechanisms may be involved in the occurrence of syncope once a pulmonary embolism has developed, such as vasodepressor or cardioinhibitory mechanisms.26-28 In addition, when a clot dislodges from the venous system and lodges in the pulmonary circulation, it may induce arrhythmias when it passes through the heart. Hence, even smaller clots could be a potential cause of syncope. Studies addressing the mechanisms that trigger syncope in patients who have limited obstruction of the pulmonary arteries are warranted.

In conclusion, among patients who were hospitalized for a first episode of syncope and who were not receiving anticoagulation therapy, pulmonary embolism was confirmed in 17.3% (approximately one of every six patients). The rate of pulmonary embolism was highest among those who did not have an alternative explanation for syncope.