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Myths in Emergency Medicine: Statistical Hoodwinkery and Bad Medicine All Syncope Patients Don't Need a PE Workup

Spiegel, Rory MD

doi: 10.1097/01.EEM.0000511939.89015.2d
Myths in Emergency Medicine

Dr. Spiegelis a clinical instructor in emergency medicine at Stony Brook Medical Center. Visit his blog at, follow him on Twitter @emnerd_, and read his past articles at





It is quite uncommon while reading the results of a clinical trial that one can hear the collective gasp of sorrow from emergency physicians worldwide. Maybe it was my own anguish at realizing the disastrous consequences this particular trial will have on emergency medicine, but I am certain it was a unique moment of shared consciousness — and wincing.

The study in question? The Pulmonary Embolism in Syncope Italian Trial (PESIT) claimed that one in six patients admitted to the hospital following an initial syncopal event will have a pulmonary embolism. (New Engl J Med 2016;375[16]:1524.)

Prandoni, et al., examined 560 patients admitted to 11 Italian hospitals after an initial syncopal episode regardless of the suspected cause of the event. All 560 patients underwent a protocolized assessment for pulmonary embolism, including risk stratification using the Wells score, a D-dimer when appropriate, and either a CTPA or V/Q scan in high-risk patients and those with a positive D-dimer assay.

The authors reported that 97 of the 560 patients (17.3%) prospectively enrolled were found to have a pulmonary embolism. These results, if true, are practice-changing. In fact, the New England Journal of Medicine's tweet about the study read, “1 in 6 patients with syncope (+) for PE after ER presentation.” One in six is an impressive and terrifying figure, but these results are so discordant from what we all observe in day-to-day clinical practice that they fly in the face of our communal experience.

The most obvious concern is whether these pulmonary emboli identified on CT and V/Q scan were responsible for the patients' syncopal events or just unfortunate incidental bystanders. Previous data have consistently demonstrated that the majority of patients admitted to the hospital for syncope do not undergo evaluation for pulmonary embolism and do well. Patients in these cohorts were not subjected to universal screenings for pulmonary embolism, and experienced minimal adverse events. (Ann Emerg Med 2006;47[5]:448 and 2008;52[2]:151.)

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A Result of Overdiagnosis

The few who experienced adverse events were typically not caused by pulmonary emboli. Does this mean we are missing pulmonary embolism in 17 percent of the patients we admit to the hospital for syncope? Likely, no. The PESIT results are likely in large part from overdiagnosis. I think even the authors of this manuscript realize this potential source of bias because the entire supplemental appendix is full of radiographic proof of the cohorts' clot burden, as if such evidence will convince us of the clinical importance of these anatomic findings. But radiographic filling defects do not directly translate into clinical pathology. In fact, almost half of the positive CTPAs were deemed to be false-positive findings in the accuracy-defining study, PIOPED-2, in low-risk patients who underwent CT imaging for pulmonary embolism. (N Engl J Med 2006;354[22]:2317.)

Overdiagnosis aside, let us for a moment suppose these results actually represent clinically important pulmonary emboli. This still does not justify a global diagnostic strategy to identify an embolic cause of syncope in every patient presenting to the ED. Unfortunately, it is impossible to discern from the published manuscript, but it seems the patients who presented with syncope from a true physiologically relevant pulmonary embolism are clinically distinguishable from those without an embolic etiology. The patients in the PESIT trial with pulmonary emboli found on imaging had significantly more episodes of tachycardia, tachypnea, and hypotension; obvious signs of lower extremity DVT; and more often presented with cancer than the patients with a negative workup for pulmonary embolism.

It is also important to note that this is not a cohort of 97 pulmonary emboli in 560 patients, as it will inevitably be portrayed. Rather this was 97 (3.8%) radiographic pulmonary emboli in 2584 patients presenting to the ED for a syncopal event. Only the patients admitted to the hospital after an ED workup for syncope were enrolled into the PESIT cohort. The majority of patients presenting to the ED were discharged home without further workup. This means one in 26 patients presenting to the ED will have a pulmonary embolism found on imaging. The large majority of these will be incidental findings, and the remainder will be clinically obvious.

Our clinical experience can be misleading at times. Sometimes empiric evidence should call into question our long-standing practice patterns, but then there are times when the evidence is in such conflict with our shared experience that nothing is to be done but question its validity. There is no doubt that these results will be misinterpreted over the next few days, weeks, and years.

We will now be tasked with performing invasive diagnostic workups in patients with no clinical signs or symptoms of pulmonary emboli. Any emergency physician will tell you not to order a CTPA on a patient in whom you do not wish to know the results. Likewise, do not order a D-dimer in a patient for whom you have no intention of acquiring further imaging. Prandoni, et al., have perpetrated the systematic equivalent of this diagnostic absurdity.

To translate these results into meaning that all patients presenting to the ED after a syncopal event require a workup for pulmonary embolism is not only statistical hoodwinkery, it is bad medicine. These patients will be exposed to needless and harmful downstream workups, radiation, and anticoagulation. We have chased the ghost of pulmonary embolism far beyond the reaches of good clinical practice. And this quixotic quest has left a path of overdiagnosis and unnecessary treatments in its wake. Someone has to stop this madness at some point, and I offer that the time is here and now.

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