It is quite uncommon that while reading the results of a clinical trial one feels the universal gasp of sorrow released from the hearts and minds of Emergency Physicians worldwide. Maybe it was my own personal anguish at the realization of the disastrous consequences the results of a recent trial published in the NEJM will have on the practice of Emergency Medicine, but I am almost certain it was a unique moment of shared consciousness. In fact, with the release of the Pulmonary Embolism in Syncope Italian Trial (PESIT) examining the prevalence of pulmonary embolism in patients admitted to the hospital with syncope, the global wince of practicing Emergency Physicians was almost palpable (1).
Prandoni et al examined 560 patients presenting to 11 hospitals in Italy admitted 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 via the Well’s 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 of the 560 patients prospectively enrolled, 97 (17.3%) were found to have a pulmonary embolism. Now these results, if true, are practice changing. In fact, the NEJM’s twitter quote read “1 in 6 patients with syncope (+) for PE after ER presentation”. 1 in 6 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 were just unfortunate incidental bystanders. Previous data has consistently demonstrated the majority of patients admitted to the hospital for syncope do not undergo evaluation for pulmonary embolism and do well. In these cohorts, patients were not subjected to universal screenings for pulmonary embolism, and experienced minimal adverse events (2,3). The few that experienced adverse events were typically not due to pulmonary emboli. Does this mean we are missing pulmonary embolism in 17% of the patients we admit to the hospital for syncope? Likely, no. The PESIT results are in a large part likely due to over-diagnosis. I think even the authors of this manuscript realize this potential source of bias, as the entire supplemental appendix which supports this manuscript 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, in the accuracy defining study, PIOPED-2, in low risk patients who underwent CT-imaging for pulmonary embolism, almost half of the positive CTPAs were deemed to be false positive findings (4).
But over-diagnosis 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 patients presenting to the Emergency Department. Unfortunately, it is impossible to discern from the published manuscript, but it seems the patients who presented with syncope due to a true physiologically relevant pulmonary embolism are clinically distinguishable from those without an embolic etiology. The patients in the PESIT trial with pulmonary embolisms found on radiographic imaging had significantly more episodes of tachycardia, tachypnea, hypotension, obvious signs of lower extremity DVT, and more often presented with cancer than the patients with a negative workup for pulmonary embolism.
Furthermore, it is important to note, this is not a cohort of 97 pulmonary embolisms in 560 patients as it will inevitably be portrayed. Rather this was 97 (3.8%) radiographic pulmonary embolisms in 2584 patients presenting to the Emergency Medicine for a syncopal event. Only the patients admitted to the hospital after an Emergency Department workup for syncope were enrolled into the PESIT cohort. The majority of patients presenting to the Emergency Department were discharged home without further workup. This means 1 in 26 patients presenting to the Emergency Department will have a pulmonary embolism found on imaging. The large majority of these will be incidental findings and the remainder will be clinically obvious.
There are times when our clinical experience is misleading. When empiric evidence should call into question our long standing practice patterns. But there are times when the evidence is in such conflict with our shared experience, there is nothing to be done but to questions 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 embolisms. 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 who 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 Emergency Department after a syncopal event require a work-up for pulmonary embolism is not only statistical hoodwinkery, but is just 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 over-diagnosis and unnecessary treatments in its wake. At some point someone has to stop this madness. I offer that time is here and now.
- Prandoni, Paolo et al. Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope. New England Journal of Medicine,375,16;1524-1531 2016
- Quinn J, Mcdermott D, Stiell I, Kohn M, Wells G. Prospective validation of the San Francisco Syncope Rule to predict patients with serious outcomes. Ann Emerg Med. 2006;47(5):448-54.
- Birnbaum A, Esses D, Bijur P, Wollowitz A, Gallagher EJ. Failure to validate the San Francisco Syncope Rule in an independent emergency department population. Ann Emerg Med. 2008;52(2):151-9.
- Stein PD, Fowler SE, Goodman LR, et al. Multidetector computed tomography for acute pulmonary embolism. N Engl J Med. 2006;354(22):2317-27.