The Impending Pulmonary Embolism Apocalypse

After many years of intense effort, our work in recognizing overdiagnosis and over-treatment of pulmonary embolism has been paying off. With the PERC, with adherence to evidence-based guidelines, and with a responsible approach to resource utilization, it is reasonable to suggest we’re making headway into over-investigating this diagnosis.

Prepare for all that hard work to be obliterated.

This is a prospective study of patients admitted to the hospital for syncope, evaluating each in a systematic fashion for the diagnosis of PE. Consecutive admissions with first-time syncope, who were not currently anticoagulated, underwent risk-stratification using Wells score, D-dimer testing if indicated, and ultimately either CT pulmonary angiograms or V/Q scanning. The top-line result, the big scary number you’re likely seeing circulating the medical and lay news: “among 560 patients hospitalized for a first-time fainting episode, one in six had a pulmonary embolism.”

Prepare for perpetual arguments with the admitting hospitalist for the next several eternities: “Could you go ahead an get a CTPA? You know, 17% of patients with syncope have PE.”

I’d like to tell you they’re wrong, and this study is somehow flawed, and you’ll be able to easily refute their assertions. Unfortunately, yes, they are wrong, and this study is flawed – but it won’t make it any easier to prevent the inevitable downstream overuse of CT.

The primary issue here is the almost certain inappropriate generalization of these results to dissimilar clinical settings. During the study period, there were 2,584 patients presenting to the Emergency Department with a final diagnosis of syncope. Of these, 1,867 were deemed to have an obvious or non-serious alternative cause of syncope and were discharged home. Thus, less than a third of ED visits for syncope were admitted, and the admission cohort is quite old – with a median age for admitted patients of 80 (IQR 72-85). There is incomplete descriptive data given regarding their comorbidities, but the authors state admission criteria included “severe coexisting conditions” and “a high probability of cardiac syncope on the basis of the Evaluation of Guidelines in Syncope Study score.” In short, their admission cohort is almost certainly older and more chronically ill than many practice settings.

Then, there are some befuddling features presented that would serve to inflate their overall prevalence estimate. A full 40.2% of those diagnosed with pulmonary embolism had “Clinical signs of deep-vein thrombosis” in their lower extremities, while 45.4% were tachypneic and 33.0% were tachycardic. These clinical features raise important questions regarding the adequacy of the Emergency Department evaluation; if many of these patients with syncope had symptoms suggestive of PE, why wasn’t the diagnosis made in ED? If even only the patients with clinical signs of DVT were evaluated prior to admission, those imaging studies would have had a yield for PE of 65%, and the prevalence number seen in this study would drop from 17.3% to 10.3%. Further evaluation of either patients with tachypnea or tachycardia might have been similarly high-yield, and further reduced the prevalence of PE in admitted patients.

Lastly, any discussion regarding a prevalence study requires mention of the gold-standard for diagnosis. CTPA confirmed the diagnosis of PE in 72 patients in this study. Of these, 24 involved a segmental or sub-segmental pulmonary artery – vessels in which false-positive results typically represent between one-quarter to one-half. Then, V/Q scanning was used to confirm the diagnosis of PE in 24 patients. Of these, the perfusion defect represented between 1% and 25% of the area of both lungs in 12 patients. I am not familiar with the rate of false-positives in the context of small perfusion defects on V/Q, but, undoubtedly a handful of these would be as well.  Add this to the inadequate ED evaluation of these patients, and suddenly we’re looking at only a handful of true-positive occult PE in this elderly, chronically ill cohort with syncope.

My view of this study is that its purported take-home point regarding the prevalence of PE in syncope is grossly misleading, yet this “one in six” statistic is almost guaranteed to go viral among those on the other side of the admission fence.  This study should not change practice – but I fear it almost certainly will.

“Prevalence of Pulmonary Embolism among Patients Hospitalized for Syncope”

http://www.nejm.org/doi/full/10.1056/NEJMoa1602172

9 thoughts on “The Impending Pulmonary Embolism Apocalypse”

  1. Agree with you here. Also I will make the assumption that the US has a different threshold to admit patients to the hospital compared to Italy. This will certainly be incorrectly generalized to the US population and probably all patients who present with syncope. Wonder what the cost will be with all of these additional CT scans….

  2. I think it’s interesting how many of these patients presenting with syncope had only relatively small PE’s on imaging—I can’t think of a reason why a segmental or subsegmental PE should cause a significant loss in cardiac output. Either my understanding of how PEs cause syncope is very flawed, or (as you suggest) these abnromal scans are more incidental or artifactual than than truly positive.

    1. The physiology is complicated; it’s not just fractional obstruction of the pulmonary tree, but a spiraling cascade of vasoconstrictive mediators and right ventricular afterload. Could these have been larger, proximal PEs that underwent lysis and lodged in the distal circulation? Or, perhaps, many of them are false-positives (or even chronic PE), completely unrelated to the index presentation. You’d hope something like the NEJM would do more to contextualize these data, considering their potential worldwide impact on practice.

  3. Do you mind providing a source for this statement “24 involved a segmental or sub-segmental pulmonary artery – vessels in which false-positive results typically represent between one-quarter to one-half”? I do not doubt that there are high false positive rates with these tiny peripheral PEs, but I can’t seem to find a study demonstrating these specific numbers.

    1. Hutchinson BD, Navin P, Marom EM, et al. Overdiagnosis of pulmonary embolism by pulmonary CT angiography. AJR Am J Roentgenol. 2015;205:271-277.

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