Should patients with first syncopal episodes be evaluated for PE?

- Kenny Lin, MD, MPH

The evaluation of patients with syncope has changed minimally over the years, with considerable continuity between recommendations in American Family Physician reviews published in 2005, 2011, and most recently, in the March 1, 2017 issue. But the field received an unexpected jolt last October, when Dr. Paolo Prandoni and colleagues published a cross-sectional study in the New England Journal of Medicine that calculated a surprisingly high prevalence of pulmonary embolism (PE) of 17.3% in patients hospitalized for a first episode of syncope. In this study, 230 of 560 patients at 11 Italian hospitals who did not have a low pretest probability of PE by the Wells rule and negative D-dimer assay underwent computed tomographic pulmonary angiography (CTPA) or ventilation-perfusion lung scans. 97 of these patients had evidence of PE. Overall, the investigators identified PE in 25% of patients with no alternative explanation for syncope and 13% of patients with an alternative explanation.

Standard algorithms for syncope evaluation focus on identifying cardiac and neurally mediated causes and do not include routine testing for PE. The question raised by the Italian study is if all inpatients with syncope warrant an evaluation, since nearly 1 in 6 patients may have PE. There are good reasons to think twice about doing so. First, we don't know if the prevalence of PE in this study was representative of the general population of adults hospitalized for syncope, as it only included patients admitted from emergency departments (and not patients initially evaluated in primary care settings). Second, the study did not determine if PE was the etiology of syncope, as opposed to an incidental finding. This is important because evidence suggests that the enhanced sensitivity of CTPA for detecting small, subsegmental PE is increasing overdiagnosis and overtreatment of clinically insignificant clots. Finally, the absence of a comparison group means that it is not known if the systematic workup for PE affected the patients' prognosis, if at all.

A retrospective cross-sectional study in JAMA Internal Medicine recently addressed the generalizability question by using clinical and administrative data from 4 hospitals in Toronto to estimate the prevalence of PE in 1305 patients with a first episode of syncope who were not receiving anticoagulation at the time of admission. 120 of these patients received CTPA, ventilation-perfusion scan, and/or compression ultrasonography, resulting in the diagnosis of PE in 18 patients. As opposed to the Italian study, where all persons received at least a D-dimer test, the decision to evaluate for PE was driven by clinical judgment. Nonetheless, of 146 patients in the Toronto study who received any test for PE (presumably those with the highest pretest probability), only 12% were positive, and the overall prevalence of PE was a mere 1.4%. The authors concluded that "there is little, if any, justification for routine testing for [venous thromboembolism] in all patients hospitalized for a first episode of syncope."

Based on both studies, I agree that evidence does not support routine testing in patients with syncope. In those with signs or symptoms of PE, another clinical decision rule may be used to confidently rule out the diagnosis without resorting to the less sensitive Wells rule or less specific D-dimer test, where a positive result often leads to unnecessary CTPA.