The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology recently issued updated guidelines for diagnosis and management of acute pulmonary embolism (PE), the first update since 2008. “New data has extended or modified our knowledge in respect of optimal diagnosis, assessment and treatment of patients with PE,” according to the guidelines, which were published in the European Heart Journal.
The authors recommended use of D-dimer testing in the diagnostic work-up of PE, but cautioned that results must be considered in the context of patients’ clinical presentation. “The negative predictive value of D-dimer testing is high and a normal D-dimer level renders acute PE or [deep vein thrombosis] unlikely. On the other hand, fibrin is also produced in a wide variety of conditions such as cancer, inflammation, bleeding, trauma, surgery and necrosis.” Because of this, “positive predictive value of elevated D-dimer levels is low and D-dimer testing is not useful for confirmation of PE,” they explained.
Additionally, quantitative enzyme-linked immunosorbent assay (ELISA) or ELISA-derived D-dimer assays have a diagnostic sensitivity of 95% or better, the guidelines state, and “can therefore be used to exclude PE in patients with either a low or a moderate pre-test probability.” Also, a negative ELISA D-dimer, along with clinical probability, can be used in emergency departments to exclude PE without more testing in 30% of patients who are suspected to have it.
Whole-blood agglutination assays and quantitative latex-derived assays have diagnostic sensitivity of less than 95% and “thus are often referred to as moderately sensitive,” according to the new guidelines. “In outcome studies, those assays proved safe in ruling out PE in PE-unlikely patients, as well as in patients with a low clinical probability.” However, the safety of these tests in ruling out PE as a diagnosis has not yet been established in the category of intermediate clinical probability, the authors explained. “Point-of-care tests have moderate sensitivity, and data from outcomes studies in PE are lacking, with the exception of a recent primary care-based study using the Simplify D-dimer assay, in which the three month thromboembolic risk was 1.5% in PE-unlikely patients with a negative D-dimer,” they wrote.
Because the specificity of D-dimer in suspected PE cases drops with age, recent research suggests it’s best to use age-adjusted cutoffs to improve performance of this test in elderly patients. D-dimer also is more frequently higher in patients who have cancer, as well as in hospitalized patients and in pregnant women. “Thus, the number of patients in whom D-dimer must be measured to exclude one PE (number needed to test) varies between 3 in the emergency department” and ≥10 for hospitalized and pregnant patients, and those with cancer. “The negative predictive value of a (negative) D-dimer test remains high in these situations,” the authors stated.
The guidelines also review cardiac-related laboratory tests and biomarkers. “In normotensive patients with PE, the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low,” the authors wrote.
Delving deeper into cardiac markers, “elevated troponin concentrations were associated with high mortality both in unselected patients . . . and in haemodynamically stable patients,” the authors explained. “The results were consistent for troponin I or –T; however other reports have suggested a limited prognostic value of elevated troponins in normotensive patients.” Also, heart-type fatty acid-binding protein, which is an early indicator of myocardial injury, was found to have prognostic value for acute PE.
Looking at kidney-related biomarkers, the guidelines discuss elevated serum creatinine and decreased (calculated) glomerular filtration rates, which they found to be tied to 30-day all-cause mortality for acute PE.
Read the guidelines online.