Classic Article:
PIOPED Investigators
The PIOPED Investigators. Value of ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753-2759.
Background
The risk of untreated pulmonary embolism requires either the diagnosis or the exclusion of this diagnosis when clinical suspicion exists. The reference test for pulmonary embolism, standard pulmonary angiography, is invasive and expensive, and carries with it a measurable procedural risk.
Non-invasive diagnostic tests, including ventilation/perfusion (V/Q) scintigraphy, have been used to detect perfusion defects consistent with pulmonary embolism, though the performance characteristics of this diagnostic test were not well known prior to 1990. This study was designed to evaluate the sensitivity and specificities of ventilation/perfusion lung scans for pulmonary embolism in the acute setting.
Methods
This prospective, multi-center study evaluated V/Q scintigraphy on a random sample of 931 patients. A composite reference standard was used because only 755 patients underwent scintigraphy and pulmonary angiography. Clinical follow-up and subsequent diagnostic testing were employed in untreated patients with low clinical probabilities of pulmonary embolism who did not undergo angiography. Clinical assessment of the probability of pulmonary embolism was determined on the basis of the clinician’s judgment, without systematic prediction rules.
Results
Almost all patients with pulmonary embolism had abnormal ventilation/perfusion lung scans of high, intermediate, or low probability. Unfortunately, most patients without pulmonary embolism also had abnormal studies, limiting the utility of this test. Clinical follow-up and angiography revealed that pulmonary embolism occurred among 12% of patients with low-probability scans.
Conclusions
V/Q scintigraphy is useful in establishing or excluding the diagnosis of pulmonary embolism in only a minority of patients, where clinical suspicion of pulmonary embolism is concordant with the diagnostic test findings. The likelihood of pulmonary embolism in patients with a high pre-test probability of pulmonary embolism and a high probability scan is 95%, while in low probability patients with a low probability or normal scan the probability is 4% or 2%, respectively.
Commentary
This original PIOPED study established the diagnostic characteristics of V/Q scintigraphy and demonstrated, for the first time, evidence of the role of clinical assessment and prior probability in a diagnostic strategy for pulmonary embolism. Although subsequent studies have significantly advanced our knowledge of clinical prediction and diagnostic strategies in venous thromboembolism, the first PIOPED study continues to serve as an example of a high-quality, multi-center diagnostic test study utilizing a composite reference standard in a difficult-to-study disease. Unfortunately, the results of this study demonstrated that V/Q scintigraphy performs well for only a minority of patients. The majority of patients (72%) had clinical probabilities of pulmonary embolism and ventilation/perfusion scan results, which yielded post-test probabilities of 15-86%, leaving, in many cases, enough remaining diagnostic uncertainty to warrant additional testing.—TO TH