ORLANDO--Acute pulmonary embolism (PE) is extremely common. "The annual incidence in the United States ranges between 250,000 and 500,000 cases, translating to about 55,000 deaths per year," said Kenneth V. Leeper, MD, associate professor of medicine at Emory University in Atlanta.

Quick, accurate detection of PE is therefore essential, stressed Dr. Leeper, who discussed new approaches to PE diagnosis at the 29th Annual Educational and Scientific Symposium of the Society of Critical Care Medicine. Among the diagnostic methods covered were D-dimer testing, helical computed tomography (CT), and magnetic resonance angiography (MRA).

Pulmonary arteriography is considered the gold standard for PE diagnosis, but this invasive procedure is not without risk. Thus, researchers have long sought a better alternative. The ventilation/perfusion lung scan has been the preferred noninvasive test for PE, primarily because of a lack of better noninvasive tests; but its diagnostic accuracy is limited. For example, about 10 years ago, the PIOPED (Prospective Investigation of Pulmonary Embolism Diagnosis) study found that the lung scan could accurately diagnose or rule out PE only in a minority of study subjects--those with high, low, or very low probability of PE.[1] Scanning was inconclusive among subjects with intermediate probability of PE, which represented the majority of cases.

Several new diagnostic tests have been suggested as alternatives to the lung scan, including assays for circulating D-dimer, which is a byproduct of fibrinolysis. Two types of D-dimer tests are currently available in many different brands. Enzyme-linked immunosorbent assays (ELISAs) are time-consuming and complex and therefore, must often be performed in batches. In contrast, latex agglutination tests can be done individually, and the results are usually available in less than 30 minutes. "However, there has been a wide range of negative predictive values for these tests, from 67% to 97%," Dr. Leeper said. One explanation for this is that studies of latex agglutination tests often did not use pulmonary arteriography for comparison.

However, one recent study did compare five latex agglutination tests to pulmonary arteriography in 103 patients with suspected PE; it found that latex agglutination tests had sensitivities of 97% to 100% and negative predictive values of 94% to 100% for PE. Specificity, however, was only 19% to 29%.[2]

Circulating D-dimer levels are elevated in patients with PE as well as in those with sepsis and other inflammatory conditions. Thus, these assays are unlikely to eclipse lung scanning, because their specificity markedly declines in patients with comorbid disease.

"So, what we can conclude about the D-dimer test is that a positive result has no value whatsoever in establishing the diagnosis of acute PE," Dr. Leeper said. But a negative D-dimer test, whether it is done by ELISA or latex agglutination, has an excellent negative predictive value, making it a useful part of the diagnostic workup.

IMAGING TESTS FOR PE

Helical CT and MRA have the best chance of supplanting ventilation/perfusion scanning and perhaps even pulmonary arteriography. According to Dr. Leeper, pooled data have shown that helical CT has an 83% sensitivity, a 94% specificity, a 91% positive predictive value, and an 88% negative predictive value for PE. Its sensitivity and specificity for central clots are even better, he noted.

Preliminary data released in 1998 from a large ongoing European study further support the use of helical CT in PE diagnosis. "The sensitivity and specificity for the helical CT scan were 94% and 96%, respectively," Dr. Leeper reported.

MRA has demonstrated comparable accuracy with greater safety.[3] However, "both the spiral CT scan and the pulmonary arteriogram use an intravenous contrast that can promote nephrotoxicity," cautioned Dr. Leeper. In addition to being safer, MRA can diagnose deep vein thrombosis and PE simultaneously.

Echocardiography may also contribute to PE diagnosis by revealing cardiac abnormalities associated with PE, including right ventricular dilatation or hypokinesis, tricuspid regurgitation, and a shift of the intraventricular septum into the left ventricle. In some cases, echocardiography may detect a clot in the right ventricular chamber.

In patients with pulmonary hypertension secondary to PE, researchers have found a unique transesophageal echocardiography pattern. The pattern, which is characterized by preservation of wall motion at the right ventricular apex but akinesis at the mid-right ventricular free wall, has shown a diagnostic accuracy of 92% for PE.

"Transesophageal echocardiography can be used in the intensive care unit to establish a diagnosis of PE," he added. "It can usually pick up a clot in the main stem of the pulmonary artery and also in the right main pulmonary artery." It also has excellent sensitivity and specificity for central pulmonary emboli.

--Timothy Begany

References
1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;263:2753-2759.
2. Quinn DA, Fogel RB, Smith CD, et al. D-dimers in the diagnosis of pulmonary embolism. Am J Respir Crit Care Med. 1999;159(Pt 1):1445-1449.
3. Meaney JF, Weg JG, Chenevert TL, et al. Diagnosis of pulmonary embolism with magnetic resonance angiography. N Engl J Med. 1997;336:1422-1427.

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