PHILADELPHIA—In the decade since the first PIOPED (Prospective Investigation Of Pulmonary Embolism Diagnosis) study was released,[1] a host of new techniques for diagnosing venous thromboembolism (VTE) have been developed. How does the evidence for these new techniques stack up? What role should they play today?

At the annual meeting of the American College of Chest Physicians, several experts discussed the state of the art regarding new techniques for diagnosing VTE, including serial compression ultrasonography, digital subtraction angiography (DSA), spiral computed tomography (CT), and D-dimer testing.[2]

LOWER-EXTREMITY TESTING

In patients with suspected pulmonary embolism (PE), serial evaluation of the lower extremities can be useful for managing suspected VTE. C. Gregory Elliott, MD, Professor of Medicine at the University of Utah in Salt Lake City, recommends compression ultrasonography for this purpose.

Lower-extremity evaluation in conjunction with ventilation-perfusion (V/Q) scanning is a good alternative to pulmonary angiography for PE diagnosis, due to the latter’s invasiveness, cost, and lack of availability, said Dr. Elliott, who is also Chief of the Pulmonary Division at LDS Hospital. The landmark PIOPED study showed that V/Q scans are non-diagnostic in nearly 60% of suspected cases; the use of lower-extremity testing allows anticoagulants to be withheld safely from some patients.

At present, Dr. Elliott recommends that selected low-risk patients undergo serial compression ultrasonography because its accuracy was demonstrated in a study of patients with suspected PE who had non-diagnostic V/Q scans.[3] In all of these patients, the clinical suspicion for PE was low or moderate. The study authors used compression ultrasonography to image the lower extremities four times during a two-week period. Of the 702 patients examined, 665 had four negative studies; these patients were observed, but they were not given anticoagulants. Symptomatic VTE subsequently developed in only three (0.5%) of these patients.

Serial impedance plethysmography (IPG) is similarly accurate for diagnosing proximal deep venous thrombosis, said Dr. Elliott, but “most of us have probably never used IPG.” Most studies of serial IPG have included only patients with adequate cardiopulmonary reserve—not those with cardiopulmonary conditions such as chronic obstructive pulmonary disease or right heart failure.

Lower-extremity studies must be done serially to accurately detect VTE, Dr. Elliott emphasized. Furthermore, these studies should include the calf, despite the low PE risk associated with calf-vein thrombi. “We could forget about calf-vein thrombi if it were not for the fact that these thrombi propagate proximally and become dangerous deep vein thrombi,” he remarked.

An emerging approach to evaluation of the lower extremities is indirect CT venography of the veins from the diaphragm or pelvis to the proximal calf. “Some would say this is one-stop shopping, because you can do a CT pulmonary angiogram at the same time,” said Dr. Elliott. But indirect CT venography still requires further research, he believes; there are no rigorous outcome studies evaluating this technique, even though it is already being used in combination with CT angiography at some institutions.

LUNG STUDIES

A new form of pulmonary angiography—DSA—is as accurate as its cut-film predecessor. Indeed, two recent studies have shown that its sensitivity and specificity for PE are 92% and 100%, respectively, compared with 69% and 100%, respectively, for cut-film angiography.[4,5] DSA offers good resolution, real-time imaging, and the ability to manipulate images. “Every institution will eventually change to this, since the older equipment is no longer available for purchase,” predicted Deborah A. Quinn, MD, an Instructor in Medicine at the Harvard Medical School in Boston.

However, V/Q scanning is still the best evaluated test for initial examination; in fact, perfusion scanning alone is acceptable when full V/Q scanning cannot be done, Dr. Quinn said. Relative to pulmonary angiography, perfusion scanning alone has a high sensitivity and specificity for PE diagnosis.[6] “But with a combined V/Q scan, you can rule out more people,” she stated.

Spiral CT has become popular despite the lack of a multicenter trial to confirm its accuracy in PE diagnosis. However, such a trial—PIOPED II—is now under way. Since PIOPED II will include 1,000 patients, “we should be able to determine the true clinical sensitivity and specificity of this test,” Dr. Quinn explained.

Single-center studies have suggested that the sensitivity and specificity of spiral CT may be suboptimal, acknowledged Victor F. Tapson, MD, an Associate Professor of Pulmonary and Critical Care Medicine at Duke University in Durham, North Carolina. Thus, the results of PIOPED II are eagerly awaited to confirm or allay concerns about the technique. “Many of us rely on negative CTs, and I am starting to worry a bit more about doing that,” he admitted.

COAGULATION ASSESSMENT

D-dimer tests generally have about 97% sensitivity but only 43% specificity for PE. “In other words, there are many false-positives,” said Roger D. Yusen, MD, an Assistant Professor of Pulmonary and Critical Care Medicine at Washington University in St. Louis. Therefore, firm recommendations for D-dimer testing were not specified in the latest American Thoracic Society guidelines for VTE diagnosis.[7] However, its strengths may win it a role in the next guidelines, Dr. Yusen suggested.

One strength is a high negative predictive value—about 97%. This may make D-dimer testing most useful in patients with a low pretest probability for PE and in populations with low disease prevalence. But because of its limits as a solo test, Dr. Yusen recommends that D-dimer testing should be used only in conjunction with other forms of evaluation for suspected PE.

—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. Elliott CG, Quinn DA, Yusen RD, Tapson VF. Diagnosing pulmonary embolism in the 21st century. Presented at: Annual Meeting of the American College of Chest Physicians, November 6, 2001; Philadelphia, Pa.
3. Wells PS, Ginsberg JS, Anderson DR, et al. Use of a clinical model for safe management of patients with suspected pulmonary embolism. Ann Intern Med. 1998;129:997-1005.
4. Hagspiel KD, Polak JF, Grassi CJ, et al. Pulmonary embolism: comparison of cut-film and digital pulmonary angiography. Radiology. 1998;207:139-145.
5. Johnson MS, Stine SB, Shah H, et al. Possible pulmonary embolus: evaluation with digital subtraction versus cut-film angiography—prospective study in 80 patients. Radiology. 1998;207:131-138.
6. Miniati M, Pistolesi M, Marini C, et al. Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Am J Respir Crit Care Med. 1996;154:1387-1393.
7. Tapson VF, Carroll BA, Davidson BL, et al. The diagnostic approach to acute venous thromboembolism. Clinical practice guideline. American Thoracic Society. Am J Respir Crit Care Med. 1999;160: 1043-1066.