1. New Diagnostic Approaches for Suspected Pulmonary Embolism Jim Holliman, M.D., F.A.C.E.P. Director, Center for International Emergency Medicine Professor of Surgery and Emergency Medicine Penn State University Hershey, Pennsylvania, U.S.A.

2. New Diagnostic Approaches for Suspected Pulmonary Embolism (PE) : Lecture Outline ƒArterial blood gases (ABG's) ƒD-Dimer assay ƒPlasma DNA assay ƒSpiral Computed Tomography (CT) ƒElectron Beam CT ƒMagnetic Resonance Imaging (MRI) ƒTransesophageal echocardiography (TEE)

3. Utility of ABG's in PE Cases ƒNormal alveolar / arterial (A-a) gradient occurs in 10 to 23 % of PE cases –As high as 38 % in those without prior cardiopulmonary disease ƒCan have increased A-a gradient from pneumonia, COPD, etc. ƒPositive predictive value < 50 % ƒSo, ABG is really useless to rule in or out PE –Don't obtain unless needed for other reasons

4. Use of D-Dimer Assay for PE Cases ƒIs specific degradation product of cross- linked fibrin ƒFound in acute thrombotic conditions : –PE, Deep Venous Thrombosis (DVT) –Hepatic insufficiency (cirrhosis) –Malignant neoplasms –Recent trauma or surgery –Preeclampsia –Sepsis

5. D-Dimer Assays ƒELISA –Uses monoclonal antibodies against D-dimer – Colorimetric, quantitative result –Cumbersome, requires trained lab personnel, slow to get results –Sensitivity & neg. predictive value > 90 % –Poor specificity (30 to 50 %) –Lack of standardized calibration between different types of tests

6. D-Dimer Assays (cont.) ƒLatex Agglutination (LA) –4 commercially available types –Use latex particles coated with monoclonal antibodies to D-dimer, which agglutinate with plasma containing > a preset D-dimer level –Must be done in lab but are quick –Sensitivity poorer than ELISA (47 to 92 %) –Low specificity (48 to 60 %) –Negative predictive value (89 %) too low to be clinically useful

7. New Rapid D-Dimer Assays ƒSimpliRED –Can be done in 5 minutes at bedside –Sensitivity 94 % (similar to ELISA) in one study but later study showed higher miss rate ƒNYCO-CARD –Uses plasma so must be done in lab, but is quick –Sensitivity 88 to 92 % –Needs more study to decide if really as sensitive as ELISA

8. Conclusions About Use of D- Dimer Assays for PE Dx ƒSince levels decrease from event of onset, are not reliable if testing delayed ƒMore specific in patients without comorbid conditions ƒIf negative, may be used to avoid further testing (angio) in patients with low clinical suspicion and indeterminate screening radiologic tests (V/Q or spiral CT scan )

9. Use of Plasma DNA Assay to Dx PE ƒUses counterimmunoelectrophoresis with serum from SLE patients containing antibodies to DNA ƒCirculating DNA found in PE patients ƒSensitivity for PE 82 % & specificity 85 % in one study of 49 cases ƒNo standardized inter-lab kit available ƒReduced sensitivity with time from event (if Sx > 7 days)

10. Use of Plasma DNA Assay (cont.) ƒPositive in many other conditions : –Major surgery or burns –Corticosteroid Rx –Hemodialysis –Chemotherapy –Active SLE –Sickle cell crisis –Liver failure

11. Conclusions About Use of DNA Assays for Dx of PE ƒNot as sensitive as D-Dimer ƒSame confounding false positive factors as D-dimer ƒNot generally clinically useful at this time

12. Use of Spiral CT for Dx of PE ƒFirst reported in 1992 ƒMost studies done so far show sensitivity for central pulmonary artery clots > 90 % ƒLess sensitive for subsegmental clots (63 to 80 %) ƒCan make alternative Dx in some patients ƒRequires alteration of CT technique for most accurate (sensitive) results

13. Changes in CT Technique Needed for Accuracy in Dx of PE by Spiral CT ƒMust first get noncontrast scan of thorax ƒContrast must be scanned at first pass thru pulm. artery ƒMust use rapid power injection of contrast ƒ20 second breath hold allows best visualization of segmental arteries ƒMust be careful not to misinterpret hilar nodes as intraluminal clot

14. Spiral computed tomography scan showing clots in the anterior segmental artery of the right upper lobe

15. Embolus in the right pulmonary artery ; curved arrows show a previously known esophageal cancer

16. Filling defects (clots) in the interlobar pulmonary arteries

17. “Saddle” pulmonary embolus

18. Embolus in anterior left upper lobe segmental artery

19. Scan of same patient 5 weeks later (on Coumadin) showing complete clot resolution

20. Spiral CT showing distal clot in the left lower lobe

22. Advantages of Spiral CT to Dx PE ƒLess expensive than angiography ƒShort time for scan ƒCan be done on relatively unstable patients ƒUses less contrast than angio ƒCan find other thoracic Dx's ƒNo mortalities reported from procedure ƒClose to 100 % sensitivity for clinically significant PE's

23. Electron Beam CT for Dx of PE ƒStudies so far show about same sensitivity as for spiral CT (> 90 %) ƒFalse negative for some peripheral subsegmental clots (same as for spiral CT) ƒNo cross comparison reports versus spiral CT yet

24. Magnetic Resonance Imaging (MRI) for Dx of PE ƒAbout same sensitivity as spiral CT ƒMay also miss subsegmental clots ƒDoes not require iodine based contrast ƒMRI has high accuracy for leg DVT, so combined leg and chest scan may prove useful for some patients ƒCurrently usually more expensive than spiral CT

25. Transesophageal Echocardiography (TEE) for Dx of PE ƒSensitivity is 58 to > 80 % for central clots ƒMay miss clot on one side when bilateral ƒCan be done even during CPR ƒCan be done on patients who cannot be moved for other studies ƒDependent on operator skill

26. Transesophageal echo showing snake-like pulmonary embolus (TH)

27. Comments on Pulmonary Angiography ƒPIOPED study reported : –Mortality 0.5 % –Major complications in 1.0 % –Minor complications in 5 % ƒHowever, current use of smaller catheters (5F instead of 6 to 7 F) and nonionic contrast may be making this safer than previously reported ƒLow agreement (k = 0.4 to 0.5) between different radiologists in interpretation of subsegmental clots

28. Proposed Diagnosis Sequence for Suspected PE First, Spiral CT Positive Treat for PE Negative Doppler US of legs D-Dimer Positive Negative Indeterminate Positive Negative Stop Consider MRI or angio

29. Another proposed workup algorithm

31. Conclusions About Spiral CT Use in Suspected PE ƒFewer indeterminate results than V/ Q scan ƒBecause of the lack of interobserver consistency in interpreting peripheral clots on pulmonary angios, accuracy of spiral CT may be close to that of angio ƒSpiral CT is cheaper, faster, and has less complications than angio ƒCombination scheme of spiral CT and leg US shown cost-effective

32. Conclusions About Use of Other Modalities in Dx of PE ƒD-Dimer only helpful if negative –Then may help exclude PE & obviate further testing in low suspicion patients already screened by V/Q or spiral CT ƒDNA assay not useful yet ƒTEE may be tried first in the unstable patient –Will need additional study if negative ƒElectron beam CT technique probably equivalent to spiral CT ƒSome false negatives relative to angio in prior reports may reflect the often extended time period between the 2 studies compared

33. Further Studies Needed on Dx of PE ƒDetermine sensitivity of newer D- Dimer tests in larger groups of patients with proven PE ƒFollowup studies to determine safety of schemes involving stopping workup short of angio ƒRedetermine current complication rates for angio