New Diagnostic Approaches for Suspected Pulmonary Embolism

1. New Diagnostic Approaches for Suspected Pulmonary Embolism

2. New Diagnostic Approaches for Suspected Pulmonary Embolism (PE) : Lecture Outline • Arterial blood gases (ABG's) • D-Dimer assay • Plasma DNA assay • Spiral Computed Tomography (CT) • Electron Beam CT • Magnetic Resonance Imaging (MRI) • Transesophageal echocardiography (TEE)

3. Utility of ABG's in PE Cases • Normal alveolar / arterial (A-a) gradient occurs in 10 to 23 % of PE cases • As high as 38 % in those without prior cardiopulmonary disease • Can have increased A-a gradient from pneumonia, COPD, etc. • Positive predictive value < 50 % • So, 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 • Is specific degradation product of cross-linked fibrin • Found in acute thrombotic conditions : • PE, Deep Venous Thrombosis (DVT) • Hepatic insufficiency (cirrhosis) • Malignant neoplasms • Recent trauma or surgery • Preeclampsia • Sepsis

5. D-Dimer Assays • ELISA • 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.) • Latex 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 • SimpliRED • Can be done in 5 minutes at bedside • Sensitivity 94 % (similar to ELISA) in one study but later study showed higher miss rate • NYCO-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 • Since levels decrease from event of onset, are not reliable if testing delayed • More specific in patients without comorbid conditions • If 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 • Uses counterimmunoelectrophoresis with serum from SLE patients containing antibodies to DNA • Circulating DNA found in PE patients • Sensitivity for PE 82 % & specificity 85 % in one study of 49 cases • No standardized inter-lab kit available • Reduced sensitivity with time from event (if Sx > 7 days)

10. Use of Plasma DNA Assay (cont.) • Positive 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 • Not as sensitive as D-Dimer • Same confounding false positive factors as D-dimer • Not generally clinically useful at this time

12. Use of Spiral CT for Dx of PE • First reported in 1992 • Most studies done so far show sensitivity for central pulmonary artery clots > 90 % • Less sensitive for subsegmental clots (63 to 80 %) • Can make alternative Dx in some patients • Requires alteration of CT technique for most accurate (sensitive) results

13. Changes in CT Technique Needed for Accuracy in Dx of PE by Spiral CT • Must first get noncontrast scan of thorax • Contrast must be scanned at first pass thru pulm. artery • Must use rapid power injection of contrast • 20 second breath hold allows best visualization of segmental arteries • Must 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 • Less expensive than angiography • Short time for scan • Can be done on relatively unstable patients • Uses less contrast than angio • Can find other thoracic Dx's • No mortalities reported from procedure • Close to 100 % sensitivity for clinically significant PE's

23. Electron Beam CT for Dx of PE • Studies so far show about same sensitivity as for spiral CT (> 90 %) • False negative for some peripheral subsegmental clots (same as for spiral CT) • No cross comparison reports versus spiral CT yet

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

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

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

27. Comments on Pulmonary Angiography • PIOPED study reported : • Mortality 0.5 % • Major complications in 1.0 % • Minor complications in 5 % • However, current use of smaller catheters (5F instead of 6 to 7 F) and nonionic contrast may be making this safer than previously reported • Low 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 Negative Doppler US of legs Treat for PE Negative Indeterminate Positive D-Dimer Stop Negative Positive Consider MRI or angio Stop

29. Another proposed workup algorithm

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

32. Conclusions About Use of Other Modalities in Dx of PE • D-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 • DNA assay not useful yet • TEE may be tried first in the unstable patient • Will need additional study if negative • Electron beam CT technique probably equivalent to spiral CT • Some 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 • Determine sensitivity of newer D-Dimer tests in larger groups of patients with proven PE • Followup studies to determine safety of schemes involving stopping workup short of angio • Redetermine current complication rates for angio