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.

New Diagnostic Approaches for Suspected Pulmonary Embolism (PE) : Lecture Outline

ƒ Arterial blood gases (ABG's)ƒ D-Dimer assayƒ Plasma DNA assayƒ Spiral Computed Tomography

(CT)ƒ Electron Beam CTƒ Magnetic Resonance Imaging

(MRI)ƒ Transesophageal

echocardiography (TEE)

Utility of ABG's in PE Cases

ƒ Normal alveolar / arterial (A-a) gradient occurs in 10 to 23 % of PE cases–As high as 38 % in those without prior cardiopulmonary disease

ƒ Can have increased A-a gradient from pneumonia, COPD, etc.

ƒ Positive predictive value < 50 %ƒ So, ABG is really useless to rule in or

out PE–Don't obtain unless needed for other reasons

Use of D-Dimer Assay for PE Cases

ƒ Is specific degradation product of cross-linked fibrin

ƒ Found in acute thrombotic conditions :–PE, Deep Venous Thrombosis (DVT)–Hepatic insufficiency (cirrhosis)–Malignant neoplasms–Recent trauma or surgery–Preeclampsia–Sepsis

D-Dimer Assays

ƒ 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

D-Dimer Assays (cont.)

ƒ 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

New Rapid D-Dimer Assays

ƒ SimpliRED–Can be done in 5 minutes at bedside–Sensitivity 94 % (similar to ELISA) in one study but later study showed higher miss rate

ƒ 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

Conclusions About Use of D-Dimer Assays for PE Dx

ƒ Since levels decrease from event of onset, are not reliable if testing delayed

ƒ More specific in patients without comorbid conditions

ƒ 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 )

Use of Plasma DNA Assay to Dx PE

ƒ Uses counterimmunoelectrophoresis with serum from SLE patients containing antibodies to DNA

ƒ Circulating DNA found in PE patientsƒ Sensitivity for PE 82 % & specificity

85 % in one study of 49 casesƒ No standardized inter-lab kit

availableƒ Reduced sensitivity with time from

event (if Sx > 7 days)

Use of Plasma DNA Assay (cont.)

ƒ Positive in many other conditions :–Major surgery or burns–Corticosteroid Rx–Hemodialysis–Chemotherapy–Active SLE–Sickle cell crisis–Liver failure

Conclusions About Use of DNA Assays for Dx of PE

ƒ Not as sensitive as D-Dimerƒ Same confounding false positive

factors as D-dimerƒ Not generally clinically useful at

this time

Use of Spiral CT for Dx of PE

ƒ First reported in 1992ƒ Most studies done so far show

sensitivity for central pulmonary artery clots > 90 %

ƒ Less sensitive for subsegmental clots (63 to 80 %)

ƒ Can make alternative Dx in some patients

ƒ Requires alteration of CT technique for most accurate (sensitive) results

Changes in CT Technique Needed for Accuracy in Dx of PE by Spiral CT

ƒ Must first get noncontrast scan of thoraxƒ Contrast must be scanned at first pass

thru pulm. arteryƒ Must use rapid power injection of contrastƒ 20 second breath hold allows best

visualization of segmental arteriesƒ Must be careful not to misinterpret hilar

nodes as intraluminal clot

Spiral computed tomography scan showing clots in the anterior

segmental artery of the right upper lobe

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

Filling defects (clots) in the interlobar pulmonary arteries

“Saddle” pulmonary embolus

Embolus in anterior left upper lobe segmental artery

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

Spiral CT showing distal clot in the left lower lobe

Advantages of Spiral CT to Dx PE

ƒ Less expensive than angiographyƒ Short time for scanƒ Can be done on relatively unstable

patientsƒ Uses less contrast than angioƒ Can find other thoracic Dx'sƒ No mortalities reported from

procedureƒ Close to 100 % sensitivity for

clinically significant PE's

Electron Beam CT for Dx of PE

ƒ Studies so far show about same sensitivity as for spiral CT (> 90 %)

ƒ False negative for some peripheral subsegmental clots (same as for spiral CT)

ƒ No cross comparison reports versus spiral CT yet

Magnetic Resonance Imaging (MRI) for Dx of PE

ƒ About same sensitivity as spiral CT

ƒ May also miss subsegmental clots

ƒ Does not require iodine based contrast

ƒ MRI has high accuracy for leg DVT, so combined leg and chest scan may prove useful for some patients

ƒ Currently usually more expensive than spiral CT

Transesophageal Echocardiography (TEE) for Dx of PE

ƒ Sensitivity is 58 to > 80 % for central clots

ƒ May miss clot on one side when bilateral

ƒ Can be done even during CPRƒ Can be done on patients who

cannot be moved for other studiesƒ Dependent on operator skill

Transesophageal echo showing snake-like pulmonary embolus (TH)

Comments on Pulmonary Angiographyƒ PIOPED study reported :

–Mortality 0.5 %–Major complications in 1.0 %–Minor complications in 5 %

ƒ However, current use of smaller catheters (5F instead of 6 to 7 F) and nonionic contrast may be making this safer than previously reported

ƒ Low agreement (k = 0.4 to 0.5) between different radiologists in interpretation of subsegmental clots

Proposed Diagnosis Sequence for Suspected PE

First, Spiral CT

Positive

Treat for PE

Negative

Doppler US of legs

D-Dimer

PositiveNegative

Indeterminate

Positive

Negative

Stop

StopConsider MRI or angio

Another proposed workup algorithm

Conclusions About Spiral CT Use in Suspected PE

ƒ Fewer indeterminate results than V/ Q scan

ƒ 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

ƒ Spiral CT is cheaper, faster, and has less complications than angio

ƒ Combination scheme of spiral CT and leg US shown cost-effective

Conclusions About Use of Other Modalities in Dx of PE

ƒ 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

ƒ DNA assay not useful yetƒ TEE may be tried first in the unstable patient

–Will need additional study if negativeƒ Electron beam CT technique probably equivalent

to spiral CTƒ Some false negatives relative to angio in prior

reports may reflect the often extended time period between the 2 studies compared

Further Studies Needed on Dx of PE

ƒ Determine sensitivity of newer D-Dimer tests in larger groups of patients with proven PE

ƒ Followup studies to determine safety of schemes involving stopping workup short of angio

ƒ Redetermine current complication rates for angio