Clinical Utility of CT in the Diagnosis of Pulmonary Embolism

8/3/2019 Clinical Utility of CT in the Diagnosis of Pulmonary Embolism

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ELSEVIER

CLINICAL UTILITY OF COMP UTED TOMOGRAP HYIN THE DIAGNOSIS OF P ULMONARY EMBOLISM

THOMAS J. RUSSI, MD, DANIEL M. LIBBY, MD,AND CLAUDIA I. HENSCHKE, PHD, MD

This prospective clinical pilot study describes theclinical utility and cost effectiveness of computed to-mography (CT) with contrast in the diagnosis andmanagement of pulmonary embolism. The setting isa university teaching hospital, and the 20 patients,26 to 81 years old, were found to have CT findingsconsistent with pulmonary embolism. Intraluminalpulmonary artery clots were observed on CT andcontributed to clinical management, often obviatingpulmonary arteriography. CT, particularly spiral CT,may demonstrate pulmonary embolism and offersadvantages over ventilation-perfusion lung scanningand pulmonary arteriography in making the diagno-sis of pulmonary embolism in high-risk patients or pa-tients with preexisting parenchymal lung disease.0 Elsevier Science Inc., 1997KEY WOKDS:Pulmonary embolism; Computed tomography; Helical

computed tomography

INTRODUCTIONPulmonary embolism affects approximately 630,000individuals in the United States each year but is dis-covered antemortem in only a third (1, 2). In two-thirds of patients, clinical assessment combined with

From the Division of Pulmonary and Critical Care Medicine,Department of Medicine (T.J.R., D.M.L.), and the Department ofRadiology (C.I.H.). The New York Hospital-Cornell Medical Cen-ter, New York, New York.Address reprint requests to: Daniel M. Libby, MD, 407 East70th Street, New York, NY 10021.Received November 15, 1995; accepted December 3, 1995.Presented at the American Thoracic Society annual meeting.Seattle, Washington, May 22,1995, and published in abstract formin the Am erican Journal of Respiratory and Criti cal Care Medi-cine. April 1995; 115[4):A633.

ventilation-perfusion lung scans is unable to estab-lish or exclude the diagnosis of pulmonary embolism(3). Despite the development of impedance plethys-mography and Doppler sonographic studies of thelower extremities to detect deep vein thrombosis (4).pulmonary arteriography is not infrequently neces-sary to establish the diagnosis of pulmonary embo-lism. Because pulmonary arteriography is invasive,costly, and associated with morbidity and mortality(s-7), a definitive noninvasive, cost-effective test forthe diagnosis of pulmonary embolism has been sought.

Remy-Jardin et al. (8) and Goodman et al. (9) stud-ied consecutive patients with helical computed to-mography (CT) who had angiographic confirmationof pulmonary embolism and found CT to have a highsensitivity and specificity. We performed a prospec-tive pilot study utilizing computed tomography toassess the clinical utility of CT in the diagnosis ofpulmonary embolism.

METHODSFrom July 1993 to January 1995,20 patients in whomCT diagnosed pulmonary embolism by demonstrat-ing intraluminal clot in the pulmonary arterial sys-tem were encountered. Some patients underwentsubsequent CT, which documented resolution of em-boli after treatment.

CT was performed on the GE advantage scannerusing contrast injection. If pulmonary embolism wasnot suspected prior to CT, we performed our stan-dard protocol of administering up to 150 cc of non-ionic contrast (Omnipaque, Winthrop Pharmaceuti-cals) via an automatic injector pump. If pulmonaryembolism was suspected, 50 cc of contrast was in-jected (1 cc/s), and scans were obtained, after a 40-sdelay, from the aortic arch to the inferior hilar struc-

CLINICAL IMAGING 1997;21:175-1820 Elsevier Science Inc., 1997655 Avenue of the Americas, New York, NY 10010

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tures using 5-mm collimation during a single breathhold. Images were reconstructed by l-mm intervalswith a field of view concentrating on the central pul-monary arteries. The diagnosis of pulmonary embo-lism was made after a radiologist without knowledgeof the results of other diagnostic studies reviewedthe reconstructed CT images.

RESULTSAmong the 20 patients, 10 were female, and the aver-age age was 63 (see Table 1). Thirteen patients hadpreexisting lung disease, 7 had underlying malignan-cies, and 4 had clinically evident cardiovascular dis-ease. All but 3 presented with dyspnea or chest pain.CT contributed to both the diagnosis and manage-ment of pulmonary embolism in our patients and of-fered advantages over pulmonary arteriography andventilation-perfusion lung scanning in selected pa-tients. Prior to CT, 11 patients had undergone a ven-tilation-perfusion scan, 6 of which were interpretedas high probability for pulmonary embolism, 4were indeterminate, and 1 was low probabilityfor pulmonary embolism. In 19 of 20 patients, CT es-tablished the definitive diagnosis of pulmonary em-bolism. In only 1 patient was pulmonary arteriogra-phy required, and in this patient, in confirmed theCT diagnosis. CT was then repeated to document clotresolution 2 months later. CT avoided the risks ofcessation of anticoagulation and catheter insertionfor pulmonary arteriography in patients who had re-current emboli while anticoagulated. Pulmonary ar-teriography was also avoided in high-risk patientswho were septic (patient ll), had advanced emphy-sema (patients 2, 3), or who had severe pulmonaryhypertension (patients 4,6,19,20). In one individual(patient 13), the CT finding of right ventricular clotexplained the lack of improvement after inferiorvena cava filter insertion. Serial CT studies demon-strated improvement or lack of improvement of pul-monary emboli while on anticoagulation. In oneindividual with severe pulmonary hypertension (pa-tient 6) where repeated pulmonary arteriographywould have entailed unacceptable risk, serial CTstudies led to the recommendation of pulmonary an-gioscopy and possible thromboendarterectomy. CTpermitted the differentiation of clot from tumor com-pression of the pulmonary artery (patient 7). It re-vealed unsuspected pulmonary embolism in five pa-tients (patients 3,4, 14,15, 17). In three patients whowere unstable due to severe gas exchange abnormali-ties associated with preexisting parenchymal lungdisease and systemic hypotension, CT circumventedthe risks of pulmonary arteriography and the likely

nonspecificity and delay of ventilation-perfusionlung scanning (patients 8, 13, 9).

Representative case reports and CT images (Fig-ures 14) follow.Patient 4This 6i-year-old female with a history of rheumaticmitral and tricuspid regurgitation and chronic atria1fibrillation presented with shortness of breath, feverof 102F, and chest soreness. Chest X ray revealedcardiomegaly and a moderate right pleural effusion.Thoracentesis revealed a transudate. Tracheoesopha-geal echocardiography showed a vegetation on theatria1 side of the mitral valve and 4 + mitral regurgita-tion. CT revealed unsuspected pulmonary emboli inthe right and left interlobar pulmonary arteries and asmall pericardial effusion (Figure 1). Doppler studiesof the lower extremities were negative for deep ve-nous thrombosis. The patient was treated with intra-venous heparin followed by Coumadin and empiricantibodies for culture-negative endocarditis. Aftercardiac catheterization, she underwent mitral valvereplacement.Patient 6This 68-year-old female developed pleuritic chestpain 2 years prior to this admission, and a diagnosisof pulmonary embolism was made at another institu-tion by ventilation-perfusion lung scan. She wastreated with heparin followed by Coumadin for 3months. She then experienced progressive dyspneaand weight loss over the next year. The physicalexam upon admission showed jugular venous dis-tension, accentuation of the pulmonic component ofthe second heart sound, clear lung fields, and lowerextremity venous varicosities. Chest X ray showedenlargement of the main right and left pulmonary ar-teries. Arterial blood gases breathing room air showed~0, 64-mm Hg, pC0, 26-mm Hg, pH 7.47. Two-dimensional echocardiography with doppler showednormal left ventricular function, dilated right-sidedchambers, and flattening of the interventricular sep-tum consistent with right ventricular pressure over-load. There was severe tricuspid regurgitation with atricuspid regurgitant jet velocity of 4.9 m/s corre-sponding to a peak systolic tricuspid valve gradientof %-mm Hg and a right ventricular systolic pressureof 105-mm Hg. Due to severe pulmonary hyperten-sion, pulmonary arteriography was deferred. CT re-vealed central clot in intralobar pulmonary arteries(Figure 2). After 9 months of treatment with Cou-madin, repeat CT showed little change. The patientis being evaluated for pulmonary angioscopy andthromboendarterectomy.


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TABLE 1. Patient Characteristics

Pa- Age/tient Sex

Underlyingdisease

PreexistingPresentingsymptomsphysical

Ventilationperfusion Relative

scan finding Pulmonary contraindication[probability angiog. to pulmonary

lung disease exam for PE) finding arteriography1 67 1' Recent CABG

2 65 M Ischemiccardiomyo-pathy3 66 M Lung CA

4 67 M RHD mitraldisease

5 81 M Prostate CA.atria1 fibril-lation

6 68 F None

7 26 F Colon CA

8 67 I: Total knee re-placement

9 72 F Gastric ulcer10 74 M Recurrent be-.

nign pleuralmesothelioma

11 60 1: Metastaticbreast cancer,sepsis

12 61 M Ischemic cardio-myopathy

13 65 F Metastaticrectal CA

14 69 M None

15 56 M Lymphoma16 40 M AIDS; DVT17 79 M CVA18 28 F Breast CA19 78 I None20 75 I None

None

Severe COPD

COPDCongestive

heartfailure

None

Pulmonaryhyperten-sion; PE inpast

None

Adult respira-tory distresssyndrome

NoneNone

Lungmetastases

Lungmetastases

Sarcoidosis

NoneLung CALung noduleLung

metastasesIPFPE 10 years

prior

Dyspnea, tach- Indeter-ypnea, rales minate

Pleuritic chest Indeter-pain, dyspnea minateand tachypnea

Dyspnea, NDtachypnea

Fever, chest pain ND

ND

ND

NDND

Dyspnea, pleu- Lowritic chestpain, hemop-tysis

Dyspnea, weight Highloss, RVfailure

Positivefor clot

ND

Dyspnea High ND

Dyspnea, chest NDpain, hypo-tension

Dyspnea, syn- HighcopeLeg edema, Indeter-dyspnea, minatehypotension

Chills, rigors, Highdyspnea

ND

NDND

ND

Dyspnea, Indeter-hemoptysis, minaterales

Dyspnea, NDtachypnea

Fever, cough, NDmental statuschanges

Leg edema NDPleuritic chest ND

pain; dyspneaCough NDDyspnea HighFever; dyspnea ND

ND

NDND

NDNDNDNDND

Dyspnea;tachypnea

High ND

Anticoagulated;recent heartsurgery

Severe COPD

Severe COPD.hypoxemia

Passive pulmonaryhypertension

None. serialstudies needed

Severe pulmonaryhypertension byEcho-Dopplers

None

Severe respiratoryfailure onrespirator

NoneSevere respiratory

failureSepsis

None

Terminalcondition

None

NoneAnticoagulatedAnticoagulatedNonePulm hyperten-

sion; hypoxemiaSevere pulm.

hypertension:RV dysfunction

Clinicaladvantage

of CT Dx ofpulmonary

emboliAvoided PAgram;

IVC filterplaced

Avoided PAgram;RA clot detected

Unsuspected PEUnsuspected PE

Serial studies needed:avoided PAgram

Avoided PAgram

Differentiated tumorcompression fromclot

Avoided PAgram;IVC filter placed

Avoided PAgramAvoided PAgram

Avoided PAgram;confirmed PE

Avoided PAgram

Avoided PAgram;clot in RV detected

IJnsuspected PE

Ilnsuspected PEAvoided PAgramUnsuspected PE;

clot in LV detectedSource of clot in SVCAvoided V/Q scan

and PAgramAvoided PAgram;

demonstratedextent of clot

Abbreviations: CA = cancer; CABG = coronary artery bypass graft surgery; COPD = chronic obstructive pulmonary disease: WA = cerebrovascularaccident: DVT = deep venous thrombosis; F = female; IPF = idiopathic pulmonary fibrosis: IVC = inferior vena cava: LV = left ventricle; M = male: ND =not done; PAgram = pulmonary arteriogram; PE = pulmonary embolus: RA = right atrium; RHD = rheumatic heart disease: V/Q = ventilation perfusion.


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FIGURE 1. CT with contrast on patient 4 demonstratingfilling defects (arrows) in the right and left intralobar pul-monary arteries. There is also a small pericardial effusion.

Patient 11This 60-year-old woman was admitted to The NewYork Hospital with fever to 103F, chills, rigors,cough, and dyspnea. Her past history was notable formetastatic adenocarcinoma of the breast treatedsince 1988 with mastectomy, systemic chemother-apy, and tamoxifen. In 1993 she developed a left hi-lar mass that at bronchoscopy, was found to be meta-static breast carcinoma. She was subsequently treatedwith radiation therapy to the mass and further che-motherapy. A Broviac catheter had been placed inJanuary 1994. Blood cultures from the Broviac cathe-ter on admission grew Streptococcus fecalis. Chestradiography showed subsegmental atelectasis at theleft lung base and a widened mediastinum. A venti-lation-perfusion lung scan was interpreted as highprobability for pulmonary embolism. CT showedregression of the hilar mass and also confirmed pul-monary emboli in the lobar branches to the rightlower and middle lobes (Fig. 3). The patientimproved and was discharged after treatment withintravenous antibiotics, removal of the Broviac cath-eter, and anticoagulation with heparin followed byCoumadin.Patient 13This 65-year-old female with a history of metastaticrectal carcinoma to the liver and lungs presentedwith acute shortness of breath. Physical examinationshowed tachypnea and hepatomegaly. CT was per-formed to assess the known metastatic disease to thelung; it revealed unsuspected extensive intraluminal

filling defects in the lobar pulmonary arteries of theleft upper and lower lobes as well as clot in the rightventricle (Fig. 4). Two-dimensional echocardiogra-phy with Doppler confirmed the right ventricularclot and also showed 3 + tricuspid regurgitation, ele-vated pulmonary arterial pressures, and dilated right-sided structures. The patient was treated with intra-venous heparin, and, after persistent rectal bleeding,an inferior vena cava umbrella filter. She has failedto improve and was not considered a candidate forfurther intervention.

DISCUSSIONPulmonary embolism often occurs in patients withserious concomitant medical conditions, particularlyright ventricular dysfunction and pulmonary hyper-tension. Although usually considered a low-risk pro-cedure, in these circumstances pulmonary arteriog-raphy, considered the definitive diagnostic procedurefor pulmonary embolism, is more hazardous, (5-7)and a less invasive study would be desirable. Wehave found contrast-enhanced CT to be useful in thediagnosis and management of pulmonary embolismin such patients. This study, however, was not de-signed to assess the sensitivity and specificity of CTcompared to pulmonary arteriography and ventila-tion-perfusion lung scans.

The diagnosis of pulmonary embolism by CT wasinitially described in 1978 (10). Prior to the introduc-tion of spiral or helical CT scanning, visualization ofthe pulmonary vasculature by CT was limited by theprolonged scanning time, which resulted in respira-tory and cardiac motion artifact. In addition, priorscanners had other technical limitations resultingfrom beam collimation and computer software. Limi-tations of conventional CT compared to pulmonaryarteriography included the less accurate visualiza-tion of small vessels due to motion and partial vol-ume averaging making it difficult to differentiatebetween intraluminal filling defects and imagingartifacts in lobar pulmonary arteries (8, 11-14). Spi-ral or helical CT permits better visualization of thecentral pulmonary artery and its proximal branches.During a single breath hold of 20 s, the entire CT scanof these vessels can be obtained. Usual doses of con-trast with spiral CT are between 50 and 100 cc com-pared to the typical pulmonary arteriogram whichutilizes 250-300 cc. Overlapping l-mm spiral CT im-ages may be reconstructed to increase the ability toresolve questions about intraluminal filling defects.Clinically silent or unsuspected pulmonary em-bolism is a recognized but troublesome medicalcondition (15). In a retrospective study of 4500 con-


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FIGURE 2. Spiral CT scan with contrast of patient 6 show-ing the dilated main right and left pulmonary arteries. Clots[arrows) are seen in the right intralobar artery (A), right lowerlobe pulmonary artery (B), and left lobar artery (C).

secutive conventional CTs, pulmonary emboli wereobserved in 25 (11). In 13 of 25, pulmonary emboliwere clinically unsuspected or silent. In 5 of our 20patients, pulmonary embolism was also unsuspected.

Spiral CT has been prospectively compared topulmonary arteriography. In a study (8) of 42 consec-utive patients, 18 found to have pulmonary embo-lism by arteriography had an abnormal CT, yielding100% sensitivity. All patients with normal pulmo-nary arteriograms had a normal CT, a 100% negativepredictive value. One false-positive CT was encoun-tered, yielding 96% specificity. The finding of cen-tral emboli in the main, lobar, and segmental pulmo-nary arteries by CT correlated precisely with thearteriographic findings. CT reliably depicted emboli

in second- to fourth-generation pulmonary vessels.An intersegmental lymph node misinterpreted as afilling defect was the cause of the single false-posi-tive spiral CT. In a more recent prospective study, CThad a sensitivity of 86% and a specificity of 92% inthe detection of central vessel pulmonary emboli,but a lower sensitivity and specificity (63 and 89%,respectively) in smaller vessels (9).While the negative predictive value of pulmonaryarteriography has been established, it has not beenconfirmed as conclusively for CT. In one study of147 patients with normal pulmonary arteriograms,no patient experienced pulmonary emboli when leftuntreated for 6 months (16). A comparable study ofCT has not been performed.


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FIGURE 3. CT scan with contrast in patient 11 showingfilling defect [arrow) in the right middle lobar pulmonaryartery.

Relative advantages, risks, and financial cost ofCT, pulmonary arteriography, and ventilation-perfu-sion lung scanning are depicted-in Table 2. In our in-stitution, the financial cost of CT or ventilation-per-fusion lung scan is 15-20% of the cost of pulmonaryarteriography. The dye load for CT is considerablyless than that for pulmonary arteriography, and CTavoids the risk of catheter insertion. Given the lowerfinancial cost and lower medical risk of CT com-pared to pulmonary arteriography, and assumingcomparable sensitivity and specificity of CT andpulmonary arteriography for detecting central em-

boli (8, 9) and a higher sensitivity and specificity ofCT compared to ventilation-perfusion scanning (3),CT might assume a prominent place in a clinical di-agnostic algorithm. The actual selection of the test(s)depends on a variety of clinical variables includingthe likelihood of pulmonary embolism in a given pa-tient population.

To help select the most appropriate diagnostictest, the cost effectiveness of CT for pulmonary em-bolism should be compared to the standard algo-rithm for the diagnosis of pulmonary embolismwhich usually recommends a ventilation-perfusionlung scan followed by pulmonary arteriography. Es-timates of cost effectiveness should consider notonly the costs, sensitivity, and specificity detailed inTable 2 but also the risk of contrast reactions, othermorbidity and mortality risks of each of the tests andthe results of subsequent treatment or lack of treat-ment. The mortality and morbidity of the diagnostictest increases its effective cost (17,18). The cost ofmortality may be estimated to be $100,000 and costof morbidity to be $10,000 as additional hospitaliza-tion and treatment may be required. For CT, the like-lihood of mortality and morbidity, respectively, areestimated to be 0.001 and 4%. The effective cost ofCT increases from $759 to $1106. Similarly, the costof the pulmonary arteriogram increases from $4653to $5253 assuming the probability of mortality to be0.04% and the probability of morbidity to be 2%.The cost of the ventilation-perfusion scan does notchange as there is no morbidity or mortality associ-ated with this test. The final test comparison shouldalso consider the sensitivity and specificity of thetest. However, even using conservative values of

FIGURE 4. CT scan with contrast in patient 13 demonstrating previously unsuspected large clot (black arrow) in the rightventricle (A) as well as clot (white arrows) in the lobar pulmonary arteries to the left lower and right lower lobes (B).


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TABLE 2. Comparison of CT, Pulmonary Arteriography, and Ventilation-Perfusion Lung Scan in theDiagnosis and Management of Pulmonary Embolism

Risk to patientChargeSerial studies to evaluate therapyMay reveal intracardiac clotDisclose unsuspected pathology in

parenchyma and mediastinumDye loadUtility in central or massive embolismPhysician and technician timeVisualization of small emboliRisk with pulmonary hypertension and

RV dysfunction, coagulopathies,respiratory failure, cardiac diseaseor sepsis

Sensitivit!Specificit\

CT -Low$758.50Ideal, easy to

performYesYesCl00 ccGoodLowUncertainLow

100% (8)96% (81

Pulmonaryarteriography

Ventilation-perfusionscan

Relatively high (5)$4653.00Only under special

circumstancesNoUnlikely200-300 ccUncertainHighGoodHigh

Negligible$862.00Easy to performNoNo

None[JncertainIntermediateIlncertainI.ow

90-100 (3) 33-95% (3)100% (3, 161 25% (3)

CharRed at The New York Hospital-Cornell Medical Center July 1. 1995. ncludes charges for both physician interpwtation and technical components.R&r&es appear in parenthe&.

85% for the sensitivity and specificity of CT, this testhas a lower effective cost than the standard algo-rithm (18, 19).

In conclusion, in light of the improved visualiza-tion of the pulmonary arterial system with advancesin imaging technology, CT may prove to be an attrac-tive alternative to pulmonary arteriography and ven-tilation-perfusion lung scanning for the diagnosis ofpulmonary embolism. We have found it to be mostuseful for those patients who are too ill to undergopulmonary arteriography due to serious general me-dial conditions, severe pulmonary parenchymal dis-ease, or severe pulmonary hypertension with rightventricular dysfunction. Preexisting parenchymallung disease often results in nonspecific ventilationand perfusion abnormalities, rendering radionuclidelung scans nonspecific, costly, and time-consumingstudies. There may be situations where spiral CTshould be the initial study to diagnose pulmonaryembolism. When the clinical suspicion for pulmo-nary embolism is high, the effective cost of ventila-tion-perfusion lung scanning followed by pulmonaryangiogram, if necessary, may far exceed that of CT(17, 18). As risk-free studies such as pulmonary mag-netic resonance angiography are perfected, their ef-fective cost in some circumstances may becomeequal to or lower than other diagnostic modalities in-cluding CT and pulmonary arteriography (19). Botha prospective study examining clinical outcome inpatients without evidence for pulmonary embolismon CT and a study of the sensitivity and specificityof CT compared to pulmonary arteriography and

ventilation-perfusion lung scanning need to be doneto clarify the indications for CT in the diagnosis andmanagement of pulmonary embolism.

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Clinical Utility of CT in the Diagnosis of Pulmonary Embolism

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