Incidence and significance

N. Reed Dunnick, M.D., graduated from Cornell University Medical College, and afrer two years in internal medicine at the University of Rochester, he served in the Public Health Service at the National Institutes of Health. He received his residency training in diagnostic radiology at the Stanford University Medical Center before returning to the NIH as a staflradiologist. In 1980, Dr. Dunnick joined the faculty of Duke University where he is now Professor of Radiology and Director of the Division of Diagnostic Imaging.

Glenn E. Newman, M.D., is an Assistant Professor in the Department of Radiologv at Duke University Medical Center. He received his medical degree from Duke University and served on the Surgical House-Stafl before going to the National Heart and Lung Institute at the NZH. He completed his residency in diagnostic radiology at Duke and took fellowships in Nuclear Medicine and Vascular/Znterventional Radiology. Dr. Newman’s investigational interests are in vascular/interventional radiology especially cardiopulmonary imaging.

Louis M. Perlmutt, M.D., is an Assistant Professor of Radiology in the Vascular and Znterventional Radiology Section at Duke University Medical Center. He received his medical education at the University of North Carolina at Chapel Hill, and completed his radiology residency at the Mt. Sinai Hospital in New York. Dr. Perlmutt completed a cardiovascular fellowship at the Brigham and Women’s Hospital in Boston and took a special fellowship with Dr. Anders Lunderquist in Lund, Sweden, before joining the stag at Duke. His special interests include vascular and interventional radiology of the chest.

Simon D. Braun, M.D., received his medical degree from Emory University School of Medicine. Dr. Braun completed a residency in diagnostic radiology at McGill University and Duke University, including two years of fellowship in vascularlinterventional radiology. Dr. Braun spent four years as an Assistant Professor of Vascular/Znterventional Radiology at Duke University Medical Center, and currently is primarily responsible for vascular/interventional radiology at Memorial Mission Hospital, Asheville, North Carolina. Cur-r

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PULMONARY

Pulmonary embolism is one of the most difficult clinical problems faced today. It is a common entity with significant morbidity and mortality. Effective therapy exists, yet that therapy is often assocomplications. Therapy must, ciated with therefore, be reserved for those patients in whom the diagnosis can be made with a high degree of confidence. The clinical manifestations of pulmonary emboli are protean, and the signs and symptoms of acute pulmonary embolism are often misinterpreted as those of ischemic heart disease or primary respiratory disease. The clinical history and physical findings of acute pulmonary embolism are nonspecific, and laboratory tests offer little help in deciding among the many diagnostic possibilities. Thus, radiologic help is needed. Three radiologic examinations are commonly used to examine the patient referred for suspected pulmonary embolism, each with a specific role. The value and limitations of these examinations must be clearly understood if pulmonary emboli are to be effectively diagnosed in the large number of cases where signs and symptoms suggest their presence. This manuscript reviews the clinical setting and significance of pulmonary embolism. The diagnostic findings, including laboratory studies, are discussed. Indications for specific radiologic examinations and the techniques of performing and interpreting them are described. Finally, an approach to the patient with suspected pulmonary embolism is suggested. It is hoped that a thorough understanding of this problem will result in improved care for our patients.

Curr

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EMBOLISM

INCIDENCE

AND

SIGNIFICANCE

Although the precise incidence of pulmonary embolism is unknown, it is documented with sufficient frequency to be recognized as a common clinical problem. In 1975, Dalen and Alpert published the largest report to date on the annual incidence of pulmonary embolism in the United States.’ They stated that there were more than 600,000 cases per year and suggested that pulmonary embolism was the direct cause of death or contributed to death in approximately 200,000 cases. Of approximately 630,000 cases of pulmonary embolism, 67,000 patients (11%) died within the first hour. The diagnosis was not made in 400,000 (71%) of the 563,000 patients who survived beyond the first hour, and 120,000 (30%) of these patients subsequently died. However, in the 163,000 cases where the diagnosis was made and therapy instituted, there were only 13,000 deaths (8%). It is therefore evident that the correct diagnosis must be made and therapy instituted in as large a number of cases as possible. It is also apparent that, over the past 12 years, these numbers have probably increased. There has been an increase in the population of the United States and an even greater increase in the number of elderly persons within that population. Furthermore, improvements in medical care are keeping patients with an increased risk of venous thrombosis and pulmonary embolism alive longer. Increased sutvival of patients with an underlying malignancy, an increase in the number of surgical procedures, wider use of hormonal agents for birth control, and more frequent use of venous catheters all contribute to an increase in the number of patients with pulmonary emboli. The medical significance of this disease process a-J3

includes the morbidity and mortality of the disease itself, the morbidity and mortality of therapy regimens, and the potential for the development of chronic pulmonary embolism and pulmonary hypertension with its attendant morbidity and mortality. Each of the diagnostic tests needed to assess patients suspected of having a pulmonary embolus involves some risk that must also be considered. In addition, we cannot ignore the economic significance of this disease process to the medical community and to the nation: prolonged hospitalization, the costs of confirmatory diagnostic examinations, lost work days, and the expenses of following patients and administering anticoagulants over prolonged periods of time. Death from pulmonary embolism is usually associated with obstruction of more than 50% of the pulmonary vascular bed which results in a marked rise in pulmonary vascular resistance and pulmonary artery pressure leading to car pulmonale or acute right ventricular failure. Patients who survive the initial episode of embolization will suffer a variety of symptoms, which may include dyspnea, tachypnea, and chest pain. Poor oxygenation may result from an increase in dead space as ventilated portions of the lung are not perfused because of total obstruction by emboli. Furthermore, with shunting, portions of the lung with diminished perfusion may become poorly ventilated because of atelectasis secondary to decreased surfactant production. Hemoptysis and bloody pleural effusion may result from pulmonary infarction that usually occurs only in individuals with significant underlying chronic pulmonary or cardiovascular disease. In those patients in whom the diagnosis is made and therapy instituted, these acute changes are reversible and the patient should ultimately return to a normal state of health. PREVENTION Pulmonary embolism is associated with a wide variety of medical and surgical problems. In 1986, the National Heart, Lung, and Blood Institute (NHLBI) and the National Institutes of Health Office of Medical Applications of Research organized a Concensus Development Conference on the Prevention of Venous Thrombosis and Pulmonary Embolism.’ This conference concluded that the use of screening tests for deep venous thrombosis as a marker of pulmonary embolism was justified by both the known pathophysiology of PE and the link between a reduction in deep venous thrombosis and a reduction in PE. The report further stated that the medical community should endeavor to initiate measures to prevent deep venous thrombosis and pulmonary embolism, since preventive regimens are simpler and safer than 2434

therapeutic regimens and are equally effective. In addition, prevention would greatly reduce the cost of medical care. The conference attempted to identify the patients at greatest risk for deep venous thrombosis and pulmonary embolism together with the preventive regimens that would be most effective for these groups. Surgical patients believed to be at risk included patients more than 40 years old undergoing general surgical procedures, orthopedic patients undergoing hip and knee reconstruction, urologic patients undergoing prostatectomy, particularly by the transvesical route, and patients with multiple trauma. Gynecologic patients between the ages of 40 and 70 years with no additional risk factors had a moderate risk of pulmonary embolism, but gynecologic patients more than 40 years old with increased risk factors such as prior deep venous thrombosis, varicose veins, infection, malignancy, obesity, or hormonal therapy had a high risk of developing pulmonary embolism. Medical patients at risk for deep venous thrombosis and pulmonary embolism were those with inherited disorders such as antithrombin III deficiency, dysfibrinogenemia, and disorders of plasminogen and plasminogen activation. Acquired risk factors include pregnancy, lupus coagulant factor, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria, carcinomatosis, acute myocardial infarction, congestive heart failure, atria1 fibrillation, cardiomyopathy, constrictive pericarditis, hormonal therapy (including birth control pills), advanced age, immobility from any cause (including arthritides, stroke, and obesity), polycythemia rubra Vera, and inflammatory bowel disease. All of these medical and surgical conditions contribute to the three physiologic factors responsible for in situ thrombosis: stasis (a reduction of blood flow within the veins), injury to the venous intima, and a hypercoagulable state. Since specific patient populations at increased risk can be identified, preventive therapy may be instituted. Preventive regimens in both surgical and medical groups include low-dose heparin, dextran, external pneumatic compression, graduated compression elastic stockings, elevation of the lower extremities, and early mobilization. It is the difficult task of our clinical colleagues to identify which preventive regimens are most effective for their particular patients.

DIAGNOSIS CLINICAL PRESENTATION Since pulmonary tients predisposed Curr

f’robl

emboli usually develop in pato venous thrombosis, the signs Diagn

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and symptoms of pulmonary embolism must be distinguished from those of the existing condition or disease process. In many cases, such as those developing after surgery, this underlying condition can be clearly separated from the symptoms of pulmonary embolus. When pulmonary embolism occurs, the symptoms can often be recognized for what they are. In other cases, as in elderly patients with congestive heart failure, the symptoms are superimposed on a chronic disability and may be difficult to separate from the underlying disease. In both types of patient, the signs and symptoms of pulmonary embolism are nonspecific. Dyspnea is the most common symptom. This vague complaint is often difficult to assess, but it is typically out of proportion to the underlying condition or to the findings on the chest radiograph. Pleuritic chest pain is the second most frequent complaint and presumably arises from pulinfarction. Anxiety, cough, monary and, occasionally, hemoptysis may also occur, although significant blood loss is uncommon.

LABORATORY

TESTS

The physical examination reflects the changes occurring after a pulmonary embolism. The findings are so nonspecific that additional help is needed from laboratory tests. One of the most commonly measured parameters is the arterial oxygen pressure (Pao,). Fewer than 10% of patients suffering from pulmonary embolism will have Paoz greater than 90 mm Hg. Unfortunately, many other patients, especially those with underlying heart or lung disease, will also have a Paoz less than SO mm Hg. This measurement alone is, therefore, insufficient evidence to diagnose embolism. The electrocardiogram (ECG) may reflect the increased strain on the heart caused by elevated pulmonary artery pressures from the embolism. The ECG findings that are most specific are the pattern of acute car pulmonale &-Q-T31 and T wave inversion in leads V, through V.,. However, this complex is infrequently seen. Other changes that suggest acute pulmonary embolism include a transient right bundle branch block, right axis deviation, and right ventricular hypertrophy. A variety of nonspecific changes such as ventricular or atrial ectopy, paroxysmal atria1 fibrillation, and paroxysmal atria1 flutter are also frequently encountered.

CHEST

RADIOGRAPH

Neither the clinical presentation nor the laboratory results are sufficiently specific to permit a Curr

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confident diagnosis of pulmonary embolism. Thus, further radiologic evaluation is needed. A chest radiograph is essential to the evaluation and treatment of patients suspected of having a pulmonary embolus. Well-penetrated, upright posteroanterior and lateral films should be obtained if possible. Unfortunately, many patients are too ill to stand or othenvise cooperate, and portable films must suffice. Most patients with pulmonary embolism will have some abnormality on the chest radiograph. However, the clinical symptoms are out of proportion to the chest radiograph. Among 41 patients with documented pulmonary embolism, Moses and co-workers found a normal chest radiograph in only 3.3 The most common abnormalities they encountered were pulmonary infiltrates, pleural effusions, and atelectasis. Other abnormalities seen less often included elevation of the hemidiaphragm, cardiomegaly, congestive heart failure, pulmonary hypertension, and focal oligemia. These findings are, however, nonspecific and may also occur in many other diseases4 Most pulmonary emboli occur in the lower lobes, reflecting the effects of gravity on the hemodynamic flow pattern of the pulmonary arteries in the erect position. Because of redistribution of flow in the pulmonary arteries in the supine position, emboli more often involve the posterior segments and may occur in either the upper or lower lobes. The right lung is involved slightly more often than the left lung, and the posterior basal segment is the segment most frequently affected. A pulmonary infiltrate appears when there has been either pulmonary hemorrhage or infarction. Hemorrhage is more likely to progress to infarction in patients with underlying heart disease than in patients without cardiac impairment.5 The pulmonary opacity seen in infarction is homogeneous and segmental in distribution.6 Thus, a wedgeshaped opacity whose base is contiguous with the pleural surface is seen. Often referred to as “Hampton’s hump,” this appearance suggests pulmonary embolism, but is not often seen (Fig 1).7 Resolution of these parenchymal opacities is quite variable. If infarction has occurred, resolution can be expected in about 3 weeks. An area of infarction may occasionally progress to cavitation (Fig 21.’ If there has been hemorrhage but no infarction, clearing will occur in 7 to 10 days. Resolution is usually by contraction, and a linear density representing atelectasis or fibrosis is often seen.’ If no pulmonary infarction or hemorrhage occurs, the chest radiograph may be normal. More commonly, however, changes in the heart or the pulmonary arteries will be seen. Pulmonary artery oligemia, either general or focal, and an increase

FIG 1. Hampton’s confirms

hump. A, the wedge-shaped, the embolus (arrow).

pleural

based

opacity

in the right

in the size of the ipsilateral main pulmonary artery reflect changes due to pulmonary embolism. The hilar vessel is distended by the thrombus, and the distal vessels decrease in caliber. In extreme cases where 70% or more of the pulmonary arterial tree is occluded, there may be an increase in the peripheral vascular resistance sufficient to cause enlargement of the hilar vessels. Acute car pulmonale due to widespread peripheral pulmonary emboli or a massive central embolus is rare but may appear on the chest radiograph as cardiac enlargement, particularly of the right ventricle. The most specific finding on the chest radiograph is enlargement of the central vessels and segmental or lobar oligemia (Fig 3). Westermark described this sign in 193S1’; it is one of the few chest film findings that strongly suggests the presence of pulmonary embolism. However, even this appearance requires a normal lung for comparison, and other abnormalities often preclude using the contralateral lung as a normal control. Pleural effusion is a common manifestation of pulmonary embolism and usually indicates that infarction has occurred. The amount of the effusion is usually modest, but it may obscure the parenchymal changes. The absence of specific radiographic findings has made the chest radiograph unreliable for the diagnosis of pulmonary embo1ism.l However, it can be quite useful in excluding other conditions that can mimic pulmonary embolism clinically. Pneumothorax, rib fracture, lung cancer, pulmo206

costophrenic

angle

suggests

PE. 6, pulmonary

arteriography

nary metastases, aortic aneurysm, or pneumonia may each occur in a setting that suggests pulmonary embolism. Identification of these findings on the chest radiograph may obviate a time-consuming diagnostic workup so that attention is immediately directed to the appropriate lesion. The chest radiograph is also essential in interpreting the next appropriate radiographic examination, the radionuclide ventilation-perfusion (V/Q) scan. Interpretation of this study depends on a normal radiograph; perfusion defects are far less significant in areas of radiographic abnormality than they are in a “normal” region.

VENTILATION-PERFUSION

IMAGING

Ventilation-perfusion imaging is currently the only noninvasive imaging modality that has any documented sensitivity and specificity in the diagnosis of pulmonary embolism.12-‘4 Yet it is not without limitations. The pathophysiologic basis of V/Q imaging is persistent ventilation but absent perfusion in those regions where pulmonary embolism has occurred. The V/Q scan is sensitive to perfusion changes, but such changes are not specific for pulmonary embolism. However, the sensitivity and specificity of V/Q imaging are a clear improvement over the uncertainty of a clinical diagnosis. The only study having significantly greater sensitivity and specificity than V/Q imaging is pulmonary angiography.12-16 Curr

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FIG 2. Cavitary pulmonary infarct. A, the opacity that pulmonary infarction had occurred

in the right

lower

lobe

proved

History The evolution of radionuclide V/Q imaging began approximately 32 years ago. In 1955, Knipping et al. first documented the feasibility of evaluating ventilation noninvasively using a nonabsorbable noble gas, radioactive xenon.” Subsequently, Ernst

FIG 3. Westermark sign. Enlargement and peripheral oligemla strongly Curr

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of the main right suggests PE.

November/December

pulmonary

1988

artery

to be due

to PE B, this evolved

into a cavitary

lesion

indicating

et al. demonstrated noninvasive pulmonary perfusion imaging using nonbiodegradable radiopharmaceuticals, radioactive gold-labeled charcoal particles.18 Clinical use of pulmonary perfusion imaging was, however, delayed until the development of biodegradable radiopharmaceuticals. In 1964, Taplin et al. reported photoscanning the liver, spleen, lung, and other organs using biodegradable macroaggregates of albumin labeled with iodine-131.” Also in 1964, Wagner et al. reported using the same radiopharmaceutical exclusively for pulmonary perfusion imaging and for diagnosing pulmonary embolism.” By 1964, the feasibility of V/Q lung imaging had thus been shown, but its clinical usefulness had not been established. Moreover, images at that time were generally obtained by rectilinear scanners rather than gamma cameras. Invented in 1958 by Anger, gamma cameras permitted faster data acquisition, had higher count rate capacities and provided better resolution than rectilinear scanners.21 These gamma cameras were not in general use throughout the United States until approximately 1970. Moreover, no one strongly advocated performing ventilation lung imaging in conjunction with perfusion imaging until 1970 when DeNardo et al. documented the clinical 207

value of both studies in patients suspected of having pulmonary embolism.” Thus, the Urokinase Pulmonary Embolism Trial WPET) was performed before ventilation imaging was routinely paired with perfusion imaging. The study was done with macroaggregated albumin labled with 1311, an imperfect radiopharmaceutical, on a rectilinear scanner.23, 24 Nevertheless, this study prompted the development and use of available capabilities in cameras and radiopharmaceuticals. Moreover, this UPET study provided not only invaluable data concerning the natural history, course, and clinical management of pulmonary embolism, but also established the unreliability of a purely clinical diagnosis of pulmonary embolism. Since that time numerous reports have addressed the sensitivity and specificity of V/Q imaging of pulmonary embolism, as well as the criteria used in interpreting images and establishing the diagnosis of pulmonary embolism.25-3z In 1977, Robin challenged physicians to consider the existing misuse of V/Q imaging, especially the overreliance on its diagnostic accuracy.33 This article stimulated both rebuttals and investigations, many of them derived from retrospective data analysis. Since 1977, there has been a reassessment of the usefulness of V/Q imaging. A large multicenter study that documents the role of V/Q imaging in establishing the probability of pulmonary embolism and guiding patient management has been completed.34-3” A prospective multicenter study, Prospective Investigation of Pulmonary Embolism Diagnosis IPIOPED), which was designed to correlate V/Q imaging with pulmonary angiography, has been completed, but the results have not yet been published.

Technique Many nuclear medicine physicians disagree over the proper technique for performing V/Q imaging. Controversial issues include the choice of appropriate radiopharmaceuticals, the order of performing the ventilation and perfusion scans, the technique of obtaining the images, and the position of the patient. This controversy has resulted in a great deal of variation among institutions. Each method has its advantages and disadvantages. Ventilation imaging is performed with the patient in the recumbent position. Generally, the patient practices the technique several times before the gas is injected. This procedure allows the patient to become more relaxed and comfortable with the closed system ventilatory apparatus and hence increases the likelihood of obtaining technically adequate, diagnostic quality images. After sufficient practice, approximately 20 mCi of xenon-133 gas (T:, 5.2 days; 80 KeV) is injected into 208

the closed system ventilatory apparatus during maximum inspiration by the patient. Images are obtained in the posterior projection only. The initial ventilation image, often called the wash-in or$rst breath image, has an activity pattern that generally corresponds to the normally ventilated lung. Two equilibrium images are then obtained while the patient is rebreathing the gas for 3 to 5 minutes. Last, wash-out images are obtained at l-minute intervals for 4 or 5 minutes or until almost all of the gas is exhaled. The purpose of the three sets of ventilation images is to distinguish normally ventilated from abnormally ventilated lung. The equilibrium images ‘permit the gas to enter the abnormally ventilated lung via collateral air drift and represent both the normally and abnormally ventilated lung. The wash-out images represent air trapping in the abnormally ventilated lung. Ventilation images may also be obtained with krypton-Slm gas, which is superior to 133Xe in many respects. The short half-life of 81mKr (13 seconds) results in a very low radiation dose to the patient and allows images to be obtained in a variety of projections. Furthermore, ‘lrnKr does not contaminate the ventilation equipment. The higher energy of ‘l”‘Kr (KeV 190) permits the ventilation images to be obtained after the perfusion studies without suffering degradation from the downscatter of the technetium. However, the half-life of the ‘lmKr generator is only 4.5 hours, an inconvenience when studies are needed 24 hours/day. This additional expense involved with ‘lmKr has limited its general application.14 Perfusion imaging is also performed with the patient in the recumbent position. Approximately 500,000 particles of macroaggregated albumin labeled with approximately 5 mCi of technetium99m (T:, 6 hours; 140 KeV) is injected intravenously. These particles are localized in the precapillary pulmonary arterial system, and the images represent instantaneous perfusion. Images are obtained from the posterior, anterior, right and left lateral, and right and left posterior oblique projections . The radiopharmaceutical is injected, and imaging is performed with the patient in the recumbent position to lessen image degradation from patient motion. Furthermore, the supine position helps to redistribute both pulmonary blood flow and pulmonary ventilation so that there is a lesser gradient from the bases to the apices of the lungs. Finally, the V/Q images are compared with a current chest radiograph and interpreted. The chest radiograph is not a substitute for ventilation images, but the information it provides is, nonetheless, important. Cur-r

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Interpretation

TABLE

1.

Differential Perfusion

Diagnosis Mismatch

Disputes over the technique of V/Q imaging and the choice of radiopharmaceuticals are trivial in comparison to the disagreement over the interpretation and role of V/Q imaging in the diagnosis of pulmonary embolism. A pulmonary embolus results in nonperfusion of lung that is normally ventilated and does not contain an opacity on the chest radiograph. However, a perfusion defect in itself is nonspecific, because almost all pulmonary diseases can alter regional lung perfusion.37-3g Diseases that can cause a perfusion defect and thus may mimic pulmonary embolism are listed in Table 1. V/Q images are currently interpreted according to many published reference criteria and are given interpretations of normal, low, intermediate, indeterminate, and high probabilities for pulmonary embolism. Three commonly used schemes are enumerated in Table 2. It is not the meaning or significance of a low, intermediate, indeterminate, or high probability classification that is questioned but the criteria used in assigning these levels of probability.

of Ventilation-

Pulmonary embolism (acute) Pulmonary embolism (chronic) Pneumonia Pulmonary aspiration Bronchogenic carcinoma Radiation therapy (remote) Thoracotomy Sung resection) Emphysema Mediastinal fibrosis Tuberculosis Collagen vascular disease Sarcoidosis (IV) Intravenous drug abuse Lymphangitic carcinoma Embolism (air, fat) Pulmonary hypertension Mitral valve disease Sickle cell disease Pulmonary artery agenesis/stenosis Pulmonary arteriovenous malformation Pulmonary veno-occlusive disease Pulmonary artery sarcoma

TABLE Diagnostic McNeil

1. Normal

2. Schemes* Criteria

Biello

perfusion

(4)

1. Normal

1. Multiple Q defects with ventilation (VI match 2. Single subsegment V/Q mismatch

1. Single segment V/Q mismatch 2. Mixed V/Q match and mismatch 3. Q defect with matched CXR 4. Single lung V/Q mismatch 5. Single lobe V/Q mismatch 6. Multiple V/Q mismatches with largest being subsegmental 1. Multiple V/Q largest being 2. Multiple V/Q largest being 3. Multiple V/Q largest being

*Small = <25% Curr

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mismatches lung mismatches lobar mismatches segmental

of anatomic

Criteria

with with with

segment;

November/December

PIOPED

Normal perfusion (41

1. Normal perfusion (41 or Q defects from extrinsic etiologies

Low Probability 1. Small V/Q mismatches 2. V/Q matchtes) without densityties on chest radiograph (CXR) 3. Q defectls) much smaller than densities on CXR

1. Small Q defect(s) regardless of V or CXR findings 2. Q defect much smaller than CXR defect W irrelevant) 3. V/Q match in 5 50% one lung or % 75% of one third of lung. CXR normal or nearly normal 4. One moderate Q defect with normal CXR (V irrelevant) 5. Nonsegmental Q defects

Indeterminate or Intermediate Probability 1. Diffuse, severe chronic obstructive pulmonary disease ICOPDJ 2. Q defect(s) same size as densityties) on CXR 3. Single moderate V/Q mismatch without matched density on CXR High Probability 1. Q defectkl much larger than density(ies1 on CXR 2. One large or multiple moderate Q mismatch without matched density on CXR

moderate

1988

= 25%-75%

of anatomic

Criteria

segment;

1. Abnormality not “high” or “low”

defined

by either

1. Two or more large Q defects with V and CXR normal V/ 2. Two or more large Q defects where Q is much larger than either matching V or CXR 3. Two or more moderate Q defects and one large Q defect with V and CXR normal 4. Four or more moderate Q defects with V and CXR normal large = 75% of anatomic segment.

FIG 4. Low-probability V/Q study for PE. A, chest radiograph demonstrates cardiomegaly and an interstitial pattern compatible with pulmonary edema from congestive heart failure. B, ventilation images demonstrate symmetric activity in each lung during the wash-in (W/j, equilibrium (E), and wash-out (WO) phases of the study. C, perfusion images demonstrate symmetric activity in each lung with only nonsegmental defects. The circular areas of reduced activity, especially on the RAO projection, represent ECG leads.

In general, perfusion defects from pulmonary emboli are large and occupy 75% or more of a bronchopulmonary segment. Smaller defects may also be caused by emboli but are less specific. Defects caused by emboli also tend to extend to the pleural surface. If an area of normally perfused lung separates the defect from the pleural surface, the defect is not likely to be due to an embolus4’ Most patients with pulmonary embolism will have more than one perfusion defect. The UPET study showed an average of eight different segments involved by emboli.23 It is unusual to see only a single defect on the perfusion images in a patient with pulmonary embolism. Although few V/Q studies are considered normal, this result carries a high level of diagnostic certainty. Since to date pulmonary embolism has not been confirmed by pulmonary angiography in a patient with a normal V/Q study, a normal study virtually excludes pulmonary embolism. A V/Q study interpreted as low probability is associated with a 10% to 15% incidence of pulmonary embolism (Fig 4). Emboli in these patients are usually small and nonocclusive in nature. Therefore, perfusion defects are not seen on the perfusion images. Patients with low probability V/Q studies undergo pulmonary angiography infrequently unless the clinical suspicion of embolic disease is high. 210

Intermediate probability V/Q studies are associated with a 30% to 40% incidence of pulmonary embolism (Fig 5). Patients with intermediate V/Q studies frequently undergo pulmonary angiography to verify the presence or absence of emboli. Indeterminate V/Q studies are associated with a 33% incidence of pulmonary embolism.41 These patients also need pulmonary angiography to establish the diagnosis. High probability V/Q studies are associated with a 64% to 90% incidence of pulmonary embolism (Fig 6). These patients undergo pulmonary angiography if anticoagulation is contraindicated and the diagnosis must be confirmed before therapy is instituted. Less commonly, patients with high probability V/Q studies undergo pulmonary angiography when they are known to have pulmonary or mediastinal disease that can mimic pulmonary embolism. In these cases, the pulmonary angiogram is performed to exclude pulmonary embolism. There are well-founded reasons for the controversy over the reference criteria used to classify a V/Q study into one of the five probability levels. Since the prevalence of pulmonary embolism is not established with certainty, it is difficult to assess the probability level for any V/Q pattern. The literature addressing pulmonary embolic disease contains very few prospective studies that correCur-r Probl

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FIG 5. Intermediate probability V/Q study for PE. A, chest radiograph demonstrates mild cardiomegaly and bibasilar air space processes. ventilation images demonstrate asymmetric activity in each lung with decreased activity (ventilation) in each base. This correlates the chest radiograph. C, perfusion images demonstrate nonsegmental and segmental defects predominantly in each base.

late state of the art V/Q imaging and pulmonary angiography. Too many investigations and publications are retrospective and therefore introduce selection bias. Moreover, V/Q imaging should be used to establish a level of probability, not to prove the diagnosis. Thus, those reports using V/Q studies as conclusive diagnostic evidence should be regarded with some skepticism. Thus, a conservative interpretation of V/Q studies is encouraged. This should be followed by pulmonary angiography in the following instances: 1. When a patient Curr

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in whom November/December

there is a high clin1988

B, with

ical index of suspicion has a low probability V/Q study. 2. When a patient has an intermediate or indeterminate V/Q study. 3. When a patient has a high probability V/Q study and a contraindication to anticoagulation therapy. Common examples include recent postoperative patients, patients with peptic ulcer disease, or patients with a recent cerebrovascular accident. 4. When a patient has a high probability V/Q study and pulmonary or mediastinal disease that is known to mimic pulmonary embolism.34-41 211

FIG 6. High-probability V/Q study for PE. A, chest radiograph demonstrates a normal cardiac silhouette and no pulmonary opacities. B, ventilation images demonstrate symmetric activity (ventilation) of each lung during the wash-in (W/J and equilibrium (E) images of the study, but there is retention of activity in each lung during the wash-out (WO) phase of the study. C, perfusion images demonstrate multiple bilateral segmental (or larger) perfusion defects.

Correlation Pulmonary

of Ventilation-Pevusion Angiography

Imaging

and

The LJPET study results, published in 1970, and the work of McNeil et al. correlating V/Q imaging and pulmonary angiography served as the most commonly accepted reference criteria for the interpretation of V/Q imaging through the 197Os.“26 Since 1977, the criteria suggested by Biello et al. have become widely used.27 According to these criteria, a low probability study indicates a 4% to 22% probability of pulmonary embolism in retrospective and prospective studies. A high probability study indicates an 85% to 90% probability. The most recent review from Duke University Medical Center demonstrated similar probabilities.41 Intermediate and indeterminate probabilities, although different by definition, had probabilities of approximately 33% for pulmonary embolism. The relatively wide range of probabilities relates to many 212

factors. There is a predominance of retrospective studies composed of small patient groups whose selection was biased. In addition, only 7% to 15% of the patient population having V/Q studies subsequently undergoes pulmonary angiography. The techniques of V/Q imaging and pulmonary angiography have concerned some critical readers. The reference criteria for interpreting V/Q images and pulmonary angiograms have varied from report to report. Last, there is also some variation among observers and even within the same observer in interpreting these examinations. The difference in pulmonary emboli in low and high probability V/Q studies has also been investigated.41’ 42 The chief differences are in the size and location of the emboli. In patients with low probability V/Q studies and embolic disease documented by pulmonary angiography, the emboli are small, peripherally located, and generally nonocCurr

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elusive. Since they are nonocclusive, these emboli are either not demonstrable on perfusion images or are demonstrable only as a small perfusion defect. In contrast, in patients with high probability V/Q studies and embolic disease documented by pulmonary angiography, the emboli are large, centrally located and generally have occlusive elements. Thus, perfusion images demonstrate single or multiple large perfusion defects. PULMONARY ANGIOGRAPHY Indications In general, the diagnostic approach to pulmonary embolism begins with less invasive procedures. The.many noninvasive procedures that are nonspecific are important because they exclude other diagnostic possibilities (myocardial infarction, arrhythmia, pneumothorax, and pneumonia) whose clinical presentation may mimic pulmonary embolism. After other diagnostic possibilities have been excluded, almost all patients undergo radionuclide V/Q imaging, which not only establishes the relative probability of pulmonary embolism, but also serves as a guide should the patient subsequently undergo angiography. Pulmonary angiography is indicated when more information than that provided by less invasive studies is required (Table 3). There are two indications for angiography following the V/Q imaging study. The first is an apparent discrepancy between the clinical probability of pulmonary embolism and the results of the V/Q scan. Second, if invasive therapy such as embolectomy or infusion thrombolytic therapy is contemplated, embolism should be proved with pulmonary angiography. If caval interruption is considered because of recurrent pulmonary emboli, the embolic process should be similarly confirmed. The most frequent indication for pulmonary angiography is the need for greater certainty than the radionuclide V/Q scan provides. An indeterminate scan is one in which other disease processes such as chronic obstructive lung disease preclude evaluation of the lungs for the presence or absence of pulmonary embolism. In these circumstances we can only point out to the referring physician what TABLE Indications

3. for Pulmonav

Angiography

Contraindication to anticoagulation and high-probability study Plan to use thmmholytic therapy Contemplate caval interruption High clinical suspicion and low-probability V/Q study Indeterminate or intermediate probability V/Q study An underlying process that may cause a perfusion defect

Curr

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1988

V/Q

proportion of patients falling into that category will have a pulmonary embolus. Most of these patients should be studied with pulmonary angiography. Patients with a low probability V/Q scan are unlikely to have pulmonary emboli. However, those patients with a high clinical suspicion of embolism may represent a subgroup in which it is appropriate to perform a pulmonary arteriogram.43 Fortunately, the relative safety of pulmonary arteriography allows it to be used in a relatively large number of cases without fear that the complications will exceed the expected benefit of increased diagnostic certainty. Contraindications The strongest contraindication to pulmonary arteriography is a normal V/Q lung scan. Documented pulmonary embolism has not been reported in a patient with a normal V/Q scan and is extremely unlikely.44 An embolism may be present in patients with “low, low probability” V/Q scans and, in certain circumstances, it may be appropriate to study these patients despite the fact that pulmonary embolism is unlikely. Relative contraindications include a history of allergy to contrast medium, the presence of elevated right ventricular pressures, bleeding diatheses, renal failure, and a left bundle branch block. In patients with a previous reaction to contrast material, premeditation with corticosteroids is administered either intravenously or orally for 12 to 24 hours before the angiogram. In patients who have had a more severe reaction, H, and H, receptor antagonists may also be used. Intramuscular diphenhydramine (50 mg) and intravenous cimetidine (300 mg) are given just before the study. A member of the respiratory therapy team should be nearby in case intubation is required. Pulmonary hypertension, right ventricular dysfunction, or both have long been viewed as a relative contraindication to pulmonary angiography. If the right ventricular pressures (pulmonary artery pressure and right ventricular end-diastolic pressure) are elevated, studies are sometimes aborted because of the common belief that pulmonary angiography significantly increases morbidity and mortality in these patients. A large group of patients with elevated right ventricular pressures who underwent pulmonary angiography was recently reviewed. It was found that the incidence of major nonfatal complications was the same for patients with elevated right ventricular pressures as for those with normal pressures. The incidence of death, however, was approximately 2% to 3% higher in patients with severe pulmonary hypertension and moderate right ventricular dysfunction. These data suggest that there 213

is increased mortality if the right ventricular enddiastolic pressure is greater than 20 mm Hg and the pulmonary artery pressure is greater than 70 mm Hg.15 It is unclear, however, to what degree the pulmonary arteriogram contributed to the deaths of those patients. They were all gravely ill and showed signs of cardiac decompensation. It is entirely possible that the pulmonary arteriogram was incidental to the clinical course. In this group of patients, the risk of death from the arteriogram is certainly less than the risk of death from undiagnosed pulmonary embolism or the morbidity from indiscriminate use of anticoagulant therapy.45 Elevated right ventricular pressures need not necessarily be a contraindication to pulmonary angiography. Furthermore, subselective contrast injections into the area of highest probability for embolism will reduce the load on the heart and should be better tolerated. The use of the new low osmolar or nonionic contrast agents may also benefit this group of patients. Bleeding abnormalities should be corrected before the study. The possibility of myocardial perforation has essentially been eliminated by use of the Grollman-type pigtail catheter. However, the needle may accidentally enter the femoral artery during attempts to access the femoral vein. Since the femoral vein is deeper than the femoral artery, it is possible to pass the needle through the artery into the vein. Subsequent dilations and catheter exchanges would then be made through both the front and back walls of the femoral artery. Since penetration of the femoral artery would not be recognized, postprocedural compression would be adequate for venous puncture only and would be insufficient to tamponade the arterial puncture. In those patients in whom it is not possible to correct bleeding problems, the arm approach is recommended. In patients with mild renal failure, adequate hydration should be instituted. Forced fluids and mannitol diuresis have also been advocated to minimize contrast induced renal failure. In patients with moderate to severe renal failure, dialysis should be considered after the arteriogram, if necessary. The volume of contrast can also be limited by performing a limited study directed only at those areas of the V/Q lung scan that are most abnormal. A temporary pacemaker should be placed in patients with a left bundle branch block before the study to avoid complete heart block. Irritation of the myocardium by the catheter can generate a right bundle branch block, which, in conjunction with a preexisting left bundle branch block, may result in complete heart block. If there are other preexisting conduction defects or arrhythmias, a 214

recent myocardial infarction, or other uncertainties, cardiology consultation should be sought.

Technique

A well-maintained standard angiographic fluoroscopy table with single plane rapid serial filming capability is the minimum requirement for highquality pulmonary angiography. The addition of features such as biplane filming capability, spot cameras, LJ or C arms, and tine and digital subtraction add to the convenience of the study and may result in a reduced contrast volume. Biplane filming or digital subtraction techniques should also improve speed and safety. The angiography suite should also be equipped with an ECG monitor and a physiologic monitor for the measurement of right ventricular pressures. A paper recorder should be integrated into the system to record pressure tracings and the ECG. A life support cart should be readily available, and all members of the angiography team should be familiar with its use. When a pulmonary angiogram is requested, it is the responsibility of the radiologist to discuss the case with the referring physician and review all pertinent radiologic studies. We strongly recommend a radionuclide lung scan before performing a pulmonary angiogram because it may render the angiogram unnecessary. If the angiogram is needed, the lung scan will direct the angiographer to the most abnormal areas of the lung. Once the decision to perform a pulmonary angiogram has been made, the procedure and its most common risks should be explained to the patient, and informed consent should be obtained. Only clear liquids and oral medications are allowed after midnight. The patient must have an IV line placed before the procedure. Routine on call medications include 0.6 mg of atropine, 50 to 75 mg of meperidine, and 25 mg of promethazine given intramuscularly. Coagulation studies and creatinine levels are obtained, and the ECG is examined to rule out acute myocardial insufficiency, a conduction defect, or a cardiac arrhythmia. If the patient has been heparinized, heparin is stopped 2 to 4 hours before the study. The pulmonary angiogram should be performed by an experienced angiographer well versed in the anatomy of the right ventricle and pulmonary arteries and in the pressures of each segment of the heart. The right ventricle may be approached through either the arm or groin. Most radiologists are more familiar and more comfortable with the groin approach and generally start there, using the percutaneous Seldinger technique. Because the angiogram requires a large amount of contrast at Curr

Probl

Diagn

Radial,

November/December

1988

high flow rates (usually 30 to 50 ml at 15 to 25 ml/ second), a wide-bore catheter is required. For the groin approach, a no. 5 or 7 French Grollman-type pigtail catheter with multiple side holes is generally employed. Stiff, straight no. 8 French multiside-hole catheters of the National Institutes of Health (NIH) type are no longer used because of the recognized complication of myocardial perforation.14 The groin is shaved, prepped, and anesthetized with 5 to 10 ml of bupivacaine, a fairly long-acting local anesthetic. The common femoral vein below the inguinal ligament is the best insertion site. In a thin patient, the location of the inguinal ligament may be determined by palpation of bony landmarks of the pelvis, and the.vein can be located by its medial relationship to the palpable femoral artery. If the patient is obese and it is difficult to palpate the bony landmarks, the inguinal ligament or the femoral artery, fluoroscopy may be used to locate the femoral head and determine the presumed location of the common femoral vein. The femoral artery courses diagonally across the medial one third of the femoral head, and the vein should be located medial to the artery. The inguinal crease is an unreliable landmark for locating the inguinal ligament. Once the needle is inserted, the stylet is removed and a syringe or extension tubing with a syringe is connected to the hub of the needle. Gentle suction is applied as the needle is slowly withdrawn. With return of venous blood, the tubing is removed from the needle hub, and a guide wire is passed through the needle into the vein and advanced into the inferior vena cava. The tip of the guide wire is followed fluoroscopically, because it could pass into the right ventricle and cause potentially dangerous arrhythmias. If the guide wire fails to advance properly, one of two problems may have developed. Usually the guide wire has entered the ipsilateral ascending lumbar vein (Fig 7). If so, the wire is retracted into the external iliac vein and passage into the inferior vena cava is again attempted. If this attempt proves unsuccessful, a dilator or curved catheter can be used to reorient the course of the guide wire so that it advances into the inferior vena cava. The second circumstance in which a guide wire may fail to advance is when the inferior vena cava or ipsilateral iliac vein is occluded, either by thrombus or extrinsic compression (Fig 8). In either instance, the procedure should be performed from the arm. Once access to the inferior vena cava is gained, the angiographic catheter is passed over the guide wire and advanced into the right atrium. We generally do not inject contrast before advancing the Cur-r

Probl

Diagn

Radio&

November/December

1988

FIG 7. Spot

film

of pelvis

showing

the

right

ascending

lumbar

vein

(ar-

row).

FIG 8. Inferior vena vena cava.

cavogram

showing

complete

occlusion

of the Inferior

215

catheter through the vena cava unless its advance is impeded. Contrast injection may be prudent, however, to prevent inadvertent embolization if a caval mural thrombus is present. Nonoccluding caval thrombi may be difficult to see with a hand injection, and a formal cavogram may be required (Fig 9). The likelihood of the presence and dislodgement of caval clot is low, and cavography is seldom performed. Once the catheter enters the right atrium, pressures are recorded. The secondary curve of the Grollman catheter is designed to cross the tricuspid valve; however, it is often useful to exaggerate this curve by inserting a deflecting guide wire or the back end of a heavy-duty 0.038 in. (0.97-mm) guide wire, which has been acutely curved (Fig 10). The tip of this curved guide wire is placed proximal to the origin of the pigtail portion of the catheter. The wire-catheter combination is rotated to the plane of the tricuspid valve. At this point, the end of the Grollman catheter usually passes through the tricuspid valve and into the right ven-

FIG 9. Inferior vena cavogram left renal vein (arrow). 216

showing

a mural

thrombus

just

below

the

tricle. The catheter is then advanced over the fixed guide wire using clockwise torque. It is pushed across the pulmonic valve and passed out into a pulmonary artery. The catheter usually seeks the left pulmonary artery, a position that is accepted if either the left or both pulmonary arterial trees are to be studied. If the right pulmonary artery is the highest probability area on the V/Q scan, the catheter should be manipulated into the right side. Pulmonary artery pressures are recorded, and a test injection is performed to estimate the required flow rate. In general right ventricular pressures are not determined because of the high frequency of ventricular ectopy. However, if pulmonary artery hypertension is present, it may be useful to pull the catheter back into the right ventricle to measure the right ventricular end diastolic pressure (RVEDP). In each of the three deaths from pulmonary angiography reported by Mills et al., the RVEDP was greater than 20 mm Hg.15 If high pulmonary artery pressures are found, the study can be modified by more selective injections using less contrast material. Studies are not necessarily aborted because of high pressures. Pressures, however, can be a useful guide in the clinical care of the patient, and their values are always included in the chart. The tip of the Grollman catheter is placed in the descending pulmonary artery on the side that, according to the V/Q scan, is most likely to demonstrate embolism. Generally, 30 to 50 ml of contrast is injected at a rate of 15 to 25 ml/second, depending on pulmonary arterial blood flow. Rapid serial films are obtained at three/second for 4 seconds (a total of 12 films). After the study, the patient is placed on bedrest for 1 to 4 hours, with frequent checking of vital signs and fluid replacement. Excessive bedrest should be avoided in these patients because it may contribute to venous stasis and clot formation. Thus, early ambulation should be encouraged if possible. Some consider the arm approach to be a safer approach because of the possibility of thrombus in the inferior vena cava or arterial injury at the puncture site. However, this concept has not been confirmed by clinical studies. It is also generally considered easier to traverse an enlarged right ventricle by the arm approach. An antecubital vein may be accessed either percutaneously or by a cut-down. The basilic vein is the preferred entry site because it is a more direct route to the subclavian vein. However, if access through the basilic vein is impossible, the cephalic vein can be used and the acute angle of entry of the central cephalic vein with the subclavian vein can be negotiated with a movable core guide wire, a curved catheter, or both. One technique for gaining access to a vein in the antecubital fossa uses a 19-gauge butterfly Curr

Probl

Diagn

Radial,

November/December

1988

FIG 10. Passage of catheter through the heart into the pulmonary arteries. A, the tip of a Grollman catheter is in the right atrium. 8, passage of the catheter through the tricuspid valve is aided by a curved back end of a heavy-duty guide wire. C, the catheter is torqued counter clockwise and advanced across the pulmonic valve and into the main pulmonary artery. D, the catheter is advanced into the descending left pulmonary artery. E, the catheter is withdrawn from the left pulmonary artery and torqued toward the right pulmonary artery. F, the catheter is subsequently advanced into the descending branch of the right pulmonary artery.

scalp vein needle and a 0.025-in. (0.64-mm) guide wire. The tubing of the butterfly needle is sterilely removed with a scalpel. The superficial vein, preferably the basilic, is entered with the 19-gauge needle. When blood returns, the 0.025-in. guide wire is passed through the needle into the vein. The needle is then removed and a no. 5 French dilator is passed over the guide wire. Once the dilator is positioned, the 0.025-in. wire may be withCur-r

Probl

Diagn

Radiol,

November/December

1988

drawn and a larger one substituted to lead the pigtail catheter into the superior vena cava and right atrium. Once a wire is in the right atrium, a pigtail catheter is passed over the wire and advanced into the right atrium where pressures are obtained. A tip deflecting wire is then passed into the catheter up to the pigtail portion, and the tip of the catheter is subsequently deflected into the right ventricle. De217

flection is maintained as the catheter is advanced off the wire, through the pulmonic valve and passed selectively into a pulmonary artery. The pulmonary arteriogram is then performed as described for the femoral vein approach. One additional advantage of this approach is that bedrest is not required after the procedure.

Contrast

Material

The use of the newer contrast agents, either low osmolar ionic or nonionic, is controversial. It has been shown experimentally that these agents promote fewer changes in various physiologic parameters than do ionic contrast media. However, the clinical significance of these differences is not clear.46 For example, research done on dogs has found a smaller increase in pulmonary artery pressures after injection of nonionic contrast.47’48 However, in a study that we performed to compare the effects of iopamidol 370 and sodium meglumine diatrizoate 370 on pulmonary artery pressures, no signifiant difference was found.4g Greater comfort is an apparent advantage in the

FIG 12. Right pulmonary angiogram branch of the right middle

Right pulmonary arteriogram defects (arrowheads). 218

showing

several

large

central

filling

defect

in a segmental

use of low-osmolarity agents. Most patients reported that the uneasy sensation of warmth commonly experienced with conventional ionic contrast agents was completely absent. Furthermore, since patients coughed less as a result of the injection, motion artifact was seen less often than with ionic contrast materials. Since motion artifact is reduced, the film quality is improved,4s particularly when magnification oblique runs are made. A similar finding was reported by a group comparing ioxaglate 320 with sodium meglumine diatrizoate 370.50 Whether or not the newer agents result in fewer allergic reactions and decreased nephrotoxicity remains in question. Until the issues are better defined, it appears that there are only three clear advantages of low-osmolarity contrast over conventional agents: greater patient comfort, diminished incidence of coughing, and consequently, less motion artifact. These advantages must be weighed against the significantly higher cost of the newer contrast agents.51

Angiographic

FIG 11.

showing a filling lobe (arrow).

Features

The pulmonary arteriogram should be interpreted after each contrast injection. Once the diagnosis of pulmonary embolism is made, the examination is terminated. The goal of the arteriogram is to document the disease process rather than quantitate the extent of embolization. The aim of therapy is to prevent the next embolic episode. The signs of acute pulmonary embolism may be considered as either primary or secondary. The angiographic sine qua non of acute pulmonary embolism is an intraluminal filling defect or vessel cutoff with a tongue of thrombus projecting into the column of contrast (Figs 11 to 13). In general a biplane angiogram is sufficient to detect or exCurr

Probl

Diagn

Radial,

November/December

1988

elude the presence of pulmonary emboli. If equivocal information is found, an oblique angiogram (usually with the side down) is made subselectively. Magnification technique may be required to demonstrate more elusive emboli (Fig 141.5’ The V/ Q scan can also be used to determine the proper projection for best demonstrating pulmonary embolism.53 Secondary signs include areas of diminished perfusion, a prolonged arterial phase, tortuous peripheral vessels, and a delayed venous phase. These findings are nonspecific and may be seen in obstructive pulmonary disease, severe mitral stenosis, bronchial asthma, and left ventricular failure. Pulmonaxy embolism should not be diagnosed on these findings alone.54 A variety of nonembolic pathologies may be demonstrated by pulmonary arteriography in the workup of pulmonary embolism. These include arteritis (Fig 151, primary and metastatic pulmonary arterial neoplasms, extrinsic compression of the pulmonary artery by either granulomatous or neoplastic hilar lymph nodes (Fig 16),55 and pulmonary arteriovenous malformations.

FIG 13. Left pulmonary arteriogram showing branch of the left upper lobe (arrow).

a filling

defect

in a segmental

Complications The possible complications arising during pulmonary angiography may be classified as those due to the catheterization procedure, adverse reactions to contrast material, and those due to altered hemodynamics secondary to contrast injection. In one large series from this and an affiliated institution, Mills et al. reported the incidence of

FIG Value 3 of selective arteriography. gram 1 showing a clear-cut filling Cur-r Probl

Diagn

Radiol,

A, left pulmonary defect

November/December

in a distal

artenogram showing segmental branch 1988

an apparently

normal

study.

6, selective

left lower

lobe

arteno-

219

-

-

FIG 15. Close-up

of segmental

branches

of right

pulmonary

arteriogram

shows

complications in 1,350 pulmonary arteriograms.15 Among the complications were 14 myocardial perforations, none of which was fatal. These occurred exclusively in catheterizations performed with a stiff no. 8 French multiside-hole straight NIH-type catheter (Fig 17).15 Use of the Grollman-type pigtail catheter has eliminated this complication. The other significant group of complications related to catheter manipulation is the generation of arrhythmias (usually ventricular). If ventricular premature contractions occur, they are usually caused by catheter irritation of the right ventricle. These contractions will subside when the catheter is either withdrawn or passed out into the pulmonary artery. If the catheter cannot negotiate the right ventricle without causing excessive extrasystolic beats, 100 mg of lidocaine may be given intravenously and will usually control ventricular irritability and allow placement of the catheter in the pulmonary artery. There are a number of complications (excluding allergic) that may be caused by the secondary hemodynamic effects of contrast injection. These complications include angina, acute respiratory distress, a variety of arrhythmias, cardiac arrest, and death secondary to acute car pulmonale. The incidence of major nonfatal complications from contrast injection is on the order of 2%, and the overall incidence of death is approximately 0.1%. It is generally believed that the presence of pulmonary hypertension, right ventricular dysfunction, or both significantly increases the risk of a fatal 220

a focal

narrowing

(arrow)

in a patient

with a vasculitis.

outcome. However, it has been found that there is only a modest increase in the risk of mortality in this group of patients.16 Contrast reactions remain a significant problem. Their onset is unpredictable even where there is a history of previous contrast reaction, In these patients, the precautions, including premeditation, previously outlined should be taken. Although still an unresolved issue, low-osmolarity contrast material is associated with fewer adverse reactions than conventional contrast and is recommended for use in patients with a history of previous contrast reactions.56

OTHER MODALITIES Because of the expense of sophisticated angiographic equipment, the need for specialized personnel and the morbidity of conventional pulmonary angiography, noninvasive techniques for the direct visualization of thrombus have been investigated. Anecdotal experience with computed tomography (CT) has been reported.57’58 Thrombus has been demonstrated as a filling defect in the pulmonary artery on an enhanced scan (Fig 18). If the thrombus is sufficiently large, decreased vascular@ of the lung supplied by the involved pulmonary artery may be demonstrated. Small pulmonary emboli will, however, remain very difficult to detect by CT because its spatial resolution is limited. Cum

Probl

Diagn

Radio&

November/December

1988

FIG 17.

FIG 16. Right pulmonary arteriogram showing compression scending pulmonary artery and an absence of filling

of the defects.

de-

Although in its infancy, magnetic resonance imaging (MRI) has shown promise in the direct detection of pulmonary emboli. Magnetic resonance imaging has successfully imaged relatively large central pulmonary emboli (Fig 19).5gs60 However, the problem of spatial resolution is even greater with MRI than it is with CT. The final method of direct visual examination of pulmonary emboli is angioscopy. This procedure has been successfully performed in the laboratory and in a few patients. Because of its invasiveness and its probable inability to demonstrate small peripheral emboli, this procedure will probably not gain widespread use.61’ 62 It was hoped that IV digital subtraction angiography (DSA) would match the sensitivity and specificity of pulmonary angiography. The technique is less expensive, safer, faster, and certainly easier to perform than conventional pulmonary angiography. Intravenous DSA involves percutaneous placement of a catheter in either the superior vena Curr

Probl

Diagn

Radial,

November/December

1988

Lateral projection showing space due to a perforation phy (arrows).

contrast occurring

lying during

within the pulmonary

pericardial arteriogra-

cava, inferior vena cava, or right atrium through a peripheral vein. Contrast is injected, and images of the pulmonary arteries are acquired (Fig 20). The feasibility of the technique was tested in dogs. Reilley et al. created absorbable gelatin sponge (Gelfoam) emboli and imaged the lungs with V/Q scans, conventional pulmonary angiography, and IV DSA. They found the sites of embolization on 75% of the V/Q scans, 93% of the pulmonary angiograms, and 75% of the arterial phase of an IV DSA. When combined with the parenchymal phase, identification of all sites of emboli was accomplished by IV DSA.63 Another animal study achieved similar good results.“4 Results in patients, however, have not been as consistently promising. In an early study, Kollath and Riemann touted the efficacy of IV DSA in 220 patients.“5 However, they did not compare it with conventional pulmonary angiography. Ludwig et al. compared IV DSA with radionuclide scintigraphy and found IV DSA to be superior.66 Pond et al. 221

It is clear that conventional pulmonary angiography remains the procedure of choice for the definitive diagnosis of pulmonary embolism.

UNRESOLVED

FIG 18. Contrast-enhanced pulmonary outflow

CT scan showing large tract and left pulmonary

filling defects within artery (arrows).

the

found IV DSA to be 97% as accurate as conventional arteriography when adequate examinations were obtained.67 The study was inadequate in only 2 of the 33 patients studied. However, in a study involving 25 patients, Gutierrez et al. concluded that IV DSA lacked adequate specificity and sensitivity for the diagnosis of pulmonary emboli in subsegmental pulmonary arteries6’ Intra-arterial DSA may also be used in certain instances. It has the advantage of requiring lower contrast volumes. Because no film is used, it is performed more quickly. Its disadvantages include decreased spatial resolution and motion and misregi str -ation -artifact.

PULMONARY

EMBOLISM

In most patients, pulmonary emboli are broken up by the endogenous lytic system. Resolution of these fibrinous clots is usually completed within several weeks. In approximately 1% of patients, however, this process does not occur, and the thrombi become fibrotic and adhere to the arterial walls .6g,7o These unresolved pulmonary emboli obstruct pulmonary arterial flow and lead to increased vascular resistance and pulmonary hypertension. The chest radiograph is abnormal in most of these patients, cardiomegaly being the most frequent finding. Other commonly noted abnormalities include enlargement of central pulmonary arteries, mosaic oligemia, azygos vein enlargement, volume loss, atelectasis, and pleural effusion.71 The radionuclide V/Q scan is abnormal in patients with unresolved pulmonary emboli, but it does not permit a distinction between unresolved and acute emboli. The arteriographic signs of unresolved pulmonary emboli are, however, entirely different from those of an acute embolus. The organized thrombus that adheres to the vessel wall causes focal narrowing (Fig 21) or complete occlusion of the artery (Fig 22). In some patients, short weblike stenoses or eccentric plaques from retracting thrombi may also be seen.” If surgical thrombectomy is

FIG Magnetic resonance high intensity signal 222

image of central right pulmonary corresponding to a large pulmonary

embolus. embolus

Cardiac gated (A) coronal and (B) axial images in the right descending pulmonary artery, Cur-r Probl

Diagn

Radial,

of the thorax

November/December

show

a

1988

FIG 20. A, left pulmonary similar

to those

arteriogram of conventional

showing extensive arteriogram.

filling

defects

in central

vessels.

B, IV DSA.

Anteropostenor

contemplated, bronchial to demonstrate patency distal to the occlusion.

projection

showing

findings

arteriography is needed of the pulmonary artery

THERAPY

FIG 21. Chronic narrowed Cur-r

Probl

PE. Left pulmonary segmental branch Diagn

Radid,

arteriogram (arrows).

November/December

demonstrating

1988

a diffusely

Once pulmonary embolism has been diagnosed therapy must be instituted. Pulmonary embolism may be treated medically, surgically, or by interventional radiologic techniques. To better understand this therapy, we will briefly review the coagulation and fibrolytic pathways. Coagulation occurs via a cascade system in which each activated clotting factor has an enzymatic effect on the next factor precursor, converting those inactive precursors to activated forms. There are two coagulation pathways: the extrinsic and the intrinsic. Although the different pathways are initiated separately, the final pathway is a common one. The extrinsic pathway begins with the activation of factor VII by local tissue thromboplastin. Tissue thromboplastin is not normally present in the bloodstream (hence the term extrinsic), and its release is associated with local tissue injury. The intrinsic pathway begins with the activation of factor XI by a complex of factor XII, prekallikrein, and high molecular weight kininogen. These three activating compounds are normally found in the bloodstream (hence the term intrinsic) and become active by binding to abnormal endothelium or exposed subendothelial tissue to form an activated surface localized complex. The two path223

FIG 22. Chronic PE. Left pulmonary arteriogram sion of most of vessels to the left lung. defects.

showing complete Note the absence

occluof filling

ways merge for the final three steps in clot formation. Both activated factor VII from the extrinsic pathway and activated factor IX from the intrinsic pathway serve to activate factor X, which converts prothrombin to thrombin. Thrombin then converts fibrinogen to fibrin, the final product, and the clot is formed. The fibrinolytic pathway is far less complex. The active agent is plasmin, which is formed physiologically by the activation of its precursor, fibrinbound plasminogen, by a number of potential fibrin-bound activators. Plasmin readily digests fibrin into much smaller, soluble fragments (fibrin split products). Plasmin may proteolytically degrade other clotting factors, including V, VIII, prothrombin, fibrinogen, and possibly IX and XI. The most common form of medical therapy is anticoagulation, and heparin is the first line drug. Heparin prohibits the propagation of an existing clot while allowing the body’s endogenous fibrinolytic system to degrade it slowly. Heparin interferes with blood coagulation by inhibiting the ac224

tivation of factor IX by activated factor XI (intrinsic pathway) and by acting as a potent antithrombin (common pathway) to inhibit the conversion of fibrinogen to fibrin. Its effectiveness is measured by the activated partial thromboplastin time (APIT test. Unfortunately, despite its wide use, heparin is not a benign drug. It is the most common cause of drug-related complications in hospitalized patients. Serious bleeding complications have been reported in.lO% to 15% of patients who were being treated with appropriately adjusted doses.‘“’ i4 Systemic heparinization is accomplished with an IV loading dose of 5,000 to 20,000 units, followed by 800 to 1,000 units/hour intravenously, a regimen intended to prolong the APIT by a factor of approximately 2. Patients begin oral anticoagulation with warfarin sodium toward the completion of heparin therapy, which is generally 7 to 10 days. This agent works by inhibiting the hepatic production of four vitamin K,-dependent factors (VII, IX, X, and prothrombin) involved in clotting. Warfarin is usually administered for 6 weeks to 6 months and is also associated with morbidity from bleeding complications. Its effectiveness is measured by the prothrombin time (PT) test, which should be prolonged by a factor of approximately 2. Warfarin is administered orally, requires a loading dose of 15 to 30 mg, and is followed by a daily maintenance dose of 2 to 20 mg. The next line medical approach is the administration of a thromboly-tic agent, either streptokinase or urokinase. Streptokinase generates thrombolysis by formation of an equimolar complex with circulating plasmin, plasminogen, or both. This complex activates the remaining circulating plasminogen and a lytic state is activated. Since streptokinase antibodies will be present in some patients, large loading doses may be necessary to overcome inactivation of the streptokinase. Urokinase activates circulating plasminogen directly to initiate lysis. Urokinase is produced by the kidney where it acts normally on any clot in the urinary collecting system. Since urokinase occurs naturally in the body, antibodies to urokinase are not present. Thus, the therapeutic effect is more predictable than when streptokinase is used.75 Urokinase is, however, far more expensive than streptokinase in equivalent therapeutic doses. Radiologists have become familiar with streptokinase and urokinase, which in low doses are used for the treatment of arterial occlusion. In pulmonary embolism, however, much higher doses of these agents must be administered, and as a result, a systemic fibrinolytic state is achieved in all patients with attendant bleeding complications. Following a loading dose of 250,000 units, streptoCurr

Probl

Diagn

Radial,

November/December

1988

kinase is administered intravenously at the rate of 100,000 units/hour for 24 hours. Urokinase administered intravenously has a loading dose and an hourly maintenance dose of 2,000 units/lb. of body weight/hour and is administered for 12 to 24 hours. For both drugs the thrombin time WI’) test should be prolonged by a factor of approximately 2. In the early 1970s the UPET study group demonstrated that this thrombolytic agent could significantly improve the status of hemodynamically unstable patients within the first 24 hours. However, these drugs showed no significant difference in recurrence rates of pulmonary embolism and had significantly higher rates of bleeding complications. Forty-five percent of patients receiving urokinase and heparin had bleeding complications compared with only 27% of those given heparin aloneT3 A newer agent, tissue-type plasminogen activator (TPA), has shown great promise. It has a high affinity for existing fibrin clot and in physiologic amounts binds only to the local fibrin-bound plasminogen. Therefore, only local plasmin activation and fibrinolysis occur. Even with higher doses, significantly less activation of circulating plasminogen should occur so that emboli may be dissolved as efficiently while creating less of a systemic fibrinolytic state. One would expect, therefore, that this drug would result in a lower rate of bleeding complications. Surgical methods of therapy include local venous thrombectomy, interruption of the inferior vena cava, and pulmonary embolectomy. Venous thrombectomy, the direct removal of venous thrombi, is rarely employed because it has not been shown to be effective. Interruption of the inferior vena cava can be effective in the short term because most pulmonary emboli arise from thrombi in the deep veins of the lower extremities and pelvis. Interruption may be accomplished by total ligation, partial plication, or the use of compressive plastic clips. However, interruption of the inferior vena cava does not completely prevent subsequent embolism. Emboli may arise in the inferior vena cava between the point of interruption and the renal veins, in veins of the upper extremities and neck, or in the right atrium and right ventricle themselves. Furthermore, as soon as the inferior vena cava is occluded, collateral routes of venous return develop. As these collateral vessels enlarge, they may serve as alternate routes by which progressively larger emboli can reach the lungs. Thus, interruption of the inferior vena cava is most useful in the acute setting where it may prevent major pulmonary emboli until the underlying condition that causes the venous thrombi can be controlled. Curr

Probl

Diagn

Radio&

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1988

Caval interruption is an open operative procedure of some seriousness and is associated with its own morbidity and mortality. Pulmonary embolectomy involves the surgical removal of large pulmonary emboli from the main pulmonary arteries or major branch vessels. It requires an open thoracotomy and is indicated only for patients who demonstrate persistent and refractory hypotension in the acute phase?” Obviously, this procedure is also associated with a high morbidity and mortality; it is rarely performed. Tnyo methods of radiologic intervention have been described. The first, which has never gained widespread popularity, is that of transvenous catheter embolectomy. This technique was developed by Greenfield in the early 1970s77 and involves passing a catheter with a cup-shaped suction tip through the right ventricle into the pulmonary circulation and aspirating the clots. The second procedure is the percutaneous placement of a filter in the inferior vena cava. The most important indications for placement of these filters include an absolute contraindication to anticoagulation therapy, a true complication of anticoagulation, recurrent emboli in the face of appropriately managed, full anticoagulation, or car pulmonale . The first caval filter was reported by MobinUddin and co-workers.78 Its popularity was limited because it tended to migrate to the right ventricle and pulmonary circulation and also tended to generate caval thrombosis. The Greenfield filter7’ has been shown to be highly effective (Fig 23) and is associated with fewer complications than the Mobin-Uddin filter. It too may migrate or be displaced (tilting) without migration. Because of the geometry of the filter, a tilted filter is much less effective than one that is properly placed. In addition to these problems, a few cases of caval perforation have been reported. However, these and other complications as well as recurrent emboli occur relatively infrequently. The Greenfield filter is usually placed through either a jugular or femoral venous cut-down and, thus, requires surgical access. A number of investigators have recently demonstrated that the filter may be placed percutaneously through a no. 24 French sheath with few significant sequelae at the puncture site.80’ ‘l In this technique, femoral venous puncture should be performed with a hollow-stylet, one-wall needle to help ensure that the femoral artery, which may lie more ventrally than laterally to the vein, is not traversed during venous puncture. After the position of the renal veins has been identified by cavography, the venotomy may be dilated with serial Amplatz dilators or, more simply, with an &mm balloon on which the final

have diminished.83 In Europe, Gunther et al. are investigating a filter that combines many of the best features of the other filters and may ultimately become the filter of choice.84 It may be placed through a no. 10 French sheath, does not suffer from tilting, has not been noted to migrate, and is also retrievable.

SUMMARY

FIG 23. Greenfield vena cava

filter. A Greenfield filter below the renal veins.

has

been

placed

in the inferior

dilator and introducer sheath have been backmounted. Following placement of the sheath and removal of its dilator, the filter is introduced. (This step should be done quickly, because a no. 24 French sheath, which is not occluded, allows for a great flow of blood.) The filter, in its introducer, effectively occludes the lumen of the sheath. Once it has exited the inner end of the sheath, bleeding can again occur. Therefore, the sheath should be removed and the groin manually compressed while final positioning of the filter is accomplished. Once the filter is appropriately placed and its introducer removed, 10 minutes of compression will generally suffice to achieve hemostasis. Fewer than 10% of patients will develop deep venous thrombosis in the lower extremity as a result of the procedure, and this incidence may be further reduced by elevating the extremity, using antiembolism stockings, or both. Another filter design, the bird’s nest filter,8z is under investigation and may be more easily placed through a no. 10 French sheath. This filter and placement technique show great promise, although migration has been noted to occur more frequently than with other filters. Lund et al. have described an experimental retrievable filter that may be placed prophylactically and may be removed when the risks of embolism

Pulmonary embolism is a common medical problem whose incidence is likely to increase in . our aging population, Although it is life-threatening, effective therapy exists. The treatment is not, however, without significant complications. Thus, accurate diagnosis is important. Unfortunately, the clinical manifestations of pulmonary embolism are nonspecific. Furthermore, in many patients the symptoms of an acute embolism are superimposed on underlying chronic heart or lung disease. Thus, a high index of suspicion is needed to identify pulmonary emboli. Laboratory parameters, including arterial oxygen tensions and electrocardiography, are as nonspecific as the clinical signs. They may be more useful in excluding another process than in diagnosing pulmonary embolism. The first radiologic examination is the chest radiograph, but the clinical symptoms are frequently out of proportion to the findings on the chest films. Classic manifestations of pulmonary embolism on the chest radiograph include a wedgeshaped peripheral opacity and a segmental or lobar diminution in vascular@ with prominent central arteries. However, these findings are not commonly seen and, even when present, are not specific. Even less specific findings include cardiomegaly, pulmonary infiltrate, elevation of a hemidiaphragm, and pleural effusion. Many patients with pulmonary embolism may have a normal chest radiograph. The chest radiograph is essential, however, for two purposes. First, it may identify another cause of the patient’s symptoms, such as a rib fracture, dissecting aortic aneurysm, or pneumothorax. Second, a chest radiograph is essential to interpretation of the radionuclide V/Q scan. The perfusion scan accurately reflects the perfusion of the lung. However, a perfusion defect may result from a variety of etiologies. Any process such as vascular stenosis or compression by tumor may restrict blood flow. In addition, areas of the lung that are not well ventilated will be poorly perfused. Thus, a ventilation scan and a chest radiograph are essential to optimal interpretation of the perfusion scan. Ventilation/perfusion scans are interpreted as CWT Probl

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degrees of probability of pulmonary embolism. Emboli are not present in patients with a normal V/Q scan. An embolus is unlikely (lo%-15%) among patients with a low-probability V/Q scan. However, small emboli that are nonocclusive may be present, and pulmonary arteriography may be used to further evaluate patients with a high clinical suspicion of pulmonary embolus. An intermediate probability or indeterminate V/ Q scan provides little diagnostic information, and pulmonary angiography should probably be performed. A high-probability V/Q scan indicates that pulmonary embolism is likely. Since these patients are referred for suspected embolism, the scan results confirm the clinical impression, and appropriate therapy should be instituted. However, if the patient has ‘another disease process such as a lung tumor, or vasculitis that could also cause a perfusion defect, pulmonary arteriography should be performed. Also, if anticoagulation therapy is contraindicated, pulmonary arteriography should be used to confirm the need for therapy. Pulmonary angiography should be undertaken in a well-equipped vascular laboratory by experienced physicians. Pressure monitors should be available, and skilled nurses must be present. Most angiographers prefer the vascular approach through the femoral vein, but the basilic vein of the antecubital fossa can be an excellent route if there is cardiomegaly or occlusion of the inferior vena cava. If pulmonary artery pressures are normal, routine contrast injections can be safely performed. If there is pulmonary hypertension, a subselective injection into the area of highest probability is indicated. The use of nonionic or low osmolar contrast agents will probably prove safer than conventional ionic agents. The nonionic agents may also provide better quality studies by decreasing patient motion. The goal of the pulmonary arteriogram is to identify the disease process (pulmonary embolism) so that appropriate therapy can be instituted to prevent the next embolus. The examination is therefore terminated when an embolus is detected. It is not necessary to examine both lungs or quantitate the amount of embolic material. Heparin therapy, followed by oral anticoagulant medication, is sufficient to prevent a recurrence in most patients. An attempt should also be made to eliminate the risk factors leading to the formation of deep venous thrombi. These efforts will, however, be unsuccessful in some patients. In this situation caval interruption can be undertaken. Caval filters have now largely replaced surgical plication as a method of preventing recurrent pulmonary emboli in cases where heparin therapy fails or the medical condition prevents anticoaguCurr

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lation. These filters can now be placed percutaneously, avoiding the need for surgical venous access. An increased awareness of pulmonary embolism together with refinements in interpretation of the V/Q scan should improve our ability to identify patients with pulmonary emboli. Uncertain cases should be referred for pulmonary arteriography, which in experienced hands is quite safe. Improvements in therapy such as TPA or percutaneous caval filters promise an even better outcome for these patients. ACKNOWLEDGMENT

We appreciate the secretarial assistance erly R. Johnson and Janice Waters.

of Bev-

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