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Thoracic Imaging |
1 From the Departments of Pulmonology (I.T.L., F.R., S.P., A.B.T.) and Radiology (I.M., J.R., M.R.J.), University Center Hospital Calmette; Boulevard Jules Leclerc, 59037 Lille Cedex, France; and Medical Research Group, Equipe d’Accueil No. 2682, Lille, France (I.M., J.R., M.R.J.). Received May 11, 2001; revision requested June 8; revision received August 1; accepted September 17. Address correspondence to M.R.J. (e-mail: mremy-jardin@chru-lille.fr).
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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MATERIALS AND METHODS: Three hundred thirty-four patients, including 215 patients with pulmonary disease (group 1) and 119 patients with no history of respiratory disorder (group 2), were referred for thin-collimation CT angiography of the pulmonary circulation as the first-line diagnostic test. Patients with negative angiograms who had not received anticoagulation therapy and who could be clinically followed up at 3 months, 6 months, and 1 year were considered in the final study groups (n = 185); 135 patients had lung disease (group 3), and 50 patients had no history of a respiratory disorder (group 4).
RESULTS: Between groups 3 and 4, no significant differences were found in the referral location, age, and risk factors. Confident evaluation of pulmonary arteries down to the subsegmental level was performed in 31 (23%) patients in group 3 and in 15 (30%) in group 4 (P = .5). Three episodes of acute pulmonary embolism (PE), all fatal, were diagnosed in group 3 patients; two cases occurred 14 days and one case occurred 6 months after the negative spiral CT scan. The negative predictive value of spiral CT angiography was 98% (175 of 178) in the study group in which follow-up was performed, with no significant difference between the values in groups 3 (98% [132 of 135]) and 4 (100% [50 of 50]).
CONCLUSION: Underlying respiratory disease does not affect the negative predictive value of thin-collimation CT angiography, which appears to be a reliable tool in the work-up in this subgroup of patients with acute PE.
© RSNA, 2002
Index terms: Computed tomography (CT), angiography, 60.12116 • Embolism, pulmonary, 60.72 • Emphysema, pulmonary, 60.751 • Pneumoconiosis, 60.772
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Over the last 10 years, several studies have shown that spiral computed tomographic (CT) angiography is useful for detecting central and segmental PE (3–8). Improvement in CT technology has further improved the accuracy of CT angiography in the detection of peripheral endoluminal clots, in particular at the level of the subsegmental pulmonary arterial bed (9–11). However, no special attention has been directed toward the diagnosis of acute PE by using CT angiography in patients with underlying respiratory disease. Therefore, the purpose of the present investigation was to evaluate the effect of prior pulmonary disease on the diagnostic utility of CT angiography in routine clinical practice.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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The population referred for CT angiography included 334 patients (231 men, 103 women; age range, 18–90 years; mean age, 58.3 years ± 1.1 [SD]). Among them, 215 patients had a history of coexistent chronic lung disease (group 1), whereas 119 patients had no history of respiratory disorder prior to the episode in which they were suspected of having PE (group 2). Underlying lung disease in group 1 patients included COPD in 192 patients and miscellaneous lung disorders in 23 patients, that is, complicated coal worker’s pneumoconiosis (n = 13), idiopathic pulmonary fibrosis (n = 5), sarcoidosis (n = 2), chronic respiratory failure linked to kyphoscoliosis and past tuberculosis (n = 2), and pulmonary amyloidosis (n = 1).
In patients with COPD, pulmonary function test results were available in 129 of 192 of them. The mean forced expiratory volume in 1 second (FEV1) in percent and liter (± standard error of the mean [SEM]) were, respectively, 55.6% ± 1.9 and 1.69 L ± 0.6. The mean ratio of FEV1 to slow vital capacity (± SEM) was 56.6 ± 1.3. Severity of COPD was assessed according to the American Thoracic Society criteria (12): grade 1, FEV1 greater than 50% (64 [50%] patients); grade 2, FEV1 between 35% and 50% (40 [31%] patients); and grade 3, FEV1 less than 35% (25 [19%] patients).
For the purpose of evaluating the negative predictive value of CT angiography in our patients, we analyzed those patients in our study population without evidence of thromboembolic disease who were not receiving anticoagulation therapy and who could be clinically followed up. Patients were excluded if (a) they had, within 24 hours of undergoing a spiral CT with negative findings, undergone another type of imaging (ie, US or angiography) that depicted endoluminal clots; (b) they had received anticoagulation therapy for any reason (eg, prior deep venous thrombosis, PE, or cardiac disease); (c) they had undergone placement of an inferior vena cava filter; or (d) they had documented PE in the previous 3 months. Patients were followed up at 3 months, 6 months, and 1 year by the same pulmonologist (I.T.L.). Deaths, subsequent admission to a hospital, new symptoms, and use of anticoagulants were recorded. The detailed analysis of the patient’s medical records and the discussion with the physician in charge of the patient at the time of death were of crucial importance in determining the cause of death.
In all study patients, either the patient, the patient’s family, or the referring physician were interviewed by phone at 3 months, 6 months, and 1 year. Patients lost to follow-up were excluded from the study. The charts and supporting data regarding every patient who died were thoroughly reviewed by the pulmonologist. We recorded the patient’s referral location, that is, emergency department, outpatient clinic, inpatient clinic, or intensive care unit, at the time of initial imaging; the presence of risk factors; and findings of any other imaging performed. This study protocol was approved by our local ethics committee, which did not require informed patient consent.
Spiral CT Angiography
Spiral CT angiograms of the pulmonary circulation were obtained with a single-section CT scanner (Somatom Plus 4A; Siemens Medical Systems, Forchheim, Germany) with a 0.75-second per revolution scanning time. According to the patient’s breath-hold capabilities, two acquisition protocols were used. Patients were scanned with a 2-mm (n = 245) to 3-mm (n = 89) collimation and a pitch of 1.7–2.0; the scanning collimation was chosen according to the patient’s breath-hold capabilities. The patients received an injection of 120–140 mL of a contrast agent with a 24%–30% concentration at a rate of 4 mL/sec. The starting delay was selected according to the patient’s hemodynamic characteristics and varied between 12 and 15 seconds for patients with normal hemodynamic status and between 18 and 20 seconds for patients suspected of having pulmonary hypertension and/or heart failure of the right side of the heart that was determined on the basis of chest radiographic findings.
Contiguous CT scans were systematically reconstructed and read during the course of the routine clinical work-up by either one of four subspecialty-trained chest radiologists who were experienced in evaluating spiral CT scans for acute PE. The presence of endoluminal clots on CT scans was considered diagnostic of embolism; central emboli included thrombi within main arteries, lobar arteries, or both; peripheral thrombi included endoluminal clots within segmental and/or subsegmental branches.
According to the technical quality of spiral CT scans, two levels of confidence in excluding PE were systematically considered. Spiral CT angiograms were considered negative down to the subsegmental level when a detailed analysis of central and peripheral pulmonary arteries was possible owing to an excellent degree of arterial enhancement of the area of interest on images devoid of respiratory motion artifacts. When suboptimal arterial enhancement and/or motion artifacts were observed at part of the examination, confident depiction of subsegmental clots was not possible. Therefore, in the absence of endoluminal clots within central and segmental arteries on such images, spiral CT scans were considered negative down to the segmental level. When confident exclusion of PE on spiral CT scans was limited to central arteries, a spiral CT scan was interpreted as inconclusive.
Statistical Analysis
Statistical analyses were performed with software (Statview; Abacus Concepts, Berkeley, Calif). Differences between groups were evaluated by means of the 
2 test. Differences in age, blood gas values, and functional respiratory test results were compared by using the Mann-Whitney U test. Differences were considered significant when the P value was less than .05.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Among the 334 patients who underwent spiral CT angiography, 149 patients were not followed up because of (a) the presence of PE on CT scans (81 [24%] patients) (Table 4) or isolated deep venous thrombosis (16 [5%] patients); or (b) an inconclusive spiral CT scan (38 [11%]). Fourteen (4%) patients who were not receiving anticoagulants, including seven patients from group 1 and seven patients from group 2, were lost to follow-up, leading to a final study group of 185 patients (130 men, 55 women; mean age, 58.2 years ± 1.1 [± SEM]; age range, 25–78 years). Among them, 135 patients had underlying lung disease (group 3), and 50 patients had no history of respiratory disorder (group 4). Underlying lung disease in group 3 patients included COPD in 125 patients and miscellaneous lung disorders in 10 patients, including coal worker’s pneumoconiosis (n = 5), chronic respiratory failure (n = 2), idiopathic pulmonary fibrosis (n = 2), and pulmonary amyloidosis (n = 1).
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The clinical presentations of the 185 patients with negative spiral CT scans are summarized in Table 5. For COPD patients, pulmonary function test results were available in 86 of the 125 patients. The mean FEV1 in percent and liter (± SEM) was, respectively, 53.8% ± 2.3 and 1.6 L ± 0.08. The mean ratio of FEV1 to slow vital capacity (± SEM) was 55.4 ± 1.6. Severity of COPD was grade 1, FEV1 greater than 50%, in 39 (45%) patients; grade 2, FEV1 between 35% and 50%, in 28 (32%) patients; and grade 3, FEV1 less than 35%, in 19 (22%) patients.
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At 3 months, subsequent PE was diagnosed in two patients, and PE led to the patient’s death in both cases. One patient was a 61-year-old man with underlying obstructive pulmonary disease (grade 1 COPD) who had never had risk factors for PE. The fatal event occurred 14 days after spiral CT angiography, which had been performed 18 days after a right pneumonectomy for lung carcinoma. This patient did not undergo V-P scintigraphy and had a negative US examination of the lower limb. The second case of subsequent PE was observed in a 40-year-old woman with chronic respiratory failure due to kyphoscoliosis who was receiving long-term oxygen therapy. The fatal event occurred 14 days after the CT angiographic examination, which initially was indicated because the patient was suspected of having acute PE after surgery for hip fracture. This second patient did not undergo V-P scintigraphy, and findings of US examination of the lower limb were negative.
At 6 months, subsequent PE was diagnosed in one patient. This fatal event occurred in a 78-year-old woman 5 months after CT angiography. This patient with underlying grade 2 COPD who was receiving long-term oxygen therapy had no risk factors for PE. She did not undergo V-P scintigraphy or US examination of the lower limb.
CT angiograms were negative for PE down to the segmental pulmonary arteries in all three patients, with an excellent degree of arterial enhancement and no respiratory motion artifacts. In the first and third patient, the accuracy of CT was limited to the segmental arteries because of an inadequate selection of the region to be scanned, which did not include the subsegmental arteries of the lower lung zones. In the second case, presence of kyphoscoliosis was responsible for atelectatic bands in the lower zones of the lung, which precluded a reliable analysis of the subsegmental arteries. At the time of the fatal outcome, each patient was admitted to the respiratory intensive care unit for severe onset of acute respiratory failure with marked cyanosis, which was refractory to oxygen therapy and mechanical ventilation. In the absence of autopsy confirmation, acute PE was considered as the most likely cause of the patients’ deaths. No additional cases of subsequent PE were diagnosed at 1 year. The prevalence of clinically apparent PE 1 year after a negative spiral CT scan was 2% (three of 185 patients).
The cumulative number of deaths from all causes at 3 months, 6 months, and 1 year was 13, 19, and 28, respectively. The negative predictive value for spiral CT angiography was 98% (98% in group 3 and 100% in group 4).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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Despite the absence of autopsy findings to confirm the diagnosis, clinicians in charge of these patients assumed that the diagnosis was acute PE on the basis of the clinical presentation after exclusion of alternative diagnoses. Two episodes occurred in the early follow-up period, both of which occurred 14 days after the negative spiral CT examination was performed, whereas one episode was diagnosed at 6 months. It has been previously emphasized that clinical events suggestive of acute PE occurring within 3 months after negative diagnostic investigations are performed correspond to actual recurrent PE, whereas any clinical episode occurring later should be interpreted as a new occurrence rather than as a venous thromboembolism that was missed at initial imaging (13–15).
Following this assumption, we could classify the episode of PE at 6 months as a new occurrence and the other ones as episodes of recurrent PE during the 3-month follow-up period. However, there is no consensus on this approach, leading us to classify the three episodes as recurrent PE for further comparison with previously published data. Consequently, the negative predictive value of CT angiography in our population was 98%. With regard to the influence of prior pulmonary disease on the diagnostic accuracy of CT angiography, it should be pointed out that the presence of underlying respiratory disease did not affect the negative predictive value of CT angiography, which was 98% in group 3 and 100% in group 4.
To date, seven studies have addressed this issue by using clinical outcome instead of pulmonary angiography to determine the clinical validity of spiral CT scans interpreted as negative for PE (11,15–20) (Table 6). This approach is directly related to the widespread acceptance of spiral CT angiography by clinicians as a first-line minimally invasive diagnostic test for PE in routine clinical practice. Among these studies, four of them included a 3-month follow-up (15–17), whereas a follow-up of at least 6 months was considered in the remaining three investigations (18–20). The prevalence of PE after a negative spiral CT scan in the present study (ie, 2%) is in the range of previously reported results, which varied from 0% to 3%. These results cannot be compared in the absence of precise descriptions of the overall image quality, which is known to influence the accuracy of spiral CT in the detection of acute PE.
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Our results confirm that a negative spiral CT angiogram down to the segmental level does not exclude PE in smaller branches. Despite the controversy regarding the clinical importance of isolated subsegmental clots, they have been shown to be responsible for acute clinical symptoms in patients with impaired pulmonary circulation caused by underlying lung disease (8). In cases of high clinical suspicion of PE, the spiral CT angiograms that are negative down to the segmental arterial level should be completed at pulmonary angiography. However, this theoretical statement has obvious limitations, since one should not expect high-quality pulmonary angiograms, especially at the level of the subsegmental arterial bed, in such patients. From a practical standpoint, a negative CT angiogram is usually considered together with the results of color Doppler US of the lower extremity. In the absence of deep venous thrombosis, there is a frequent reluctance on the part of clinicians to request pulmonary angiography if emboli down to the segmental level have been ruled out (as observed in two of three cases of recurrent PE reported in the present study). The recent introduction of multisection CT technology is expected to simplify this approach by means of a substantial increase in the proportion of diagnostic examinations down to the subsegmental level in routine clinical practice (27). Whereas the initial population of 334 patients referred for CT angiography included a majority of patients with underlying lung disease (215 [64%] vs 119 [36%] patients without preexisting respiratory disorder), one would have expected a higher rate of indeterminate CT angiograms in this subgroup of patients, who are usually short of breath and thus more frequently unable to maintain strict apnea. The lack of a significant difference between the frequency of indeterminate CT angiograms observed in group 1 (11%) and group 2 (12%) contradicts such a statement, probably because the main reasons for suboptimal CT angiograms, such as poor signal-to-noise ratio, severe dyspnea, and/or suboptimal vascular enhancement, can also be encountered in this subgroup of patients.
Several limitations of this study should be emphasized. First, our population underwent a clinical follow-up, as reported in the majority of follow-up studies after a negative CT angiogram, instead of repeated diagnostic examinations. Second, the diagnosis of recurrent PE was not objectively assessed in the absence of confirmation with autopsy findings. However, this diagnosis was the most likely to consider on the basis of the clinical presentation after management by senior intensive care unit physicians. Moreover, one should consider the diagnostic work-up of patients with acute PE in the present study. In our institution, the detection of acute PE is mainly with spiral CT as the first-line examination, because of the low likelihood that diagnostic scintigrams were obtained in patients with abnormal chest radiographs, that is, the majority of patients evaluated, and also because of the nonavailability of scintigraphy at the site.
The apparent lack of a statistically significant difference in the number of indeterminate V-P scans between the subgroups of patients with and without underlying respiratory disease was also caused by a bias in the selection of patients who underwent V-P scintigraphy. Compared with the Prospective Investigation of Pulmonary Embolism Diagnosis, or PIOPED, study in which every patient underwent scintigraphy, the patients with COPD who had abnormal chest radiographs and those who were receiving oxygen therapy who were included in the present study were not referred to the Department of Nuclear Medicine. One should also emphasize a weakness observed in this article as in all previously published imaging studies that attempted to establish the validity of negative imaging tests by means of clinical follow-ups for PE. Patients who seemed to have normal clinical findings at follow-up might have had a PE, which seems much better tolerated by some patients than others. Therefore, negativity cannot be proved with such a study design.
In summary, our results suggest that the presence of underlying respiratory disease does not affect the negative predictive value of thin-collimation CT angiography, which appears to be a reliable tool in the work-up in this subgroup of patients with acute PE.
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FOOTNOTES |
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Author contributions: Guarantors of integrity of entire study, J.R., I.T.L., M.R.J.; study concepts and design, J.R., M.R.J.; literature research, M.R.J.; clinical studies, A.B.T., F.R., I.T.L., S.P.; data acquisition, I.M., M.R.J.; data analysis/interpretation, M.R.J., I.T.L.; statistical analysis, I.T.L.; manuscript preparation, I.T.L., M.R.J.; manuscript definition of intellectual content and editing, M.R.J.; manuscript revision/review, M.R.J., J.R.; manuscript final version approval, M.R.J.
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODS RESULTSDISCUSSIONREFERENCES |
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