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Digital Subtraction versus Film-Screen Angiography for Detecting Acute Pulmonary Emboli: Evaluation in a Porcine Model
Abstract
To compare the diagnostic performance of digital subtraction angiography (DSA) to that of film-screen angiography (FSA) for detecting acute pulmonary embolism (PE) in a porcine model.
DSA and FSA were performed in 13 pigs before and after central venous administration of autologous emboli. Results were compared to findings at necropsy with use of ex vivo pulmonary angiography to guide pathologic sectioning. The sensitivity and predictive value of a positive case for detecting each embolus were computed for each pulmonary artery branch order and compared with use of 95% confidence intervals. Interobserver variability among three readers for individual PE detection was calculated.
Pathologic examination of the lungs revealed 100 total PEs (location by vessel order: 1st = 1, 2nd = 0, 3rd = 15, 4th = 32, > 5th = 52). On average, FSA review identified 72 (72%) emboli and DSA review, 65 (65%). There was no significant difference in sensitivity or predictive value of a positive case between DSA and FSA for detecting emboli (P > .05). There was similar agreement among readers for individual PE detection with DSA (mean, 84%) and FSA (mean, 80%).
The diagnostic performance of DSA is equivalent to that of FSA for detecting emboli in porcine PA branches. Interobserver agreement for individual PE detection is similar for both imaging techniques.
... The first direct comparison with film-screen angiography for the detection of acute PE was in an animal model. 16 Although film-screen techniques identified a greater number of emboli, there were no significant differences in the sensitivity or positive predictive value for the two techniques, or in the intraobserver agreement among readers. These results were, however, obtained under the following idealized circumstances: the animals were anesthetized, and there were no limits for radiation and contrast material dosage or, indeed, for the time allotted for the performance of the study and its interpretation. ...
Study objective
To compare digital to conventional film-screen pulmonary angiography for the diagnosis of acute pulmonary embolism (PE) in a clinical population.
Design
Retrospective review of patient data, ventilation/perfusion ( V˙/ Q˙) lung scintigraphy reports, and pulmonary angiographic reports.
Setting
University hospital, division of interventional radiology.
Patients and methods
Patient data from 307 film-screen and 266 digital angiograms were analyzed for demographics, V˙/ Q˙ lung scintigraphy findings, and pulmonary artery pressures to define patient populations. The interpretations of film-screen pulmonary angiography were then compared with digital angiography interpretations for the entire group of interventional radiologists as well as the two interventionists who practiced throughout the study interval to determine any difference in rates of diagnosis of acute PE between the two techniques.
Results
There was no significant difference between the patient populations studied by film-screen or digital techniques for the data reviewed. Digital angiography utilized significantly more contrast material (digital, 173 mL; film-screen, 145 mL; p < 0.01) and a greater number of angiographic views (digital, 3.6 views per patient; film-screen, 3.4 views per patient; p = 0.04) when compared with film-screen angiography. There was no difference between the two techniques in the rates of diagnosis of acute PE, for individual radiologists or overall.
Conclusions
Digital and film-screen pulmonary angiography possess equivalent diagnostic capabilities for acute PE as used in a clinical setting.
... The first direct comparison with film-screen angiography for the detection of acute PE was in an animal model. 16 Although film-screen techniques identified a greater number of emboli, there were no significant differences in the sensitivity or positive predictive value for the two techniques, or in the intraobserver agreement among readers. These results were, however, obtained under the following idealized circumstances: the animals were anesthetized, and there were no limits for radiation and contrast material dosage or, indeed, for the time allotted for the performance of the study and its interpretation. ...
To compare digital to conventional film-screen pulmonary angiography for the diagnosis of acute pulmonary embolism (PE) in a clinical population.
Retrospective review of patient data, ventilation/perfusion (V/Q) lung scintigraphy reports, and pulmonary angiographic reports.
University hospital, division of interventional radiology.
Patient data from 307 film-screen and 266 digital angiograms were analyzed for demographics, V/Q lung scintigraphy findings, and pulmonary artery pressures to define patient populations. The interpretations of film-screen pulmonary angiography were then compared with digital angiography interpretations for the entire group of interventional radiologists as well as the two interventionists who practiced throughout the study interval to determine any difference in rates of diagnosis of acute PE between the two techniques.
There was no significant difference between the patient populations studied by film-screen or digital techniques for the data reviewed. Digital angiography utilized significantly more contrast material (digital, 173 mL; film-screen, 145 mL; p < 0.01) and a greater number of angiographic views (digital, 3.6 views per patient; film-screen, 3.4 views per patient; p = 0.04) when compared with film-screen angiography. There was no difference between the two techniques in the rates of diagnosis of acute PE, for individual radiologists or overall.
Digital and film-screen pulmonary angiography possess equivalent diagnostic capabilities for acute PE as used in a clinical setting.
... Another caveat concerns the use of pulmonary CT angiography as the gold standard for the determination of pulmonary embolism in this study. Although catheter pulmonary angiography has been considered the gold standard for the detection of pulmonary embolism, catheter pulmonary angiography and pulmonary CT angiography have similar sensitivity and specificity when compared to necropsy in animal models of pulmonary embolism [14,15]. Both imaging techniques also suffer from similar limitations in the evaluation of subsegmental pulmonary embolism [16,17]. ...
Our goal was to use the results of a quantitative D-dimer assay to determine the need for pulmonary CT angiography in patients suspected of having acute pulmonary embolism.
From July 2001 to December 2002, 755 patients underwent pulmonary CT angiography for the evaluation of acute pulmonary embolism. A rapid, fully automated quantitative D-dimer assay was obtained in more than half the patients. The electronic medical records of the patients were subsequently reviewed to analyze the negative predictive value of the D-dimer assay in the diagnostic workup of acute pulmonary embolism and to determine the outcome of the patients who had negative findings on both D-dimer assay and pulmonary CT angiography at 3-month follow-up.
Of the 755 patients who underwent pulmonary CT angiography, 666 (88.2%) had negative findings, 73 (9.7%) had positive findings, and 16 (2.1%) were indeterminate. A total of 426 patients underwent both pulmonary CT angiography and D-dimer level evaluation, and 84 of these had negative findings (< 0.4 microg/mL) on D-dimer assay. Eighty-two of the 84 patients with negative findings on D-dimer assay had negative findings on pulmonary CT angiography; two were indeterminate and both subsequently had low-probability ventilation-perfusion studies. Among patients with positive D-dimer assays, no one with a level between 0.4 and 1.0 microg/mL had pulmonary CT angiography with findings positive for pulmonary embolism.
A quantitative D-dimer assay was effective in excluding the need for pulmonary CT angiography and had high negative predictive value when the D-dimer level was less than 1.0 microg/mL.
... These vessels also lie near the spatial resolution limits of digital subtraction pulmonary angiography (61). We hypothesized that the pulmonary arterial injection used in pulmonary angiography might distend these subsegmental vessels, making them more visible. ...
... Functional imaging in small animals can be addressed particularly well using x-ray digital subtraction angiography (DSA), given the ease of use and its ability to capture rapid physiological changes in blood flow [1]. Extensive work ranging from initial studies first suggested by Mistretta et al. in the 1970s to evaluating the efficacy of subtraction angiography in clinical diagnosis has been done in canines, porcines, and humans23456789101112. Scaling DSA to the higher temporal and spatial resolutions encountered in the rodent requires unique approaches for an optimal small animal DSA imaging system. ...
The availability of genetically altered animal models of human disease for basic research has generated great interest in new imaging methodologies. Digital subtraction angiography (DSA) offers an appealing approach to functional imaging in small animals because of the high spatial and temporal resolution, and the ability to visualize and measure blood flow. The micro-injector described here meets crucial performance parameters to ensure optimal vessel enhancement without significantly increasing the total blood volume or producing overlap of enhanced structures. The micro-injector can inject small, reproducible volumes of contrast agent at high flow rates with computer-controlled timing synchronized to cardiopulmonary activity. Iterative bench-top and live animal experiments with both rat and mouse have been conducted to evaluate the performance of this computer-controlled micro-injector, a first demonstration of a new device designed explicitly for the unique requirements of DSA in small animals. Injection protocols were optimized and screened for potential physiological impact. For the optimized protocols, we found that changes in the time-density curves for representative regions of interest in the thorax were due primarily to physiological changes, independent of micro-injector parameters.
While portable bedside chest radiography has remained the principle thoracic imaging technique for intensive care unit (ICU) patients, other modalities have gained acceptance in the diagnostic evaluation and treatment of these critically ill individuals. Included among these techniques are bedside ultrasonography and nuclear medicine, as well as computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine performed in the radiology department in selected situations. This chapter reviews the efficacy of currently available imaging studies and their latest developments as they apply to the identification of monitoring and therapeutic devices, as well as their value in diagnosing abnormalities of the lungs, heart, mediastinum and pleura.
Venous thromboembolic disease (VTD), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major cause of morbidity and mortality throughout the world. Anticoagulation has been demonstrated to be beneficial in the treatment of VTD, but it is not without its risks. Thus, definitive diagnosis of DVT and PE should be obtained prior to initiation of anticoagulation. Because clinical examination is insufficient for the diagnosis of VTD, it must be supplemented by serologic or imaging studies, or both. D-Dimer assays, when negative, may help to exclude VTD. Doppler ultrasound examination may reliably diagnose femoropopliteal thrombus. The diagnosis of PE should be based on detailed clinical examination followed by appropriate studies, including chest radiography, electrocardiography, ventilation/perfusion (V/Q) lung scintigraphy, and, if those studies are inconclusive, pulmonary arteriography. The use of spiral computed tomography in the diagnosis of PE is undergoing evaluation and may prove useful in the diagnostic algorithm; however, its current sensitivity (approximately 85% for segmental and larger emboli) weighs against its widespread use as the final diagnostic modality. The current evaluation of VTD is discussed, and a diagnostic algorithm is proposed here.
Ziel: Die Entwicklung von Modellen zur Evaluierung der Spiral-CT und 3D-Rekonstruktion im Nachweis der akuten Lungenembolie (LE) Ziel: Die Entwicklung von Modellen zur Evaluierung der Spiral-CT und 3D-Rekonstruktion im Nachweis der akuten Lungenembolie (LE)
im Ex-vivo-Experiment. im Ex-vivo-Experiment.
Material und Methoden: Standardisierte künstliche Emboli definierter Größe und Geometrie wurden in Schweinelungen eingebracht. Ausgüsse der embolisierten Material und Methoden: Standardisierte künstliche Emboli definierter Größe und Geometrie wurden in Schweinelungen eingebracht. Ausgüsse der embolisierten
Gefäßbäume mit röntgenkontrastgebendem Kunstharz simulierten das CT-morphologische Vollbild einer Lungenembolie. Die Bilddaten Gefäßbäume mit röntgenkontrastgebendem Kunstharz simulierten das CT-morphologische Vollbild einer Lungenembolie. Die Bilddaten
wurden dreidimensional rekonstruiert und die Exaktheit der detektierten Emboluslokalisation durch Korrelation mit dem Originalpräparat wurden dreidimensional rekonstruiert und die Exaktheit der detektierten Emboluslokalisation durch Korrelation mit dem Originalpräparat
verifiziert. verifiziert.
Messungen an technischen Probekörpern mit eingeschlossenen Emboli definierter Größe sollten die Messgenauigkeit der kombinierten Messungen an technischen Probekörpern mit eingeschlossenen Emboli definierter Größe sollten die Messgenauigkeit der kombinierten
Spiral-CT-/3D Rekonstruktion in Abhängigkeit von deren Orientierung zur z-Achse und von der Rekonstruktionstechnik (standardisiert Spiral-CT-/3D Rekonstruktion in Abhängigkeit von deren Orientierung zur z-Achse und von der Rekonstruktionstechnik (standardisiert
und kontrastadaptiert) aufzeigen. und kontrastadaptiert) aufzeigen.
Ergebnisse: Für die Detektion und Lokalisation ergab sich eine Übereinstimmung zwischen Spiral-CT-/3D-Rekonstruktion und dem Originalpräparat Ergebnisse: Für die Detektion und Lokalisation ergab sich eine Übereinstimmung zwischen Spiral-CT-/3D-Rekonstruktion und dem Originalpräparat
von ∼ 91%. Die Messungen der technischen Probekörper ergaben deutliche Abweichungen in Abhängigkeit von der Größe, der Orientierung von ∼ 91%. Die Messungen der technischen Probekörper ergaben deutliche Abweichungen in Abhängigkeit von der Größe, der Orientierung
zur z-Achse und der Rekonstruktionstechnik. Hierbei traten Überschätzungen von bis zu 4 mm, Unterschätzungen von bis zu 2,2 zur z-Achse und der Rekonstruktionstechnik. Hierbei traten Überschätzungen von bis zu 4 mm, Unterschätzungen von bis zu 2,2
mm auf. Bei Präparaten mit Höhen von 14–26 mm traten Schwankungen in einer Größenordnung von ca. ±1,5 mm (∼ 6–11%) auf. mm auf. Bei Präparaten mit Höhen von 14–26 mm traten Schwankungen in einer Größenordnung von ca. ±1,5 mm (∼ 6–11%) auf.
Schlussfolgerung: Die vorgestellten Ex-vivo-Modelle sind zur Simulation der akuten Lungenembolie gut geeignet. Die Genauigkeit der Embolusdetektion Schlussfolgerung: Die vorgestellten Ex-vivo-Modelle sind zur Simulation der akuten Lungenembolie gut geeignet. Die Genauigkeit der Embolusdetektion
wird durch Lokalisation, Größe, Orientierung und Rekonstruktionstechnik beeinflusst. wird durch Lokalisation, Größe, Orientierung und Rekonstruktionstechnik beeinflusst.
Purpose: To develop a model for simulation the CT morphologic situation of acute pulmonary embolism, to evaluate the accuracy of spiral Purpose: To develop a model for simulation the CT morphologic situation of acute pulmonary embolism, to evaluate the accuracy of spiral
CT and 3D reconstruction in the detection of artificial emboli and to investigate the influence of the orientation of emboli CT and 3D reconstruction in the detection of artificial emboli and to investigate the influence of the orientation of emboli
depending on z-axis orientation. depending on z-axis orientation.
Materials and Methods: Standardized artificial emboli made of wax and of defined size and shape were positioned into the pulmonary arteries of porcine Materials and Methods: Standardized artificial emboli made of wax and of defined size and shape were positioned into the pulmonary arteries of porcine
lungs. Castings of the embolized pulmonary arterial trees were made by injection of a special opaque resin. After performance lungs. Castings of the embolized pulmonary arterial trees were made by injection of a special opaque resin. After performance
of spiral CT the data sets of the emboli and the pulmonary arteries were post-processed. The 3D segmentations were compared of spiral CT the data sets of the emboli and the pulmonary arteries were post-processed. The 3D segmentations were compared
with the anatomic preparation to evaluate the accuracy of spiral CT/3D reconstruction-technique. with the anatomic preparation to evaluate the accuracy of spiral CT/3D reconstruction-technique.
Technical specimens simulating CT-morphology of acute embolized vessels underwent spiral CT in six different positions with Technical specimens simulating CT-morphology of acute embolized vessels underwent spiral CT in six different positions with
respect to the z-axis. The CT data were reconstructed using a standardized and a contrastadapted method with interactive correction. respect to the z-axis. The CT data were reconstructed using a standardized and a contrastadapted method with interactive correction.
The 3D emboli were analysed under qualitative aspects, and measurements of their extent were done. The 3D emboli were analysed under qualitative aspects, and measurements of their extent were done.
Results: In nearly 91%, there was complete agreement between CT and the corresponding findings at the anatomical preparation. Measurements Results: In nearly 91%, there was complete agreement between CT and the corresponding findings at the anatomical preparation. Measurements
of the 3D reconstructed technical specimens showed discrepancies of shape and size in dependence of the size of the original of the 3D reconstructed technical specimens showed discrepancies of shape and size in dependence of the size of the original
preparation, orientation and reconstruction technique. Overestimation up to 4 mm and underestimation to 2,2 mm were observed. preparation, orientation and reconstruction technique. Overestimation up to 4 mm and underestimation to 2,2 mm were observed.
Measurements of preparations with heights from 14 to 26 mm showed variances of ±1,5 mm (∼ 6–11%). Measurements of preparations with heights from 14 to 26 mm showed variances of ±1,5 mm (∼ 6–11%).
Conclusion: The presented models are suitable to simulate CT morphology of acute pulmonary embolism under ex-vivo conditions. Accuracy Conclusion: The presented models are suitable to simulate CT morphology of acute pulmonary embolism under ex-vivo conditions. Accuracy
in the detection of artificial emboli using spiral CT/3D reconstruction is affected by localization, size and orientation in the detection of artificial emboli using spiral CT/3D reconstruction is affected by localization, size and orientation
of the emboli and the reconstruction technique. of the emboli and the reconstruction technique.
Rationale and objectives:
The authors performed this study to determine if there were differences in vascular caliber measured on angiograms obtained with the injection protocol used for spiral computed tomography (CT) versus that used for pulmonary angiography.
Materials and methods:
The authors studied seven juvenile anesthetized pigs by using a prospective repeated measures experimental design. All pigs received injections of nonionic contrast material via catheters in the brachial vein, superior vena cava, main pulmonary artery, and left pulmonary artery. Weight-adjusted injection rates and volumes ranged from 0.05 mL/kg/sec (3.5 mL/sec, spiral CT protocol) to 0.56 mL/kg/sec (40 mL/sec, pulmonary angiography protocol). Heart rate and pulmonary artery and systemic artery pressures were recorded. During each injection, identically positioned pulmonary angiograms were obtained at full inspiration. Vessel diameters were measured at identical locations after each injection by two observers. The relationship between vessel diameter and hemodynamic parameters and injection site and rate was assessed with analysis of variance.
Results:
At suspended full inspiration, no statistically significant difference (P > .05) in vessel diameter or hemodynamic parameters was found between the different injection sites or rates. There was no difference in vascular caliber between systole and diastole.
Conclusion:
The improved detection of subsegmental pulmonary emboli at pulmonary angiography compared with contrast material-enhanced spiral CT is not due to differences in vascular distention.
The increasing use of small animals in basic research has spurred interest in new imaging methodologies. Digital subtraction angiography (DSA) offers a particularly appealing approach to functional imaging in the small animal. This study examines the optimal x-ray, molybdenum (Mo) or tungsten (W) target sources, and technique to produce the highest quality small animal functional subtraction angiograms in terms of contrast and signal-difference-to-noise ratio squared (SdNR2). Two limiting conditions were considered-normalization with respect to dose and normalization against tube loading. Image contrast and SdNR2 were simulated using an established x-ray model. DSA images of live rats were taken at two representative tube potentials for the W and Mo sources. Results show that for small animal DSA, the Mo source provides better contrast. However, with digital detectors, SdNR2 is the more relevant figure of merit. The W source operated at kVps >60 achieved a higher SdNR2. The highest SdNR2 was obtained at voltages above 90 kVp. However, operation at the higher potential results in significantly greater dose and tube load and reduced contrast quantization. A reasonable tradeoff can be achieved at tube potentials at the beginning of the performance plateau, around 70 kVp, where the relative gain in SdNR2 is the greatest.
Pulmonary embolism is a potentially fatal disorder. Information about the outcome of clinically recognized pulmonary embolism is sparse, particularly given that new treatments for more seriously ill patients are now available.
We prospectively followed 399 patients with pulmonary embolism diagnosed by lung scanning and pulmonary angiography, who were enrolled in a multicenter diagnostic trial. We reviewed all hospitalizations, all new investigations of pulmonary embolism, and all deaths among the patients within one year of diagnosis.
Of the 399 patients, 375 (94 percent) received treatment for pulmonary embolism, usually conventional anticoagulation. Only 10 patients (2.5 percent) died of pulmonary embolism; 9 of them had clinically suspected recurrent pulmonary embolism. Clinically apparent pulmonary embolism recurred in 33 patients (8.3 percent), of whom 45 percent died during follow-up. Ninety-five patients with pulmonary embolism (23.8 percent) died within one year. The conditions associated with these deaths were cancer (relative risk, 3.8; 95 percent confidence interval, 2.3 to 6.4), left-sided congestive heart failure (relative risk, 2.7; 95 percent confidence interval, 1.5 to 4.6), and chronic lung disease (relative risk, 2.2; 95 percent confidence interval, 1.2 to 4.0). The most frequent causes of death in patients with pulmonary embolism were cancer (in 34.7 percent), infection (22.1 percent), and cardiac disease (16.8 percent).
When properly diagnosed and treated, clinically apparent pulmonary embolism was an uncommon cause of death, and it recurred in only a small minority of patients. Most deaths were due to underlying diseases. Patients with pulmonary embolism who had cancer, congestive heart failure, or chronic lung disease had a higher risk of dying within one year than did other patients with pulmonary embolism.
To assess interobserver agreement in the interpretation of digital subtraction angiographic (DSA) images and conventional angiograms in patients with nondiagnostic lung scans.
One hundred thirty of 397 consecutive patients (65 men, 65 women; mean age, 57 years; age range, 18-92 years) in this prospective cohort study underwent angiography. Conventional, selective series were obtained between 1991 and 1992 in 45 patients, and intraarterial DSA series were obtained between 1992 and 1994 in 85 patients. All angiograms were read immediately by the attending radiologist, independently by two radiologists after 6 months, and later by means of consensus of the two radiologists.
Results of the two methods were comparable. Interobserver disagreement occurred in 20%-36% (n = 9-16) of patients with conventional images and 4%-11% (n = 3-9) of patients with DSA images. Initial diagnoses were changed after the images were reviewed by means of consensus in 20% and 12% of patients with conventional and DSA series, respectively. In 70% of these patients, initial findings were false-positive; in 25%, inconclusive; and in 5%, false-negative.
Interobserver agreement is better with selective, intraarterial DSA than with conventional techniques.
Purpose: To provide a clinical approach to the diagnosis of pulmonary embolism.
Data Identification: An English-language literature search using MEDLINE (1982 to 1990) and bibliographic reviews of textbooks and review articles.
Study Selection: In addition to several reviews, studies that evaluated the diagnostic technology of pulmonary embolism were selected. Preference was given to studies with a prospective design, particularly those done within the past decade.
Data Extraction: Studies were assessed independently by three unblinded observers. Data were chosen to describe the efficacy of diagnostic technology on the basis of disease prevalence, sensitivity and specificity, and predictive value.
Results of Data Analysis: A normal lung scan or pulmonary angiogram rules out the diagnosis of clinically important pulmonary embolism with at least 95% certainty. Lung scan interpretations indicating high or low probability have approximately a 15% error in diagnosing or ruling out pulmonary embolism. The accuracy of either scan result improves when the clinical suspicion of pulmonary embolism matches the lung scan result. Serial impedance plethysmography of the lower extremities may exclude thromboembolism with 95% certainty in patients without high-probability lung scan results or cardiopulmonary disease.
Conclusions: The combination of clinical suspicion and the results of the lung scan and impedance plethysmography appear to offer acceptable diagnostic accuracy in evaluating many patients suspected of having pulmonary embolism. The usefulness of this approach for patients with cardiopulmonary disease is still unknown.
The hospital course of 144 consecutive patients with pulmonary embolism (PE) demonstrated by pulmonary angiography was reviewed to determine the mortality of patients with treated PE. Twelve patients (8%) died of PE, and eight died of causes other than PE; 124 (86%) survived. Pulmonary embolism was the primary cause of death in only four of the 12 patients who died of PE. Pulmonary embolism contributed to the death of eight other patients, each of whom had associated potentially lethal disease, particularly heart disease.
The most important factor affecting mortality was shock due to acute right ventricular failure secondary to massive PE (mortality, 32%). Mortality was not related to magnitude of PE per se; the mortality of patients with massive PE without shock (6%) was the same as that for patients with submassive PE (5%).
Patients with PE who survive long enough to have the diagnosis established and appropriate prophylactic therapy begun have an excellent prognosis, unless they have associated severe medical disease.
(JAMA 236:1477-1480, 1976)
Pulmonary embolism (PE) is often overlooked. If the physician maintains a high level of suspicion, the diagnosis (or its exclusion) usually becomes clarified. The ventilation/perfusion lung scan remains the primary noninvasive diagnostic test. Since the conclusion of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED), criteria for the ventilation/perfusion lung scan or perfusion scan alone have been strengthened. Contrast-enhanced spiral computed tomography appears to have potential, but it is not yet fully tested. Magnetic resonance angiography is in the early stages of investigation. A strategy of diagnosis based on a combination of ventilation/perfusion lung scans and serial noninvasive leg tests for deep venous thrombosis may spare the patient the costs, risks, and discomforts of pulmonary angiography. Treatment of PE is primarily anticoagulation. Low-molecular-weight heparins for the initial period of anticoagulation appear to be efficacious, easier to use than unfractionated heparin, and associated with less heparin-induced thrombocytopenia. Thrombolytic therapy, in the opinion of most investigators, should be reserved for unstable patients or patients who remain hypoxic while receiving oxygen. Catheter-tip fragmentation of the embolus occasionally is accomplished successfully.
(C) 1998 Lippincott Williams & Wilkins, Inc.
• An accurate diagnosis of pulmonary embolism is essential to prevent excessive morbidity and mortality from lack of therapy or inappropriate anticoagulation. Clinical signs and symptoms are reported to be nonspecific, although published studies do not allow calculation of true specificity. Since certain clinical characteristics or groups of findings may be sensitive enough for pulmonary embolism, the diagnosis is unlikely in their absence. Ventilation-perfusion lung scanning has high sensitivity but variable specificity for pulmonary embolism. Patients with scans showing multiple segmental or lobar perfusion defects with normal ventilation have a high probability of pulmonary embolism. Scans with less extensive perfusion abnormalities or matching ventilation defects do not reliably exclude pulmonary embolism. Pulmonary angiography Is the most definitive procedure for diagnosing pulmonary embolism. Digital subtraction pulmonary angiography and radiolabeled platelet scanning are promising but require more extensive validation before routine use.
(Arch Intern Med 1986;146:961-967)
Pulmonary angiograms and pulmonary lung perfusion scans on 162 patients with pulmonary embolism were comparatively analyzed. Among the expert angiographic panel members who independently evaluated the studies there was consistent agreement on the diagnosis, size of the emboli, and severity. Consistency of agreement among the expert pulmonary lung perfusion scan panelists was considerably less. These data demonstrate that, in addition to the lack of specificity of the lung perfusion scan for the diagnosis of pulmonary thromboemboli, there is a considerable problem of interpretation in this patient population.
Selektive intraarterielle DSA der Lungengefäße wurde an 70 Patienten vorgenommen, bei denen eine akute Lungenembolie vermutet wurde. Es wurde ein Einschwemmkatheter Swan-Ganz zur Lungenangiographie verwendet. Das Auflösungsvermögen betrug 3,3 Linienpaare/mm bei der DSA und 6,0 Linienpaare/mm bei der konventionellen Lungenangiographie (CPA). Die Bildqualität des Angiogramms wurde ermittelt durch Bestimmung der feinsten dargestellten Verästelungen der großen Lungenarterie. Der mittlere darstellbare Verästelungsgrad bei der intraarteriellen DSA betrug 4,71 (Bereich 3-7). Bei 10 Patienten, an denen sowohl intraarterielle DSA als auch eine konventionelle Lungenangiographie durchgeführt wurden, ergaben sich in der Darstellung der peripheren Arterien keinerlei Unterschiede (im Mittel 4,70 bei beiden Modalitäten). Die intraarterielle DSA ermöglicht eine raschere Durchführung des Verfahrens, eine Einsparung an Filmmaterial und Kontrastmitteln und vermittelt eine gute Darstellung selbst schwierig erschließbarer Gebiete. Das Auflösungsvermögen der derzeitig verfügbaren Geräte gestattet eine ausreichende Definition subsegmentaler Gefäße. Die Verwendung des Einschwemm-Ballonkatheters erleichtert wesentlich die Durchführung der Untersuchung und reduziert das Risiko katheterinduzierter Herzarrhythmien auf ein Minimum.
Summary
Selective intraarterial digital subtraction angiography (IA-DSA) of the pulmonary vessels was performed in 70 patients suspected of acute pulmonary embolism. A flow-directed Swan-Ganz pulmonary angiography catheter was used. The spatial resolution of the equipment used was 3.3 lp/mm for DSA and 6.0 lp/mm for conventional pulmonary angiography (CPA). Image quality of the angiograms was assessed by determining the highest visible branching division of the main pulmonary artery. The mean visible branching division for IA-DSA was 4.71 (range 3-7). In 10 patients where IA-DSA and CPA were performed during the same procedure there was no difference in visualization of peripheral arteries (mean 4.70 visible order for both modalities). IA-DSA makes the procedure rapid, saves on films and contrast material and allows good visualization of areas where exposure is difficult. The spatial resolution of state-of-the-art equipment permits sufficient definition of subsegmental vessels. The use of the flow-directed balloon catheter makes the examination easy to perform and minimizes the risk of catheter induced cardiac arrhythmias.
In 47 patients with pulmonary thromboembolism, selective pulmonary arteriograms disclosed complete or incomplete obstructions of various arterial branches, intra-arterial filling defects, decrease in volume of affected lung segments, and changes in caliber of involved arteries. In 76 other patients with a variety of disorders including left ventricular failure, pneumonia, pulmonary tumor, abscess, bulla, fibrosis, or pulmonary emphysema, the pulmonary arteries were patent to the subsegmental level, showing neither filling defects nor obstructive lesions. Selective pulmonary arteriography has proved practical and relatively safe in our hands. We recommend it as a useful means of establishing the presence and extent of pulmonary thromboemboli, and of determining their location.
Ten rabbits received 24 to 76 intravenous injections of finely divided thrombi prepared by a modification of Chandler's apparatus. Eight rabbits were killed soon after the last injection (group A) and two rabbits were allowed to survive for 4 months after the last introduction of thrombi (group B). Ten rabbits received repeated saline injections only, and six animals underwent no manipulation whatever. Six test rabbits and six control rabbits underwent catheterization of the pulmonary artery. The pulmonary arteries of each lung received injections of radiopaque material and were x-rayed; multiple blocks were selected from each lobe of each lung, cut, and stained with Weigert's elastic Van Gieson's stain, which permitted measurement of arterial medial thickness. Sections were also stained with hematoxylin and eosin and Martius scarlet blue. The results of catheterization showed that only mild pulmonary hypertension had been induced. Histologically, thromboemboli had become incorporated into the wall of the arteries. Concentric intimal thickening included an "onionskin" arrangement and was more prevalent than eccentric configuration. Medial hypertrophy of almost all vessels was found. The onionskin arrangement in an occasional precapillary vessel was also encountered. More severe histologic grades of pulmonary hypertension were not seen. The two group B animals showed recent thrombi, which suggested that once intimal thickening had occurred the process of fresh thrombotic superimposition continues, resulting in progression of the lesions. The experimental findings were compared with 13 patients (thromboembolic pulmonary hypertension (eight) and primary pulmonary hypertension (five)) and with 181 patients reported in the literature. Features such as the onionskin type of intimal thickening in muscular arteries and precapillary vessels have been suggested as points of distinction between these two conditions. These features have been reproduced in these experiments. Despite the fact that more severe histologic grades of pulmonary hypertension were not produced, it is suggested that these experiments lend support to the concept that primary pulmonary hypertension may have a thromboembolic etiology in at least some patients.
Acute deep-vein thrombosis is usually treated with intravenous heparin for a number of days, then with oral anticoagulants for weeks to months. We have compared adjusted-dose warfarin sodium with fixed low-dose subcutaneous heparin in the prevention of recurrent deep-vein thrombosis. Sixty-eight patients with acute deep-vein thrombosis confirmed by venography were treated with intravenous heparin and then randomized to secondary prophylaxis. Nine of 35 patients receiving subcutaneous heparin, but none of 33 receiving warfarin sodium, had new episodes of objectively documented venous thromboembolism (P = 0.001). Seven patients on warfarin sodium experienced bleeding complications (of which four were major), as compared with no patients receiving subcutaneous heparin (P less than 0.005). Thus, adjusted-dose warfarin sodium is more effective than low-dose subcutaneous heparin in preventing recurrent venous thromboembolism, but its use is accompanied by a significant risk of bleeding.
To determine the accuracy and limitations of Xe-133 ventilation and Tc-99m perfusion lung images (V-P images) in detecting pulmonary emboli (PE), these studies were performed in 23 dogs after experimental production of PE by a modified Wessler technique. Fourteen of the animals also underwent selective pulmonary angiography. Xenon-133 abnormalities were seen immediately after embolization in two of the 23 animals (8.7%). Perfusion images revealed the location of 83% of emboli that completely obstructed pulmonary vessels, but only 26% of those that partially obstructed flow. Defects were seen with 97% of emboli that completely occluded vessels larger than 2.0 mm in diameter, but in only 66% of those occluding smaller vessels. Oblique perfusion images provided the only evidence of the perfusion defect associated with five of 88 (5.7%) angiographically proven emboli. V-P imaging is a sensitive technique for detecting PE unless the emboli lodge in very small vessels or incompletely obstruct a vessel. Xenon-133 abnormalities occur infrequently following PE, and should not be a common cause for a false-negative V-P match in clinical practice.
Selective pulmonary arteriography, with superselective magnification views of the lung bases or other areas where abnormalities are shown on perfusion lung scans, performed within 24-48 hours after the onset of symptoms, can effectively rule out clinically significant pulmonary thromboembolism. One hundred and eighty consecutive patients (minimum follow up, six months) with suspected pulmonary embolism and negative pulmonary arteriograms were studied. Not one of the 167 untreated patients died as a result of thromboembolic disease during the acute illness (20 died from unrelated causes), and none of the 147 patients who survived suffered "recurrent embolism" during follow up.
Previous experimental studies have contributed to the diagnosis and management of pulmonary embolism in patients. However, most experimental techniques to produce pulmonary embolism used material with a structure and composition quite unlike the pulmonary emboli which occur in patients. This report describes a method to induce pulmonary embolism by using a subcutaneously implanted prosthetic graft for thrombus formation. Dogs were prepared by anastomosis of the graft from the distally ligated carotid artery to the proximally ligated femoral artery to provide initial blood flow which led to gradual graft occlusion by laminar deposition of fibrin and blood elements. Seven of 10 animals examined developed a large quantity of formed thrombus within the graft 5 days following implantation. A subsequent intravenous administration of a quantity of 0.2 g/kg of animal weight produced a massive pulmonary embolus which caused hemodynamic alterations in all 36 animals studied and proved lethal in four. Pulmonary embolism was induced in 20 dogs and the systemic arterial pressure, pulmonary arterial pressure, pulmonary arterial blood flow, left atrial pressure, static and dynamic lung compliance were observed for a 2-hr period. One group of 10 dogs was subjected to pulmonary embolism using fresh autologous blood clot, and the other group of 10 dogs was subjected to formed thrombus obtained by gradual occlusion of a prosthetic graft anastomosed to the carotid and femoral arteries and placed subcutaneously. Neither group of animals demonstrated significant alterations of systemic blood pressure. However, two animals died and two other animals developed significant hypotension in the group of 10 animals subjected to formed thrombus pulmonary embolism. None of the animals subjected to autologous blood clot developed significant hypotension. The pulmonary artery pressure increased in animals subjected to clot but returned to control values within 60 min. A much larger increase in pulmonary artery pressure was observed following embolism using formed thrombus and the pulmonary artery pressure remained elevated for the duration of study. Pulmonary mean blood flow did not change significantly in dogs subjected to clot but decreased significantly for a 60-min period in dogs subjected to formed thrombus. Left atrial pressure increased and static and dynamic compliance decreased significantly in dogs subjected to formed thrombus embolism, but no significant changes occurred in dogs which received fresh blood clot. This study documented significant differences in hemodynamic and ventilatory alterations induced by material with different mechanical properties. In addition, these observations indicate that the approach to inducing pulmonary embolism using thrombus recovered from a subcutaneous graft represents a useful experimental technique for evaluation of pulmonary embolism.
Pulmonary embolism is being overdiagnosed and overtreated, especially in previously normal women using oral contraceptives, with undesirable consequences in heparin treatment. This is in part a consequences of high estimates of its occurrence based on postmortem data and in part of technologic developments in diagnostic methods. Blood gas data are not diagnostically very helpful. Perfusion scans should be used, largely to exclude the diagnosis. Ventilation scans are only occasionally helpful and are expensive. Pulmonary angiography is the most accurate diagnostic means currently available. Further studies are needed to elucidate the prevalence and natural life history of pulmonary embolism in the previously healthy person.
The hospital course of 144 consecutive patients with pulmonary embolism (PE) demonstrated by pulmonary angiography was reviewed to determine the mortality of patients with treated PE. Twelve patients (8%) died of PE, and eight died of causes other than PE; 124 (86%) survived. Pulmonary embolism was the primary cause of death in only four of the 12 patients who died of PE. Pulmonary embolism contributed to the death of eight other patients, each of whom had associated potentially lethal disease, particularly heart disease. The most important factor affecting mortality was shock due to acute right ventricular failure secondary to massive PE (mortality, 32%). Mortality was not related to magnitude of PE per se; the mortality of patients with massive PE without shock (6%) was the same as that for patients with submassive PE (5%. Patients with PE who survive long enough to have the diagnosis established and appropriate prophylactic therapy begun have an excellent prognosis, unless they have associated severe medical disease.
The authors sought to develop a reliable animal model for experimental pulmonary infarction, to evaluate it with radiologic-pathologic correlation, and to determine the use of high-resolution computed tomography (HRCT) in monitoring parenchymal lung damage due to infarction.
Selective left lower lobe pulmonary artery occlusion was performed in seven Yorkshire pigs with transcatheter silicone elastomer injection. After occlusion, 99m technetium (99mTc) macroaggregated albumin perfusion lung scans and sequential in vivo HRCT lung scans were obtained from days 0 to 46. The in vivo radiologic findings were correlated with specimen radiography, specimen HRCT, and histologic findings.
A complete and permanent arterial occlusion was achieved, involving up to three orders of branching distal to the catheter. An anatomically defined perfusion defect was seen on 99mTc lung scans corresponding to the occluded area. HRCT changes consisted of confluent densities progressing to mixed alveolar and interstitial opacities within the first week after embolization. In the follow-up period, marked parenchymal clearing was observed. In all cases after pulmonary artery occlusion, the histologic findings were characteristic of pulmonary infarction and demonstrated alveolar edema, hemorrhage, limited alveolar wall damage, and septal thickening followed by residual fibrosis.
Using this model, it is feasible to produce pulmonary infarction in the pig which may potentially be useful to study the pathophysiologic and radiologic changes of pulmonary infarction.
Selective intra-arterial digital subtraction angiography (IA-DSA) of the pulmonary vessels was performed in 70 patients suspected of acute pulmonary embolism. A flow-directed Swan-Ganz pulmonary angiography catheter was used. The spatial resolution of the equipment used was 3.3 lp/mm for DSA and 6.0 lp/mm for conventional pulmonary angiography (CPA). Image quality of the angiograms was assessed by determining the highest visible branching division of the main pulmonary artery. The mean visible branching division for IA-DSA was 4.71 (range 3-7). In 10 patients where IA-DSA and CPA were performed during the same procedure there was no difference in visualization of peripheral arteries (mean 4.70 visible order for both modalities). IA-DSA makes the procedure rapid, saves on films and contrast material and allows good visualization of areas where exposure is difficult. The spatial resolution of state-of-the-art equipment permits sufficient definition of subsegmental vessels. The use of the flow-directed balloon catheter makes the examination easy to perform and minimizes the risk of catheter induced cardiac arrhythmias.
Computed tomography (CT) has proven useful in the diagnosis of central pulmonary embolism; however, its ability to detect peripheral emboli has not been established. The authors evaluate the usefulness of ultrafast CT (UFCT) in detecting experimental peripheral pulmonary emboli. Three Gelfoam emboli measuring 0.7 x 1.5 cm were introduced into the pulmonary arteries of each of seven dogs, and contiguous, 3-mm, axial UFCT images from the lung apex to the base were obtained after the administration of a contrast bolus. After scanning, the dogs were killed, and the locations of the emboli were determined by a pulmonary pathologist blinded to the imaging results. Concomitantly, the locations of the emboli on the UFCT images were determined by consensus of three chest radiologists blinded to the autopsy results. All 21 emboli were identified on UFCT images; the locations of the emboli corresponded exactly with the autopsy findings. The authors conclude that UFCT can reliably detect Gelfoam emboli in second- to fourth-division pulmonary vessels. Further studies are needed to determine if in vivo blood clots can be similarly visualized.
The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) addressed the value of ventilation/perfusion scans in acute pulmonary embolism (PE). The present study evaluates the risks and diagnostic validity of pulmonary angiography in 1,111 patients who underwent angiography in PIOPED:
Complications were death in five (0.5%), major nonfatal complications in nine (1%), and less significant or minor in 60 (5%). More fatal or major nonfatal complications occurred in patients from the medical intensive care unit than elsewhere: five of 122 (4%) versus nine of 989 (1%) (p less than 0.02). Pulmonary artery pressure, volume of contrast material, and presence of PE did not significantly affect the frequency of complications. Renal dysfunction, either major (requiring dialysis) or less severe, occurred in 13 of 1,111 (1%). Patients who developed renal dysfunction after angiography were older than those who did not have renal dysfunction: 74 +/- 13 years versus 57 +/- 17 years (p less than 0.001). Angiograms were nondiagnostic in 35 of 1,111 (3%), and studies were incomplete in 12 of 1,111 (1%), usually because of a complication. Surveillance after negative angiograms showed PE in four of 675 (0.6%). Angiograms, interpreted on the basis of consensus readings, resulted in an unchallenged diagnosis in 96%.
The risks of pulmonary angiography were sufficiently low to justify it as a diagnostic tool in the appropriate clinical setting. Clinical judgment is probably the most important consideration in the assessment of risk.
Spontaneous thrombo-embolism is an extremely rare disease in swine. We observed such a disease in a mini-pig. The animal attracted attention, because it did not eat its fill and breathed hamperally and shallowly but without stridor. Blood gas analysis and ECG findings indicated changes like in an acute pulmonary infection. 24 h after it had been admitted to our animal pasture the animal was dead. The reason was a pulmonary thrombo-embolism.
Since its introduction in 1960, the family of kappa statistics has been scrutinized for theoretical and methodological problems. A summary of recommendations made by researchers in the area is given in Table 3. Citations listing the various forms and applications of kappa are provided to assist researchers in finding the form of kappa appropriate to their needs. Readers interested in more technical treatments of any of the issues discussed herein may find the appended references helpful.
Two thrombosis models for the evaluation of thrombolytic agents in small animals (less than 100 g) were evaluated: an iodine-125 fibrin-labeled rat plasma clot in the inferior caval vein of 3-4-week-old rats and a pulmonary embolus in adult hamsters that had been obtained by injection of a 125I fibrin-labeled human plasma clot. The extent of thrombolysis was determined by continuous external monitoring of radioisotope over the thrombus region and by ex vivo recovery of residual clot.
In the rat model, infusion of solvent for 60 minutes was associated with mean +/- SEM lysis within 90 minutes of 13 +/- 3% (n = 8) by external counting and 26 +/- 4% (n = 8) by radioisotope recovery. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) over 60 minutes caused dose-dependent progressive clot lysis; with 0.5 mg/kg, producing a plasma level of 0.14 +/- 0.04 microgram/ml, lysis was 64 +/- 9% (n = 4) by external gamma counting and 78 +/- 4% (n = 4) by residual isotope in the vein segment and was not associated with significant fibrinogen or alpha 2-antiplasmin breakdown. In the hamster model, infusion of solvent for 60 minutes was associated with lysis within 90 minutes of 19 +/- 4% (n = 11) by external gamma counting and 31 +/- 3% (n = 14) by residual radioisotope. Intravenous rt-PA during 60 minutes resulted in dose-dependent progressive thrombolysis; with 0.5 mg/kg, producing a plasma level of 0.14 +/- 0.01 micrograms/ml, lysis was 50 +/- 4% (n = 4) by external gamma counting and 78 +/- 5% (n = 4) by residual radioactivity, without an extensive decrease in fibrinogen or alpha 2-antiplasmin. Parallel experiments in the rabbit jugular vein thrombosis model with a rabbit blood clot with intravenous infusion over 4 hours produced 7 +/- 2% (n = 9) lysis with solvent and dose-dependent progressive lysis with rt-PA; with 1 mg/kg, producing a plasma level of 0.20 +/- 0.03 microgram/ml, lysis was 56 +/- 7% (n = 7) by external gamma counting and 61 +/- 7% (n = 7) by residual radioactivity, without extensive consumption of fibrinogen or alpha 2-antiplasmin.
These two thrombosis models in small animals are as reproducible and quantitative as the extensively used rabbit jugular vein thrombosis model. The hamster pulmonary embolism model is superior because it is simpler and more straightforward and allows the performance of as many as 10 experiments by one investigator in 1 day.
A normal lung perfusion isotope scan can exclude pulmonary emboli. However, the demonstration of lung emboli presents problems, as an abnormal lung perfusion scan can have various causes. Some of these can be excluded if the perfusion scan is assessed in combination with a chest X-ray and a ventilation scan. In this study, 21 patients with an abnormal perfusion scan were also examined using digital subtraction angiography (DSA) of the lungs. With the help of DSA it was possible to differentiate between the various causes of a lung perfusion defect on the isotope scan by having a sufficiently reliable pulmonary angiogram. From experience it appears that the quality of the pulmonary angiogram confined to the first three divisions obtained with DSA, is comparable with that from a conventional pulmonary angiogram. A perfusion isotope scan is the initial screening modality for suspected lung emboli, if this shows an abnormality, DSA seems to be indicated as the next step.
Digital subtraction angiography (DSA) performed via a peripheral vein was compared prospectively with selective conventional pulmonary angiography (CPA) in 54 patients suspected of having pulmonary embolism (PE). All patients also underwent ascending venography. In contrast to the conventional pulmonary angiograms, all of which were considered satisfactory, 13 of 54 digital subtraction angiograms (24%) were technically unsatisfactory. The interpretable digital subtraction angiograms had 81% sensitivity and 64% specificity. With DSA, one cannot exclude the diagnosis of PE on the basis of normal angiograms (27% false-positive results) as one can with perfusion scanning. On the other hand, DSA showed good sensitivity (94%) in medium to major PE. Therefore it may be the technique of choice in the screening of life-threatening PE for which curative emergency treatment with thrombolytic agents or embolectomy is often necessary.
An accurate diagnosis of pulmonary embolism is essential to prevent excessive morbidity and mortality from lack of therapy or inappropriate anticoagulation. Clinical signs and symptoms are reported to be nonspecific, although published studies do not allow calculation of true specificity. Since certain clinical characteristics or groups of findings may be sensitive enough for pulmonary embolism, the diagnosis is unlikely in their absence. Ventilation-perfusion lung scanning has high sensitivity but variable specificity for pulmonary embolism. Patients with scans showing multiple segmental or lobar perfusion defects with normal ventilation have a high probability of pulmonary embolism. Scans with less extensive perfusion abnormalities or matching ventilation defects do not reliably exclude pulmonary embolism. Pulmonary angiography is the most definitive procedure for diagnosing pulmonary embolism. Digital subtraction pulmonary angiography and radiolabeled platelet scanning are promising but require more extensive validation before routine use.
To determine the association of duration of warfarin anticoagulant therapy after hospitalization for venous thromboembolism with the probability of recurrent thromboembolism and with the risks of hemorrhage, medical records of 2,422 patients hospitalized in 1970 through 1980 with pulmonary embolism, thrombophlebitis, or both were reviewed. Multivariate life-table analyses were performed for 370 patients who had positive results of venography or pulmonary angiography, or who had lung scanning evidence of a "high probability" of pulmonary embolism and no history of the disease. For these patients, warfarin therapy for more than six weeks was not associated with a lower risk of recurrent thromboembolism when compared with warfarin therapy for one through six weeks (risk of recurrence for seven to 26 weeks of treatment 0.8; 95 percent confidence limits 0.3 and 2.5; risk of recurrence for more than 26 weeks of treatment 1.1; 95 percent confidence limits 0.4 and 3.1). The longer the warfarin therapy, the higher the risk of medically important complications from therapy. From one week through five years, the probability of major hemorrhage increased almost linearly: 10 percent for 12 weeks, 18 percent at one year, 26 percent at two years, and 41 percent at five years. This study suggests that intensive, long-term warfarin anticoagulation, in patients with a first episode of venous thromboembolism and no predisposing condition, is associated with more toxicity than efficacy and should be abandoned.
With current high-resolution equipment and proper case selection, intravenous digital subtraction angiography (IVDSA) can consistently demonstrate pulmonary emboli greater than 2.0 mm in size. IVDSA is less traumatic than conventional pulmonary angiography and is preferable for high-risk cases such as patients with pulmonary arterial hypertension. For successful IVDSA studies patients should be able to hold their breath for 10 to 20 seconds. IVDSA should not be used in patients who are extremely dyspneic, who cannot suppress a cough, or who have a low cardiac output. In these instances selective intraarterial DSA is preferable.
An electrode-stasis model which produces a deep vein thrombus in canine femoral vein is reported. The thrombus produced resembles a human thrombus on light microscopy. The fibrin crosslinkage in both thrombus and pulmonary embolus is similar to human fibrin crosslinked .
The reinvestigation of the original and modified apparatus for producing thrombi and the additional alterations which yielded the best results is reported. The thrombi thus produced were introduced into the pulmonary arteries of rabbits and the sequence of organization was studied. Organization proceeded along uniform lines and simulated those closely observed in the human.
Of 458 patients treated with anticoagulants after an initial embolism, 92% survived as compared to 42% of the patients in whom anticoagulants were withheld because of medical contraindications. Anticoagulation also lowered the incidence of recurrent pulmonary embolisms from 47% to 8%. Furthermore, the mortality among patients developing recurrent pulmonary embolisms was reduced from 55% to 16%. These figures suggest that the indications for anticoagulation should be extended to some patients hitherto considered to have borderline indications. 57 patients had inferior vena cava ligation. There was 1 postoperative death, and only 3 patients developed recurrent pulmonary embolisms.
In order to investigate the possible contribution of the lipids of organizing thrombi to those of atherosclerotic plaques, the organization of autologous pulmonary thromboemboli in 8-12 week old Yorkshire pigs was studied at intervals from 6 hours to 4 weeks. Thrombi were prepared in vitro in Chandler rotating loops. There was a considerable loss of protein and total lipid in the interval from 6 hours to 5 days. No subsequent total lipid accumulation occurred. DNA content did not alter significantly. Free cholesterol and phospholipids accounted for > 85% of the total lipid, and both decreased in concentration from 6 hours to 5 days. Cholesterol ester, triglycerides and free fatty acids each comprised < 5% of the total lipid at all periods of organization, during which small increases in these lipids occurred. Spontaneous aortic fatty streaks and fibrous plaques of 5-7 1 2 year old pigs contained greater amounts of total lipid, phospholipids, free cholesterol and particularly cholesterol ester than the organizing thromboemboli, in spite of the transformation of the latter into fibrofatty plaques at 3-4 weeks. This study indicates that pulmonary thromboemboli may organize into fibrofatty lesions with many morphological features of atherosclerotic plaques. However, the lipid profile of organizing thromboemboli did not evolve towards that characteristic of the atherosclerotic plaque, suggesting that plaque lipids are largely derived from a source other than that of organizing thrombi.
Pulmonary angiography is the most specific test available for the diagnosis of acute pulmonary embolism. This technique can safely be performed in critically ill patients. In 367 consecutive studies our incidence of complications has been 4 per cent, and there has been only one death. Hemodynamic studies done as part of the procedure permit evaluation of the severity and the pathophysiology of acute pulmonary embolism. The two diagnostic angiographic findings of pulmonary embolism are intraluminal filling defects and cutoff arteries. Oligemia and asymmetry of blood flow are frequently seen in pulmonary embolism, but are not specific. These latter two abnormalities may occur in chronic lung disease or congestive heart failure without pulmonary embolism. Using these diagnostic criteria in 247 patients studied because of a clinical diagnosis of acute pulmonary embolism, a definitive diagnosis (either definite pulmonary embolism or negative) was established by angiography in 74 per cent. In 9 per cent the diagnosis was probable pulmonary embolism, and in 17 per cent the findings were equivocal for pulmonary embolism. Application of these diagnostic criteria results in minimal false posiive angiographic diagnoses. False negative diagnoses may occur if embolism is limited to peripheral branches of the pulmonary vasculature that are not visualized by current angiographic techniques. The incidence of symptomatic pulmonary embolism limited to these small arteries is uncertain. The primary limitation of this technique is, that in patients with underlying heart disease or chronic lung disease, the results of angiography may be equivocal. The application of new techniques of magnification angiography and/or selective cineangiography offer promise in enhancing the recognition of embolism in this group of patients.
SCINTILLATION scanning of the lungs is being used with increasing frequency as a means of establishing the diagnosis of pulmonary thromboembolism.1 2 3 4 5 6 Little information is available, however, concerning the reliability and specificity of the technic in reflecting the presence and extent of intra-arterial lesions. Since arteriography of the lung permits identification of structural changes within the pulmonary arteries7 8 9 10 11 12 13 it serves as a way of assessing the accuracy of the scan in the diagnosis of thromboembolic disease. Therefore, we performed selective pulmonary arteriography and radioisotopic lung scans in patients suspected of having pulmonary thromboembolism and in patients known to have other cardiorespiratory . . .
Detection of pulmonary emboli was investigated using electrocardiographically gated (EKG-gated) intravenous digital subtraction angiography (DSA) in 6 anesthetized and paralyzed dogs. Six autologous blood clots were introduced into the internal jugular vein of each dog and both conventional pulmonary angiography and EKG-gated DSA performed in frontal and oblique projections. When two observers scored any definite or equivocal embolus as positive, sensitivity was 82.1% for one and 92.9% for the other; the respective positive predictive values (PPV) were 88.5% and 65%. When only definite emboli were considered positive, sensitivity was 75% for one observer and 71.4% for the other; PPV was 100% for both. The authors conclude that DSA can demonstrate individual emboli with good sensitivity and excellent precision. If several emboli are present, EKG-gated DSA should prove highly accurate; however, care must be taken because overinterpretation is more likely with DSA than with conventional pulmonary angiography.
An overview of the natural history of pulmonary embolism is outlined. The annual incidence of pulmonary embolism in the United States is probably in excess of 630,000. Of this group 67,000 (11 per cent) die within one hour of the event before definitive diagnosis and management, and 563,000 (89 per cent) survive the event for at least one hour so that there may be sufficient opportunity for diagnosis and therapy. In this 'early survivor' group the diagnosis is not made in 400,000 patients (71 per cent). In this group, 120,000 patients ultimately succumb because the mortality of untreated pulmonary embolism approximates 30 per cent. However, in the 163,000 early survivors in whom a diagnosis is made and appropriate therapy is unstituted, the survival rate is 92 per cent and the mortality is only 8 per cent. Clearly, the proper management of pulmonary embolism improves survival, and it is the focus of this article to review the natural history of pulmonary embolism as it relates to the appropriateness of several alternative therapeutic strategies.
Thromboembolism is a frequent and often lethal complication of many medical diseases and surgical procedures. Streptokinase, a bacterial non-enzymatic protein, and urokinase, an enzyme obtained from human urine, are both potent activators of the human fibrinolytic system, and have been extensively investigated as a means of medical treatment of this condition. Although it is well established that these agents can clear obstructed vessels in roughly 50% of cases, the fact that they induce relatively extensive systemic fibrinogen breakdown and a serious haemorrhagic diathesis has prevented their general application for thrombolysis. The physiological plasminogen activator in blood (blood activator), which is probably released from the vascular wall (vascular activator) and is identical or at least very similar to the activator extracted from human organs (tissue activator), differs from urokinase (for references see ref. 1). This activator has a markedly higher fibrinolytic to fibrinogenolytic ratio than urokinase in vitro1 and might therefore constitute a better thrombolytic agent. We have developed a purification method for tissue plasminogen activator from a human melanoma cell line which enables us to produce milligramme quantities on a laboratory bench scale2 and we have now compared its thrombolytic effect with that of urokinase in an experimental animal model. We have found that tissue plasminogen activator causes thrombolysis at lower doses than urokinase, without extensive plasminogen activation in the circulating blood and without haemostatic breakdown.
We studied 243 patients in whom 248 pulmonary angiograms were performed because of suspected pulmonary embolism. Ventilation and perfusion lung scanning in 140 of them revealed 38 to be in low and high probability groups. Of 19 patients with subsegmental and nonsegmental perfusion defects that were matched with ventilation defects, none had pulmonary embolism. Conversely, angiography was positive in 17 of 19 patients with multiple segmental or lobar perfusion defects in areas of normal ventilation. Doppler flow examinations of the veins of the legs showed normal flow in 61 of 79 (77 percent) patients with pulmonary emboli and, therefore, were insensitive indicators of embolism. There was no mortality from angiography, and serious complications occurred in 2 percent of the patients. Anticoagulation in 83 patients was associated with bleeding in 25, two of whom died. The data indicate that ventilation-perfusion lung scanning can be used to separate many of the patients suspected of having pulmonary embolism who need anticoagulant treatment from those who do not. However, there is a considerable number of patients with nonspecific abnormalities on lung scan. For this group of patients with nonspecific abnormalities, the risk of complications from empiric treatment with anticoagulant drugs is probably greater than the risk of complications from pulmonary angiography. Further, our data show that patients with negative angiography have a very low risk of subsequent pulmonary embolism. In this group of patients, therefore, pulmonary embolism should be demonstrated by angiography before long-term anticoagulant therapy is prescribed.
To evaluate image quality, safety, and clinical validity of selective, intraarterial, pulmonary digital subtraction angiography (DSA) with use of a flow-directed, balloon-tipped catheter in patients with suspected acute pulmonary embolism (PE).
Pulmonary DSA was performed in 211 patients with suspected PE. Subselective magnification series were obtained with nonionic contrast material. Clinical outcome of patients with a negative pulmonary DSA study was assessed by means of retrospective analysis of their medical records, with a minimum follow-up of 3 months.
Among the 211 patients, DSA image quality was excellent in 129 (61.1%), adequate in 79 (37.4%), and poor in three (1.4%). Two angiograms (0.9%) were nondiagnostic. No complications occurred. Of 129 patients with negative DSA in whom anticoagulants were withheld, 16 died of disorders other than PE; one (0.9%, 95% confidence interval 0.0%, 4.2%) of 113 patients alive at 3 months returned after 3 weeks with possible PE.
Pulmonary DSA with the flow-directed catheter is a safe procedure and provides good to excellent image quality. Anticoagulants can be withheld in patients suspected of having PE when pulmonary DSA results are negative.
We compared the conspicuity of acute pulmonary emboli with contrast-enhanced spiral computed tomography (CT) and two- and three-dimensional time-of-flight magnetic resonance (MR) techniques. Seven dogs who received experimental pulmonary emboli and one control were imaged with spiral CT and with 2-D (FMPVAS and FASTCARD) and 3-D time-of-flight MR. Blinded, independent, prospective evaluations of the CT and MR images by two MR radiologists and two chest radiologists were then compared to the location of the emboli as determined by subsequent pathologic evaluation of the excised lungs. Embolus/blood contrast-to-noise ratios (CNRs) were calculated on both MR and CT images for pulmonary emboli that could be identified. Fifty emboli ranging from 1.0 to 5.5 mm (mean, 2.7, +/- 0.14 SEM) in diameter and from 3.0 to 60 mm (mean, 28.1 +/- 1.9 SEM) in length were found in the seven embolized dogs on pathologic examination. Three of the four radiologists identified more thrombi on CT images than they did on their best MR pulse sequence (FASTCARD) and with greater confidence. The fourth radiologist identified an equal percentage of clot on CT and FASTCARD images with confidence slightly greater on FASTCARD MR than on spiral CT. Mean CNR for the best MR technique was 43.4 (+/- 3.9 SEM) and for CT was 20.7 (+/- 1.3 SEM). In general, pulmonary emboli were detected more accurately on contrast-enhanced spiral CT than on MR. This occurred although the embolus/blood CNR was higher on MR than on CT. Better pulmonary embolus conspicuity on CT images was attributed to better spatial resolution and fewer artifacts on CT than on MR. One MR radiologist performed equally well with both spiral CT and FASTCARD techniques, suggesting that experience may be a factor in performance.
Ultrafast computed tomography (UFCT) has proven useful, but is of limited practical application in the diagnosis of central pulmonary embolism; however, its ability to detect more peripheral emboli has not been established. In this study, the use of contrast-enhanced UFCT images for the detection of autologous peripheral pulmonary emboli in the pig is evaluated.
A single autologous embolus measuring 0.7 x 1.5 cm was introduced into the superior vena cava of eight pigs. Contiguous, 3-mm axial UFCT images from the lung apex to the base were obtained before and after the introduction of the embolus. After scanning, the pigs were killed, and the thorax was removed intact and was frozen in a dry ice-alcohol mixture. Later, the thorax was sliced at 10-mm thicknesses, and the locations of the emboli were determined by a pulmonary pathologist blinded to the imaging results. Concomitantly, the locations of the emboli were determined by consensus of three chest radiologists blinded to the autopsy results.
In 6 of 8 animals with emboli, the embolus location correlated exactly with the autopsy findings. In one, the embolus was on the same side, but 1.6 cm further distal. In the other, a marking suture was identified, but no clot was identified on the pathologic or UFCT examination. In the eight animals scanned before the introduction of the embolus, no embolus was found. Interobserver agreement was 100%.
Ultrafast computed tomography has the potential to detect autologous emboli in second- to fourth-division pulmonary vessels. Further studies are needed to determine if in vivo emboli can be similarly visualized.
Two separate groups of clinical investigators have provided new information and divergent approaches to the management of acute pulmonary embolism (PE). In this position paper, investigators from both groups (Prospective Investigation of Pulmonary Embolism Diagnosis [PIOPED] and Canadian study groups) have utilized the combined scientific database in order to rationalize seemingly polarized diagnostic recommendations into a single practical algorithm.
An in-depth review established the relative risks of deep venous thrombosis (DVT) and the related accuracy of diagnostic tests. In PIOPED, 640 of 887 patients at risk for PE had either an intermediate probability ventilation/perfusion (V/Q) scan or a V/Q scan probability that was discordant with the prior estimate of probability by clinical assessment. The risk of PE in these patients was 16 to 88 percent (average, 34 percent). In this group, we calculated the probability of PE assuming that tests for DVT had been performed and that 50 percent of patients with PE have detectable proximal DVT. By calculation, 108 in 640 patients of whom the diagnosis of PE was uncertain, would have shown proximal DVT. In 239 of these 640 patients, tests for DVT would have been negative and the risks of PE in these patients is calculated to be less than 10 percent.
Therefore, we calculate that in 347 of 640 patients, confident recommendations for treatment or no treatment could have been given without pulmonary angiography. Accordingly, in the PIOPED study group of 887 patients, the need for pulmonary angiography would have been reduced from 640 (72 percent) to 293 patients (33 percent).
In conclusion, a diagnostic strategy that includes the clinical evaluation, V/Q scan, and evaluation for DVT would decrease the number of patients who require pulmonary angiography from 72 to 33 percent.
Numerous investigators have observed that pulmonary emboli are rapidly lysed in a canine model system. This study was undertaken to delineate the unique mechanism that accounts for the rapid dissolution of pulmonary emboli in mongrel dogs.
Canine plasminogen activator (PA) activity (2.6 +/- 1.1 IU/mL acidified platelet-poor plasma [PPP], < 0.3 IU/mL acidified whole blood serum [WBS], mean +/- SD; n = 6) and PA inhibitor activity (6.1 +/- 2.6 U/mL PPP, 35.4 +/- 7.8 U/mL WBS; n = 6) were determined in standard plasminogen-based chromogenic assays. Analysis of canine PPP, WBS, platelet lysates, and primary canine endothelial cell (EC) cultures by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fibrin autography revealed a plasminogen-dependent lytic zone at 45-kd relative molecular mass that was shown to be related to urokinase-type PA (u-PA) by its selective inhibition through amiloride. Analysis of canine platelets on standard 125I fibrin plate assays revealed a net fibrinolytic activity. In a clot lysis assay system, canine platelets were able to stimulate fibrinolysis when layered on the outside of fibrin clots containing autologous PPP. Moreover, net fibrinolytic activity of primary canine pulmonary artery endothelial cells was higher than the activities expressed by canine aortic or carotid artery endothelial cells.
Rapid lysis of pulmonary emboli in mongrel dogs appears to be a result of 1) the high u-PA activity in canine PPP and 2) the predominant association of u-PA activity with canine platelets and canine pulmonary artery endothelial cells.
To determine how often emboli detected angiographically in peripheral pulmonary arterial branches would be missed with cross-sectional imaging.
Seventy-nine of 88 consecutive pulmonary angiograms interpreted as positive for pulmonary emboli were reviewed retrospectively to detect pulmonary emboli. Three angiograms interpreted as negative when reviewed retrospectively were excluded. Findings of 76 angiograms in 76 patients (32 men, 44 women; aged 19-85 years) were correlated with the results of scintigraphy (n = 72) and Doppler ultrasound (n = 60), clinical presentation (n = 76), and follow-up with chart review (n = 72).
Two hundred five emboli were identified. Nineteen patients had solitary emboli. Sixty emboli were in the upper lobes. The largest arterial branch with pulmonary embolism was lobar in 14 patients, segmental in 38, subsegmental in 20, and smaller in three.
If cross-sectional imaging can depict emboli in only segmental and larger arterial branches, then emboli in 23 of 76 patients (30%) would have been missed with cross-sectional imaging.
Prevention of venous thrombosis and pulmonary embolism