Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED)

To assess the value of perfusion lung scan in the diagnosis of pulmonary embolism, we prospectively evaluated 890 consecutive patients with suspected pulmonary embolism. Prior to lung scanning, each patient was assigned a clinical probability of pulmonary embolism (very likely, possible, unlikely). Perfusion scans were independently classified as follows: (1) normal, (2) near-normal, (3) abnormal compatible with pulmonary embolism (PE+: single or multiple wedge-shaped perfusion defects), or (4) abnormal not compatible with pulmonary embolism (PE-: perfusion defects other than wedge-shaped). The study design required pulmonary angiography and clinical and scintigraphic follow-up in all patients with abnormal scans. Of 890 scans, 220 were classified as normal/or near-normal and 670 as abnormal. A definitive diagnosis was established in 563 (84%) patients with abnormal scans. The overall prevalence of pulmonary embolism was 39%. Most patients with angiographically proven pulmonary embolism had PE+ scans (sensitivity: 92%). Conversely, most patients without emboli on angiography had PE- scans (specificity: 87%). A PE+ scan associated with a very likely or possible clinical presentation of pulmonary embolism had positive predictive values of 99 and 92%, respectively. A PE- scan paired with an unlikely clinical presentation had a negative predictive value of 97%. Clinical assessment combined with perfusion-scan evaluation established or excluded pulmonary embolism in the majority of patients with abnormal scans. Our data indicate that accurate diagnosis of pulmonary embolism is possible by perfusion scanning alone, without ventilation imaging. Combining perfusion scanning with clinical assessment helps to restrict the need for angiography to a minority of patients with suspected pulmonary embolism.     

Enhanced expression of bcl-2 inhibits apoptosis in cultured human keratinocytes

Intravenous heparin followed by oral warfarin sodium is effective for preventing recurrent thromboembolism in patients who have pulmonary embolism or proximal vein thrombosis. The effectiveness of intravenous heparin depends on obtaining an adequate anticoagulant response early during therapy. A validated heparin protocol should be used to ensure that an adequate anticoagulant response is obtained as soon as possible. Low molecular weight heparin has the practical advantage that it does not require monitoring and dose finding. If thrombolytic therapy is indicated, it is safer for many patients to base management on the noninvasive diagnosis rather than performing pulmonary angiography. In patients suspected to have pulmonary embolism who have nondiagnostic lung scan and adequate cardiorespiratory reserve, serial noninvasive leg testing is a practical approach that avoids pulmonary angiography, identifies patients who have proximal vein thrombosis requiring treatment, and avoids the risks of anticoagulant treatment in the majority of patients.     

Clinical diagnosis and management of the patient with deep venous thromboembolism and acute pulmonary embolism

Pulmonary embolism is the third most common acute cause of death in the United States. There are approximately 500,000 cases annually in this country, leading to death in 50,000. Subjective symptoms and objective findings can oftentimes be confusing and nonspecific. A pulmonary embolism is defined as an occlusion of one or more pulmonary vessels by material that has traveled there from outside of the lung and is usually caused by a dislodged thrombus that originated in the deep veins of the legs or pelvis. Risk factors include older age, prior thromboembolism, immobility, cancer, chronic disease, congestive heart failure, pelvic and lower extremity surgery, varicosities, obesity, and oral contraception. This article will discuss current modalities that are used in the evaluation of deep venous thromboembolism and pulmonary embolism and include ventilation/perfusion scan, ultrasonography, impedance plethysmography, pulmonary angiography, and newer tests including D-dimer assays and spiral computed tomography. Medical management including simple and complex decision making, anticoagulation, and thrombolytic therapy will also be discussed. An ounce of prevention is worth a pound of gold--identification of risk factors and the use of appropriate therapeutic measures can reduce an individual's risk for deep venous thromboembolism and pulmonary embolism.     

Non-invasive diagnosis of venous thromboembolism in outpatients

BACKGROUND: We designed a simple and integrated diagnostic algorithm for acute venous thromboembolism based on clinical probability assessment of deep-vein thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower-limb venous compression ultrasonography, and lung scan to reduce the need for phlebography and pulmonary angiography. METHODS: 918 consecutive patients presenting at the emergency ward of the Geneva University Hospital, Geneva, Switzerland, and H?pital Saint-Luc, Montreal, Canada, with clinically suspected venous thromboembolism were entered into a sequential diagnostic protocol. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months. FINDINGS: A normal D-dimer concentration (<500 microg/L by a rapid ELISA) ruled out venous thromboembolism in 286 (31%) members of the study cohort, whereas DVT by ultrasonography established the diagnosis in 157 (17%). Lung scan was diagnostic in 80 (9%) of the remaining patients. Venous thromboembolism was also deemed absent in patients with low to intermediate clinical probability of DVT and a normal venous ultrasonography (236 [26%] patients), and in patients with a low clinical probability of PE and a non-diagnostic result on lung scan (107 [12%] patients). Pulmonary angiography and phlebography were done in only 50 (5%) and 2 (<1%) of the patients, respectively. Hence, a non-invasive diagnosis was possible in 866 (94%) members of the entire cohort. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 1.8% (95% CI 0.9-3.1). INTERPRETATION: A diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis in the vast majority of outpatients with suspected venous thromboembolism, and appeared to be safe.     

The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism

This paper describes the role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Inability to compress the common femoral or popliteal vein is usually diagnostic of a first episode of deep venous thrombosis in symptomatic patients (positive predictive value of about 97%). Full compressibility of both of these sites excludes proximal deep venous thrombosis in symptomatic patients (negative predictive value of about 98%). In patients with suspected deep venous thrombosis or in those who present with suspected pulmonary embolism but have a nondiagnostic lung scan, the subsequent risk for symptomatic venous thromboembolism is very low (<2% during 6 months of follow-up) provided that ultrasonography of the proximal veins remains normal in the course of 1 week (suspected deep venous thrombosis) or 2 weeks (suspected pulmonary embolism). Anticoagulation and further diagnostic testing can usually be safely withheld in these situations. Venous ultrasonography is much less reliable for the diagnosis of asymptomatic, isolated distal, and recurrent deep venous thrombosis than for the diagnosis of a first episode of proximal deep venous thrombosis in symptomatic patients. Clinical evaluation of the probability of deep venous thrombosis or pulmonary embolism, preferably by using a validated clinical model, complements venous ultrasonographic findings and helps to identify patients who would benefit from additional (often invasive) diagnostic testing. Thus, venous ultrasonography is thought to be a very valuable test for the diagnosis and management of patients with suspected deep venous thrombosis or pulmonary embolism.     

Analysis of immunoglobulin genes in splenic marginal zone lymphoma suggests ongoing mutation

BACKGROUND: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.     

Experimentally induced nasal hypersecretion does not reduce the efficacy of intranasal levocabastine

Pulmonary tumor embolism is an often missed antemortem diagnosis in patients with cancer and respiratory failure. Although rare, this complication is an important cause of additional morbidity. Referred for radionuclide pulmonary perfusion and ventilation scintigraphy, a typical pattern of multiple subsegmental peripheral defects on perfusion lung scanning without matching ventilation defects, suggesting a high probability of pulmonary thromboembolism, often leads to false conclusions. We present a case of bilateral multiple subsegmental mismatched defects in lung ventilation perfusion scintigraphy, where autopsy confirmed the diagnosis of pulmonary tumor embolism, secondary to an undifferentiated ductal type adenocarcinoma of the pancreas. Pulmonary tumor embolism is an entity to keep in mind in patients treated for carcinoma presenting with (sub) acute dyspnea.     

Diagnosis of deep venous thrombosis and pulmonary embolism

Diagnostic evaluation in the patient with suspected deep vein thrombosis (DVT) and pulmonary embolism (PE) includes a clear correlation between clinical probability, test selection and test interpretation. Real-time B-mode ultrasound with color Doppler remains the imaging technique of choice in suspected DVT. The ventilation/perfusion (V/Q) lung scan is the preferred diagnostic modality in suspected PE. The D-dimer assay may be useful in excluding PA. New diagnostic techniques, including spiral computerized tomography may further modify the diagnostic algorithm.     

Study on antifertility effect of a novel LHRH antagonist in male rats

The diagnosis of pulmonary embolism is even in contemporary clinical practice problematical. Pulmonary angiography is used in our departments very little due to its invasive character. The method of choice for diagnosis remains therefore perfusion scintigraphy of the lungs, in this country frequently without ventilation scintigraphy as it is not available in the majority of our departments of nuclear medicine. In recent years in the diagnostic algorithms also assessment of D-dimers was started, i.e. assessment of products of fibrinolysis assessed by monoclonal antibodies. The authors tried to find out how many patients admitted to the medical department for diagnosis of pulmonary embolization may have a false positive diagnosis on the basis of pulmonary scintigraphy. During the period III/96 to V/96 a total of 18 patients from the medical clinic with suspected pulmonary embolism were examined where the value of D-dimers(latex test) was assessed and at the same time perfusion scintigraphy was performed. With regard to the highly negative predictive value of D-dimer assessment the authors focused their attention on patients with a suspect or positive lung scan (i.e. treated on account of pulmonary embolism) while D-dimers were negative. Of 13 patients with suspect or possible pulmonary embolism, as assessed by scintigraphy, four had negative dimers(30%). With regard to the 90% reported negative predictive value, based on the literature, thus three of these patients were unnecessarily admitted to hospital and treated. The authors assume that assessment of D-dimers should be part of the examination protocol due to its non-pretentious character and low price as compared with costs of hospitalization.     

Treatment of venous thromboembolism

There have been some important advances in the treatment of venous thromboembolism during the past 18 months. A randomized trial has confirmed earlier observations indicating an adequate initial heparin effect is required to prevent recurrent venous thromboembolism, and it is critical to achieve this effect within the first 24 hours of therapy. The need to use a validated protocol for administering intravenous heparin is now firmly established. The clinician has a choice between two protocols that have been validated by randomized trials and provide both effective and safe heparin therapy. For patients with clinically suspected pulmonary embolism, the clinician now has a practical noninvasive strategy that avoids pulmonary angiography, identifies patients with proximal-vein thrombosis who require treatment, and avoids the need for treatment and further investigation in the majority of patients.     

A comparative analysis of pulmonary perfusion scans with pulmonary angiograms

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.     

DTPA aerosol in ventilation/perfusion scintigraphy for diagnosing pulmonary embolism

The use of lung scintigraphy in evaluating suspected pulmonary embolism (PE) is controversial. Several diagnostic methods have been described for lung scans, of which the most widely applied uses 99mTc-MAA for perfusion, 133Xe for ventilation and PIOPED diagnostic criteria. This study evaluates the accuracy of lung scintigraphy using an alternative ventilation agent, 99mTc-diethylenetriamine pentacetic acid (DTPA) aerosol, and specific criteria. METHODS: Diagnostic criteria for DTPA aerosol ventilation were prospectively applied to 5017 patients over a 9-yr period. Lung scan interpretations were analyzed for frequency of occurrence, and results were compared to those of angiography in 455 patients. RESULTS: Scans were interpreted as normal, low or high probability in 79% of patients and as either indeterminate or medium probability in 21% of patients. Three patients had normal scans and negative angiography. In patients with low-probability scans, 111 angiograms were performed: 103 (93%) were negative, and 8 (7%) were positive. In patients with indeterminate scans, 114 angiograms were performed: 85 (75%) were negative, and 29 (25%) were positive. In patients with medium-probability scans, 149 angiograms were performed: 86 (58%) were negative, and 63 (42%) were positive. In patients with high-probability scans, 78 angiograms were performed: 6 (8%) were negative, and 72 (92%) were positive. CONCLUSION: These results indicate that lung scintigraphy using DTPA aerosol and our criteria is accurate in diagnosing and stratifying risk of pulmonary embolic disease. Compared with 133Xe and PIOPED criteria, DTPA ventilation and our criteria reduced the false-negative rate in low-probability scans (7% versus 16%, p < 0.005) and decreased the fraction of intermediate-probability scans (21 % versus 39%, p < 0.01).     

Seven new cases of Cayler cardiofacial syndrome with chromosome 22q11.2 deletion, including a familial case

Pulmonary lymphangitic carcinomatosis (PLC) is an unusual presentation of diffuse infiltrative lung disease. In this report we present two cases secondary to breast cancer; the diagnosis was made by means of transbronchial lung biopsy or postmortem examination. The goal of this study was to analyze the scintigraphic pattern of pulmonary perfusion performed with technetium-99m macroaggregated albumin (99mTc-MAA) in the hope of achieving improved recognition of PLC and its subsequent diagnosis. Upon admission, both patients underwent routine clinical exams followed by chest X-rays. The second patient also underwent CT examination, and both were ultimately examined using pulmonary perfusion scintigraphy with 99mTc-MAA. In the various exams performed, the most reliable and easily identified diagnostic finding turned out to be a characteristic 'fragmented' lung pattern revealed with the perfusion lung scan. Unfortunately, in both cases the patients' conditions rapidly worsened and death occurred shortly following scintigraphy. We were able to conclude that the recognition of the mentioned fragmented scintigraphic lung pattern may be useful in suspected PLC, whereas the nonspecific clinical presentation of this pathology makes diagnosis extremely difficult, with the most significant results being achieved through a comparison of scintigraphic and high resolution CT data.     

Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism

BACKGROUND: Patients with suspected pulmonary embolism often have nondiagnostic lung scans and may present in circumstances where lung scanning is unavailable. Levels of D-dimer, a fibrin-specific product, are increased in patients with acute thrombosis; this may simplify the diagnosis of pulmonary embolism. OBJECTIVE: To determine the sensitivity and specificity of a whole-blood D-dimer assay in patients with suspected pulmonary embolism and in subgroups of patients with low pretest probability of pulmonary embolism or nondiagnostic lung scans. DESIGN: Prospective cohort. SETTING: Four tertiary care hospitals. PATIENTS: 1177 consecutive patients with suspected pulmonary embolism. MEASUREMENTS: All patients underwent an assessment of pretest probability by use of a standardized clinical model, a D-dimer assay, ventilation-perfusion lung scanning, and bilateral compression ultrasonography. Patients in whom pulmonary embolism was not initially diagnosed were followed for 3 months. Accordingly, patients were categorized as positive or negative for pulmonary embolism. RESULTS: Of the 1177 patients, 197 (17%) were classified as positive for pulmonary embolism. Overall, the D-dimer assay showed a sensitivity of 84.8% and a specificity of 68.4%. In 703 patients (3.4%) with a low pretest probability of pulmonary embolism, the likelihood ratio associated with a negative D-dimer test result was 0.27, resulting in a posterior probability of 1.0% (95% CI, 0.3% to 2.2%). In 698 patients with nondiagnostic lung scans (previous probability, 7.4%), the likelihood ratio associated with a negative D-dimer test result was 0.36, resulting in a posterior probability of 2.8% (CI, 1.4% to 4.8%). CONCLUSIONS: A normal D-dimer test result is useful in excluding pulmonary embolism in patients with a low pretest probability of pulmonary embolism or a nondiagnostic lung scan.     

Comparison between morphologic changes seen on high-resolution CT and regional pulmonary perfusion seen on SPECT in patients with cystic fibrosis

OBJECTIVE: To evaluate the relationship between morphologic findings seen on high-resolution computed tomography (HRCT) of the lung and regional lung perfusion depicted on single photon-emission computed tomography (SPECT) pulmonary perfusion imaging in patients with cystic fibrosis. MATERIALS AND METHODS: Ten HRCT and 10 technetium-99 m macroaggregated albumin SPECT pulmonary perfusion imaging studies were performed on eight young adult patients who were considered to be clinically well and have mild to moderate cystic fibrosis. HRCT scans of the chest were evaluated using a CT scoring system which included grading of bronchiectasis, peribronchial thickening, hyperlucency, bullae, collapse/consolidation, and mucus plugging. Each lung was divided into six anatomic zones which were independently scored. A lung perfusion score (between 0 and 100), reflecting the percentage of compromised lung, was estimated for each zone. Axial lung perfusion SPECT images were matched anatomically to HRCT images. Lung function was considered compromised when the counts per pixel were less than 25 % of the count level seen in an area of the same patient's lung which was judged to be normal. RESULTS: There was a statistically significant relationship (P = 0.0001) between HRCT total scores and SPECT lung perfusion scores as well as between hyperlucency scores by HRCT and the SPECT lung perfusion scores. However, the HRCT score was a poor predictor of the lung perfusion score in zones with intermediate HRCT scores, which constituted 106 of 120 zones. CONCLUSION: Morphologic changes depicted by HRCT correlate with decreased lung pefusion on SPECT. However, HRCT changes accurately predict regional lung function only in the most normal and severely diseased lung zones.     

Electron-beam computed tomography: preliminary experiences in the Netherlands]

The difference between computer tomography (CT) and electron beam tomography (EBT) is that for CT the x-ray tube rotates in a ring round the patient, and for EBT the x-ray beam rotates itself. As a result, with EBT the speed of making images is not limited by the mechanical rotation of the tube, and 16 images can be made per second. An EBT scan of a whole thorax takes 9 seconds. Specific application areas are fast moving organs and patients who cannot remain in one position for long, e.g. children and intensive care patients. Research is being conducted into the possibilities of this non-invasive technique for the demonstration of coronary artery lesions, pulmonary embolism, pulmonary metastases and dynamic examination of the major respiratory tract. Costs of an EBT scan currently amount to Dfl. 450.--but they will probably decrease as this imaging system is developed further. The exposure to radiation is about the same as that caused by a (spiral) CT.     

Significance of inhalation and perfusion scintigraphy for the diagnosis of pulmonary embolism (author's transl)

Inhalation and perfusion scintigrams, general radiological examination of the thorax and an EKG were done on 43 patients with clinically suspected pulmonary embolism. In 11 cases, the clinical diagnosis could be confirmed on the basis of the scintigraphic examination. In the remaining 32 patients, an embolich event could be excluded by pulmonary scintigram, radiological examination and later the clinical course. A synopsis of clinical observations, X-ray and scintigraphy, therefore, permitted a basically reliable diagnosis of pulmonary embolism; selective pulmonary angiography should be used only in exceptional cases.     

Diagnosis of pulmonary embolism with magnetic resonance angiography

BACKGROUND: Diagnosing pulmonary embolism may be difficult, because there is no reliable noninvasive imaging method. We compared a new noninvasive method, gadolinium-enhanced pulmonary magnetic resonance angiography, with standard pulmonary angiography for diagnosing pulmonary embolism. METHODS: A total of 30 consecutive patients with suspected pulmonary embolism underwent both standard pulmonary angiography and magnetic resonance angiography during the pulmonary arterial phase at the time of an intravenous bolus of gadolinium. All magnetic resonance images were reviewed for the presence or absence of pulmonary emboli by three independent reviewers who were unaware of the findings on standard angiograms. RESULTS: Pulmonary embolism was detected by standard pulmonary angiography in 8 of the 30 patients in whom pulmonary embolism was suspected. All 5 lobar emboli and 16 of 17 segmental emboli identified on standard angiograms were also identified on magnetic resonance images. Two of the three reviewers reported one false positive magnetic resonance angiogram each. As compared with standard pulmonary angiography, the three sets of readings had sensitivities of 100, 87, and 75 percent and specificities of 95, 100, and 95 percent, respectively. The interobserver correlation was good (k=0.57 to 0.83 for all vessels, 0.49 to 1.0 for main and lobar vessels, and 0.40 to 0.81 for segmental vessels). CONCLUSIONS: In this preliminary study, gadolinium-enhanced magnetic resonance angiography of the pulmonary arteries, as compared with conventional pulmonary angiography, had high sensitivity and specificity for the diagnosis of pulmonary embolism. This new technique shows promise as a noninvasive method of diagnosing pulmonary embolism without the need for ionizing radiation or iodinated contrast material.     

Comparative properties of the Charcot-Leyden crystal protein and the major basic protein from human eosinophils

The angiographic, scintigraphic, and clinical data of 40 patients were reviewed in order to define the role of 133Xe ventilation studies in the radionuclide detection of pulmonary embolism. Two independent observers interpreted the perfusion images, and several weeks later reinterpreted them in conjunction with 133Xe ventilation studies. Overall diagnostic accuracy was significantly improved (p less than 0.05) when the xenon studies were included. The combined studies were slightly more sensitive and significantly more specific (p less than 0.05) for pulmonary embolism than the perfusion images alone.     

Thromboembolic disease in patients undergoing total knee replacement

In a prospective study fo the incidence of deep-vein thrombosis in thirty patients undergoing total knee replacement, all patients had clinical examinations and 125I fibrinogen scanning, while those suspected of having deep venous thrombosis also had confirmatory venography. Sixteen (53 per cent) of the thirty patients had thromboembolic disease; nine had thrombi only in the limb operated on; four had bilateral deep venous thrombi; and three had pulmonary embolism. In nine patients who took aspirin regularly the incidence of thromboembolism was 11 per cent, while in the eight who did not take aspirin or any other antiplatelet drug the incidence was 88 per cent, a difference which was highly significant (p = 0.003).