Pierre-François Unger

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 Hôpital 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.

Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism

The potential of plasma measurement of D-dimer (DD), a specific derivative of crosslinked fibrin, for diagnosis or exclusion of pulmonary embolism was investigated in a prospective series of 171 consecutive patients who attended an emergency department with suspected pulmonary embolism. The diagnosis was made or excluded by means of a clinical decision-making process which included clinical evaluation, ventilation-perfusion (VQ) lung scan, and, as indicated, pulmonary angiography, venography, or non-invasive examination of the leg veins. Pulmonary embolism was diagnosed by this process in 55 (32%) of 170 patients with sufficient data. All but 1 of these 55 patients had a DD concentration of 500 micrograms/l or above. The sensitivity and specificity of this cutoff concentration for the presence of pulmonary embolism were 98% and 39%, respectively, which give positive and negative predictive values of 44% and 98%. Among the 115 patients (68%) who had inconclusive VQ scans, 31 were diagnosed as having pulmonary embolism. 29 of the remaining 84 patients without pulmonary embolism had DD concentrations below 500 micrograms/l, which means that further diagnostic procedures could have been avoided in a quarter of the patients with inconclusive VQ scans. The sensitivity of the plasma measurement of DD remained high even 3 and 7 days after presentation (96% and 93%). Plasma measurement of DD therefore has a definite place in the diagnostic procedure for suspected acute pulmonary embolism in attenders at emergency departments: a concentration below 500 micrograms/l rules out the diagnosis.

Impact of a public campaign on pre-hospital delay in patients reporting chest pain.

OBJECTIVE: To decrease pre-hospital delay in patients with chest pain. DESIGN: Population based, prospective observational study. SETTING: A province of Switzerland with 380000 inhabitants. SUBJECTS: All 1337 patients who presented with chest pain to the emergency department of the Hôpital Cantonal Universitaire of Geneva during the 12 months of a multimedia public campaign, and the 1140 patients who came with similar symptoms during the 12 months before the campaign started. MAIN OUTCOME MEASURES: Pre-hospital time delay and number of patients admitted to the hospital for acute myocardial infarction (AMI) and unstable angina. RESULTS: Mean pre-hospital delay decreased from 7h 50 min before the campaign to 4 h 54 min during it, and median delay from 180 min to 155 min (P < 0.001). For patients with a final diagnosis of AMI, mean delay decreased from 9 h 10 min to 5 h 10 min and median delay from 195 min to 155 min (P < 0.002). Emergency department visits per week for AMI and unstable angina increased from 11.2 before the campaign to 13.2 during it (P < 0.02), with an increase to 27 (P < 0.01) during the first week of the campaign; visits per week for non-cardiac chest pain increased from 7.6 to 8.1 (P = NS) during the campaign, with an increase to 17 (P < 0.05) during its first week. CONCLUSIONS: Public campaigns may significantly reduce pre-hospital delay in patients with chest pain. Despite transient increases in emergency department visits for non-cardiac chest pain, such campaigns may significantly increase hospital visits for AMI and unstable angina and thus be cost effective.

Diagnostic accuracy of Doppler-echocardiography in unselected patients with suspected pulmonary embolism

This study investigates the diagnostic value of echocardiography in patients with suspected pulmonary embolism. Doppler-echocardiography was performed in fifty consecutive patients, predominantly presenting in the emergency ward, with clinically suspected pulmonary embolism. Patients were classified as having or not pulmonary embolism by a sequential non-invasive strategy including lung scan, D-dimer measurement and lower limb venous compression ultrasonography, pulmonary angiography being performed in case of an inconclusive non-invasive work-up. The prevalence of pulmonary embolism was 36% (18 of 50 patients). Right ventricular dilatation on 2-D echocardiography associated to a tricuspid regurgitation velocity > or =2.7 m/s, corresponding to a pulmonary systolic pressure > or =39 mmHg, were present in 12 of the 18 patients (67%) with and in two of the 32 patients (6.3%) without pulmonary embolism. They were, however, absent in five of the 18 patients (28%), in whom the definite diagnosis of pulmonary embolism was made. The combination of these both echocardiographic criteria yielded a sensitivity of 67% and a specificity of 94%, positive predictive value was 86% and negative predictive value was 83%. The diagnostic performance of these two combined echocardiographic criteria, when present, permitted to reach in patients with a high clinical pre-test probability of pulmonary embolism the post-test probability values above 90%. On the other hand, the absence of these two Doppler-echocardiographic criteria did not allow to exclude pulmonary embolism, except in presence of a low pre-test probability. The findings of our study show that Doppler-echocardiography in patients with high clinical suspicion of pulmonary embolism may represent a potentially useful screening technique for the diagnosis of the disease permitting prompt initiation of treatment. However, the method does not allow to exclude pulmonary embolism in all patients with intermediate or high clinical suspicion of the disease.

Rapid bedside whole blood cardiospecific troponin T immunoassay for the diagnosis of acute myocardial infarction

Abstract In conclusion, this new bedside whole blood cTT immunoassay possesses similar or better sensitivity and specificity than creatine kinase-MB for diagnosing acute myocardial infarction, and is easier and faster to use. It is therefore a promising new test for very early diagnosis of acute myocardial infarction; further validation and a comparison with creatine kinase-MB subform determinations are needed in larger groups of patients.

Contribution of D-dimer plasma measurement and lower-limb venous ultrasound to the diagnosis of pulmonary embolism: A decision analysis model

The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) study has shown that clinical evaluation and lung scanning may substantiate or exclude pulmonary embolism with reasonable probability in approximately half of the patients in whom it is suspected; for the remainder, pulmonary angiography is considered the gold standard diagnostic test. We performed a decision analysis to assess the potential of two noninvasive tests, D-dimer plasma measurement and lower-limb B-mode venous ultrasound, for reducing the number of pulmonary angiograms necessary to diagnose pulmonary embolism. Our decision model addresses hypothetical patients in the emergency ward with suspected pulmonary embolism and abnormal lung scan results. Results show that D-dimer measurements of less than 500 micrograms/L could be used reliably to exclude pulmonary embolism in patients with an abnormal but not high-probability (inconclusive) lung scan. D-dimer measurements of greater than 500 micrograms/L have no positive predictive value for pulmonary embolism and should be followed by ultrasound, which may replace pulmonary angiography when it discloses deep venous thrombosis. Pulmonary angiography should be performed when ultrasound is negative because of its presumably low sensitivity for deep venous thrombosis in patients with pulmonary embolism. A D-dimer measurement of less than 500 mu/L does not exclude pulmonary embolism in patients with a high clinical suspicion of pulmonary embolism. On the basis of the results of the PIOPED study, we calculated that the combination of D-dimer measurement and ultrasound might reduce the requirement for pulmonary angiography by one third among patients with inconclusive scan results and intermediate clinical probability of pulmonary embolism.

Applicability of decision analysis to everyday clinical practice: a controlled feasibility trial

Objective: To determine whether decision analysis is applicable to routine management of suspected pulmonary embolism in an emergency care setting.Design: Controlled feasibility trial.Setting: Emergency center of a university hospital.Patients: Outpatients (n=84) admitted with clinical and scintigraphic evidence of pulmonary embolism.Interventions: Patients were treated either with the usual clinical work up for pulmonary embolism (control group) or using a decision analysis model with three options: no action; angiography followed by treatment if positive; treatment without angiography.Results: All six senior residents in the decision analysis group agreed to fully participate for the 16 months of the study. Summarizing the decision analysis model in a graph was critical to obtain acceptance from all the physicians. Decision analysis (n=43) and control (n=41) patients underwent similar numbers of angiographies. However, angiographies for patients who had intermediate clinical probabilities of pulmonary embolism, between 25 and 75%, were more frequent in the decision analysis group (9/13=69%) than in the control group (7/20=35%). Agreement between clinical probability and lung-scan result was stronger in the decision analysis group.Conclusions: Decision analysis was successfully used to manage all patients suspected of having pulmonary embolism admitted to an emergency center during the 16-month trial. There was no insuperable obstacle to acceptance of clinical decision analysis by the physicians. Decision analysis may have resulted in a better discrimination between low and intermediate clinical probabilities of pulmonary embolism.

Do Physicians Modify Their Prehospital Management of Patients in Response to a Public Campaign on Chest Pain

The goals of this study were to analyze the impact of a public campaign on chest pain on physicians involved in the prehospital care of patients with this symptom, in terms of physician delay, rates of immediate hospitalization, and of transportation by ambulance. Prehospital delays and decisions for all 866 patients with chest pain managed by the community and generalist physicians or by emergency physicians, who presented to the emergency department of a teaching hospital during the 12 months of the campaign, were compared with those of all 749 patients with similar presentations during the 12 months before it. When community and generalist physicians were involved, median (110 minutes) physician delay did not decrease during the campaign, whereas it decreased from 65 to 56 minutes (p <0.003) when emergency physicians were involved. Rates of immediate hospitalization (73%) and of transportation by ambulance (47%) of patients managed by community and generalist physicians were unaffected by the campaign, whereas they increased from 96% and 89%, respectively, to 98% (p = 0.09) and 94% (p <0.02) when emergency physicians were involved. Similar observations were made in patients with confirmed acute myocardial infarction and unstable angina and remained highly significant after adjustment for differences in clinical characteristics. Thus, community and generalist physicians did not significantly modify their prehospital management of patients with chest pain despite a public campaign. To be successful, guidelines on the matter have to be developed with the active participation of these physicians.

737–3 Rapid Whole Blood Bedside Cardiac Troponln T Immunoassay for the Diagnosis of Acute Myocardial Infarction

Cardiac troponin T (cTT) is a regulatory contractile protein normally not found in the blood. Its detection in the circulation has been shown to be a sensitive and specific marker for acute myocardial infarction (AMI). The Elisa cTT presently requires at least 90 minutes, which is too long to be useful in emergency situations. We tested a new rapid bedside whole blood immunoassay for cTT in 32 consecutive patients admitted to the Geneva University Hospital for suspected AMI, with an onset of pain within 12 hours. The new rapid assay, the Elisa cTT, the creatine kinase (CK) and creatine kinase-MB (CK-MB) were performed at admission, 4 and 8 hours after admission. The rapid assay was positive in all 25 patients subsequently shown to have an AMI. In the 7 patients without AMI, the assay was negative in 6, and positive in 1 (myopericarditis). At each time of the three measurements, the rapid assay had a similar or a better sensitivity and specificity than CK-MB or Elisa cTT. Already 4 hours after admission, the rapid assay reached a sensitivity of 100%, which is better than the CK-MB (96%). Results of the rapid assay were obtained in 15 minutes, even less in all positive cases, and the time to get a positive result correlated with the cTT Elisa and CK-MB levels. Our results allowed us to conclude that, while considerably more rapid than conventional assays, this new bedside whole-blood troponin T assay also has equal or better sensitivity and specificity than the other tests. In addition, we would like to stress the simplicity of this rapid assay, that can be performed on the spot, without laboratory infrastructure or equipment.