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The impact of residual pulmonary obstruction on the outcome of patients with pulmonary embolism is uncertain.We recruited 647 consecutive symptomatic patients with a first episode of pulmonary embolism, with or without concomitant deep venous thrombosis. They received conventional anticoagulation, were assessed for residual pulmonary obstruction through perfusion lung scanning after 6 months and then were followed up for up to 3 years. Recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension were assessed according to widely accepted criteria.Residual pulmonary obstruction was detected in 324 patients (50.1%, 95% CI 46.2-54.0%). Patients with residual pulmonary obstruction were more likely to be older and to have an unprovoked episode. After a 3-year follow-up, recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension developed in 34 out of the 324 patients (10.5%) with residual pulmonary obstruction and in 15 out of the 323 patients (4.6%) without residual pulmonary obstruction, leading to an adjusted hazard ratio of 2.26 (95% CI 1.23-4.16).Residual pulmonary obstruction, as detected with perfusion lung scanning at 6 months after a first episode of pulmonary embolism, is an independent predictor of recurrent venous thromboembolism and/or chronic thromboembolic pulmonary hypertension., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2017.)

In the setting of acute pulmonary embolism (PE), pulmonary infarction is deemed to occur primarily in individuals with compromised cardiac function.The current study was undertaken to establish the prevalence of pulmonary infarction in patients with acute PE, and the relationship between infarction and: age, body height, body mass index (BMI), smoking habits, clot burden, and comorbidities.The authors studied prospectively 335 patients with acute PE diagnosed by computed tomographic angiography (CT) in 18 hospitals throughout central Italy. The diagnosis of pulmonary infarction on CT was based on Hampton and Castleman's criteria (cushion-like or hemispherical consolidation lying along the visceral pleura). Multivariable logistic regression was used to model the relationship between covariates and the probability of pulmonary infarction.The prevalence of pulmonary infarction was 31%. Patients with infarction were significantly younger and with significantly lower prevalence of cardiovascular disease than those without (P < 0.001). The frequency of infarction increased linearly with increasing height, and decreased with increasing BMI. In logistic regression, the covariates significantly associated with the probability of infarction were age, body height, BMI, and current smoking. The risk of infarction grew with age, peaked at approximately age 40, and decreased afterwards. Increasing body height and current smoking were significant amplifiers of the risk of infarction, whereas increasing BMI appeared to confer some protection.Our data indicate that pulmonary infarction occurs in nearly one-third of the patients with acute PE. Those with infarction are often young and otherwise healthy. Increasing body height and active smoking are predisposing risk factors.

Purpose: The aim of the study was to establish whether the duration of anticoagulant (AC) therapy can be tailored, on an objective basis, by using ventilation/perfusion single-photon emission computed tomography (V/P SPECT) and to assess the extent of residual perfusion defects over time. In particular, we addressed the following: (a) is the extent of perfusion recovery at 3 months of initial pulmonary embolism (PE) diagnosis a satisfactory criterion for deciding the duration of oral AC? (b) Is it safe to withdraw AC at 3 months if perfusion recovery is complete?, Patients and Methods: Of 269 consecutive patients with suspected PE, 100 patients were diagnosed with PE using V/P SPECT. Sixty-seven patients with acute PE were followed up clinically and with V/P SPECT at 3 months. Sixty-four patients were subject to review and examination using V/P SPECT for a period of 6 months and 33 were followed up only clinically. Therapy was terminated after 3 months if perfusion was normalized, and patients were free of symptoms and the risk of hypercoagulability. Initial extension of PE did not have an impact on decision making., Results: PE extension varied from 10 to 70% in the acute stage. After 3 months, complete resolution of PE was found in 48 patients. The treating pulmonologist decided to terminate therapy in 35 (73%) patients and to continue AC in 13 patients because of persistent risk factors. Six months later, at the second control stage, 53 patients had complete recovery of pulmonary perfusion. Eleven patients still had perfusion defects at 6 months. No recurrence was identified at 6 months in the 35 patients whose therapy was terminated after 3 months. No bleeding effects were observed in any of the patients during the 6-month follow-up., Conclusion: This study shows that AC therapy can be tailored, on an objective basis, by using V/P SPECT. Normalization of perfusion at 3 months of initial PE diagnosis was a reliable indicator that AC could be safely withdrawn in patients who were without hypercoagulability risk.

Unlabelled: Ventilation/perfusion tomography (V/P SPECT) is a recommended method for diagnosing and follow-up of pulmonary embolism (PE). Moreover, it is possible to recognize other pathologies in addition to PE, such as pneumonia, COPD and left heart failure (LHF). The objective of this prospective study was to identify frequency of ancillary findings among patients with suspected PE. Patients, material, method: 331 consecutive patients with suspected PE were examined and classified with V/P SPECT. Patients were followed up clinically and by means of other laboratory tests., Results: 80 patients had a normal V/P SPECT and no clinical consequences in the follow-up. PE had 104 patients: 23 of them had also additional findings. Among the remaining 147 patients, pneumonias were shown in 82, acute in 75 patients and 7 had chronic post inflammatory state. COPD was present in 42 patients, in 3 combined with pneumonia. Sign of LHF was observed in 10: in 7 the acute LHF diagnosis was established, 3 were classified as having a chronic cardiopulmonary disease. Furthermore, in 16 patients, the V/P pattern was suggestive of a tumour. The clinical outcomes were 6 lung tumours, 3 empyema, one sarcoidosis, 2 were unclarified and 4 were lost in the follow-up., Conclusion: V/P SPECT identifies a high prevalence of other cardiopulmonary diseases among patients with a clinical suspicion of PE. Ancillary findings with V/P SPECT clarified patients' symptoms and had an impact on the treatment. These findings were verified by a clinical outcome by the follow-up over three months.

Background: Few studies investigated the relationship between fibrinolysis abnormalities and residual pulmonary perfusion defects after acute pulmonary embolism (PE)., Objective: To assess the fibrinolytic profile in patients with prior PE in relation to the extent of scintigraphically detectable residual perfusion abnormalities., Patients and Methods: We studied 71 consecutive patients with a prior episode of PE, who were examined after one year of the incident embolic event, and at least one month after anticoagulation withdrawal. They underwent lung scintigraphy to assess the recovery of pulmonary perfusion, echocardiography and chest radiography to look for signs of pulmonary hypertension. Clot formation and lysis were evaluated by two turbidimetric methods: Clot and Lysis Assay and Clot Lysis Time. We also measured the in vitro plasmin-mediated lysis of fibrin from purified fibrinogen, and the circulating levels of fibrinolytic inhibitors. The sample was split in two categories based on the extent of residual perfusion defects: <10% (n=53), ≥ 10% (n=18)., Results: Patients with perfusion defects >10% had significantly longer lysis time (p<0.05), and higher levels of plasminogen activator inhibitor-1 (p<0.01) than those with perfusion defects <10%. The time interval between symptoms onset and PE diagnosis (time-to-diagnosis) was significantly longer in patients with perfusion defects >10% than in the others (p=0.005). In multivariate logistic regression, both lysis time and time-to-diagnosis were independently associated with perfusion defects >10% (p<0.001). None of the sampled patients had echocardiographic or radiologic signs of pulmonary hypertension., Conclusion: Prolonged time-to-diagnosis and fibrinolysis imbalance are independent predictors of incomplete perfusion recovery after acute PE., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: Ventilation/perfusion tomography (V/PSPECT), with new interpretation criteria and newer tracers for ventilation imaging, has markedly improved the diagnostic yield in acute pulmonary embolism (PE). Here, we evaluated the diagnostic performance of perfusion SPECT (PSPECT) without ventilation imaging., Methods: We studied 152 patients with clinically suspected PE who had been examined with both V/PSPECT and multidetector computed tomographic angiography (MD-CTA). The diagnosis or exclusion of PE was decided by the referring clinician based on both the V/PSPECT and/or MD-CTA findings in combination with the clinical findings. PSPECT images were retrospectively examined by a physician with experience in the interpretation of planar perfusion scans who was blinded to clinical, V/PSPECT and MD-CTA data. PSPECT images were interpreted without the aid of chest radiography. All the patients who were deemed to have PE were given anticoagulant therapy., Results: Of the 152 patients, 59 (39%) received a final diagnosis of PE, and 19 (32%) had associated cardiopulmonary diseases such as pneumonia, COPD, or left heart failure. PSPECT correctly identified 53 (90%) of the 59 patients with PE. The specificity was 88 of 93 (95%). None of the PSPECT images was rated nondiagnostic. PSPECT yielded an overall diagnostic accuracy of 93% (95% confidence interval, CI, 87-96%). At the observed PE prevalence of 39 %, the positive and negative predictive values of PSPECT were 91% (95% CI, 80-97%) and 94% (95% CI, 86-97%), respectively., Conclusion: In managing critically ill patients, PSPECT might be a valid alternative to V/PSPECT or MD-CTA since it was able to identify most patients with PE with a low false-positive rate and no inconclusive results.

The stratification of recurrence risk after a first episode of venous thromboembolism (VTE) is an important topic of research, especially in patients with pulmonary embolism (PE). Elevated D-dimer levels and residual vein obstruction (RVO) at compression ultrasonography have been studied as predictors of recurrence after withdrawing oral anticoagulant treatment (OAT). It is still unknown if residual perfusion defects (PD) on lung scintigraphy are related to recurrent PE. In the present study, we evaluated the association of PD with PE recurrence. The relationship between PD, elevated D-dimer levels, and RVO was also investigated. We prospectively followed 236 consecutive patients who survived a first episode of objectively confirmed PE, with or without deep-vein thrombosis. After at least three months of OAT, treatment was withdrawn in 139 patients. D-dimer levels were evaluated at one month of OAT withdrawal, RVO was measured, and perfusion lung scan (P-scan) was performed to evaluate PD. During follow-up, 20 patients experienced a recurrent episode of VTE. Elevated D-dimer levels were significantly associated with VTE recurrence, (p=0.003). RVO was present in 22% of the patients with recurrence and in 7.5% of those without (p=0.07). No significant association was found between PD >10% and VTE recurrence, D-dimer, or RVO. In conclusion, we confirmed the positive predictive value of elevated D-dimer levels for recurrent VTE. Residual PD on lung scintigraphy are neither predictive of recurrence nor related to D-dimer levels or RVO.

Background: Pulmonary embolism (PE) is diagnosed with imaging techniques such as ventilation/perfusion (V/P) lung scintigraphy or multidetector computed tomography of the pulmonary arteries (MDCT). Lung scintigraphy can be performed with planar (V/P PLANAR) and tomographic (V/P SPECT) techniques. V/P SPECT has higher sensitivity and specificity than V/P PLANAR. As nephrotoxic contrast media are not used during V/P SPECT, examinations can be repeated for evaluation of resolution of perfusion defects after PE. However, the value of residual perfusion defects identified using V/P SPECT for the prediction of recurrent PE has not been thoroughly evaluated., Material and Methods: We evaluated resolution and recurrence of PE in 227 patients (mean age 63 ± 17 years, 134[59%] women) with PE undergoing ≥ 2 SPECT examinations in 2005-2007. PE was defined as minor (<20% perfusion defect on SPECT, n=86), medium (20-50% perfusion defect on SPECT, n=99), or major (>50% perfusion defect on SPECT, n=42)., Results: At second V/P SPECT examination, complete resolution of perfusion defects had occurred in 45 (52%) patients with minor PE after 8.2 ± 7.4 months, in 29 (29%) of patients with medium PE after 6.2 ± 5.9 months, and in 2(5%) of patients with major PE after 6.5 ± 0.7 months. During 47 ± 24 months of follow up, 37(16 %) patients suffered recurrent PE. Of these 37, 34 (92%) showed residual perfusion defects at the second V/P SPECT examination. Recurrence of PE was also predicted by advanced age and female gender. However, in multivariate regression analysis, recurrence was only predicted by age (p=0.0013) and residual perfusion defect on V/P SPECT (p=0.0039)., Conclusion: In conclusion, complete resolution of PE was common in patients with minor PE, whereas residual perfusion defects were widespread in patients with medium and major PE. PE patients identified with persistent perfusion defects at follow-up SPECT have a high risk of PE recurrence., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Although pulmonary embolism (PE) and deep vein thrombosis (DVT) share many risk factors, it is uncertain whether thrombophilic abnormalities may impact differently on the development of these two clinical manifestations of venous thromboembolism (VTE). To give further insight into this issue, we estimated the association of PE with different types of thrombophilia and evaluated whether these abnormalities have a different prevalence in patients presenting with PE, alone or associated with DVT, as compared with those with isolated DVT. In this study 443 consecutive patients with a first episode of VTE and 304 matched healthy controls underwent laboratory screening for thrombophilia, including natural anticoagulants, factor V Leiden and prothrombin G20210A polymorphisms, antiphospholipid antibodies, homocysteine, factor VIII, and lipoprotein(a). Of the 443 patients, 224 patients had isolated DVT, 144 had combined DVT/PE, and 75 had isolated PE. At least one thrombophilic abnormality was detected in 72.8% of DVT, 66% of DVT/EP, and 60% of isolated PE patients. A high prevalence of hyperhomocysteinemia and elevated lipoprotein(a) levels was found in all patients with no significant differences among the three groups. The prevalence of prothrombin G20210A polymorphism and of elevated factor VIII levels was significantly higher in patients with DVT and DVT/PE than in controls, but not in those with isolated PE, whereas factor V Leiden polymorphism was associated with isolated DVT but not with DVT/PE or isolated PE. In conclusion, the thrombophilic burden seems different in isolated PE versus DVT with or without PE, suggesting that PE may encompass a different pathophysiological process of thrombosis to DVT., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Pulmonary embolism (PE) is a common and potentially fatal disease that is still underdiagnosed. The objective of our study was to reappraise the clinical presentation of PE with emphasis on the identification of the symptoms and signs that prompt the patients to seek medical attention., Methodology/principal Findings: We studied 800 patients with PE from two different clinical settings: 440 were recruited in Pisa (Italy) as part of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISAPED); 360 were diagnosed with and treated for PE in seven hospitals of central Tuscany, and evaluated at the Atherothrombotic Disorders Unit, Firenze (Italy), shortly after hospital discharge. We interviewed the patients directly using a standardized, self-administered questionnaire originally utilized in the PISAPED. The two samples differed significantly as regards age, proportion of outpatients, prevalence of unprovoked PE, and of active cancer. Sudden onset dyspnea was the most frequent symptom in both samples (81 and 78%), followed by chest pain (56 and 39%), fainting or syncope (26 and 22%), and hemoptysis (7 and 5%). At least one of the above symptoms was reported by 756 (94%) of 800 patients. Isolated symptoms and signs of deep vein thrombosis occurred in 3% of the cases. Only 7 (1%) of 800 patients had no symptoms before PE was diagnosed., Conclusions/significance: Most patients with PE feature at least one of four symptoms which, in decreasing order of frequency, are sudden onset dyspnea, chest pain, fainting (or syncope), and hemoptysis. The occurrence of such symptoms, if not explained otherwise, should alert the clinicians to consider PE in differential diagnosis, and order the appropriate objective test.

Purpose of Review: Pulmonary embolism is the most serious complication of venous thromboembolism, with an elevated case/fatality rate. Patients who survived a first episode of pulmonary embolism should be evaluated for the risk of recurrence and of chronic thromboembolic pulmonary hypertension (CTEPH)., Recent Findings: The risk of recurrence is higher in patients with unprovoked pulmonary embolism than in those with transient risk factors. Persistent risk factors, such as active cancer and antiphospholipid antibodies, are associated with high risk of recurrence. Recently, elevated D-dimer levels after discontinuation of therapy have been identified as a risk factor for recurrence. CTEPH is characterized by intravascular organization of emboli and occurs in 0.5-1% of cases. Some patients with CTEPH have impaired fibrinolysis, likely due to a structural abnormality of fibrin or fibrin clot. Echocardiography often reveals signs of pulmonary hypertension. This should be confirmed by direct measurement of pulmonary artery pressures at right heart catheterization., Summary: CTEPH patients should receive life-long anticoagulation for preventing recurrent pulmonary embolism. Pulmonary endarterectomy is the treatment of choice for patients with proximal pulmonary vascular occlusion. Patients with predominantly distal pulmonary vascular occlusion are candidates for pharmacological treatment. All patients with unprovoked pulmonary embolism should be evaluated for long-term anticoagulation.

After a first episode of pulmonary embolism (PE), two major problems need to be considered: risk of recurrence when anticoagulation is stopped, and risk of chronic thromboembolic pulmonary hypertension (CTPH). We followed prospectively consecutive patients who survived a first episode of PE, with or without deep vein thrombosis, to assess the incidence of venous thromboembolism (VTE) recurrences and of symptomatic and asymptomatic CTPH. After 3-6 months of oral anticoagulant therapy (OAT) patients underwent transthoracic echocardiography for measuring transtricuspid (rV-rA) gradient. When rV-rA gradient was >35 mmHg further evaluations were performed to rule in or out CTPH. During follow-up patients who developed persistent dyspnea were re-evaluated. In patients who underwent OAT withdrawal D-dimer (DD), prothrombin fragment 1 + 2 (F1 + 2), and thrombophilia were evaluated one month after warfarin discontinuation. Overall, 239 patients, 118 males, median age 59(16-89) years, were followed up for a median time of 36(9-192) months. Nine patients had rV-rA gradient >30 mmHg and ≤35 mmHg, and one of 37 mmHg. Among patients with normal rV-rA gradient, one developed persistent dyspnea 55 months after the first event and CPTH was confirmed. Among 206 patients who stopped OAT, 23(11.2%) had VTE recurrence, 11 PE(48%). Elevated DD and F1 + 2 levels after stopping OAT were significantly associated with recurrence. None of patients with recurrent VTE had elevated rV-rA gradient. In our series the incidence of CTPH after a first episode of PE was 0.4%. VTE recurrence and elevated DD and F1 + 2 levels seemed not to be related to the development of CTPH.

As emphasized in Part 1 of these guidelines, the diagnosis of pulmonary embolism (PE) is confirmed or refuted using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). To reduce the costs, the risks associated with false-negative and false-positive diagnoses, and unnecessary radiation exposure, preimaging assessment of clinical probability is recommended. Diagnostic accuracy is approximately equal for MDCT and planar V/P(SCAN) and better for tomography (V/P(SPECT)). V/P(SPECT) is feasible in about 99% of patients, while MDCT is often contraindicated. As MDCT is more readily available, access to both techniques is vital for the diagnosis of PE. V/P(SPECT) gives an effective radiation dose of 1.2-2 mSv. For V/P(SPECT), the effective dose is about 35-40% and the absorbed dose to the female breast 4% of the dose from MDCT performed with a dose-saving protocol. V/P(SPECT) is recommended as a first-line procedure in patients with suspected PE. It is particularly favoured in young patients, especially females, during pregnancy, and for follow-up and research.

Pulmonary embolism (PE) can only be diagnosed with imaging techniques, which in practice is performed using ventilation/perfusion scintigraphy (V/P(SCAN)) or multidetector computed tomography of the pulmonary arteries (MDCT). The epidemiology, natural history, pathophysiology and clinical presentation of PE are briefly reviewed. The primary objective of Part 1 of the Task Group's report was to develop a methodological approach to and interpretation criteria for PE. The basic principle for the diagnosis of PE based upon V/P(SCAN) is to recognize lung segments or subsegments without perfusion but preserved ventilation, i.e. mismatch. Ventilation studies are in general performed after inhalation of Krypton or technetium-labelled aerosol of diethylene triamine pentaacetic acid (DTPA) or Technegas. Perfusion studies are performed after intravenous injection of macroaggregated human albumin. Radiation exposure using documented isotope doses is 1.2-2 mSv. Planar and tomographic techniques (V/P(PLANAR) and V/P(SPECT)) are analysed. V/P(SPECT) has higher sensitivity and specificity than V/P(PLANAR). The interpretation of either V/P(PLANAR) or V/P(SPECT) should follow holistic principles rather than obsolete probabilistic rules. PE should be reported when mismatch of more than one subsegment is found. For the diagnosis of chronic PE, V/P(SCAN) is of value. The additional diagnostic yield from V/P(SCAN) includes chronic obstructive lung disease (COPD), heart failure and pneumonia. Pitfalls in V/P(SCAN) interpretation are considered. V/P(SPECT) is strongly preferred to V/P(PLANAR) as the former permits the accurate diagnosis of PE even in the presence of comorbid diseases such as COPD and pneumonia. Technegas is preferred to DTPA in patients with COPD.

Unlabelled: We used the archived Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) data and images to test the hypothesis that reading perfusion scans with chest radiographs but without ventilation scans, and categorizing the perfusion scan as "pulmonary embolism (PE) present" or "PE absent," can result in clinically useful sensitivity and specificity in most patients., Methods: Patients recruited into PIOPED II were eligible for the present study if they had a CT angiography (CTA) or digital subtraction angiography (DSA) diagnosis, an interpretable perfusion scan and chest radiographs, and a Wells' score. Four readers reinterpreted the perfusion scans and chest radiographs of eligible patients. Two readers used the modified PIOPED II criteria and 2 used the Prospective Investigative Study of Pulmonary Embolism Diagnosis (PISAPED) criteria. The chest radiographs were read as "normal/near normal," "abnormal," or "nondiagnostic," and the perfusion scans were read as "PE present," "PE absent," or "nondiagnostic." The primary analysis used a composite reference standard: the PIOPED II DSA result or, if there was no definitive DSA result, CTA results that were concordant with the Wells' score as defined in PIOPED II (CTA positive and Wells' score > 2, or CTA negative and Wells' score < 6)., Results: The prevalence of PE in the sample was 169 of 889 (19%). Using the modified PIOPED II criteria, the sensitivity of a "PE present" perfusion scan was 84.9% (95% confidence interval [CI], 80.1%-88.8%), and the specificity of "PE absent" was 92.7% (95% CI, 91.1%-94.1%), excluding "nondiagnostic" results, which occurred in 20.6% (95% CI, 18.8%-22.5%). Using PISAPED criteria, the sensitivity of a "PE present" perfusion scan was 80.4% (95% CI, 75.9%-84.3%) and the specificity of "PE absent" was 96.6% (95% CI, 95.5%-97.4%), whereas the proportion of patients with "nondiagnostic" scans was 0% (95% CI, 0.0%-0.2%)., Conclusion: Perfusion scintigraphy combined with chest radiography can provide diagnostic accuracy similar to both CTA and ventilation-perfusion scintigraphy, at lower cost and with lower radiation dose. With modified PIOPED II criteria, a higher proportion of scans were nondiagnostic than with CTA, and with PISAPED criteria none were nondiagnostic.

In this article, we review the evolution of scintigraphy for the diagnosis of acute pulmonary embolism (PE). We begin with perfusion (Q) scintigraphy, review the development of diagnostic systems that combine ventilation (V) scintigraphy and chest radiography with the Q scan, and describe in detail the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISAPED) criteria for diagnostic categorization of the Q scan read in conjunction with the chest radiograph. Finally, we review the results obtained with the PISAPED criteria in clinical research studies. The PISAPED method for lung scan interpretation provides sensitivity and specificity for diagnosing acute PE that is comparable to V/Q scanning and to computed tomography angiography (CTA), with fewer nondiagnostic results than either V/Q or CTA. The criteria can be used effectively in a diagnostic management approach that incorporates the use of a clinical prediction rule. Clinical outcomes in patients in whom PE is excluded in this way are comparable to outcomes for patients in whom the diagnosis is excluded by CTA or conventional angiography.

Rationale: Clinical probability assessment is a fundamental step in the diagnosis of pulmonary embolism., Objectives: To develop a predictive model for pulmonary embolism based on clinical symptoms, signs, and the interpretation of the electrocardiogram., Methods: The model was developed from a database of 1,100 patients with suspected pulmonary embolism, of whom 440 had the disease confirmed by angiography or autopsy findings. It was validated in an independent sample of 400 patients with suspected pulmonary embolism (71% were inpatients). Easy-to-use software was developed for computing the clinical probability on palm computers and mobile phones., Measurements and Main Results: The model comprises 16 variables of which 10 (older age, male sex, prolonged immobilization, history of deep vein thrombosis, sudden-onset dyspnea, chest pain, syncope, hemoptysis, unilateral leg swelling, electrocardiographic signs of acute cor pulmonale) are positively associated, and 6 (prior cardiovascular or pulmonary disease, orthopnea, high fever, wheezes, or crackles on chest auscultation) are negatively associated with pulmonary embolism. In the validation sample, 165 (41%) of 400 patients had pulmonary embolism confirmed by angiography. The prevalence of pulmonary embolism was 2% when the predicted clinical probability was slight (0 to 10%), 28% when moderate (11 to 50%), 67% when substantial (51 to 80%), and 94% when high (81 to 100%). There was no significant difference between inpatients and outpatients with respect to the prevalence of pulmonary embolism in the four probability categories., Conclusions: The proposed model is simple and accurate, and it may aid physicians when assessing the clinical probability of pulmonary embolism.

Background: The diagnosis of pulmonary embolism demands flexible decision models, both for the presence of clinical confounders and for the variability of local diagnostic resources. As Bayesian networks fully meet this requirement, Bayes Pulmonary embolism Assisted Diagnosis (BayPAD), a probabilistic expert systems focused on pulmonary embolism, was developed., Methods: To quantitatively validate and improve BayPAD, the system was applied to 750 patients from a prospective study done in an Italian tertiary hospital where the true pulmonary embolism status was confirmed using pulmonary angiography or ruled out with a lung scan. The proportion of correct diagnoses made by BayPAD (accuracy) and the correctness of the pulmonary embolism probabilities predicted by the model (calibration) were calculated. The calibration was evaluated according to the Cox regression-calibration model., Results: Before refining the model, accuracy was 88.6%. Once refined, accuracy was 97.2% and 98%, respectively, in the training and validation samples. According to Cox analysis, calibration was satisfactory, despite a tendency to exaggerate the effect of the findings on the probability of pulmonary embolism. The lack of some investigations (like Spiral computed tomographic scan and Lower limbs doppler ultrasounds) in the pool of available data often prevents BayPAD from reaching the diagnosis without invasive procedures., Conclusions: BayPAD offers clinicians a flexible and accurate strategy to diagnose pulmonary embolism. Simple to use, the system performs case-based reasoning to optimise the use of resources available within a particular hospital. Bayesian networks are expected to have a prominent role in the clinical management of complex diagnostic problems in the near future.

We followed prospectively 834 consecutive patients (70% inpatients), evaluated for suspected pulmonary embolism, for a median time of 2.1 years (range, 0-4.8 yr), and compared the survival rates in patients with proven pulmonary embolism (n=320) with those without (n=514). In multivariate analysis, we modeled the probability of surviving in patients with pulmonary embolism as a function of the extent of pulmonary vascular obstruction at baseline. Among patients with pulmonary embolism, a scintigraphic follow-up was pursued to assess the restoration of pulmonary perfusion over a 1-year period. We found that massive pulmonary embolism (vascular obstruction>or=50%) is a risk factor for mortality within the first few days after onset but, subsequently, has no significant effect on survival. The adjusted risk of death in patients with massive pulmonary embolism was 8-fold higher than in patients without embolism within the first day after the incident event. By contrast, the adjusted risk of death for patients with minor or moderate pulmonary embolism (vascular obstruction<50%) was no higher than in patients without embolism at any time after onset. Most of the patients who survived a year after pulmonary embolism showed a nearly complete restoration of pulmonary perfusion with a considerable improvement in arterial oxygenation. Four (1%) of the 320 patients with pulmonary embolism at presentation developed chronic thromboembolic pulmonary hypertension. These patients featured persistent large perfusion defects in sequential lung scans. Pulmonary embolism with vascular obstruction>or=50% is a strong, independent predictor of reduced short-term survival. This underscores the need for a prompt diagnosis of the disease. Monitoring the resolution of pulmonary embolism by lung scanning may prove useful in identifying patients with persistent perfusion abnormalities who may be at risk of chronic thromboembolic pulmonary hypertension.

Two clinical models have been described to predict the probability of pulmonary embolism: the Canadian (or Wells) model, and the Geneva model. A third model has been developed recently at our institution (the Pisa model). We compared the performance of the 3 models in 215 consecutive patients with suspected pulmonary embolism. The clinical probability predicted by the models was categorized as low, intermediate, or high. In all patients, pulmonary angiography was used as the reference diagnostic standard. In patients with pulmonary embolism, the extent of pulmonary embolization was assessed on the lung scan as an index of disease severity. The prevalence of pulmonary embolism was 43.3%, and the median extent of pulmonary embolization at diagnosis was 39.8% (range, 4.5%-75.3%). The proportions of patients categorized as having low, intermediate, or high probability were, respectively: 12%, 60%, and 28%, for the Geneva model; 30%, 55%, and 15%, for the Wells model; 37%, 37%, and 26% for the Pisa model. The frequencies of pulmonary embolism in the low, intermediate, and high probability categories were, respectively: 50%, 39%, and 49% for the Geneva model; 12%, 54%, and 64% for the Wells model; 5%, 42%, and 98% for the Pisa model. Among patients with pulmonary embolism, there was a strong, positive relation between clinical probability predicted by the Pisa model and the extent of pulmonary embolization. The Pisa model proved more accurate than the 2 other models. It may be useful to physicians in defining precisely the pretest probability of pulmonary embolism.

Context: Experienced clinicians' gestalt is useful in estimating the pretest probability for pulmonary embolism and is complementary to diagnostic testing, such as lung scanning. However, it is unclear whether recently developed clinical prediction rules, using explicit features of clinical examination, are comparable with clinicians' gestalt. If so, clinical prediction rules would be powerful tools because they could be used by less-experienced health care professionals to simplify the diagnosis of pulmonary embolism. Recent studies have shown that the combination of a low pretest probability (using a clinical prediction rule) and a normal result of a D-dimer test reliably excludes pulmonary embolism without the need for further testing., Objective: To evaluate and demonstrate the accuracy of pretest probability assessment for pulmonary embolism using clinical gestalt vs clinical prediction rules., Data Sources: The MEDLINE database was searched for relevant articles published between 1966 and March 2003. Bibliographies of pertinent articles also were scanned for suitable articles., Study Selection: To be included in the analysis, studies were required to have consecutive, unselected patients enrolled; participating physicians in the studies, blinded to the results of diagnostic testing, had to estimate pretest probability of pulmonary embolism; and validated diagnostic methods had to be used to confirm or exclude pulmonary embolism., Data Extraction: Three reviewers independently scanned titles and abstracts for inclusion of studies. An initial MEDLINE search identified 1709 studies, of which 16 involving 8306 patients were included in the final analysis., Data Synthesis: A clinical gestalt strategy was used in 7 studies, and in the low, moderate, and high pretest categories, the rates of pulmonary embolism ranged from 8% to 19%, 26% to 47%, and 46% to 91%, respectively. Clinical prediction rules were used in 10 studies, and 3% to 28%, 16% to 46%, and 38% to 98% in the low, moderate, and high pretest probability groups, respectively, had pulmonary embolism., Conclusions: The clinical gestalt of experienced clinicians and the clinical prediction rules used by physicians of varying experience have shown similar accuracy in discriminating among patients who have a low, moderate, or high pretest probability of pulmonary embolism. We advocate the use of a clinical prediction rule because it has shown to be accurate and can be used by less-experienced clinicians.

Pulmonary embolism remains a challenging diagnostic problem. We developed a simple diagnostic strategy based on combination of assessment of the pretest probability with perfusion lung scan results to reduce the need for pulmonary angiography. We studied 390 consecutive patients (78% in-patients) with suspected pulmonary embolism. The pretest probability was rated low (<10%), intermediate (>10%, < or =50%), moderately high (>50%, < or =90%) or high (>90%) according to a structured clinical model. Perfusion lung scans were independently assigned to one of four categories: normal; near-normal; abnormal, suggestive of pulmonary embolism (wedge-shaped perfusion defects); abnormal, not suggestive of pulmonary embolism (perfusion defects other than wedge shaped). Pulmonary embolism was diagnosed in patients with abnormal scans suggestive of pulmonary embolism and moderately high or high pretest probability. Patients with normal or near-normal scans and those with abnormal scans not suggestive of pulmonary embolism and low pretest probability were deemed not to have pulmonary embolism. All other patients were allocated to pulmonary angiography. Patients in whom pulmonary embolism was excluded were left untreated. All patients were followed up for 1 year. Pulmonary embolism was diagnosed non-invasively in 132 patients (34%), and excluded in 191 (49%). Pulmonary angiography was required in 67 patients (17%). The prevalence of pulmonary embolism was 41% ( n=160). Patients in whom pulmonary embolism was excluded had a thrombo-embolic risk of 0.4% (95% confidence interval: 0.0%-2.8%). Our strategy permitted a non-invasive diagnosis or exclusion of pulmonary embolism in 83% of the cases (95% confidence interval: 79%-86%), and appeared to be safe.

Purpose: To develop a structured model to predict the clinical probability of pulmonary embolism., Methods: We studied 1,100 consecutive patients with suspected pulmonary embolism in whom a definite diagnosis had been established. We used logistic regression analysis to estimate the probability of pulmonary embolism based on patients' clinical characteristics; the probability was categorized as low (< or = 10%), intermediate (>10%, < or = 50%), moderately high (>50%, < or = 90%), or high (>90%)., Results: The overall prevalence of pulmonary embolism was 40% (n = 440). Ten characteristics were associated with an increased risk of pulmonary embolism (male sex, older age, history of thrombophlebitis, sudden-onset dyspnea, chest pain, hemoptysis, electrocardiographic signs of acute right ventricular overload, radiographic signs of oligemia, amputation of the hilar artery, and pulmonary consolidation suggestive of infarction), and five were associated with a decreased risk (prior cardiovascular or pulmonary disease, high fever, pulmonary consolidation other than infarction, and pulmonary edema on the chest radiograph). With this model, 432 patients (39%) were rated a low probability, of whom 19 (4%) had pulmonary embolism; 283 (26%) were rated an intermediate probability, of whom 62 (22%) had pulmonary embolism; 72 (7%) were rated a moderately high probability, of whom 53 (74%) had pulmonary embolism; and 313 (28%) were rated a high probability, of whom 306 (98%) had pulmonary embolism., Conclusion: This prediction model may be useful for estimating the probability of pulmonary embolism before obtaining definitive test results.

Transthoracic echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. Recently, the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE was determined prospectively in unselected patients using pulmonary angiography as a reference diagnostic standard. Echocardiographic criteria for diagnosing PE included the presence of any two of three abnormalities: right ventricular (RV) end-diastolic diameter > 27 mm (without RV wall hypertrophy), tricuspid regurgitation velocity > 2.7 m/s, or RV hypokinesis. These echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. Because of its inherent poor sensitivity, transthoracic echocardiography should not be used as a routine test to screen patients for suspected PE.

Pulmonary embolism (PE) is more often diagnosed post mortem by pathologists than in vivo by clinicians. The identification of practical diagnostic algorithms could reduce the rate of diagnoses first made at autopsy. The literature was reviewed for evidence-based approaches to PE diagnosis. Since the PE mortality rate greatly exceeds that of deep vein thrombosis (DVT), more emphasis was given to reports specifically dealing with PE diagnosis by objective pulmonary vascular imaging techniques than to those aimed at DVT detection. Several studies have shown that standardized clinical estimates can be effectively used to give a pretest probability to calculate, after appropriate objective testing, the post-test probability of PE. A prospective trial has shown that perfusion scanning, rather than ventilation/perfusion scanning, should be the imaging technique of first choice for the management of patients suspected of having PE. The clinical usefulness of spiral computed tomography has not as yet been firmly established. However, ongoing technological developments would probably render the technique accurate enough to replace conventional angiography. The authors propose a noninvasive diagnostic algorithm with high predictive accuracy (positive predictive value 96%; negative predictive value 98%) starting with a standardized assessment of clinical likelihood, followed by a perfusion scan and, eventually, spiral computed tomography in only a minority of patients (< 20%) with discordant clinical and scintigraphic findings.

Clinical assessment is a cornerstone of the recently validated diagnostic strategies for pulmonary embolism (PE). Although the diagnostic yield of individual symptoms, signs, and common laboratory tests is limited, the combination of these variables, either by empirical assessment or by a prediction rule, can be used to express a clinical probability of PE. The latter may serve as pretest probability to predict the probability of PE after further objective testing (posterior or post-test probability). Over the last few years, attempts have been made to develop structured prediction models for PE. In a Canadian multicenter prospective study, the clinical probability of PE was rated as low, intermediate, or high according to a model which included assessment of presenting symptoms and signs, risk factors, and presence or absence of an alternative diagnosis at least as likely as PE. The prevalence of PE in the low, intermediate, and high pretest probability categories was 3, 28, and 78%, respectively. This model relies heavily on the clinician's subjective judgement as to whether an alternative diagnosis is as likely as or more likely than PE, and, as such, it can be hardly standardized. Furthermore, the inherent complexity of the model may limit its applicability in daily clinical practice. Recently, a simple clinical score was developed to stratify outpatients with suspected PE into groups with low, intermediate, or high clinical probability. Logistic regression was used to predict parameters associated with PE. A score =/<4 identified patients with low probability of whom 10% had PE. The prevalence of PE in patients with intermediate (score 5-8) and high probability (score > or = 9) was 38 and 81%, respectively. As opposed to the Canadian model, this clinical score is standardized. The predictor variables identified in the model, however, were derived from a data base of emergency ward patients. This model may, therefore, not be valid in assessing the clinical probability of PE in inpatients. In the PISA-PED study, a clinical diagnostic algorithm was developed which rests on the identification of three relevant clinical symptoms and on their association with electrocardiographic and/or radiographic abnormalities specific for PE. Among patients who, according to the model, had been rated as having a high clinical probability, the prevalence of proven PE was 97%, while it was 3% in those with low probability. The prevalence of PE in patients with intermediate clinical probability was 41%. These results underscore the importance of incorporating the standardized reading of the electrocardiogram and of the chest radiograph into the clinical evaluation of patients with suspected PE. The interpretation of these laboratory data, however, requires experience. Future research is needed to develop standardized models, of varying degree of complexity, which may find application in different clinical settings to predict the probability of PE.

Purpose: Echocardiography is advocated by some as a useful diagnostic test for patients with suspected pulmonary embolism (PE), but its diagnostic accuracy is unknown. The present study was undertaken to determine prospectively the sensitivity and specificity of transthoracic echocardiography in the diagnosis of PE., Subjects and Methods: We examined 110 consecutive patients with suspected PE. The study protocol included assessment of clinical probability, echocardiography, and perfusion lung scanning. Pulmonary angiography was performed in all patients with abnormal scans. As echocardiographic criteria to diagnose acute PE, we used the presence of any two of the following: right ventricular (RV) hypokinesis, RV end-diastolic diameter >27 mm (without RV wall hypertrophy), or tricuspid regurgitation velocity >2.7 m/sec. Clinical estimates of PE served as pretest probabilities in calculating, after echocardiography, the posttest probabilities of PE., Results: Pulmonary angiography confirmed PE in 43 (39%) of 110 patients. Echocardiographic diagnostic criteria for PE yielded a sensitivity of 56% and a specificity of 90%. For pretest probabilities of 10%, 50%, and 90%, the posttest probabilities of PE conditioned by a positive echocardiogram were 38%, 85%, and 98%, respectively. The posttest probabilities of PE conditioned by a negative echocardiogram were 5%, 33%, and 81%, respectively., Conclusions: In unselected patients with suspected PE, transthoracic echocardiography fails to identify some 50% of patients with angiographically proven PE. Although echocardiographic findings of RV strain, paired with a high clinical likelihood, support a diagnosis of PE, the transthoracic echocardiography has to have a better sensitivity to be used as a screening test to rule out PE.

To provide clinical diagnostic criteria for pulmonary embolism (PE), we evaluated 750 consecutive patients with suspected PE who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Prior to perfusion lung scanning, patients were examined independently by six pulmonologists according to a standardized diagnostic protocol. Study design required pulmonary angiography in all patients with abnormal scans. Patients are reported as two distinct groups: a first group of 500, whose data were analyzed to derive a clinical diagnostic algorithm for PE, and a second group of 250 in whom the diagnostic algorithm was validated. PE was diagnosed by angiography in 202 (40%) of the 500 patients in the first group. A diagnostic algorithm was developed that includes the identification of three symptoms (sudden onset dyspnea, chest pain, and fainting) and their association with one or more of the following abnormalities: electrocardiographic signs of right ventricular overload, radiographic signs of oligemia, amputation of hilar artery, and pulmonary consolidations compatible with infarction. The above three symptoms (singly or in some combination) were associated with at least one of the above electrocardiographic and radiographic abnormalities in 164 (81%) of 202 patients with confirmed PE and in only 22 (7%) of 298 patients without PE. The rate of correct clinical classification was 88% (440/500). In the validation group of 250 patients the prevalence of PE was 42% (104/250). In this group, the sensitivity and specificity of the clinical diagnostic algorithm for PE were 84% (95% CI: 77 to 91%) and 95% (95% CI: 91 to 99%), respectively. The rate of correct clinical classification was 90% (225/250). Combining clinical estimates of PE, derived from the diagnostic algorithm, with independent interpretation of perfusion lung scans helps restrict the need for angiography to a minority of patients with suspected PE.

Pulmonary embolism (PE) remains a challenging diagnostic problem because it mimics other cardiopulmonary disorders. Pulmonary angiography is still the reference standard for diagnosing PE but it is costly, invasive and not readily available. Non-invasive diagnostic strategies have therefore been developed to forego pulmonary angiography in patients suspected of having PE. Ventilation/perfusion lung scanning is, at present, the most widely used non-invasive diagnostic test for PE. A high probability ventilation/perfusion scan (segmental or greater perfusion defects with normal ventilation) warrants the institution of anticoagulant therapy especially when paired with high clinical suspicion of PE. Yet, only a minority of patients with confirmed PE have high probability ventilation/perfusion scans. Ventilation/perfusion abnormalities other than those of the high probability scan should be regarded as non-diagnostic. Under these circumstances, documentation of deep vein thrombosis by non-invasive leg testing warrants anticoagulation without the need for angiography. However, a single negative venous study result does not permit to rule out PE in patients with non-diagnostic ventilation/perfusion scans. Results of a recent prospective study indicate that accurate diagnosis or exclusion of PE is possible with perfusion lung scanning alone (without ventilation imaging). Combining perfusion lung scanning with clinical assessment helps to restrict the need for angiography to a minority of patients with suspected PE.

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.