Benoît Ghaye
Robert F. Dondelinger
Received: 6 February 2007 Revised: 30 July 2007 Accepted: 28 August 2007 Published online: 5 October 2007 # European Society of Radiology 2007
When to perform CTA in patients suspected
of PE?
Abstract Venous thromboembolic disease (VTE) is a common disorder which may be associated with high morbidity or mortality when left un-treated. Specific VTE diagnosis is mandatory, as treatment is associated with significant side effects. There-fore, timely diagnostic tests are nec-essary to establish the presence or absence of VTE. Computed tomo-graphic pulmonary angiography (CTPA) has reached a high accuracy in the evaluation of pulmonary em-bolism (PE). Unfortunately, the con-tinuous decrease of the prevalence of PE in the most recent studies can lead to cost-efficacy imbalance and over-use of ionizing radiation when CTPA
is used as a single test. Therefore, no single non-invasive test is suitable for all patients and diagnostic strategies based on sequential non-invasive tests are likely to identify patients in whom anticoagulation can be withheld safely and limit the number of patients requiring more invasive or more expensive tests. The cost effectiveness of clinical stratification and D-dimer test has been demonstrated as it reduces the requirement for invasive tests. In this paper, the current role of CTPA in the diagnosis of PE will be reviewed.
Keywords Embolism . Pulmonary . CT angiography . Predictive rule
Introduction
Venous thromboembolic disease (VTE) is a common disorder, which may be associated with high morbidity or mortality when left untreated [1–4]. Furthermore, specific VTE diagnosis is mandatory, as treatment is associated with significant side effects [1]. Diagnosis of VTE is challenging, signs and symptoms being common but non-specific [1–4]. Therefore, timely diagnostic tests are necessary to establish the presence or absence of VTE.
In clinical studies, the prevalence of pulmonary embo-lism (PE) has continuously decreased from 30 to 40 % in the 1970–1980s to less than 10% in the most recent studies, leading to cost-efficacy imbalance [2, 5]. Therefore, no single non-invasive test is suitable for all patients and diagnostic strategies based on sequential non-invasive tests are likely to identify patients in whom anticoagulation can be safely withheld and limit the number of patients requiring more invasive or more expensive tests [4,6].
Over the past 15 years, computed tomographic pulmonary angiography (CTPA) has reached a high accuracy in the evaluation of PE [7–9]. Major advantages of CTPA, compared with ventilation/perfusion (V/Q) lung scan and pulmonary angiography (PA), are direct visualisation of clots
in the pulmonary arteries and ability to provide alternative diagnoses to explain the patient’s symptoms and clinical findings [8, 10–12]. The introduction of multidetectector-row CT (MDCT) has improved the evaluation of peripheral pulmonary arteries, enabling high-resolution CTPA over the entire thorax in a short breath-hold [9]. Recent studies showed that CTPA is able to investigate lung perfusion and predict severity of PE and patient outcome [13–15]. In this paper, the current role of CTPA in the diagnosis of PE is reviewed.
Risk factors, clinical features and additional examinations
The overall annual incidence of PE is 60–70 cases per 100,000; 50% occurring in hospitalised or long-term care patients, 25% in patients with recognised risk factors and 25 % being idiopathic [1]. Predisposing risk factors, accord-ing to the British Thoracic Society, are presented in Table1. Patients with proven PE often present with non-specific symptoms, including unexplained sudden onset of dyspnea, tachypnea, pleuritic chest pain, syncope, tachycardia and/or haemoptysis [2–4,16,17]. Arterial hypoxemia and hypo-B. Ghaye (*) . R. F. Dondelinger
Department of Medical Imaging, University Hospital of Liege, B 35, 4000 Liege, Belgium
e-mail: bghaye@chu.ulg.ac.be Tel.: +32-4-3667249
capnia may raise the suspicion of PE but are poorly predic-tive in assessment of the disease [4,18]. Electrocardiogram (EKG) and chest X-ray are routinely obtained, as they can suggest PE, and most importantly, evidence other diagnoses [2–4,17,19]. Biomarkers, such as cardiac troponin or brain natriuretic peptide, may give prognostic information, but are of no diagnostic value in non-massive PE [20].
Clinical stratification of patients suspected of PE A thorough clinical evaluation is the first step in setting up appropriate diagnostic strategies [4]. The clinical or pre-test probability of PE relies on data such as risk factors for VTE, history, clinical signs, symptoms, physical examination, blood gases, chest X-ray and EKG. The pretest probability stratifies patients into subgroups with different prevalence of PE and is used to assess the probability of PE after further objective testing (post-test probability). The clinical pre-diction may be implicit or explicit.
Implicit clinical prediction
The PIOPED I study showed that clinicians were able to classify patients suspected of PE into three groups showing increasing prevalence (low clinical probability, 9% prev-alence of PE; intermediate, 30%; high, 68%) using clinical assessment alone [19]. The validity of the implicit or
empiric prediction was further confirmed in other studies [16,21–24]. However, implicit prediction of a diagnosis is nevertheless linked to experience and cognitive bias.
Explicit clinical prediction
Explicit clinical prediction scores were formulated, with the aim to be standardised, didactic and accessible to less expe-rienced clinicians, expecting a better inter-observer agree-ment than implicit evaluation. The Wells score [25] (Table2) and the Geneva (or Wicki) score [26] (Table3) demonstrat-ed similar accuracy compardemonstrat-ed with implicit judgment by experts [27]. The more recent Revised Geneva score is exclusively based on history and clinical variables [28] (Table 4). Explicit scores are particularly interesting as frequent but non-specific symptoms of PE, such as dyspnea, chest pain and tachypnea, are not considered. More com-plex prediction scores, such as used in the Pisaped study, involve a larger number of variables or require interpreta-tion of chest X-ray or EKG by experts [3,4,17] (Table5). Prevalence of PE ranges from 1 to 13% (mean 10%) in low, 16 to 46% (mean 30%) in intermediate and 41 to 97% (mean 65%) in high clinical probability, depending on the scoring system used [17,25–29]. The Wells score has also been used with only two pre-test groups: patients being“unlikely for PE” or “likely for PE” [12; Table2]. Other prediction scores or rules are also proposed in the literature [30,31].
Limitations
Each explicit score has advantages and drawbacks. Thus, the Wells score has a subjective component (operator dependent) Table 2 Wells scoring system (adapted from [25])
Criteria Points
DVT signs 3
DVT or PE history 1.5
Heart rhythm >100/min 1.5
Recent surgery or immobilisation <4 weeks 1.5
Haemoptysis 1
Cancer 1
Alternative diagnosis less likely than PE 3 Clinical probability Score % probability
of PE % with this score Low <2 points 2–4 40 Intermediate 2–6 point 19–20 52–53 High >6 points 50–67 7–8 PE unlikely ≤4 points 5–8 71–72 PE likely >4 points 39–41 28–29
Table 1 Risk factors for PE (modified from [1]) Major risk factors
(relative risk 5–20)
Minor risk factors (relative risk 2–4)
Surgery Cardiovascular
–Major abdominal/pelvic surgery –Congenital heart disease –Hip/knee replacement –Congestive heart failure –Post-operative intensive care –Hypertension
Obstetrics –Superficial venous thrombosis –Late pregnancy –Indwelling central vein catheter –Caesarian section Oestrogens
–Puerperium –Oral contraceptive
Lower limb problems –Hormone replacement therapy
–Fracture Miscellaneous
–Varicose veins –COPD
Malignancy –Neurological disability –Abdominal/pelvic –Occult malignancy –Advanced/metastatic –Thrombotic disorders Reduced mobility –Long-distance sedentary travel
–Hospitalisation –Inflammatory bowel disease –Institutional care –Obesity
Miscellaneous –Other
due to the high rating of the item,“An alternative diagnosis is less likely than PE”, that may wrongly increase the proba-bility of PE. On the other hand, the Geneva score that pro-poses more objective items, such as the blood gases values, requires an arterial puncture while the patient is breathing ambient air, which cannot be obtained in some patients. Another drawback of explicit scores is the lack of considera-tion of items such as the presence of a known coagulopathy, pregnancy or the post-partum period that are likely to influ-ence the probability of PE [27,28]. Therefore, some authors suggested to override explicit scores by implicit judgment in some circumstances [27, 32]. Furthermore, the tested population should ideally not be too much different (i.e. prevalence of PE) from the population that has been evaluated for the establishment of each scoring system. As an example, contrary to the Wells score, the Geneva score and the Revised Geneva score have been derived from patients selectively admitted to the emergency department and therefore should not be applied to inpatients. Never-theless, the items entering the Wells and the Revised Geneva score are very similar.
D-dimer test
D-dimers are specific breakdown products of cross-linked fibrin circulating in the plasma. D-dimer test is widely used in patients with suspected deep venous thrombosis (DVT) or PE. Management studies have demonstrated that PE can be safely ruled out without imaging techniques in patients having a low clinical probability and a normal D-dimer test,
which occurs in 20–47% of the patients [6,12,25,29,33– 35]. Due to their higher sensitivity and predictive value, the standard or rapid ELISA and immunoturbidimetric D-dimer tests may be used to rule out VTE in low or intermediate clinical probability patients, whereas whole blood aggluti-nation assays may be used for that purpose only in low
Table 4 Revised Geneva scoring system (adapted from [28])
Criteria Points
Age >65 years 1
DVT or PE history 3
Surgery or lower limb fracture ≤1 month
2 Cancer (active or cured≤1 year) 2
Unilateral lower limb pain 3
Haemoptysis 2
Heart rhythm
75–95/min 3
>95/min 5
Pain on lower limb deep venous palpation and unilateral edema
4
Clinical probability Score % probability of PE % with this score Low 0–3 points 8–9 31–37 Intermediate 4–10 points 28 57–62 High 11 points 72–74 5–8
Table 3 Geneva (or Wicki) scoring system (adapted from [26])
Criteria Points
Age 60–79 years 1
≥80 years 2
DVT or PE history 2
Heart rhythm >100/min 1
Recent surgery 3
Chest X-ray Platelike atelectasis 1
Hemidiapragm elevated 1 PaCO2 <36 mmHg 2 36–39 mmHg 1 PaO2 <48.7 mmHg 4 48.7–59.9 mmHg 3 60–71.2 mmHg 2 71.3–82.4 mmHg 1
Clinical probability Score % probability of PE % with this score
Low 0–4 points 10 49
Intermediate 5–8 points 38 44
clinical probability patients [1, 6, 36]. Considering a 20% prevalence of PE in patients with low to intermediate or unlikely PE probability, the post-test probability after a negative D-dimer test would be only around 2%, which is similar to the PE rate in patients with normal PA [25,28]. D-dimer tests have a low specificity of 30–70% and overall a reduced yield in various clinical settings, including inpatients, critically ill patients, fever, surgery, trauma, elderly, malig-nancy, history or treatment for VTE, pregnancy and post-partum [28,33,36–38]. In such conditions, although normal values still safely rule out VTE, the clinical usefulness of the test appears to be reduced, as the proportion of patients in which VTE can be ruled out decreases from 30% to 5– 15% [36, 38]. Increasing the cut-off value of D-dimer to exclude VTE in a larger proportion of patients in those conditions remains controversial in the literature [36]. On the other hand, in patients with high clinical probability and negative D-dimer test, the use of an imaging test, such as CTPA, is justified due to the high prevalence of PE in these patients.
Alveolar dead space determination
Adding the alveolar dead space measurement to pre-test probability and D-dimer test may further twice decrease the need for imaging compared with pre-test probability and D-dimer test alone [39]. Nevertheless alveolar dead space measurement is still not available in many centres and accurate measurements cannot be obtained in a third of the patients [37,39].
Echocardiography (ECG)
Patients suspected of massive PE can first be investigated through transparietal ECG as it can assess right ventricle (RV) dysfunction due to massive PE, or diagnose entities that may mimic PE, such as myocardial infarction, aortic dissection or pericardial tamponade [2,40]. Confirmatory studies, such as CTPA will be required, when the cause of acute RV failure (i.e. emboli in the heart or proximal pul-monary arteries) is not demonstrated. One study reported that RV dysfunction at ECG has a 100% positive predictive value in case of high- or intermediate clinical probability of PE, while a negative ECG has a 98% negative predictive value for low clinical pretest of PE [41]. ECG has been shown to predict prognosis of patients with PE and give hints to appropriate treatment [42]. Otherwise patients suspected of massive PE can go directly to CTPA, as recent papers have shown that CTPA can predict severity or even mortality of the disease [13,14,43,44].
CTPA
Diagnostic studies
Studies comparing single-detector-row (SD) CTPA with PA reported 53–100% (mean 85%) sensitivity and 67–100% (mean 92%) specificity. The wide variation in results is explained in part by differences in the population studied and the technique used [7,45,46]. Using four-slice technology, two studies compared multidetector-row (MD) CTPA with Table 5 Pisaped scoring system
(adapted from [16,17]) Criteria
Symptoms Sudden-onset of dyspnea Chest pain
Fainting
EKG Acute right heart overload Chest X-ray Oligemia
Amputation of hilar artery
Consolidation compatible with infarction
Clinical probability Mean probability
of PE
% with this score
Low Absence of symptoms 6% 35%
or alternative diagnosis likely
Intermediate ≥1 symptom not otherwise explained, 46% 25% may be associated with EKG abnormality
but without chest X-ray findings of PE
High ≥1 symptom not otherwise explained 97% 40%
PA and reported 96–100% sensitivity and 89–98% specificity [11, 47], whereas the PIOPED II study reported 83% sensitivity and 96% specificity when compared with a composite reference standard [48]. One of the most debated issues is ability of CTPA to detect isolated subsegmental PE [3, 42, 49, 50]. Some important questions are still unan-swered: do we need to diagnose every PE that may be identified using invasive tests, or do we need to diagnose patients with PE that are at risk of recurrent and/or potentially fatal PE [28, 37, 51]? As a result, many investigators suggested a shift to patient outcome and accumulating data were published showing withholding anticoagulation is safe when PE is excluded on CTPA, even in patients with underlying respiratory disease [7,9,49,52]. A meta-analysis of 3,500 patients showed that CTPA has a negative predictive value of 99.1% (95% CI, 98.7–99.5%) for VTE and 99.4% (95% CI, 98.7–99.9%) for VTE related mortality [53]. The negative likelihood ratio of SD-CTPA did not differ from MD-CTPA [0.08 (95% CI, 0.05–0.13) and 0.15 (95% CI, 0.05–0.43), respectively]. In patients with low or intermediate clinical probability of PE, the clinical validity of CTPA to rule out PE is similar to that reported for PA [53].
Management studies
Single-detector-row CTPA
To reach an acceptable patient outcome, management studies have shown that SD-CTPA should be used together with clinical probability assessment, D-dimer test or ultrasound (US) of lower limb veins. [3,6,8,24,32,54,55]. The ESSEP study reported a 1.8% 3-month rate of VTE (0.8% in outpatients and 4.8% in inpatients) in low- or intermediate clinical probability and negative results for US and SD-CTPA. On the other hand, in patients with high clinical probability and negative SD-CTPA and US, additional tests are required, as 5.3% of PE were diagnosed at V/Q scan or PA in these patients [24]. Two other studies reported a 0.8–1%
overall 3-month VTE risk and 1.7% 3-month VTE risk in patients with low- or intermediate clinical probability [8,32].
Multidetector CTPA
The results of three management studies using MD-CTPA are presented in Table6. MD-CTPA was not necessary in patients with low- or intermediate (or PE unlikely) clinical probability and negative D-dimer test, as it is estimated to be safe to withhold treatment in these patients (24–34% of the population). The 3-month risk of VTE in untreated patients was 0.6–1.0% [12,35,56].
The PIOPED II study suggested that results of MD-CTPA should be interpreted in the light of explicit clinical probability. The negative predictive value of MD-CTPA was 60% in patients having a high clinical probability, and the positive predictive value was 58% in patients with a low clinical probability, suggesting that additional tests may be necessary in such circumstances. When results of CTPA were concordant with clinical probability, predictive values were much higher (89–96%) [48].
V/Q lung scan
Large trials have shown that V/Q scan is non-diagnostic to exclude or confirm PE in the majority of patients [2,3,19]. Furthermore, when V/Q scan is normal, PE can be reliably excluded, but a significant minority of high probability results are falsely positive [1, 6]. According to the BTS guidelines, V/Q scan could be performed as a first-line imaging test provided that chest X-ray is normal, no sig-nificant cardiopulmonary disease is present, standardised reporting criteria are used, and non-diagnostic results are always followed by further imaging [1]. V/Q scan should also be interpreted cautiously in patients with history of VTE [3]. In such conditions, Q lung scan decreased by 30% the number of patients requiring CTPA [57]. Miniati et
Table 6 Management studies using multidetector-row CTPA Reference Study population (n) Rate of exclusion Prevalence of PE
Patient without imaging (%)
3-month VTE risk in patients without imaging and not treated [95% CI]
3-month VTE risk in patients without PE and not treated [95% CI] Perrier et al.
2005 [35]
756 25.2% 25.7% Low and intermediate CP/negative D-dimer test (34%)
0/220 (0%) [0–2.7%)] 5/523 (1.0%) [0.4–2.2%]
Ghanima et al. 2005 [50]
al. [16,17] reported that Q lung scan, interpreted through the Pisaped scintigraphic criteria and clinical predicting rule, required a more invasive imaging technique (i.e. pulmonary angiography) in less than a quarter of the patients. V/Q scan combined with US of lower limb veins, clinical prediction and D-dimer test could be used to reduce radiation dose or to avoid iodinated CM administration, i.e. in patients with CM allergy or renal failure.
Magnetic resonance (MR) imaging
The use of contrast medium (CM) agents, such as Gadolin-ium, has been reported to achieve diagnostic quality MD-CTPA in patients with contraindications to injection of iodine [58]. While Gadolinium-based CM may be useful in patients with serious allergy-like reaction to iodine-based CM or with thyroid disease, its use cannot be currently recommended in patients with impaired renal function due to its higher nephrotoxicity compared with iodinated CM in equivalent attenuation dose and the recently reported nephrogenic systemic fibrosis in patients with end-stage renal disease or on dialysis [59,60].
To date, MRPA has not had widespread use in PE detecion, mainly because of long examination time, difficulties in patient monitoring, higher cost and limited availability or limited access of MR in most centres. Sensitivities of 71–100% and specifities of 92–100% have been reported [61–64]. Recent improvements in MR tech-nology have been reported in the detection of emboli distal to the segmental level [65]. MR is a promising method for complete morphological and functional workup in patients with VTE, including imaging of PE and DVT, perfusion imaging of the pulmonary microcirculation, ventilation imaging and assessment of the right ventricle function and flow in the pulmonary arteries, and has also the advantage to provide alternative diagnoses [64]. Its role in VTE manage-ment will be investigated in the PIOPED III study.
PA
PA has been considered the“gold standard” test for many years, but is rarely performed nowadays [2, 3, 9]. From the 1980s, PA has progressively been underused due to multiple reasons, including: perception by the clinicians and patients that the test is invasive and dangerous; vari-able availability and radiologists’ experience; large inter-observer variability; high cost; variable image quality in critically ill patients [2,3,66,67]. The risk of subsequent symptomatic or fatal VTE after negative CTPA is com-parable with negative PA (1.3 vs 1.7% and 0.5 vs 0.3%, respectively) [12, 68]. The role of PA in the subgroup of patients, in whom the diagnosis cannot be established by less invasive methods, remains currently hazy. Recent papers still recommend PA as the ultimate test in patients
without diagnosis, when it is considered unsafe to withhold anticoagulation or when it is necessary to establish a di-agnosis to manage patients with severe symptoms [2, 3].
Investigation of lower limb veins Ultrasound
Fifty to 70% of patients with proven PE had concomitant DVT [3,42,69–71]. Therefore, US of lower limb veins has been advocated as a first test to reduce the number of patients undergoing lung imaging or as a second test in patients with nondiagnostic results at V/Q scan or normal SD-CTPA [22,24,32]. Nevertheless, as the risk of death is about 18-fold higher in patients with PE than with isolated DVT, every effort should be made to prove/exclude PE [4]. It should also be noted that, even if identification of DVT may preclude the need for additional tests, a single negative US does not reliably exclude VTE in most patients, while serial US may be impractical in a routine clinical setting [4, 8,29]. Contrary to symptomatic patients, US is relatively insensitive in detecting DVT in asymptomatic patients [72]. Six to 7% of patients with negative or indeterminate SD-CTPA had DVT at US [24, 55]. Therefore patients with negative SD-CTPA must undergo imaging of lower limb veins before anticoagulation is withheld. Perrier et al. [35] found that US of femoro-popliteal veins is positive in less than 1% of patients with negative results at MD-CTPA.
Indirect CT venography
CT venography, coupled with CTPA without requiring additional CM injection, provides similar results to US for the diagnosis of DVT in femoro-popliteal veins [71]. The incremental value of adding CT venography to SD-CTPAwas reported in the range of 8–27% [71, 73]. A recent study showed that the incremental value of CT venography is not reduced when using MD-CTPA [73]. Indeed MD-CTPA may still have limitations in demonstrating small peripheral emboli [47]. Around 30% of indeterminate CTPAs or CT veno-graphies are counterbalanced by a positive result at CT venography or CTPA, respectively [73]. In the PIOPED II study, four-detector-row CTPA-CT venography had a higher sensitivity than CTPA alone (90% vs 83%), with a similar specificity (95%) [48]. The optimal use of sequential vs spiral acquisition for CT venography remains a matter of debate [74,75].
Cost-effectiveness
been shown to be related to sensitivity. A sensitivity higher than 85%, as should be obtained at MD-CTPA, is required to likely reduce mortality and improve cost-effectiveness [76, 77]. To the best of our knowledge, so far no study on the cost-effectiveness of the diagnostic work-up of PE has considered the potential of CTPA to provide alternative diagnoses or has evaluated CT venography.
Diagnostic algorithm
Figure 1 proposes a sequential diagnostic approach for patients suspected of submassive PE. First clinical
suspicion should be evaluated together with EKG, D-dimer test and chest X-ray that can provide alternative diagnoses. In patients with low or intermediate proba-bility, highly sensitive D-dimer test should be performed. Then, two options are possible: first, if patients present with symptoms or findings of DVT, US of lower limb veins could be performed given its availability, sensitiv-ity, specificity and low cost. Patients with negative US should undergo CTPA. Second option, patients be submitted directly to CTPA or combined CTPA-CT venography. In case of negative CTPA, patients without symptoms of DVT may undergo US, but the rate of positive results may be low after negative MD-CTPA.
or Low clinical probability Intermediate clinical probability High clinical probability
ELISA D-dimer test
-+ VTE excluded US CTPA or Yes + Treat CTPA -+ Pulmonary angiography ?
Clinical prediction, EKG, Chest-Xray
Clinical symptoms and signs of DVT ? No -US CTPA-CTV -Repeat CTPA ? CTPA-CTV ? ?
The approach is then more problematic in the unlikely case of persistent high clinical suspicion of PE and neither a diagnosis of VTE nor an alternative diagnosis is obtained. Three options may be followed: repeat CTPA or combined CTPA-CT venography, if quality of the first examination was suboptimal, or progress to PA. Such a strategy remains to be further validated particularly in inpatients [24]. The potential role of a Q lung scan before CTPA should be evaluated and counterbalanced by the fact that CTPA is virtually the only technique to provide alternative diagnoses. Other diagnostic algorithms are also proposed in the literature [2–4].
A particular condition: PE during pregnancy
PE is one of the leading causes of maternal death, par-ticularly in the puerperium [2, 3, 78]. Diagnosis of PE is more complicated than in the population at large, as clinical diagnosis is less specific, and pre-test clinical prediction has not been evaluated in pregnant patients, D-dimers are frequently elevated from second trimester to 4–6 weeks after delivery, and there is reluctance to expose mother and fetus to radiation [78,79]. The potential risk of radiation exposure must thus be balanced against the risk of over- or under-treatment, if PE is not correctly investigated. In this respect, CTPA delivers radiation doses that may be up to three times lower than for V/Q scan [77]. For CTPA, fetal exposure varies from 3 to 131 µGy, the dose increases with age of gestation as the fetus grows towards the thoracic scanning area [80]. The fetal risk due to radiation is
therefore considered very low, and much lower than the risk of untreated PE [78]. On the other hand, the dose delivered to the mother’s breast by CTPA is higher than by V/Q scan, but remains below the thresholds estimated to be associated with any significant risk. Nevertheless dose modulating systems or breast shields should be used when-ever possible. The fetal risk of iodinated CM is currently not known, and thyroid function tests should be performed to eliminate CM induced hypothyroidism after birth. US of lower limb veins is therefore recommended as the initial imaging technique in pregnant patients, with special focus on the iliac veins [3, 81]. In order to reduce the breast irradiation, perfusion scintigraphy or MR imaging are sug-gested as an alternative to CTPA [64,82].
Conclusion
Strict adherence to management guidelines is mandatory, as appropriateness of diagnostic strategy and criteria strongly correlate with patient outcome. Inappropriate management can increase up to a sixfold recurrence of VTE [83]. The first goal of a diagnostic strategy is to exclude VTE in as many patients as possible. This can be achieved by combination of low clinical probability and normal D-dimer test (probably also in intermediate clinical probability with negative ELISA D-dimer test), or a normal perfusion lung scan. The second step is to confirm the diagnosis of VTE using a simple and reliable test, a role devoted to MD-CTPA [6]. Studies focusing on inpatients are still needed.
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