Update on the risk stratification of acute symptomatic pulmonary thromboembolism

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BNP: péptido natriurético cerebral; Gammagrafía V/P: gammagrafía de ventilación perfusión; NT-proBNP: fragmento aminoterminal del BNP; PESI: Pulmonary Embolism Severity Index; PESIs: escala PESI simplificada; RIETE: Registro Informatizado de Enfermedad TromboEmbólica venosa; TC: tomografía computarizada; TEP: tromboembolia pulmonar; TVP: trombosis venosa profunda; VD: ventrículo derecho. Fuente: adaptada de Konstantinides et al.<a class="elsevierStyleCrossRef" href="#bib0425">8</a> y modificada por los autores." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Maestre Peiró, A. Gonzálvez Gasch, M. Monreal Bosch" "autores" => array:3 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Maestre Peiró" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Gonzálvez Gasch" ] 2 => array:2 [ "nombre" => "M." 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Maestre Peiró, A. Gonzálvez Gasch, M. Monreal Bosch" "autores" => array:3 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Maestre Peiró" "email" => array:1 [ 0 => "amaestrep@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "A." "apellidos" => "Gonzálvez Gasch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M." 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Abbreviations: BNP, brain natriuretic peptide; V/P scintigraphy, ventilation/perfusion scintigraphy; NT-proBNP, amino-terminal fragment of BNP; PESI, Pulmonary Embolism Severity Index; PESIs, simplified PESI scale; RIETE, Computerized Registry of Patients with Venous Thromboembolism; CT, computed tomography; CTA, computer tomography angiography; PTE, pulmonary thromboembolism; DVT, deep vein thrombosis; RV, right ventricle. Source: Adapted from Konstantinides et al.<a class="elsevierStyleCrossRef" href="#bib0425">8</a> and modified by the authors." ] ] ] "textoCompleto" => "BackgroundPulmonary thromboembolism (PTE) results from the partial or total occlusion of the pulmonary vascular bed by a detached thrombus (embolus) of the deep venous system, usually of the legs.Acute symptomatic PTE is the most severe manifestation of venous thromboembolism (VTE), whose overall incidence rate is 131 per 100,000 individuals/year, causing PTE in 45.9% of cases.<a class="elsevierStyleCrossRef" href="#bib0390">1</a> PTE causes 0.52% of hospital admissions, which represents a high healthcare cost in Spain.<a class="elsevierStyleCrossRef" href="#bib0395">2</a>The clinical presentation of PTE can vary. The mortality of a PTE that starts as cardiopulmonary arrest (1% of cases) is 70%. If the PTE presents as shock or arterial hypotension requiring inotropic agents (5% of cases), the risk of mortality is 30%, while for normotensive patients the risk declines to 2%.<a class="elsevierStyleCrossRefs" href="#bib0400">3–5</a>A recent study of the Computerized Registry of Patients with Venous Thromboembolism (RIETE) assessed the mortality of acute PTE. In 23,858 patients treated during a 12-year period, an overall mortality rate at 30 days of 5.9% was observed, with a significant declining trend, both for secondary to any cause (from 6.6% between 2001 and 2005 to 4.9% between 2010 and 2013) and for PTE-induced (from 3.3% to 1.8% in the same periods).<a class="elsevierStyleCrossRef" href="#bib0415">6</a>Prognostic stratification of patients with pulmonary thromboembolismTo reduce PTE mortality, it is essential to differentiate patients at high risk of adverse events from those at low risk, to indicate the most effective and efficient therapeutic alternatives in each case. Therefore, the management guidelines for massive and submassive PTE of the American Heart Association (AHA),<a class="elsevierStyleCrossRef" href="#bib0420">7</a> the 9th edition of the antithrombotic therapy guidelines of the American College of Chest Physicians (ACCP)<a class="elsevierStyleCrossRef" href="#bib0410">5</a> and the latest guidelines of the European Society of Cardiology (ESC)<a class="elsevierStyleCrossRef" href="#bib0425">8</a> recommend stratifying patients according to their early mortality risk (inhospital or during the first 30 days) into 3 categories: low, intermediate and high risk, depending on a number of risk markers and prognostic scales. The national consensus on the diagnosis, risk stratification and treatment of patients with PTE<a class="elsevierStyleCrossRef" href="#bib0430">9</a> was published in Spain in 2013 and supports these same recommendations.The hemodynamic situation at the onset of PTE has the greatest prognostic significance for short-term mortality. Patients with hypotension<a class="elsevierStyleCrossRefs" href="#bib0410">5,7</a> (systolic blood pressure <90mm Hg) or hemodynamic shock are considered at high risk. Therefore, after confirming the diagnosis through transthoracic echocardiography or thoracic multidetector computed tomography angiography (CTA), the clinical guidelines and expert recommendations propose systemic fibrinolytic therapy if the hemorrhagic risk is not high.<a class="elsevierStyleCrossRefs" href="#bib0410">5,7,8</a>After confirming the PTE with a multidetector CTA or lung scintigraphy, clinical prognostic scales are employed for hemodynamically stable patients to stratify the risk, classifying patients into low to intermediate risk groups. For low-risk patients, standard anticoagulation is indicated. Early discharge with outpatient management may be considered.<a class="elsevierStyleCrossRefs" href="#bib0410">5,7,8</a>The most complex patient group to stratify is the intermediate risk group. These are hemodynamically stable patients in their presentation, who can undergo subsequent hemodynamic instability as a consequence of a thromboembolic recurrence or an impairment in right ventricular (RV) function. Therefore, risk stratification is currently focused on differentiating (within the normotensive patient group with intermediate risk) those at low risk of early complications (low-intermediate risk) from those at high risk of adverse events (intermediate-high risk).<a class="elsevierStyleCrossRefs" href="#bib0405">4,8,10–13</a> The recommendation for intermediate risk patients is the combination of prognostic tools that assess RV dysfunction, myocardial ischemia, cardiomyocyte stress or thrombotic burden, to thereby identify those with intermediate-high risk who could benefit from intensive monitoring and reperfusion therapy (rescue fibrinolysis) if hemodynamic decompensation occurs.Prognostic clinical modelsA number of prognostic tools are employed to stratify the risk for patients with acute symptomatic PTE, mainly clinical scales, biological markers and imaging tests. In particular, to identify patients with low-risk PTE, clinical prognostic scales have shown an excellent negative predictive value (NPV) and are inexpensive and simple to apply. The scales include clinical parameters that can be obtained quickly and require no special skills or training.Two meta-analyses were published in 2012 and 2014 on the performance of clinical scales for predicting early mortality after PTE.<a class="elsevierStyleCrossRefs" href="#bib0445">12,14</a> The meta-analyses analyzed 9 and 11 clinical scales, respectively, which had been developed by various groups.<a class="elsevierStyleCrossRefs" href="#bib0460">15–25</a> The comparisons between clinical prognostic models are difficult to interpret, but when searching for low-risk patients who can be discharged early and be treated at home, high sensitivity is preferable to high specificity, thereby minimizing false negatives. Given their high sensitivity and predictive ability and after having been validated in numerous publications and in various patient subgroups,<a class="elsevierStyleCrossRefs" href="#bib0515">26–33</a> both the original Pulmonary Embolism Severity Index (PESI)<a class="elsevierStyleCrossRef" href="#bib0465">16</a> and its simplified version (PESIs)<a class="elsevierStyleCrossRef" href="#bib0490">21</a> are accepted as more valid and reliable for identifying patients with PTE and at low risk of mortality at 30 days.Another useful clinical model for classifying PTE in the low-risk group are the Hestia criteria, which help identify patients with a reduced probability of complications at 90 days, when the patients do not meet any of the parameters of the predictive model.<a class="elsevierStyleCrossRefs" href="#bib0500">23,34</a> Subsequently, these criteria have been better than the PESIs<a class="elsevierStyleCrossRef" href="#bib0560">35</a> and that of the ESC of 2008<a class="elsevierStyleCrossRef" href="#bib0565">36</a> for identifying more patients at low risk. A study has recently been published with the external validation of the Hestia criteria for predicting early mortality (inhospital and at 30 days), which showed excellent sensitivity (100%), although low specificity (27%).<a class="elsevierStyleCrossRef" href="#bib0570">37</a>All of the above-mentioned scales were developed and validated for identifying patients at low mortality risk in the first 30–90 days after the PTE but not for predicting the risk of bleeding or thromboembolic recurrence. Additionally, in the only study that assessed the predictive ability of the original PESI scale in the first days after the PTE diagnosis (specifically at 5 days), 9 of 109 patients classified as low risk presented an adverse clinical event.<a class="elsevierStyleCrossRef" href="#bib0540">31</a> In 2015, a study was published on the results of a new prognostic scale resulting from the RIETE registry, which included 11 variables (some shared with PESI and PESIs) and helped correctly identify patients with low-risk PTE, not only for mortality but also for bleeding and thrombotic recurrence, in the first 10 days after the diagnosis, with greater discriminatory capacity than the PESI and PESIs scales.<a class="elsevierStyleCrossRef" href="#bib0575">38</a> This scale has been validated in a new cohort, with very similar results both at 10 and 30 days (data awaiting publication). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the clinical scales PESI, PESIs, RIETE and the Hestia Criteria with their variables, scoring systems and risk classification.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Two new predictive rules were recently developed with a retrospective cohort of 1143 patients with PTE to identify patients with a low risk of complications in the first 14 days and who could be candidates for outpatient therapy.<a class="elsevierStyleCrossRef" href="#bib0580">39</a>BiomarkersAnother prognostic tool used for stratifying the risk of patients with PTE are biochemical markers,<a class="elsevierStyleCrossRefs" href="#bib0405">4,5,8–10,13</a> which include RV dysfunction markers such as the brain natriuretic peptide (BNP) and its amino-terminal fragment (NT-proBNP), myocardial damage markers such as troponin and other noncardiac markers such as d-dimer (DD). Plasma DD concentrations in the first quartile (<1500μg/L) have a negative predictive value (NPV) of 99% for excluding all-cause mortality at 3 months.<a class="elsevierStyleCrossRef" href="#bib0585">40</a> A meta-analysis on the usefulness of DD in risk stratification<a class="elsevierStyleCrossRef" href="#bib0590">41</a> observed that patients with acute PTE and high DD concentrations had an increased risk of early mortality, in the first 30 days and at 3 months. Another biologic noncardiac marker is plasma lactate, which recent studies have suggested as an independent predictor of poor prognosis.<a class="elsevierStyleCrossRef" href="#bib0595">42</a>RV dysfunction causes cardiomyocyte stress with the release of BNP and NT-proBNP. Both markers have shown their usefulness in predicting poor progression in acute PTE and are reliable for identifying patients with a low risk of complications, given their high NPV for mortality.<a class="elsevierStyleCrossRefs" href="#bib0600">43–45</a> Thus, a meta-analysis showed that patients with high BNP (>100pg/mL) and NT-proBNP (>1000pg/mL) concentrations had a 10% (95% confidence interval [CI] 8–13) risk of early death and a 23% (95% CI 20–26) risk of complications.<a class="elsevierStyleCrossRef" href="#bib0600">43</a> A subsequent meta-analysis produced similar results, with an odds ratio [OR] for mortality of 6.2 (95% CI 3–12.7) and 6.7 (95% CI 3.9–11.6) for complications.<a class="elsevierStyleCrossRef" href="#bib0615">46</a> A recent prospective and multicenter study established a plasma NT-proBNP concentration of 600pg/mL as an optimal cutoff for identifying high-risk patients.<a class="elsevierStyleCrossRef" href="#bib0620">47</a>Troponins are sensitive and specific biomarkers of direct myocardial damage and reflect the presence of cardiomyocyte necrosis. In acute PTE, serum troponin concentrations correlate well with RV dysfunction, although in some patients the concentrations can be initially normal and then rise after 6–12h.<a class="elsevierStyleCrossRefs" href="#bib0625">48,49</a> A meta-analysis found that a high troponin concentration reliably identifies a subgroup of normotensive patients with a higher risk of early inhospital death and death at 30 days from the PTE (OR, 5.2; 95% CI 3.2–8.3), with a positive predictive value (PPV) of 43.6% (95% CI 36.9–50.3).<a class="elsevierStyleCrossRef" href="#bib0635">50</a> Nevertheless, a later study could not confirm these results and attributed a limited prognostic value to troponin concentrations.<a class="elsevierStyleCrossRef" href="#bib0640">51</a> The introduction of high-sensitivity troponin has improved the prognostic capacity, especially for excluding patients with a risk of complications after PTE.<a class="elsevierStyleCrossRef" href="#bib0645">52</a>Several studies have been conducted to establish the predictive value of the combination of clinical scales with troponin readings in identifying low-risk patients. The NPV of this combination is similar to that obtained with the application of the PESI and PESIs scales.<a class="elsevierStyleCrossRefs" href="#bib0525">28,53</a>Imaging testsThe most widely used method in clinical practice to assess RV function is transthoracic echocardiography. Various quantitative parameters are employed to determine the degree of ventricular dysfunction (pulmonary acceleration time and ejection time, tricuspid annular plane systolic excursion [TAPSE], pulmonary arterial pressure, end-diastolic RV diameter in the parasternal long axis, ventricular end-diastolic diameter ratio in the 4C apical projection, tricuspid regurgitation peak velocity and diameter of the inferior vena cava, among others). The presence of RV dysfunction in the ultrasound is associated with a high early mortality risk, even in patients with hemodynamic stability; however, its prognostic value is limited<a class="elsevierStyleCrossRef" href="#bib0615">46</a> because the echocardiographic signs of RV overload are heterogeneous and difficult to standardize, and its PPV is low.The information obtained from multidetector CTA helps not only confirm or rule out the diagnosis of PTE but also assesses the extent of the arterial obstruction and the presence of RV dilation.<a class="elsevierStyleCrossRefs" href="#bib0655">54–56</a> In a recent meta-analysis, the ventricular dysfunction assessed using the ratio of ventricular diameters or by volumetric reconstruction of the ventricular size using cross-sectional slices offered a more exact prognostic assessment.<a class="elsevierStyleCrossRef" href="#bib0670">57</a>In terms of the thrombotic burden, this meta-analysis observed that the degree of pulmonary thrombosis and the central location of the thrombus were not predictors of overall mortality in patients with PTE, although they were associated with poorer outcomes.<a class="elsevierStyleCrossRef" href="#bib0670">57</a> The prognostic value of the concomitant presence of deep vein thrombosis (DVT) in PTE has also been studied in a meta-analysis of 10 cohorts and a total of 7868 patients, which analyzed all-cause mortality at 30 days and PTE-related complications at 90 days.<a class="elsevierStyleCrossRef" href="#bib0675">58</a> Fifty-six percent of the patients with PTE had associated DVT, 6.2% of whom died within 30 days. Of the remaining 44% with PTE and without DVT, only 3.8% died. The authors concluded that there is a significant association between the thrombotic burden (in the form of PTE associated with DVT) and the increased risk of early death (7 cohorts; OR, 1.9; 95% CI 1.5–2.4) but not with the PTE-related adverse events at 3 months (5 cohorts; OR, 1.6; 95% CI 0.8–3.4).Combined predictive modelsVarious studies have indicated that the combination of biomarkers and imaging tests or clinical data could increase the prognostic precision of each one separately.A retrospective study analyzed the all-cause mortality 30 days from the diagnosis of PTE in 141 patients. The results showed that the patients with RV dysfunction (RV/left ventricle [LV] >0.9) and troponin levels >0.10μg/L had greater mortality (38%) than those who had only one abnormal parameter (23% if troponin levels were increased, and 9% if there was ventricular dysfunction) or those for whom both were normal (5%).<a class="elsevierStyleCrossRef" href="#bib0680">59</a>Another study prospectively analyzed (in a cohort of 529 patients with hemodynamically stable PTE) the performance of the PESI scale in isolation for predicting death, recurring embolism and secondary shock at 30 days versus its combination with biomarkers (troponin and BNP) and RV dilation measured by echocardiography.<a class="elsevierStyleCrossRef" href="#bib0685">60</a> In the multivariate analysis, the factors independently related to unfavorable outcomes were the combination of intermediate-high risk in the PESI scale (grade III–V) and RV dysfunction (RV/LV >0.9). The blood biomarkers did not improve the predictive power. The grade III-V PESI score had a sensitivity of 72% and an NPV of 98%. The sensitivity and NPV of the combination of echocardiographic findings and PESI III–V were 88% and 99%, respectively.<a class="elsevierStyleCrossRef" href="#bib0685">60</a> These findings were confirmed in another study<a class="elsevierStyleCrossRef" href="#bib0690">61</a> in which the patients classified as low risk (0) using the PESIs scale showed lower overall mortality, PTE recurrence and hemorrhagic complications than those classified as low risk using echocardiography or biomarkers.RV dysfunction demonstrated by echocardiography, with or without troponin elevation, was associated with an increased risk only in the patients classified in the PESI III-IV group but did not lead to any change in the risk stratification in the lower PESI grades (I–II).<a class="elsevierStyleCrossRef" href="#bib0695">62</a>Other authors have studied whether the combination of ultrasensitive troponin and the PESIs scale is capable of improving the prognostic precision in terms of mortality at 30 days and 6 months. The authors observed that ultrasensitive troponin, with a cutoff >14pg/mL, presented high-sensitivity (87%) and NPV (98%) and could therefore be useful for safely identifying those patients with a favorable outcome. However, the ultrasensitive troponin showed no greater precision than the isolated PESIs scale, whose sensitivity and NPV were 94% and 99%, respectively.<a class="elsevierStyleCrossRef" href="#bib0650">53</a>In a prospective and multicenter study, a history of cancer, cardiogenic shock at admission, impaired mental state, a high BNP concentration and an increased RV size behaved as independent predictors of a poor prognosis at 30 days of the PTE diagnosis. With these results, a simple and practical model was developed (PREP Model), which classifies patients into 3 levels of severity, based on the score from each of those variables, which showed an overall predictive power of 84%.<a class="elsevierStyleCrossRef" href="#bib0495">22</a>Another prospective study of 591 patients with hemodynamically stable PTE showed that the identification of patients with a greater risk of death at 30 days was improved by combining right ventricular echocardiographic dysfunction or myocardial damage (expressed by increased troponin levels) with the presence of DVT. In patients with echocardiographic findings of RV overload or myocardial damage, the presence of DVT could cause thromboembolic recurrences and thus a poorer prognosis. The combination of 2 of the diagnostic tools (those that detect RV overload or myocardial damage) had greater specificity and PPV than the use of a single one. There was no added prognostic value in the predictive model that included the 3 parameters.<a class="elsevierStyleCrossRef" href="#bib0440">11</a>The Prognostic Value of Computed Tomography (PROTECT) scale was prospectively developed based on a cohort of 848 patients with hemodynamically stable PTE and was validated in a similar cohort of 529 patients. The authors identified 4 variables independently associated with an unfavorable outcome: PESIs >0, BNP >100pg/mL, troponin >0.05ng/mL and concomitant DVT in the legs. The model achieved a PPV of 26% and an overall predictive power of 75% in the original study population and 21% and 85%, respectively, in the validation cohort.<a class="elsevierStyleCrossRef" href="#bib0700">63</a>The model proposed by Bova et al.,<a class="elsevierStyleCrossRef" href="#bib0705">64</a> based on the retrospective analysis of 2874 patients with hemodynamically stable PTE, differentiated 3 groups with complication risk at 30 days, taking into account the presence of moderate hypotension, myocardial damage, RV overload and tachycardia. Three groups were established based on the score: I (0–2 points), II (3–4 points) and III (>4 points), with a complications rate of 4.2%, 10.8% and 29.2%, respectively. The Bova scale has been subsequently validated in another cohort of normotensive patients, with similar results.<a class="elsevierStyleCrossRef" href="#bib0710">65</a>The multicenter and prospective Thrombo-Embolism Lactate Outcome Study (TELOS) proposed classifying patients who have RV overload with myocardial damage and high concentrations of plasma lactate as intermediate-high risk patients.<a class="elsevierStyleCrossRef" href="#bib0715">66</a>The stratification model proposed by the ESC<a class="elsevierStyleCrossRef" href="#bib0425">8</a> has recently been evaluated in a prospective cohort of 906 patients.<a class="elsevierStyleCrossRef" href="#bib0720">67</a> This model includes clinical data, RV overload and troponin concentrations to predict mortality at 30 days of the diagnosis of PTE. The overall mortality was 22%, 7.7%, 6% and 0.5% in the high, intermediate-high, intermediate-low and low risk groups, respectively. It therefore seems that the ESC scale provides proper stratification of patients into various risk categories, although more studies are needed to use the scale as a therapeutic guide, especially in the intermediate risk group.<a class="elsevierStyleCrossRef" href="#bib0720">67</a>A recent study compared the predictive models of the ESC,<a class="elsevierStyleCrossRef" href="#bib0425">8</a> Bova et al.<a class="elsevierStyleCrossRef" href="#bib0705">64</a> and TELOS study<a class="elsevierStyleCrossRef" href="#bib0715">66</a> for identifying patients with intermediate-high risk but did not observe any differences between the models.<a class="elsevierStyleCrossRef" href="#bib0725">68</a> The study also assessed the usefulness of adding plasma lactate readings to the Bova scale, thereby achieving better identification of patients with a risk of death or shock in the first 7 days after the PTE.<a class="elsevierStyleCrossRef" href="#bib0725">68</a>Outpatient treatmentBased on several studies on outpatient treatment of PTE in selected patients, an editorial was published in 2010<a class="elsevierStyleCrossRef" href="#bib0730">69</a> that suggested that almost 50% of patients with PTE could be treated on an outpatient basis and that what was important was to properly identify these patients.However, given the perception of severity of the PTE and the lack of clinical trials on this subject,<a class="elsevierStyleCrossRefs" href="#bib0500">23,70–72</a> both the ACCP recommendations<a class="elsevierStyleCrossRef" href="#bib0410">5</a> and those of the ESC<a class="elsevierStyleCrossRef" href="#bib0425">8</a> suggest an early discharge (in the first 5 days following diagnosis) for only those patients with a low risk of early complications (level of evidence 2B); however, the criteria and clinical scales used to identify these patients are yet to be defined. According to the recommendations of a Spanish consensus in 2013,<a class="elsevierStyleCrossRef" href="#bib0430">9</a> outpatient treatment for PTE may be considered if the following requirements are met: 1) clinically stable patients with good cardiopulmonary reserve and low risk on a validated clinical scale (PESI or PESIs), 2) good social support with the possibility of rapid access to medical care and 3) assurance of treatment adherence.In light of the results of a number of meta-analyses,<a class="elsevierStyleCrossRefs" href="#bib0755">74–76</a> the recent ACCP guidelines<a class="elsevierStyleCrossRef" href="#bib0750">73</a> for the first time suggest that low-risk patients with PTE and an appropriate home environment can undergo outpatient treatment from the start and not only after an early discharge. The authors indicated the following criteria for outpatient treatment: clinically stable patients, with good cardiopulmonary reserve; no contraindications such as recent bleeding, severe renal/hepatic disease or significant thrombopenia (<70,000platelets/mm3); good treatment compliance; and that the patient is well enough for home treatment. The authors also indicated that the PESI clinical scale or its simplified version can help identify low-risk patients eligible for outpatient treatment, although without establishing a specific score for this selection. Similarly, although their reading was not suggested as something routine for low-risk patients, if RV dysfunction or increased cardiac markers (troponin, BNP or NT-proBNP) are detected, the possibility of home treatment should be ruled out.The clinical trial Home Treatment of Pulmonary Embolism (HoT-PE) is currently underway<a class="elsevierStyleCrossRef" href="#bib0770">77</a> and was designed to determine the optimal management for low-risk patients with PTE. HoT-PE will be the largest intervention study on outpatient treatment performed with low-risk patients selected using criteria adapted from the original Hestia criteria, who will be treated with the direct oral anticoagulant rivaroxaban.ConclusionRisk stratification should guide the treatment of patients with acute symptomatic PTE,<a class="elsevierStyleCrossRefs" href="#bib0410">5,7–9</a> as shown by the algorithm recommended by the authors in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. The hemodynamic condition at diagnosis continues to guide the therapeutic approach for patients with PTE. Those patients who start with hemodynamic shock or persistent arterial hypotension are considered at high risk of complications. Early reperfusion is recommended using systemic fibrinolytic treatment along with cardiorespiratory support measures.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Nevertheless, most cases of acute PTE (95%) have hemodynamic stability. The important issue with this group is identifying patients with a low risk of complications who can be treated on an outpatient basis or who can be discharged early.Currently, routine imaging or laboratory tests are not recommended for low-risk patients with PTE identified through the prognostic scales. Of these, the original PESI scale<a class="elsevierStyleCrossRef" href="#bib0465">16</a> is especially useful for reliably identifying patients with a low risk of mortality at 30 days. The PESIs scale<a class="elsevierStyleCrossRef" href="#bib0490">21</a> has a very similar predictive power and is simpler. Both the PESI and PESIs are recommended by the ACCP<a class="elsevierStyleCrossRef" href="#bib0410">5</a> and ESC<a class="elsevierStyleCrossRef" href="#bib0425">8</a> guidelines. The Hestia criteria<a class="elsevierStyleCrossRef" href="#bib0500">23</a> also seem useful for differentiating patients at low risk of complications after PTE and may be used for selecting patients who are candidates for early discharge and outpatient treatment. Lastly, the prognostic RIETE scale<a class="elsevierStyleCrossRef" href="#bib0575">38</a> has good predictive power for combined complications (mortality, hemorrhage and thromboembolism recurrence) in the first 10 and 30 days but needs to be validated externally in future studies.Although these predictive clinical models are reliable for identifying low-risk patients, it is essential that societal circumstances, family support and treatment adherence be established when proposing outpatient management for patients with PTE.<a class="elsevierStyleCrossRefs" href="#bib0425">8,9,73</a>The signs of RV dysfunction (by echocardiography, CTA or natriuretic peptide concentrations), myocardial damage markers (troponin) and the presence of concomitant DVT are useful tools for identifying patients with hemodynamically stable PTE but with an intermediate-high risk of complications. Nevertheless, more external validation studies are needed on the combined predictive models. These models need to be included in prospective clinical trials of therapeutic management as prior steps in order to integrate them into future risk stratification algorithms.Conflict of interestsThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres875318" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec863514" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres875319" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec863513" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Prognostic stratification of patients with pulmonary thromboembolism" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Prognostic clinical models" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Biomarkers" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Imaging tests" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Combined predictive models" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Outpatient treatment" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusion" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-01-30" "fechaAceptado" => "2017-02-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec863514" "palabras" => array:4 [ 0 => "Pulmonary thromboembolism" 1 => "Risk stratification" 2 => "Prognosis" 3 => "Survival" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec863513" "palabras" => array:4 [ 0 => "Tromboembolismo pulmonar" 1 => "Estratificación de riesgo" 2 => "Pronóstico" 3 => "Supervivencia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Early mortality in patients with pulmonary thromboembolism (PTE) varies from 2% in normotensive patients to 30% in patients with cardiogenic shock. The current risk stratification for symptomatic PTE includes 4 patient groups, and the recommended therapeutic strategies are based on this stratification. Patients who have hemodynamic instability are considered at high risk. Fibrinolytic treatment is recommended for these patients. In normotensive patients, risk stratification helps differentiate between those of low risk, intermediate-low risk and intermediate-high risk. There is currently insufficient evidence on the benefit of intensive monitoring and fibrinolytic treatment in patients with intermediate-high risk. For low-risk patients, standard anticoagulation is indicated. Early discharge with outpatient management may be considered, although its benefit has still not been firmly established." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La mortalidad precoz en pacientes con tromboembolia pulmonar (TEP) varía desde el 2% en pacientes normotensos al 30% en pacientes con shock cardiogénico. La estratificación actual de riesgo en la TEP sintomática incluye 4 grupos de pacientes y las estrategias terapéuticas recomendadas se basan en dicha estratificación. Los pacientes que se presentan con inestabilidad hemodinámica se consideran de alto riesgo y en ellos se recomienda el tratamiento fibrinolítico. En pacientes normotensos, la estratificación de riesgo ayuda a diferenciar entre aquellos de bajo riesgo, riesgo intermedio-bajo y riesgo intermedio-alto. Actualmente no existe suficiente evidencia sobre el beneficio de una monitorización intensiva y tratamiento fibrinolítico en pacientes con riesgo intermedio-alto. En pacientes de bajo riesgo, está indicada la anticoagulación estándar y podría considerarse la posibilidad de un alta precoz con manejo ambulatorio, aunque su beneficio no está todavía firmemente establecido." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Maestre Peiró A, Gonzálvez Gasch A, Monreal Bosch M. Actualización en la estratificación de riesgo del tromboembolismo pulmonar agudo sintomático. Rev Clin Esp. 2017;217:342–350." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2969 "Ancho" => 2425 "Tamanyo" => 291815 ] ] "descripcion" => array:1 [ "en" => "Recommended algorithm for the risk stratification of patients with pulmonary thromboembolism. * Authors’ suggestions. Abbreviations: BNP, brain natriuretic peptide; V/P scintigraphy, ventilation/perfusion scintigraphy; NT-proBNP, amino-terminal fragment of BNP; PESI, Pulmonary Embolism Severity Index; PESIs, simplified PESI scale; RIETE, Computerized Registry of Patients with Venous Thromboembolism; CT, computed tomography; CTA, computer tomography angiography; PTE, pulmonary thromboembolism; DVT, deep vein thrombosis; RV, right ventricle. Source: Adapted from Konstantinides et al.<a class="elsevierStyleCrossRef" href="#bib0425">8</a> and modified by the authors." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Classes of risk: if score ≥1, the patient cannot be treated on an outpatient basis.Abbreviations: bpm, beats/breaths per minute; PESI, Pulmonary Embolism Severity Index; RIETE, Computerized Registry of Patients with Venous Thromboembolism venous; CT: computed tomography; PTE: pulmonary thromboembolism." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Original PESI</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Age in years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic obstructive pulmonary disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate >110bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure <100mm Hg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Respiratory rate >30bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Temperature <36°C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Altered mental state \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oxygen saturation <90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">+20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Classes of risk: Class I ≤65, Class II 66–85, Class III 86–105, Class IV 106–125 and Class V ≥125 points</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Simplified PESI</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age >80 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of cancer \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic obstructive pulmonary disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate >110bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure <100mm Hg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oxygen saturation <90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Classes of risk: low risk 0 and high risk ≥1</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">RIETE</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cancer without metastases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cancer with metastases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Systolic blood pressure <100mm Hg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart rate >110bpm \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oxygen saturation <90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine clearance 30–60mL/min/1.73m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine clearance <30mL/min/1.73m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Recent bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Recent immobility >4 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Platelets <100,000 or >450,000/mm3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Classes of risk: low risk 0 and high risk ≥1</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Hestia criteria</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hemodynamic instability \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for thrombolysis or embolectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High risk of bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for supplemental oxygen for saturation >90% for 24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PTE diagnosis during the taking of anticoagulants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Need for intravenous analgesic medication for 24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Medical or social reason for 24-h hospital treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Creatinine clearance <30mL/min/1.73m2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe hepatic failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pregnancy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of heparin-induced thrombopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1477438.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Included variables and score assigned in the clinical scales original PESI, simplified PESI, RIETE and Hestia criteria." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:77 [ 0 => array:3 [ "identificador" => "bib0390" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of first and recurrent venous thromboembolism: a population-based cohort study in patients without active cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. 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Update on the risk stratification of acute symptomatic pulmonary thromboembolism

Actualización en la estratificación de riesgo del tromboembolismo pulmonar agudo sintomático

A. Maestre Peiróa,

Corresponding author

amaestrep@gmail.com

Corresponding author.

, A. Gonzálvez Gaschb, M. Monreal Boschc

a Servicio de Medicina Interna, Hospital Universitario del Vinalopó, Elche, Alicante, Spain

b Servicio de Medicina Interna, Hospital Collado Villalba, Madrid, Spain

c Servicio de Medicina Interna, Hospital Universitario Germans Trias i Pujol, Badalona, Barcelona, Spain

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    "titulo" => "Update on the risk stratification of acute symptomatic pulmonary thromboembolism"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recommended algorithm for the risk stratification of patients with pulmonary thromboembolism&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#42; Authors&#8217; suggestions&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BNP&#44; brain natriuretic peptide&#59; V&#47;P scintigraphy&#44; ventilation&#47;perfusion scintigraphy&#59; NT-proBNP&#44; amino-terminal fragment of BNP&#59; PESI&#44; Pulmonary Embolism Severity Index&#59; PESIs&#44; simplified PESI scale&#59; RIETE&#44; Computerized Registry of Patients with Venous Thromboembolism&#59; CT&#44; computed tomography&#59; CTA&#44; computer tomography angiography&#59; PTE&#44; pulmonary thromboembolism&#59; DVT&#44; deep vein thrombosis&#59; RV&#44; right ventricle&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Adapted from Konstantinides et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> and modified by the authors&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pulmonary thromboembolism &#40;PTE&#41; results from the partial or total occlusion of the pulmonary vascular bed by a detached thrombus &#40;embolus&#41; of the deep venous system&#44; usually of the legs&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Acute symptomatic PTE is the most severe manifestation of venous thromboembolism &#40;VTE&#41;&#44; whose overall incidence rate is 131 per 100&#44;000 individuals&#47;year&#44; causing PTE in 45&#46;9&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">1</span></a> PTE causes 0&#46;52&#37; of hospital admissions&#44; which represents a high healthcare cost in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The clinical presentation of PTE can vary&#46; The mortality of a PTE that starts as cardiopulmonary arrest &#40;1&#37; of cases&#41; is 70&#37;&#46; If the PTE presents as shock or arterial hypotension requiring inotropic agents &#40;5&#37; of cases&#41;&#44; the risk of mortality is 30&#37;&#44; while for normotensive patients the risk declines to 2&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">3&#8211;5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A recent study of the Computerized Registry of Patients with Venous Thromboembolism &#40;RIETE&#41; assessed the mortality of acute PTE&#46; In 23&#44;858 patients treated during a 12-year period&#44; an overall mortality rate at 30 days of 5&#46;9&#37; was observed&#44; with a significant declining trend&#44; both for secondary to any cause &#40;from 6&#46;6&#37; between 2001 and 2005 to 4&#46;9&#37; between 2010 and 2013&#41; and for PTE-induced &#40;from 3&#46;3&#37; to 1&#46;8&#37; in the same periods&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Prognostic stratification of patients with pulmonary thromboembolism</span><p id="par0025" class="elsevierStylePara elsevierViewall">To reduce PTE mortality&#44; it is essential to differentiate patients at high risk of adverse events from those at low risk&#44; to indicate the most effective and efficient therapeutic alternatives in each case&#46; Therefore&#44; the management guidelines for massive and submassive PTE of the American Heart Association &#40;AHA&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">7</span></a> the 9th edition of the antithrombotic therapy guidelines of the American College of Chest Physicians &#40;ACCP&#41;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">5</span></a> and the latest guidelines of the European Society of Cardiology &#40;ESC&#41;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> recommend stratifying patients according to their early mortality risk &#40;inhospital or during the first 30 days&#41; into 3 categories&#58; low&#44; intermediate and high risk&#44; depending on a number of risk markers and prognostic scales&#46; The national consensus on the diagnosis&#44; risk stratification and treatment of patients with PTE<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">9</span></a> was published in Spain in 2013 and supports these same recommendations&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The hemodynamic situation at the onset of PTE has the greatest prognostic significance for short-term mortality&#46; Patients with hypotension<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">5&#44;7</span></a> &#40;systolic blood pressure &#60;90<span class="elsevierStyleHsp" style=""></span>mm Hg&#41; or hemodynamic shock are considered at high risk&#46; Therefore&#44; after confirming the diagnosis through transthoracic echocardiography or thoracic multidetector computed tomography angiography &#40;CTA&#41;&#44; the clinical guidelines and expert recommendations propose systemic fibrinolytic therapy if the hemorrhagic risk is not high&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">5&#44;7&#44;8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">After confirming the PTE with a multidetector CTA or lung scintigraphy&#44; clinical prognostic scales are employed for hemodynamically stable patients to stratify the risk&#44; classifying patients into low to intermediate risk groups&#46; For low-risk patients&#44; standard anticoagulation is indicated&#46; Early discharge with outpatient management may be considered&#46;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">5&#44;7&#44;8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The most complex patient group to stratify is the intermediate risk group&#46; These are hemodynamically stable patients in their presentation&#44; who can undergo subsequent hemodynamic instability as a consequence of a thromboembolic recurrence or an impairment in right ventricular &#40;RV&#41; function&#46; Therefore&#44; risk stratification is currently focused on differentiating &#40;within the normotensive patient group with intermediate risk&#41; those at low risk of early complications &#40;low-intermediate risk&#41; from those at high risk of adverse events &#40;intermediate-high risk&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">4&#44;8&#44;10&#8211;13</span></a> The recommendation for intermediate risk patients is the combination of prognostic tools that assess RV dysfunction&#44; myocardial ischemia&#44; cardiomyocyte stress or thrombotic burden&#44; to thereby identify those with intermediate-high risk who could benefit from intensive monitoring and reperfusion therapy &#40;rescue fibrinolysis&#41; if hemodynamic decompensation occurs&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Prognostic clinical models</span><p id="par0045" class="elsevierStylePara elsevierViewall">A number of prognostic tools are employed to stratify the risk for patients with acute symptomatic PTE&#44; mainly clinical scales&#44; biological markers and imaging tests&#46; In particular&#44; to identify patients with low-risk PTE&#44; clinical prognostic scales have shown an excellent negative predictive value &#40;NPV&#41; and are inexpensive and simple to apply&#46; The scales include clinical parameters that can be obtained quickly and require no special skills or training&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Two meta-analyses were published in 2012 and 2014 on the performance of clinical scales for predicting early mortality after PTE&#46;<a class="elsevierStyleCrossRefs" href="#bib0445"><span class="elsevierStyleSup">12&#44;14</span></a> The meta-analyses analyzed 9 and 11 clinical scales&#44; respectively&#44; which had been developed by various groups&#46;<a class="elsevierStyleCrossRefs" href="#bib0460"><span class="elsevierStyleSup">15&#8211;25</span></a> The comparisons between clinical prognostic models are difficult to interpret&#44; but when searching for low-risk patients who can be discharged early and be treated at home&#44; high sensitivity is preferable to high specificity&#44; thereby minimizing false negatives&#46; Given their high sensitivity and predictive ability and after having been validated in numerous publications and in various patient subgroups&#44;<a class="elsevierStyleCrossRefs" href="#bib0515"><span class="elsevierStyleSup">26&#8211;33</span></a> both the original Pulmonary Embolism Severity Index &#40;PESI&#41;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">16</span></a> and its simplified version &#40;PESIs&#41;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">21</span></a> are accepted as more valid and reliable for identifying patients with PTE and at low risk of mortality at 30 days&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Another useful clinical model for classifying PTE in the low-risk group are the Hestia criteria&#44; which help identify patients with a reduced probability of complications at 90 days&#44; when the patients do not meet any of the parameters of the predictive model&#46;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">23&#44;34</span></a> Subsequently&#44; these criteria have been better than the PESIs<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">35</span></a> and that of the ESC of 2008<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">36</span></a> for identifying more patients at low risk&#46; A study has recently been published with the external validation of the Hestia criteria for predicting early mortality &#40;inhospital and at 30 days&#41;&#44; which showed excellent sensitivity &#40;100&#37;&#41;&#44; although low specificity &#40;27&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">37</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">All of the above-mentioned scales were developed and validated for identifying patients at low mortality risk in the first 30&#8211;90 days after the PTE but not for predicting the risk of bleeding or thromboembolic recurrence&#46; Additionally&#44; in the only study that assessed the predictive ability of the original PESI scale in the first days after the PTE diagnosis &#40;specifically at 5 days&#41;&#44; 9 of 109 patients classified as low risk presented an adverse clinical event&#46;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">31</span></a> In 2015&#44; a study was published on the results of a new prognostic scale resulting from the RIETE registry&#44; which included 11 variables &#40;some shared with PESI and PESIs&#41; and helped correctly identify patients with low-risk PTE&#44; not only for mortality but also for bleeding and thrombotic recurrence&#44; in the first 10 days after the diagnosis&#44; with greater discriminatory capacity than the PESI and PESIs scales&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">38</span></a> This scale has been validated in a new cohort&#44; with very similar results both at 10 and 30 days &#40;data awaiting publication&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the clinical scales PESI&#44; PESIs&#44; RIETE and the Hestia Criteria with their variables&#44; scoring systems and risk classification&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Two new predictive rules were recently developed with a retrospective cohort of 1143 patients with PTE to identify patients with a low risk of complications in the first 14 days and who could be candidates for outpatient therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">39</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Biomarkers</span><p id="par0070" class="elsevierStylePara elsevierViewall">Another prognostic tool used for stratifying the risk of patients with PTE are biochemical markers&#44;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">4&#44;5&#44;8&#8211;10&#44;13</span></a> which include RV dysfunction markers such as the brain natriuretic peptide &#40;BNP&#41; and its amino-terminal fragment &#40;NT-proBNP&#41;&#44; myocardial damage markers such as troponin and other noncardiac markers such as <span class="elsevierStyleSmallCaps">d</span>-dimer &#40;DD&#41;&#46; Plasma DD concentrations in the first quartile &#40;&#60;1500<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; have a negative predictive value &#40;NPV&#41; of 99&#37; for excluding all-cause mortality at 3 months&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">40</span></a> A meta-analysis on the usefulness of DD in risk stratification<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">41</span></a> observed that patients with acute PTE and high DD concentrations had an increased risk of early mortality&#44; in the first 30 days and at 3 months&#46; Another biologic noncardiac marker is plasma lactate&#44; which recent studies have suggested as an independent predictor of poor prognosis&#46;<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">42</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">RV dysfunction causes cardiomyocyte stress with the release of BNP and NT-proBNP&#46; Both markers have shown their usefulness in predicting poor progression in acute PTE and are reliable for identifying patients with a low risk of complications&#44; given their high NPV for mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0600"><span class="elsevierStyleSup">43&#8211;45</span></a> Thus&#44; a meta-analysis showed that patients with high BNP &#40;&#62;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; and NT-proBNP &#40;&#62;1000<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; concentrations had a 10&#37; &#40;95&#37; confidence interval &#91;CI&#93; 8&#8211;13&#41; risk of early death and a 23&#37; &#40;95&#37; CI 20&#8211;26&#41; risk of complications&#46;<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">43</span></a> A subsequent meta-analysis produced similar results&#44; with an odds ratio &#91;OR&#93; for mortality of 6&#46;2 &#40;95&#37; CI 3&#8211;12&#46;7&#41; and 6&#46;7 &#40;95&#37; CI 3&#46;9&#8211;11&#46;6&#41; for complications&#46;<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">46</span></a> A recent prospective and multicenter study established a plasma NT-proBNP concentration of 600<span class="elsevierStyleHsp" style=""></span>pg&#47;mL as an optimal cutoff for identifying high-risk patients&#46;<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">47</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Troponins are sensitive and specific biomarkers of direct myocardial damage and reflect the presence of cardiomyocyte necrosis&#46; In acute PTE&#44; serum troponin concentrations correlate well with RV dysfunction&#44; although in some patients the concentrations can be initially normal and then rise after 6&#8211;12<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0625"><span class="elsevierStyleSup">48&#44;49</span></a> A meta-analysis found that a high troponin concentration reliably identifies a subgroup of normotensive patients with a higher risk of early inhospital death and death at 30 days from the PTE &#40;OR&#44; 5&#46;2&#59; 95&#37; CI 3&#46;2&#8211;8&#46;3&#41;&#44; with a positive predictive value &#40;PPV&#41; of 43&#46;6&#37; &#40;95&#37; CI 36&#46;9&#8211;50&#46;3&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">50</span></a> Nevertheless&#44; a later study could not confirm these results and attributed a limited prognostic value to troponin concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">51</span></a> The introduction of high-sensitivity troponin has improved the prognostic capacity&#44; especially for excluding patients with a risk of complications after PTE&#46;<a class="elsevierStyleCrossRef" href="#bib0645"><span class="elsevierStyleSup">52</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Several studies have been conducted to establish the predictive value of the combination of clinical scales with troponin readings in identifying low-risk patients&#46; The NPV of this combination is similar to that obtained with the application of the PESI and PESIs scales&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">28&#44;53</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Imaging tests</span><p id="par0090" class="elsevierStylePara elsevierViewall">The most widely used method in clinical practice to assess RV function is transthoracic echocardiography&#46; Various quantitative parameters are employed to determine the degree of ventricular dysfunction &#40;pulmonary acceleration time and ejection time&#44; tricuspid annular plane systolic excursion &#91;TAPSE&#93;&#44; pulmonary arterial pressure&#44; end-diastolic RV diameter in the parasternal long axis&#44; ventricular end-diastolic diameter ratio in the 4C apical projection&#44; tricuspid regurgitation peak velocity and diameter of the inferior vena cava&#44; among others&#41;&#46; The presence of RV dysfunction in the ultrasound is associated with a high early mortality risk&#44; even in patients with hemodynamic stability&#59; however&#44; its prognostic value is limited<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">46</span></a> because the echocardiographic signs of RV overload are heterogeneous and difficult to standardize&#44; and its PPV is low&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The information obtained from multidetector CTA helps not only confirm or rule out the diagnosis of PTE but also assesses the extent of the arterial obstruction and the presence of RV dilation&#46;<a class="elsevierStyleCrossRefs" href="#bib0655"><span class="elsevierStyleSup">54&#8211;56</span></a> In a recent meta-analysis&#44; the ventricular dysfunction assessed using the ratio of ventricular diameters or by volumetric reconstruction of the ventricular size using cross-sectional slices offered a more exact prognostic assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">57</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">In terms of the thrombotic burden&#44; this meta-analysis observed that the degree of pulmonary thrombosis and the central location of the thrombus were not predictors of overall mortality in patients with PTE&#44; although they were associated with poorer outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">57</span></a> The prognostic value of the concomitant presence of deep vein thrombosis &#40;DVT&#41; in PTE has also been studied in a meta-analysis of 10 cohorts and a total of 7868 patients&#44; which analyzed all-cause mortality at 30 days and PTE-related complications at 90 days&#46;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">58</span></a> Fifty-six percent of the patients with PTE had associated DVT&#44; 6&#46;2&#37; of whom died within 30 days&#46; Of the remaining 44&#37; with PTE and without DVT&#44; only 3&#46;8&#37; died&#46; The authors concluded that there is a significant association between the thrombotic burden &#40;in the form of PTE associated with DVT&#41; and the increased risk of early death &#40;7 cohorts&#59; OR&#44; 1&#46;9&#59; 95&#37; CI 1&#46;5&#8211;2&#46;4&#41; but not with the PTE-related adverse events at 3 months &#40;5 cohorts&#59; OR&#44; 1&#46;6&#59; 95&#37; CI 0&#46;8&#8211;3&#46;4&#41;&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Combined predictive models</span><p id="par0105" class="elsevierStylePara elsevierViewall">Various studies have indicated that the combination of biomarkers and imaging tests or clinical data could increase the prognostic precision of each one separately&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A retrospective study analyzed the all-cause mortality 30 days from the diagnosis of PTE in 141 patients&#46; The results showed that the patients with RV dysfunction &#40;RV&#47;left ventricle &#91;LV&#93; &#62;0&#46;9&#41; and troponin levels &#62;0&#46;10<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L had greater mortality &#40;38&#37;&#41; than those who had only one abnormal parameter &#40;23&#37; if troponin levels were increased&#44; and 9&#37; if there was ventricular dysfunction&#41; or those for whom both were normal &#40;5&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">59</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Another study prospectively analyzed &#40;in a cohort of 529 patients with hemodynamically stable PTE&#41; the performance of the PESI scale in isolation for predicting death&#44; recurring embolism and secondary shock at 30 days versus its combination with biomarkers &#40;troponin and BNP&#41; and RV dilation measured by echocardiography&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">60</span></a> In the multivariate analysis&#44; the factors independently related to unfavorable outcomes were the combination of intermediate-high risk in the PESI scale &#40;grade <span class="elsevierStyleSmallCaps">III&#8211;V</span>&#41; and RV dysfunction &#40;RV&#47;LV &#62;0&#46;9&#41;&#46; The blood biomarkers did not improve the predictive power&#46; The grade <span class="elsevierStyleSmallCaps">III</span>-<span class="elsevierStyleSmallCaps">V</span> PESI score had a sensitivity of 72&#37; and an NPV of 98&#37;&#46; The sensitivity and NPV of the combination of echocardiographic findings and PESI <span class="elsevierStyleSmallCaps">III&#8211;V</span> were 88&#37; and 99&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">60</span></a> These findings were confirmed in another study<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">61</span></a> in which the patients classified as low risk &#40;0&#41; using the PESIs scale showed lower overall mortality&#44; PTE recurrence and hemorrhagic complications than those classified as low risk using echocardiography or biomarkers&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">RV dysfunction demonstrated by echocardiography&#44; with or without troponin elevation&#44; was associated with an increased risk only in the patients classified in the PESI <span class="elsevierStyleSmallCaps">III</span>-<span class="elsevierStyleSmallCaps">IV</span> group but did not lead to any change in the risk stratification in the lower PESI grades &#40;<span class="elsevierStyleSmallCaps">I&#8211;II</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">62</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Other authors have studied whether the combination of ultrasensitive troponin and the PESIs scale is capable of improving the prognostic precision in terms of mortality at 30 days and 6 months&#46; The authors observed that ultrasensitive troponin&#44; with a cutoff &#62;14<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; presented high-sensitivity &#40;87&#37;&#41; and NPV &#40;98&#37;&#41; and could therefore be useful for safely identifying those patients with a favorable outcome&#46; However&#44; the ultrasensitive troponin showed no greater precision than the isolated PESIs scale&#44; whose sensitivity and NPV were 94&#37; and 99&#37;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0650"><span class="elsevierStyleSup">53</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">In a prospective and multicenter study&#44; a history of cancer&#44; cardiogenic shock at admission&#44; impaired mental state&#44; a high BNP concentration and an increased RV size behaved as independent predictors of a poor prognosis at 30 days of the PTE diagnosis&#46; With these results&#44; a simple and practical model was developed &#40;PREP Model&#41;&#44; which classifies patients into 3 levels of severity&#44; based on the score from each of those variables&#44; which showed an overall predictive power of 84&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">22</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Another prospective study of 591 patients with hemodynamically stable PTE showed that the identification of patients with a greater risk of death at 30 days was improved by combining right ventricular echocardiographic dysfunction or myocardial damage &#40;expressed by increased troponin levels&#41; with the presence of DVT&#46; In patients with echocardiographic findings of RV overload or myocardial damage&#44; the presence of DVT could cause thromboembolic recurrences and thus a poorer prognosis&#46; The combination of 2 of the diagnostic tools &#40;those that detect RV overload or myocardial damage&#41; had greater specificity and PPV than the use of a single one&#46; There was no added prognostic value in the predictive model that included the 3 parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">11</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">The Prognostic Value of Computed Tomography &#40;PROTECT&#41; scale was prospectively developed based on a cohort of 848 patients with hemodynamically stable PTE and was validated in a similar cohort of 529 patients&#46; The authors identified 4 variables independently associated with an unfavorable outcome&#58; PESIs &#62;0&#44; BNP &#62;100<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#44; troponin &#62;0&#46;05<span class="elsevierStyleHsp" style=""></span>ng&#47;mL and concomitant DVT in the legs&#46; The model achieved a PPV of 26&#37; and an overall predictive power of 75&#37; in the original study population and 21&#37; and 85&#37;&#44; respectively&#44; in the validation cohort&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">63</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The model proposed by Bova et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">64</span></a> based on the retrospective analysis of 2874 patients with hemodynamically stable PTE&#44; differentiated 3 groups with complication risk at 30 days&#44; taking into account the presence of moderate hypotension&#44; myocardial damage&#44; RV overload and tachycardia&#46; Three groups were established based on the score&#58; <span class="elsevierStyleSmallCaps">I</span> &#40;0&#8211;2 points&#41;&#44; <span class="elsevierStyleSmallCaps">II</span> &#40;3&#8211;4 points&#41; and <span class="elsevierStyleSmallCaps">III</span> &#40;&#62;4 points&#41;&#44; with a complications rate of 4&#46;2&#37;&#44; 10&#46;8&#37; and 29&#46;2&#37;&#44; respectively&#46; The Bova scale has been subsequently validated in another cohort of normotensive patients&#44; with similar results&#46;<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">65</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">The multicenter and prospective Thrombo-Embolism Lactate Outcome Study &#40;TELOS&#41; proposed classifying patients who have RV overload with myocardial damage and high concentrations of plasma lactate as intermediate-high risk patients&#46;<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">66</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">The stratification model proposed by the ESC<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> has recently been evaluated in a prospective cohort of 906 patients&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">67</span></a> This model includes clinical data&#44; RV overload and troponin concentrations to predict mortality at 30 days of the diagnosis of PTE&#46; The overall mortality was 22&#37;&#44; 7&#46;7&#37;&#44; 6&#37; and 0&#46;5&#37; in the high&#44; intermediate-high&#44; intermediate-low and low risk groups&#44; respectively&#46; It therefore seems that the ESC scale provides proper stratification of patients into various risk categories&#44; although more studies are needed to use the scale as a therapeutic guide&#44; especially in the intermediate risk group&#46;<a class="elsevierStyleCrossRef" href="#bib0720"><span class="elsevierStyleSup">67</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">A recent study compared the predictive models of the ESC&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> Bova et al&#46;<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">64</span></a> and TELOS study<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">66</span></a> for identifying patients with intermediate-high risk but did not observe any differences between the models&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">68</span></a> The study also assessed the usefulness of adding plasma lactate readings to the Bova scale&#44; thereby achieving better identification of patients with a risk of death or shock in the first 7 days after the PTE&#46;<a class="elsevierStyleCrossRef" href="#bib0725"><span class="elsevierStyleSup">68</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Outpatient treatment</span><p id="par0165" class="elsevierStylePara elsevierViewall">Based on several studies on outpatient treatment of PTE in selected patients&#44; an editorial was published in 2010<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">69</span></a> that suggested that almost 50&#37; of patients with PTE could be treated on an outpatient basis and that what was important was to properly identify these patients&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">However&#44; given the perception of severity of the PTE and the lack of clinical trials on this subject&#44;<a class="elsevierStyleCrossRefs" href="#bib0500"><span class="elsevierStyleSup">23&#44;70&#8211;72</span></a> both the ACCP recommendations<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">5</span></a> and those of the ESC<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> suggest an early discharge &#40;in the first 5 days following diagnosis&#41; for only those patients with a low risk of early complications &#40;level of evidence 2B&#41;&#59; however&#44; the criteria and clinical scales used to identify these patients are yet to be defined&#46; According to the recommendations of a Spanish consensus in 2013&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">9</span></a> outpatient treatment for PTE may be considered if the following requirements are met&#58; 1&#41; clinically stable patients with good cardiopulmonary reserve and low risk on a validated clinical scale &#40;PESI or PESIs&#41;&#44; 2&#41; good social support with the possibility of rapid access to medical care and 3&#41; assurance of treatment adherence&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">In light of the results of a number of meta-analyses&#44;<a class="elsevierStyleCrossRefs" href="#bib0755"><span class="elsevierStyleSup">74&#8211;76</span></a> the recent ACCP guidelines<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">73</span></a> for the first time suggest that low-risk patients with PTE and an appropriate home environment can undergo outpatient treatment from the start and not only after an early discharge&#46; The authors indicated the following criteria for outpatient treatment&#58; clinically stable patients&#44; with good cardiopulmonary reserve&#59; no contraindications such as recent bleeding&#44; severe renal&#47;hepatic disease or significant thrombopenia &#40;&#60;70&#44;000<span class="elsevierStyleHsp" style=""></span>platelets&#47;mm<span class="elsevierStyleSup">3</span>&#41;&#59; good treatment compliance&#59; and that the patient is well enough for home treatment&#46; The authors also indicated that the PESI clinical scale or its simplified version can help identify low-risk patients eligible for outpatient treatment&#44; although without establishing a specific score for this selection&#46; Similarly&#44; although their reading was not suggested as something routine for low-risk patients&#44; if RV dysfunction or increased cardiac markers &#40;troponin&#44; BNP or NT-proBNP&#41; are detected&#44; the possibility of home treatment should be ruled out&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The clinical trial Home Treatment of Pulmonary Embolism &#40;HoT-PE&#41; is currently underway<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">77</span></a> and was designed to determine the optimal management for low-risk patients with PTE&#46; HoT-PE will be the largest intervention study on outpatient treatment performed with low-risk patients selected using criteria adapted from the original Hestia criteria&#44; who will be treated with the direct oral anticoagulant rivaroxaban&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusion</span><p id="par0185" class="elsevierStylePara elsevierViewall">Risk stratification should guide the treatment of patients with acute symptomatic PTE&#44;<a class="elsevierStyleCrossRefs" href="#bib0410"><span class="elsevierStyleSup">5&#44;7&#8211;9</span></a> as shown by the algorithm recommended by the authors in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; The hemodynamic condition at diagnosis continues to guide the therapeutic approach for patients with PTE&#46; Those patients who start with hemodynamic shock or persistent arterial hypotension are considered at high risk of complications&#46; Early reperfusion is recommended using systemic fibrinolytic treatment along with cardiorespiratory support measures&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">Nevertheless&#44; most cases of acute PTE &#40;95&#37;&#41; have hemodynamic stability&#46; The important issue with this group is identifying patients with a low risk of complications who can be treated on an outpatient basis or who can be discharged early&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Currently&#44; routine imaging or laboratory tests are not recommended for low-risk patients with PTE identified through the prognostic scales&#46; Of these&#44; the original PESI scale<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">16</span></a> is especially useful for reliably identifying patients with a low risk of mortality at 30 days&#46; The PESIs scale<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">21</span></a> has a very similar predictive power and is simpler&#46; Both the PESI and PESIs are recommended by the ACCP<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">5</span></a> and ESC<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> guidelines&#46; The Hestia criteria<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">23</span></a> also seem useful for differentiating patients at low risk of complications after PTE and may be used for selecting patients who are candidates for early discharge and outpatient treatment&#46; Lastly&#44; the prognostic RIETE scale<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">38</span></a> has good predictive power for combined complications &#40;mortality&#44; hemorrhage and thromboembolism recurrence&#41; in the first 10 and 30 days but needs to be validated externally in future studies&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Although these predictive clinical models are reliable for identifying low-risk patients&#44; it is essential that societal circumstances&#44; family support and treatment adherence be established when proposing outpatient management for patients with PTE&#46;<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">8&#44;9&#44;73</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">The signs of RV dysfunction &#40;by echocardiography&#44; CTA or natriuretic peptide concentrations&#41;&#44; myocardial damage markers &#40;troponin&#41; and the presence of concomitant DVT are useful tools for identifying patients with hemodynamically stable PTE but with an intermediate-high risk of complications&#46; Nevertheless&#44; more external validation studies are needed on the combined predictive models&#46; These models need to be included in prospective clinical trials of therapeutic management as prior steps in order to integrate them into future risk stratification algorithms&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interests</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Background"
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          "titulo" => "Prognostic stratification of patients with pulmonary thromboembolism"
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          "titulo" => "Prognostic clinical models"
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            0 => "Pulmonary thromboembolism"
            1 => "Risk stratification"
            2 => "Prognosis"
            3 => "Survival"
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            0 => "Tromboembolismo pulmonar"
            1 => "Estratificaci&#243;n de riesgo"
            2 => "Pron&#243;stico"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Early mortality in patients with pulmonary thromboembolism &#40;PTE&#41; varies from 2&#37; in normotensive patients to 30&#37; in patients with cardiogenic shock&#46; The current risk stratification for symptomatic PTE includes 4 patient groups&#44; and the recommended therapeutic strategies are based on this stratification&#46; Patients who have hemodynamic instability are considered at high risk&#46; Fibrinolytic treatment is recommended for these patients&#46; In normotensive patients&#44; risk stratification helps differentiate between those of low risk&#44; intermediate-low risk and intermediate-high risk&#46; There is currently insufficient evidence on the benefit of intensive monitoring and fibrinolytic treatment in patients with intermediate-high risk&#46; For low-risk patients&#44; standard anticoagulation is indicated&#46; Early discharge with outpatient management may be considered&#44; although its benefit has still not been firmly established&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La mortalidad precoz en pacientes con tromboembolia pulmonar &#40;TEP&#41; var&#237;a desde el 2&#37; en pacientes normotensos al 30&#37; en pacientes con shock cardiog&#233;nico&#46; La estratificaci&#243;n actual de riesgo en la TEP sintom&#225;tica incluye 4 grupos de pacientes y las estrategias terap&#233;uticas recomendadas se basan en dicha estratificaci&#243;n&#46; Los pacientes que se presentan con inestabilidad hemodin&#225;mica se consideran de alto riesgo y en ellos se recomienda el tratamiento fibrinol&#237;tico&#46; En pacientes normotensos&#44; la estratificaci&#243;n de riesgo ayuda a diferenciar entre aquellos de bajo riesgo&#44; riesgo intermedio-bajo y riesgo intermedio-alto&#46; Actualmente no existe suficiente evidencia sobre el beneficio de una monitorizaci&#243;n intensiva y tratamiento fibrinol&#237;tico en pacientes con riesgo intermedio-alto&#46; En pacientes de bajo riesgo&#44; est&#225; indicada la anticoagulaci&#243;n est&#225;ndar y podr&#237;a considerarse la posibilidad de un alta precoz con manejo ambulatorio&#44; aunque su beneficio no est&#225; todav&#237;a firmemente establecido&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Maestre Peir&#243; A&#44; Gonz&#225;lvez Gasch A&#44; Monreal Bosch M&#46; Actualizaci&#243;n en la estratificaci&#243;n de riesgo del tromboembolismo pulmonar agudo sintom&#225;tico&#46; Rev Clin Esp&#46; 2017&#59;217&#58;342&#8211;350&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recommended algorithm for the risk stratification of patients with pulmonary thromboembolism&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">&#42; Authors&#8217; suggestions&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; BNP&#44; brain natriuretic peptide&#59; V&#47;P scintigraphy&#44; ventilation&#47;perfusion scintigraphy&#59; NT-proBNP&#44; amino-terminal fragment of BNP&#59; PESI&#44; Pulmonary Embolism Severity Index&#59; PESIs&#44; simplified PESI scale&#59; RIETE&#44; Computerized Registry of Patients with Venous Thromboembolism&#59; CT&#44; computed tomography&#59; CTA&#44; computer tomography angiography&#59; PTE&#44; pulmonary thromboembolism&#59; DVT&#44; deep vein thrombosis&#59; RV&#44; right ventricle&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>&#58; Adapted from Konstantinides et al&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">8</span></a> and modified by the authors&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Classes of risk&#58; if score &#8805;1&#44; the patient cannot be treated on an outpatient basis&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Abbreviations</span>&#58; bpm&#44; beats&#47;breaths per minute&#59; PESI&#44; Pulmonary Embolism Severity Index&#59; RIETE&#44; Computerized Registry of Patients with Venous Thromboembolism venous&#59; CT&#58; computed tomography&#59; PTE&#58; pulmonary thromboembolism&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Original PESI</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Age in years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Male sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>History of cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic obstructive pulmonary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart rate &#62;110<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Systolic blood pressure &#60;100<span class="elsevierStyleHsp" style=""></span>mm Hg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Respiratory rate &#62;30<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Temperature &#60;36<span class="elsevierStyleHsp" style=""></span>&#176;C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Altered mental state&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oxygen saturation &#60;90&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#43;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Classes of risk&#58; Class I &#8804;65&#44; Class II 66&#8211;85&#44; Class III 86&#8211;105&#44; Class IV 106&#8211;125 and Class V &#8805;125 points</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Simplified PESI</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#62;80 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>History of cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic obstructive pulmonary disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart rate &#62;110<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Systolic blood pressure &#60;100<span class="elsevierStyleHsp" style=""></span>mm Hg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oxygen saturation &#60;90&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Classes of risk&#58; low risk 0 and high risk &#8805;1</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">RIETE</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cancer without metastases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cancer with metastases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Systolic blood pressure &#60;100<span class="elsevierStyleHsp" style=""></span>mm Hg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart rate &#62;110<span class="elsevierStyleHsp" style=""></span>bpm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oxygen saturation &#60;90&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Creatinine clearance 30&#8211;60<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Creatinine clearance &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Recent bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Recent immobility &#62;4 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Platelets &#60;100&#44;000 or &#62;450&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Classes of risk&#58; low risk 0 and high risk &#8805;1</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Hestia criteria</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hemodynamic instability&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Need for thrombolysis or embolectomy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>High risk of bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Need for supplemental oxygen for saturation &#62;90&#37; for 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PTE diagnosis during the taking of anticoagulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Need for intravenous analgesic medication for 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Medical or social reason for 24-h hospital treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Creatinine clearance &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&#47;1&#46;73<span class="elsevierStyleHsp" style=""></span>m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Severe hepatic failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>History of heparin-induced thrombopenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Included variables and score assigned in the clinical scales original PESI&#44; simplified PESI&#44; RIETE and Hestia criteria&#46;</p>"
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                    0 => array:2 [
                      "titulo" => "Epidemiology of first and recurrent venous thromboembolism&#58; a population-based cohort study in patients without active cancer"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "C&#46; Martinez"
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                            "web" => "Medline"
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                      "titulo" => "Pulmonary embolism&#44; acute coronary syndrome and ischemic stroke in the Spanish National Discharge Database"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Guijarro"
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                            2 => "D&#46; Jimenez"
                            3 => "J&#46; Trujillo-Santos"
                            4 => "R&#46; Otero"
                            5 => "R&#46; Barba"
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                      "doi" => "10.1016/j.ejim.2015.10.006"
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                        "volumen" => "28"
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                          "autores" => array:1 [
                            0 => "R&#46;H&#46; White"
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                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Circulation"
                        "fecha" => "2003"
                        "volumen" => "107"
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Article information

ISSN: 22548874
Original language: English

DOI:10.1016/j.rceng.2017.02.010

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