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Changes in PESI scores predict mortality in intermediate-risk patients with acute pulmonary embolism

Although the Pulmonary Embolism Severity Index (PESI) accurately identifies 35% of patients with acute pulmonary embolism (PE) as being low risk, some patients deemed high risk by the PESI on admission might be treated safely in the outpatient environment. This retrospective cohort study included a total of 304 consecutive patients with acute PE, classified at the time of hospital admission into PESI class III. The PESI was recalculated 48 h after admission (PESI48) and each patient reclassified into the corresponding risk category. The primary outcome of the study was all-cause mortality between day 2 and day 30 after PE diagnosis. 26 (8.5%) patients (95% CI 5.4–11.7%) died between day 2 and day 30 after PE diagnosis. Investigators reclassified 83 (27.3%) patients (95% CI 22.3–32.3%) as low risk (classes I and II) at 48 h. 30-day mortality in these patients was 1.2% (95% CI 0–3.5%) as opposed to 11.3% (95% CI 7.1–15.5%) in those who remained high risk. The net improvement in reclassification was estimated at 54% (p<0.001). In a cohort of intermediate-risk patients with acute PE, calculation of the PESI48 allows identification of those patients at very low risk of dying during the first month of follow-up.

The effects of cause of death classification on prognostic assessment of patients with pulmonary embolism

Summary.  Background: Although previous studies have provided evidence that the majority of deaths following an acute pulmonary embolism (PE) directly relate to the PE, more recent registries and cohort studies suggest otherwise. Methods: We assessed the cause of death during the first 30 days after the diagnosis of acute symptomatic PE in a consecutive series of patients. We also assessed the prognostic characteristics of the simplified Pulmonary Embolism Severity Index (sPESI) and cardiac troponin I (cTnI) obtained at the time of PE diagnosis. Results: During the first 30 days after diagnosis, 127 of the 1291 patients died (9.8%; 95% confidence interval [CI], 8.2–11.5). Sixty patients (4.6%; 95% CI, 3.5–5.8) died from definite or possible PE, and 67 (5.2%; 95% CI, 4.0–6.4) died from other causes (cancer 25, infection 18, hemorrhage 7, heart failure 7, chronic obstructive pulmonary disease 5, renal failure 1, seizures 1, unknown 3). The sPESI predicted all‐cause (odds ratio [OR], 5.97; 95% CI, 1.74–20.54; P < 0.01) and PE‐associated mortality (OR, 8.79; 95% CI, 1.12–68.79; P = 0.04). cTnI only predicted PE‐associated mortality (adjusted OR, 2.39; 95% CI, 1.25–4.57; P < 0.01). For all‐cause mortality, the sPESI low‐risk strata had a negative predictive value of 98.8% (95% CI, 97.4–100) in comparison with 91.3% (95% CI, 88.9–93.6) for the cTnI. Conclusions: Within the first 30 days after the diagnosis of acute symptomatic PE, death due to PE and death due to other causes occur in a similar proportion of patients. As cTnI only predicted PE‐associated mortality, low‐risk sPESI had a higher negative predictive value for all‐cause mortality compared with cTnI.

Validación de 2 escalas clínicas pronósticas en pacientes con tromboembolia pulmonar aguda sintomática

OBJECTIVE The aim of this study was to compare the predictive value of two clinical prognostic models, the Spanish score and the simplified Pulmonary Embolism Severity Index (sPESI), in an independent cohort of patients diagnosed of acute symptomatic pulmonary embolism (PE). METHODS We performed a retrospective analysis of a cohort composed of 1447patients with acute symptomatic PE. The Spanish score and the sPESI were calculated for each patient according to different clinical variables. We assessed the predictive accuracy of these scores for 30-day mortality, and a composite of non fatal recurrent venous thromboembolism and non fatal major bleeding, using Cstatistic, which was obtained by means of logistic regression and ROC curves. RESULTS Overall, 138 patients died (9.5%) during the first month of follow-up. Both scores showed an excellent predictive value for 30-day all-cause mortality (Cstatistic, 0.72 and 0.74), but the performance was poor for the secondary endpoint (Cstatistic, 0.60 and 0.59). The sPESI classified fewer patients as low risk (32% versus 62%; P<.001). Low-risk patients based on the sPESI had a lower 30-day mortality than those based on the Spanish score (1.1% versus 4.2%), while the 30-day rate of non fatal recurrent VTE or major bleeding was similar (2.2% versus 2.3%). CONCLUSIONS Both scores provide excellent information to stratify the risk of mortality in patients treated of PE. The usefulness of these models for nonfatal adverse events is questionable. The sPESI identified low-risk patients with PE better than the Spanish score.

Assessment of right ventricular function in acute pulmonary embolism

Background The optimal approach to assess right ventricular (RV) function in patients with acute symptomatic pulmonary embolism (PE) lacks clarity. Methods This study aimed to evaluate the optimal approach to assess RV function in normotensive patients with acute symptomatic PE. Outcomes assessed through 30‐days after the diagnosis of PE included all‐cause mortality and complicated course. Results Eight hundred forty‐eight patients were enrolled. Multidetector computed tomography (MDCT) and transthoracic echocardiography agreed on the presence or absence of RV overload in 449 (53%) patients. The combination of the simplified Pulmonary Embolism Severity Index (sPESI) and MDCT showed a negative predictive value for 30‐day all‐cause mortality of 100%. Of the 43% that had an sPESI of >0 points and MDCT RV enlargement, 41 (11.3%) experienced a complicated course that included 24 (6.6%) deaths. One hundred twenty‐nine patients (15%) had an sPESI of >0 points, MDCT, and echocardiographic RV overload. Of these, 21 (16.3%) experienced a complicated course within the first 30 days, and 10 (7.7%) of them died. Conclusions Incorporation of echocardiographic RV overload to the sPESI and MDCT did not improve identification of low‐risk PE patients, whereas it improved identification of those at intermediate‐high risk for short‐term complications.

Prognostic Significance of Right Heart Thrombi in Patients With Acute Symptomatic Pulmonary Embolism: Systematic Review and Meta-analysis

Background: For patients diagnosed with acute pulmonary embolism (PE), the prognostic significance of concomitant right heart thrombi (RHT) lacks clarity. Methods: We performed a meta‐analysis of studies that enrolled patients with acute PE to assess the prognostic value of echocardiography‐detectable RHT for the primary outcome of short‐term all‐cause mortality and the secondary outcome of short‐term PE‐related mortality. Unrestricted searches were conducted of PubMed and Embase from 1980 through January 31, 2016, and used the terms “right heart thrombi,” “pulmonary embolism,” and “prognos.*” A random effects model was used to pool study results; Begg rank correlation method was used to evaluate for publication bias; and I2 testing was used to assess for heterogeneity. Results: Six of 79 potentially relevant studies met the inclusion criteria (15,220 patients). Overall, 99 of 593 patients with echocardiography‐detectable RHT died (16.7% [95% CI, 13.8–19.9]) compared with 639 of 14,627 without RHT (4.4% [95% CI, 4.0–4.7]). RHT had a significant association with short‐term all‐cause mortality in all patients (OR, 3.0 [95% CI, 2.2 to 4.1]; I2 = 20%) and with PE‐related death (three cohorts, 12,955 patients; OR: 4.8 [95% CI, 2.0–11.3; I2 = 76%). Results were consistent for the prospective (two cohorts, 514 patients; OR, 4.8 [95% CI, 1.7–13.6]; I2 = 56%) and the retrospective (four cohorts, 14,706 patients; OR, 2.8 [95% CI, 2.1 to 3.8]; I2 = 0%) studies. Conclusions: In patients diagnosed with acute PE, concomitant RHT were significantly associated with an increased risk of death within 30 days of PE diagnosis. Trial Registry: PROSPERO registry; No.: CRD42016033960; URL: https://www.crd.york.ac.uk/prospero/

Early discharge and outpatient treatment of patients admitted for acute pulmonary embolism

From the authors: We would like to thank S.N.C. Barra and co-workers for their thoughtful response to our article [1]. We agree with the authors that prognostic assessment of patients with acute pulmonary embolism is of pivotal importance and, thus, is an area of active investigation for our group. We would like to comment on just a few of the points raised by the authors. First, the authors comment that the Low-Risk Pulmonary Embolism Decision score is the only model derived completely from haemodynamically stable patients, which they define as those without any evidence of myocardial necrosis or echocardiographic right …REFERENCES 1 Moores L, Zamarro C, Gómez V, et al. Changes in PESI score predict mortality in intermediate-risk patients with acute pulmonary embolism. Eur Respir J 2013; 41: 354–359. 2 Aujesky D, Smith KJ, Cornuz J, et al. Cost-effectiveness of lowmolecular-weight heparin for treatment of pulmonary embolism. Chest 2005; 128: 1601–1610. 3 Erkens PM, Gandara E, Wells PS, et al. Does the Pulmonary Embolism Severity Index accurately identify low risk patients eligible for outpatient treatment? Thromb Res 2012; 129: 710–714. 4 Jiménez D, Yusen RD, Otero R, et al. Prognostic models for selecting patients with acute pulmonary embolism for initial outpatient therapy. Chest 2007; 132: 24–30. 5 Moores L, Aujesky D, Jiménez D, et al. Pulmonary Embolism Severity Index and troponin testing for the selection of low-risk patients with acute symptomatic pulmonary embolism. J Thromb Haemost 2010; 8: 517–522. 6 Barra S, Paiva L, Providência R, et al. LR-PED rule: Low Risk Pulmonary Embolism Decision Rule – a new decision score for low risk pulmonary embolism. Thromb Res 2012; 130: 327–333. 7 Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27: 157–172.

Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study

BACKGROUND The inflammatory response associated with acute pulmonary embolism (PE) contributes to the development of right ventricular (RV) dysfunction. Nonsteroidal anti-inflammatory drugs (NSAIDs) may facilitate the reversal of PE-associated RV dysfunction. METHODS We randomly assigned normotensive patients who had acute PE associated with echocardiographic RV dysfunction and normal systemic blood pressure to receive intravenous (IV) diclofenac (two doses of 75mg in the first 24h after diagnosis) or IV placebo. All patients received standard anticoagulation with subcutaneous low-molecular-weight heparin (LMWH) and an oral vitamin K antagonist. RV dysfunction was defined by the presence of, at least, two of the following criteria: i) RV diastolic diameter>30mm in the parasternal window; ii) RV diameter>left ventricle diameter in the apical or subcostal space; iii) RV free wall hypokinesis; and iv) estimated pulmonary artery systolic pressure>30mmHg. Persistence of RV dysfunction at 48h and 7days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7days after randomization. RESULTS Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48h in 59% (95% confidence interval [CI], 33-82%) of the diclofenac group and in 76% (95% CI, 50-93%) of the placebo group (difference in risk [diclofenac minus standard anticoagulation], -17 percentage points; 95% CI, -47 to 17). Similar proportions (35%) of patients in the diclofenac and placebo groups had persistent RV dysfunction at 7days. Major bleeding occurred in none of patients in the diclofenac group and in 5.9% (95% CI, 0.2-29%) of patient in the placebo group. CONCLUSIONS Due to slow recruitment, our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in normotensive patients with acute PE. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342.

Assessment of coexisting deep vein thrombosis for risk stratification of acute pulmonary embolism

BACKGROUND In patients with acute pulmonary embolism (PE), studies have shown an association between coexisting deep vein thrombosis (DVT) and short-term prognosis. It is not known whether complete compression ultrasound testing (CCUS) improves the risk stratification of their disease beyond the recommended prognostic models. METHODS We included patients with normotensive acute symptomatic PE and prognosticated them with the European Society of Cardiology (ESC) risk model for PE. Subsequently, we determined the prognostic significance of coexisting DVT in patients with various ESC risk categories. The primary endpoint was a complicated course after the diagnosis of PE, defined as death from any cause, haemodynamic collapse, or adjudicated recurrent PE. RESULTS According to the ESC model, 37% of patients were low-risk, 56% were intermediate-low risk, and 6.7% were intermediate-high risk. CCUS demonstrated coexisting DVT in 375 (44%) patients. Among the 313 patients with low-risk PE, coexisting DVT (46%) did not show a significant increased risk of complicated course (2.8%; 95% confidence interval [CI], 0.8%-7.0%), compared with those without DVT (0.6%; 95% CI, 0%-3.2%), (P = 0.18). Of the 478 patients with intermediate-low risk PE, a complicated course was 14% and 6.8% for those with and without DVT, respectively (P = 0.01). Of the 57 patients that had intermediate-high risk PE, a complicated course occurred in 17% and 18% for those with and without DVT, respectively (P = 1.0). CONCLUSIONS In normotensive patients with PE, testing for coexisting DVT might improve risk stratification of patients at intermediate-low risk for short-term complications.

Risk stratification of acute pulmonary embolism based on clinical parameters, H-FABP and multidetector CT

Abstract Introduction Risk stratification of normotensive patients with acute pulmonary embolism (PE) includes the assessment of right ventricular dysfunction (RVD), biomarker levels, and a clinical score as suggested by the 2014 guidelines of the European Society of Cardiology (ESC). We performed an external validation of the prognostic performance of Heart-type Fatty Acid Binding Protein (H-FABP) and incorporated it into the new ESC algorithm. Material and methods H-FABP was measured by fully-automated immunoturbidimetry in 716 patients from the PROTECT study (PROgnosTic valuE of CT scan in haemodynamically stable patients with acute symptomatic PE). Results H-FABP ranged from 0.7 to 123.6 ng/ml (median 4.13; IQR, 2.53–6.61) and was above the cut-off of 6 ng/ml in 209 patients (29.2%). A complicated course within 30 days (death, catecholamine administration, mechanical ventilation, resuscitation) occurred in 1.1% ( n  = 3) of the 271 low risk patients with a simplified Pulmonary Embolism Severity Index (sPESI) of 0 and was particular low (0.4%), if H-FABP levels were normal. In the case of elevated H-FABP, 4.3% of patients suffered complications despite sPESI of 0. The risk for an adverse 30-day outcome increased for patients of the intermediate-low and intermediate-high risk group and was highest for the combination of sPESI ≥1 with RVD on MDCT and elevated H-FABP (odds ratio 12.3, 95% confidence interval, 3.49–43.32; P Conclusions H-FABP is suitable for risk stratification of normotensive PE patients if integrated in the new ESC algorithm and may help to identify patients with higher risk for adverse clinical events.

Management appropriateness and outcomes of patients with acute pulmonary embolism

The impact of adherence to published guidelines on the outcomes of patients with acute pulmonary embolism (PE) has not been well defined by previous studies. In this prospective cohort study of patients admitted to a respiratory department (n=2096), we evaluated whether patients with PE had better outcomes if they were acutely managed according to international guidelines. Outcomes consisted of all-cause mortality, PE-related mortality, recurrent venous thromboembolism (VTE) and major bleeding events during the first month of follow-up after diagnosis. Overall, 408 patients (19% (95% CI 18–21%)) did not receive guideline-adherent PE management. Patients receiving non-adherent management were significantly more likely to experience all-cause mortality (adjusted odds ratio (OR) 2.39 (95% CI 1.57–3.61) or PE-related mortality (adjusted OR 5.02 (95% CI 2.42–10.42); p<0.001) during follow-up. Non-adherent management was also a significant independent predictor of recurrent VTE (OR 2.19 (95% CI 1.11–4.32); p=0.03) and major bleeding (OR 2.65 (95% CI 1.66–4.24); p<0.001). An external validation cohort of 34 380 patients with PE from the RIETE registry confirmed these findings. PE management that does not adhere to guidelines for indications related to anticoagulation, thrombolytics and inferior vena cava filters is associated with worse patient outcomes. Management that does not adhere to guidelines is associated with worse outcomes in patients with acute PE http://ow.ly/vxvu30jkKuM