Regular Article Combined risk stratification with computerized tomography /echocardiography and biomarkers in patients with normotensive pulmonary embolism ☆ , ☆☆ Savas Ozsu a, ⁎, Kayıhan Karaman b , Ahmet Mentese c , Asiye Ozsu d , S.Caner Karahan c , Ismet Durmus b , Funda Oztuna a , Polat Kosucu d , Yilmaz Bulbul a , Tevfik Ozlu a a Karadeniz Technical University, School of Medicine, Department of Chest, Trabzon,Turkey b Karadeniz Technical University, School of Medicine, Cardiology, Trabzon,Turkey c Karadeniz Technical University, School of Medicine, Biochemistry, Trabzon, Turkey d Karadeniz Technical University, School of Medicine, Radiology Trabzon,Turkey abstract article info Article history: Received 17 June 2010 Received in revised form 23 August 2010 Accepted 24 August 2010 Keywords: Biomarkers Echocardiography Computerized tomography Prognosis Pulmonary embolism Background: Right ventricular dysfunction (RVD) detected by computerized tomography (CT)/echocardiog- raphy or elevated biomarkers is associated with a poor prognosis for pulmonary embolism (PE). However, these prognostic factors have not previously been concomitantly elucidated in the same patient group. Methods: This prospective study included 108 consecutive patients with normotensive PE confirmed by CT pulmonary angiography (CTPA). On admission, patient serum NT-proBNP and troponin T (Tn-T) levels were measured , and echocardiography was performed within 24 hours after diagnosis of PE. Receiver operating characteristic (ROC) analysis was performed to determine the optimal echocardiographic end-diastolic diameters of the right ventricle, the ratio of the right ventricle to left ventricle (RV/LV ratio) on CTPA, and NT- proBNP and Tn-T cut-off levels with regard to prognosis. Results: All-cause 30-day mortality was 13% and PE-related mortality was 5.6%. RVD was defined as a right/left ventricular dimension ratio ≥ 1.1 on CTPA and RV N 30 mm on echocardiography by ROC analysis. A cut-off level of NT-proBNP ≤ 90 pmol/ml had a high positive predictive value of 98% for survival, whereas NT-proBNP N 300 and Tn-T ≥ 0.027 had a negative predictive value, for all -cause deaths, of 95% and 96%, respectively. PE mortality in patients with NT-proBNP N 300 and Tn-T ≥ 0.027 reached 64%. In univariable analysis, the combination of Tn-T ≥ 0.027 ng/ml with a echocardiographic RVD were the most significant predictors of overall mortality and PE-related death [HR: 14 (95% CI: 4.6–42,) and HR: 37.6 (95% CI: 4.4–324)], respectively. In multivariable Cox's regression analysis, NT-proBNP N 300 and Tn-T ≥ 0.027 HR: 26.5 (95% CI: 4.1-169.9, p b 0.001) were the best combination to predict all-cause of mortality. Conclusions: The combination of NT-proBNP and Tn-T clearly appears to be a better risk stratification predictor than biomarkers plus RVD on CT/ echocardiography in patients with normotensive PE. © 2010 Elsevier Ltd. All rights reserved. Introduction The short-term mortality of pulmonary embolism (PE) depends on hemodynamic status of the patients, which is an independent risk factor for PE. It has been documented that the presence of hypotension in PE increases mortality 3 to 7-fold and all cause deaths from 21 to 58% [1–4]. The in-hospital mortality of patients with normal blood pressure PE has been reported to vary from 3 to 15%. Right ventricular dysfunction (RVD) confirmed by echocardiography or computerized tomography (CT) and elevated cardiac enzymes have been used to determine mortality in this PE patients [5]. In particular, biomarkers, including natriuretic peptides and cardiac troponins, have recently been the focus of interest for prognostic risk stratification in patients with normotensive PE [5–7]. In addition, a meta-analysis showed that elevated natriuretic peptide levels were associated with a 5-fold increased risk of all-cause deaths, which increased up to 8.6 fold when combined with natriuretic peptide and elevated troponin level [6]. Also, a number of studies have demonstrated a relationship between elevated serum levels of biomarkers and RVD [8–11]. Moreover, the combination of elevated biomarkers and echocardiographic RVD appears to be a particularly good predictor of mortality. Binder et al. showed that adverse Thrombosis Research 126 (2010) 486–492 Abbreviations: AUC, area under the curve; CI, confidence interval; CTPA, computerized tomography pulmonary angiography; LMWH, low-molecular- weight heparin; NPV, negative predictive value; NT-proBNP, N-terminal-proBNP; HR, hazard ratio; PE, pulmonary embolism; PPV, positive predictive value; Pts, patients; ROC, receiver operating characteristic; RV/LV, right and left ventricular ratio; RVD, right ventricular dysfunction; Troponin-T, Tn-T; UFH, unfractionated heparin. ☆ This study was conducted at Farabi Hospital, Trabzon,Turkey. ☆☆In this study we dont have any financial support. ⁎ Corresponding author. Department of Chest Diseases, Karadeniz Technical University, School of Medicine, 61080,Trabzon, Turkey. Tel.: + 90 462 377 54 07; fax: +90 462 325 70 31. E-mail address: savasozsu@gmail.com (S. Ozsu). 0049-3848/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2010.08.021 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres