Background: Controversy exists about the indication of thrombolytic therapy in the subgroup of hemodynamically stable patients with acute pulmonary embolism (PE) and right ventricular dysfunction. Brain natriuretic peptide (BNP) is excreted from the cardiac ventricles in response to cardiomyocyte stretch and can be measured with an easy-to-perform blood test. Objective: The objective of this study was to determine the predictive value of elevated BNP levels for early recurrent venous thromboembolism with or without fatal outcome in hemodynamically stable patients with acute PE. In addition, we assessed the potential clinical consequences of initiating thrombolytic therapy based on the BNP levels alone. Methods: Anested case - control study was performed within the framework of a large randomized-controlled trial totalling 2213 hemodynamically stable patients with confirmed acute, symptomatic PE. Ninety patients experienced a fatal or non-fatal recurrent venous thromboembolism during the first 3 months of follow-up (cases); Two hundred and ninety-seven patients with uneventful follow-up served as controls. Blood for BNP levels was obtained at referral and assayed in a central laboratory. Results: Cases had significantly higher mean baseline BNP levels (P = 0.0002). The odds ratio (OR) for every logarithmic (log) unit increase in BNP concentration was 2.4 (95% CI: 1.5 - 3.7). A BNP cut-off level of 1.25 pmol L-1 [the optimal point on the receiver-operating characteristic (ROC) curve] was associated with a sensitivity and specificity of 60% and 62%, respectively. In theory, for every patient correctly receiving thrombolytic therapy at this cut-off, 16 patients will receive this therapy unnecessarily. Conclusions: Brain natriuretic peptide level at presentation is significantly associated with early (fatal) recurrent venous thromboembolism in hemodynamically stable patients with acute PE. However, this relationship appears clinically insufficient to guide the initiation of thrombolytic therapy.

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Journal of Thrombosis and Haemostasis
Department of Internal Medicine

Söhne, M, ten Wolde, M, Boomsma, F, Reitsma, J.B, Douketis, J.D, & Büller, H.R. (2006). Brain natriuretic peptide in hemodynamically stable acute pulmonary embolism. Journal of Thrombosis and Haemostasis, 4(3), 552–556. doi:10.1111/j.1538-7836.2005.01752.x