amino-terminal pro-B-type natriuretic peptide (NT-proBNP) as a marker of prognosis and cardiac dysfunction in cancer

B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NTproBNP) plasma levels are commonly high at the early phase of septic shock and have been suggested to be prognostic markers for this condition. It is uncertain, however, whether this increase reflects sepsis related cardiac dysfunction. In a recent issue of Critical Care, Mokart and coworkers showed the accuracy of NTproBNP in predicting intensive care unit mortality in cancer patients with septic shock, which could help in identifying high risk cancer patients. Results from repeated transthoracic echocardiographs show that NT-proBNP on day 2 after admission was higher in patients presenting with cardiac dysfunction, whereas NT-proBNP on day 1 did not predict cardiac dysfunction. These data suggest that after an initial overexpression of NTproBNP in all septic patients, patients with cardiac dysfunction will present persistent high levels of NT-proBNP. In this issue of Critical Care, Mokart and coworkers [1] report the results of a prospective cohort study evaluating plasma amino-terminal pro-B-type natriuretic peptide (NT-proBNP) as a marker of prognosis and cardiac dysfunction in cancer patients with septic shock. They included 51 patients, mainly with hematological malignancies. By univariate analysis, Logistic Organ Dysfunction score, early NT-proBNP level and recent hematopoietic stem-cell transplantation were associated with intensive care unit (ICU) mortality. In a multivariate analysis, NT-proBNP level on day 2 was the unique parameter associated with mortality. The area under the curve was 0.87. Transthoracic echocardiography was repeated in 45 patients. NT-proBNP level on day 2 but not on day 1 was significantly higher in patients presenting a left or right cardiac dysfunction during the course of the septic shock. BNP and its amino-terminal fragment, NT-proBNP, are mainly produced by myocytes in response to a ventricular volume expansion or pressure overload. Their levels in blood are, therefore, accurate markers of ventricular dysfunction and have been shown to be associated with mortality in various cardiac diseases. In ICU patients, although BNP and NT-proBNP are not correlated with filling pressures [2,3], low levels of BNP have been shown to have a high negative predictive value for the presence of cardiogenic shock [2]. In septic shock patients, several studies have reported very high levels of BNP and NT-proBNP [4-7] and have suggested that NT-proBNP is an independent marker of prognosis in this population [6,7]. It remains unclear, however, whether NT-proBNP is high in these patients because they all present with a certain degree of cardiac dysfunction and whether the NT-proBNP level is associated with mortality by reflecting the intensity of this dysfunction. Firstly, experimental studies have shown that endotoxin and some cytokines are able to upregulate the transcription of the gene encoding BNP [8,9]; therefore, the extent of the inflammatory response could account, at least in part, for the dramatically high levels of NT-proBNP reported during septic shock. Secondly, cardiac dysfunction during sepsis is complex and can be associated with left and right as well as systolic and diastolic dysfunctions [10,11]; therefore, the respective contribution of these dysfunctions to an increase in NT-proBNP is difficult to determine. However, knowledge of the determinants of the secretion of natriuretic peptides during septic shock is necessary prior to considering NT-proBNP as a potential tool to guide therapy of these patients. Like previous reports, Mokart and coworkers show that all patients at the early phase of septic shock exhibit high levels of NT-proBNP. They also confirm the prognostic value of early NT-proBNP measurement and show that this also applies to cancer patients. As for other reports, it is noteworthy that the samples of patients are small and that the odds ratios for the effect of NT-proBNP on mortality are large. Commentary What does high NT-proBNP mean in septic shock patients? A part of the puzzle