N-Terminal ProBNP: Marker of Systolic Dysfunction or Nonspecific Indicator of Cardiac Disease?

Abstract

Accessible online at: www.karger.com/hed The clinical diagnosis of heart failure may represent a considerable challenge, particularly in the obese, in women and in the elderly [1]. Because contemporary heart failure therapy has been shown to significantly reduce mortality and the number of hospital readmissions, an early and correct diagnosis is crucial. The cost and potential side effects associated with heart failure therapy also means that overtreatment should best be avoided. The clinical syndrome of chronic congestive heart failure is often the end stage of progressive left ventricular dysfunction and is commonly preceded by an asymptomatic or oligosymptomatic latent phase. Congestive heart failure is frequently caused by systolic dysfunction of the left ventricle, but a considerable proportion of patients do have preserved systolic function [2]. Echocardiography is routinely performed by cardiologists to establish the diagnosis of impaired left ventricular systolic function, but this method requires expensive equipment and skilled operators and is not always readily available. During the past few years, B-type natriuretic peptide (BNP) and the N-terminal fragment of its prohormone, N-terminal proBNP (NT-proBNP) have emerged as promising markers of ventricular dysfunction, and biochemical tests for rapid measurement of these substances have been developed. A point-of-care test for rapid analysis of BNP was first introduced in the year 2000. Very recently, fully automated analytic systems for the determination of BNP and NT-proBNP on large hospital platforms have also become commercially available. BNP was first identified in porcine brain in 1988 [3], but was subsequently found to be present in ventricular myocardium, which is now known to be the main source of circulating BNP [4]. The main secretory stimulus for BNP (and NT-proBNP) appears to be stretch of cardiomyocytes rather than transmural pressure load [5]; circulating levels of BNP and NT-proBNP are increased in conditions characterized by volume overload and correlate with indices of hemodynamic status and ventricular function [6–8]. Although these peptides share many properties, some differences may have clinical implications. BNP is the biologically active hormone, whereas NTproBNP appears to be biologically inactive. The in vivo half-life of BNP is approximately 20 min, whereas the half-life of NT-proBNP has been estimated to be approximately 60–120 min [9]. Accordingly, BNP levels may change more rapidly than those of NT-proBNP following therapeutic interventions which affect cardiac filling [10]. Conversely, NT-proBNP may more accurately reflect the average, long-term hemodynamic status of the patient. Although both BNP and NT-proBNP have been demonstrated to be stable in full blood at room temperature for at least 24 h, the in vitro stability of NT-proBNP in serum or plasma appears to be superior to that of BNP [11]. BNP is cleared from the circulation via binding to specific