Nonheart failure-associated elevation of amino terminal pro-brain natriuretic peptide in the setting of sepsis

Abstract

O ne-half of a century has been spent debating the etiology of depressed myocardial function in septic shock (1). Brain natriuretic peptide (BNP) is a new biomarker for cardiac dysfunction, and most data in the literature associate its increased levels with depressed myocardial function (2-5). However, increased levels of BNP have also been found in critical illnesses associated with shock (eg, sepsis), apparently not related to myocardial dysfunction. In human myocardium, BNP is secreted in response to myocardial stretch. Its release promotes natriuresis and diuresis, and it has a vasodilatory effect on systemic circulation (6). As such, it reduces preload, venous return and filling pressures with a subsequent reduction in cardiac output (7). The measured BNP increases in response to increases in left ventricular (LV) end-diastolic pressure, pulmonary artery wedge pressure, atrial pressure and LV hypertrophy (8). BNP level is also associated with echocardiographic dysfunction and clinical outcomes (9). The degree of cardiac dysfunction determines the magnitude of increase in BNP level (10).The BNP gene contains an encoded protein consisting of 108 peptides, called pro-BNP (11). The cleavage of pro-BNP within the heart results in two components produced in equal amounts: BNP 32 (the active hormone) and N-terminal (NT) pro-BNP (the inactive fragment) (12). The plasma half-life of NT pro-BNP is approximately 2 h in comparison with that of BNP 32 (20 min) (13), which explains the higher level of NT pro-BNP in myocardial dysfunction (14).In addition to the documented relationship between BNP and myocardial dysfunction mentioned above, there are other conditions associated with increased BNP level that include primary pulmonary hypertension, myocarditis, cardiac allograft rejection, arrhythmogenic right ventricle with decreased LV ejection fraction (EF), renal failure, Kawasaki disease, ascitic cirrhosis and endocrine diseases (Cushing's syndrome, primary hyperaldosteronism) (8). Other patient characteristics that may influence the BNP level, independent of disease, are advancing age, probably reflecting LV subclinical abnormalities (15) and female sex, both of which result in increased BNP level (15,16). Two additional studies have confirmed the correlation of NT pro-BNP with age, but not with sex (17,18). In contrast, obesity is associated with decreased levels of BNP, probably as a result of increased clearance through a receptor contained in adipose tissue (19).Parker et al (20) demonstrated that myocardial depression is also present in human septic shock and is associated with ventricular dilation and decreased LVEF (20). We present two cases of septic shock with markedly increased levels of NT pro-BNP with no evidence of myocardial dysfunction based on evaluation using echocardiography and catheterization. Also described are possible explanations of elevated NT pro-BNP in a setting not related to myocardial dysfunction. Thus, there are situations where the predictive value of BNP is not correlated with the magn...

Myocarditis in the Setting of Cancer Therapeutics

“…Natriuretic peptides may be useful in terms of characterizing stress on the ventricle; however, they must be interpreted with caution in the setting of ICI myocarditis as they can be elevated directly through inflammatory pathways even in the setting of normal filling pressures. 26,27 Natriuretic peptides are not specific for myocarditis but may be elevated in patients with significant left ventricular dysfunction and heart failure, and are frequently elevated in ICI-associated myocarditis. 28 In addition, natriuretic peptide elevations may be particularly complex in the setting of ICI mediated myocarditis, but the elevation may be mediated by other mechanisms such as via Interleukin-6.…”

When the heart is burning: Amino-terminal pro-brain natriuretic peptide as an early marker of cardiac involvement in active autoimmune rheumatic disease

“…This relationship seems particularly important in the acute cellular cardiac allograft rejection, where inflammation plays a pivotal role [26]. Finally, another condition in which inflammation has been shown to be related with natriuretic peptide elevation independently of hemodynamics is represented by sepsis, where NT-proBNP holds a prognostic value as well [27,28].…”

B‐type natriuretic peptide monitoring in the Pediatric ICU population

“…There has also been an interest in using plasma BNP levels in patients with myocardial dysfunction related to factors other than congenital or acquired heart disease. Although previous studies in adults have suggested that BNP levels are elevated to the same extent in patients with myocardial dysfunction related to either sepsis or CHF (27,28), there are also anecdotal reports of patients with severe sepsis and elevated plasma BNP levels with normal myocardial function (29–32). The mechanisms responsible for the stimulation of the natriuretic peptide system in sepsis have not been elucidated.…”