This assay is indicated as an aid in the diagnosis of individuals suspected of having congestive heart failure and detection of mild forms of cardiac dysfunction. The test also aids in the assessment of heart failure severity in patients diagnosed with congestive heart failure. This assay is further indicated for the risk stratification of patients with acute coronary syndrome and congestive heart failure, and it can also be used for monitoring the treatment in patients with left ventricular dysfunction.
Left ventricular dysfunction can occur as a part of coronary heart disease, arterial hypertension, valvular disease, and primary myocardial disease. If the left ventricular dysfunction remains untreated and is progressive, the potential for mortality is high, e.g. due to sudden cardiac death.
Chronic cardiac insufficiency is a clinical syndrome caused by impairment of the cardiac pumping function. Based on the symptoms, the severity of cardiac insufficiency is classified in stages (New York Heart Association classification [NYHA] I‐IV). When patients are grouped according to their NYHA classification NT‐proBNP levels increase with increasing class numbers and reflect the severity of cardiac impairment. The high sensitivity of NT‐proBNP allows also the detection of mild forms of cardiac dysfunction in asymptomatic patients with structural heart disease. Clinical information and imaging procedures are used to diagnose left ventricular dysfunction.
The significance of natriuretic peptides in the control of cardiovascular system function has been demonstrated. Studies reveal that natriuretic peptides can be used for diagnostic clinical problems associated with left ventricular dysfunction. The following natriuretic peptides have been described: atrial natriuretic peptide (ANP), B‐type natriuretic peptide (BNP), and C‐type natriuretic peptide (CNP).
ANP and BNP, as antagonists of the renin‐angiotensin‐aldosterone system, influence by means of their natriuretic and diuretic properties, the electrolyte and fluid balance in an organism. In subjects with left ventricular dysfunction, serum and plasma concentrations of BNP increase, as does the concentration of the putatively inactive amino‐terminal fragment, NT‐proBNP.
ProBNP, comprising 108 amino acids, is secreted mainly by the ventricle and, in this process, is cleaved into physiologically active BNP (77‐108) and the N‐terminal fragment NT‐proBNP (1‐76).
Studies indicate that NT‐proBNP can be used in diagnostic and prognostic applications. The concentration of NT‐proBNP in serum or plasma correlates with the prognosis of the left ventricular dysfunction. Fisher, et al. found that congestive heart failure patients with NT‐proBNP values above median had a one year mortality rate of 53 % compared to 11 % in patients below median. In the GUSTO IV study which involved more than 6800 patients it was shown that NT‐proBNP was the strongest independent predictor of one year mortality in patients with acute coronary syndrome.
The test is also useful in assigning symptoms to cardiac or non‐cardiac causes, and helps to identify subjects with left ventricular dysfunction. The European Society of Cardiology Task Force for the Diagnosis and Treatment of Chronic Heart Failure recommend in their guidelines that natriuretic peptides including NT‐proBNP “may be most useful clinically as a rule out test due to consistent and very high negative predictive values”. When used with the recommended cutoff values, the proBNP assay yields negative predictive values ranging from 97 % to 100 % depending on age and gender. Changes in NT‐proBNP concentration can be used to evaluate the success of treatment in patients with left ventricular dysfunction. In addition NT‐proBNP is suitable for use in assessing vascular remodelling, and therefore contributes to the establishment of individualized rehabilitation procedures.
NT‐proBNP also represents cardiac function and indicates increased risk in patients scheduled for potentially cardiotoxic drugs or interventions causing fluid retention or volume overload (e.g. COX‐2 inhibitors, nonsteroidal anti‐inflammatory drugs).