An estimated 92 million United States (US) adults have at least 1 type of cardiovascular disease (CVD) with estimates that over 40% of the US adult population is projected to have some form of CVD by 2030.5 HF is a multifactorial systemic disease which affects over 26 million people worldwide and is increasing in prevalence.4 Due to its high morbidity and mortality, the correct diagnosis of HF and cardiac dysfunction is paramount to determine appropriate treatment regimens.
Atrial natriuretic peptide (ANP), BNP and C-type natriuretic peptide (CNP) constitute the human natriuretic peptide family. BNP was originally isolated in pig brain tissue but was also found in the cardiac ventricles and to a lesser extent in the atria. Prior to its activation BNP and NT-proBNP are stored as a 108 amino acid polypeptide precursor proBNP in the ventricles. In response to volume expansion/overload and myocyte stretch, proBNP is cleaved to produce the biologically active 32 amino acid BNP and the 76 amino acid peptide NT-proBNP which are released into the vascular system where they can be detected.1,2
The strongest indication for BNP measurement is distinguishing between cardiogenic and non-cardiogenic causes of dyspnea in an emergent setting. An elevated BNP level may indicate the need for further cardiac workup to determine the etiology of the patient’s symptoms.10
A systematic review and meta-analysis of 19 studies involving 22 patient populations with a total of 9093 patients by Battaglia, et al. in 200611 concluded that the use of BNP tests to rule out HF in different populations ranging from asymptomatic patients in a community setting to patients presenting with acute dyspnea to the emergency department found that negative results accurately rule out the diagnosis of HF especially if patients are at a relatively low risk of HF. B-type natriuretic peptide tests have the potential to guide clinical decisions, particularly in patients at lower risk in primary care and emergency departments. Applied early in the diagnostic process in patients with suspected cardiac failure, negative BNP test findings can help rule out HF and thus, avoid unnecessary referral to echocardiography. If the test result is positive, confirmation by echocardiography will generally be required. Early diagnosis of left ventricular dysfunction or HF can improve the prognosis of patients with left ventricular dysfunction without overt HF and patients with symptomatic HF.
According to the guidelines of the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) and the European Society of Cardiology, BNP and NT-proBNP are considered the most valuable and reliable biomarkers for diagnosing HF and cardiac dysfunction.6,7
Tsutsui, et al.13 in the Japanese Circulation Society/Japanese Heart Failure Society 2021 Guidelines state: ”In the diagnosis of heart failure patients should be examined first for symptoms, medical history, family history, physical findings, electrocardiogram, and chest radiographic findings. Next, the concentration of BNP or NT-BNP in the blood should be determined.”
A review article and joint scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society in 2023 the following strong evidence consensus statements are noted: 1) In patients presenting with dyspnea, measurement of BNP or NT-proBNP is useful to support a diagnosis or exclusion of HF; 2) In patients with chronic HF, measurements of BNP or NT-proBNP levels are recommended for risk stratification; 3) In patients hospitalized for HF, measurement of BNP or NT-proBNP levels at admission is recommended to establish prognosis.14
Krauser D et al. 2006 conducted a study on 599 dyspneic patients in the Emergency Department setting to determine if race or gender could influence the usefulness of NT-ProBNP levels. “In subjects with HF, there was no difference in median NT-proBNP concentrations between African American and non–African American (6196 versus 3597 pg/mL, P = 0.37). In subjects without HF, unadjusted NT-proBNP levels were lower in African American subjects than in non–African American subjects (68 versus 148 pg/mL, P < 0.03); however, when adjusted for factors known to influence NT-proBNP concentrations (age, prior HF, creatinine clearance, atrial fibrillation, and body mass index), race no longer significantly affected NT-proBNP concentrations. There was no statistical difference in median NT-proBNP concentrations between male and female subjects with (4686 versus 3622 pg/mL, P = 0.53) or without HF (116 pg/mL versus 150 pg/mL, P = 0.62). Thus, NT-proBNP is useful for the diagnosis of exclusion of acute HF in dyspneic subjects, irrespective of race or gender”.15
BNP measurements must be analyzed in conjunction with standard diagnostic tests, medical history, and clinical findings. Clinicians should be aware that certain conditions, such as ischemia, infarction, renal dysfunction, age, atrial fibrillation, inflammation, myocarditis, hyperthyroidism, use of sacubitril/valsartan, and macro-proBNPemia overestimate BNP value, whereas the presence of obesity in the setting immediately after acute coronary syndrome onset, and pericardial effusions underestimate BNP value.12
