Figure 1: Schematic of NT-proBNP secretion and release. Note that the biologically active hormone is actually BNP, and NT-proBNP is a byproduct of its formation. Due to NT-proBNP’s greater stability in circulation, the diagnostic assay tests for the NT-proBNP molecule as opposed to BNP itself. This method is valid because NT-proBNP is produced in a 1:1 fashion with BNP.
Cardiac disease, including degenerative mitral valve disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy, is associated with elevated production of BNP and, therefore, elevated formation of NT-proBNP.3-8 NT-proBNP is more stable in circulation than BNP and can be detected using standard ELISA-based technology. NT-proBNP is formed in a 1:1 ratio with BNP and can be used to help detect heart disease and determine etiology of respiratory signs in both dogs and cats.3-11
Diagnostic Indications
The differentiation of congestive heart failure from primary respiratory disease in animals that present with respiratory signs, such as coughing, wheezing, increased respiratory effort, or emergent respiratory distress, can be challenging. NT-proBNP is released in response to myocardial stretch and consequently is typically elevated in animals with congestive heart failure. As a result, markedly elevated NT-proBNP at time of presentation may help alert practitioners to a high likelihood of heart failure (as opposed to primary respiratory disease) as the cause of clinical signs.
Heart Disease in Cats
The most common acquired heart diseases in cats are hypertrophic and restrictive cardiomyopathy. These diseases present a unique diagnostic challenge because many cats with significant disease have no clinical signs for long periods of time. Moreover, physical examination findings (including heart murmurs and gallops), which are suggestive of underlying disease, can be difficult to detect in many animals.
Cats with plasma levels of NT-proBNP < 100 pmol/L are unlikely to be affected by clinically significant heart disease. In patients with mild elevations of plasma NT-proBNP levels (100 –270 pmol/L), further diagnostics, such as echocardiography, are recommended if the clinical suspicion of heart disease is high. Plasma NT-proBNP levels > 270 pmol/L indicate a high likelihood of underlying heart disease; further workup is recommended.
False-positives and false-negatives can occur and results of NT-proBNP assays should be interpreted in conjunction with history, physical examination findings, and other diagnostic tests. Most important, NT-proBNP testing reflects current heart function, and a single normal result does not preclude the possibility of disease development at a future date. Therefore, NT-proBNP testing is not recommended as a screening tool in young cats of breeding age.
Heart Disease in Dogs
Dogs with degenerative mitral valve disease or dilated cardiomyopathy generally have elevated plasma NT-proBNP levels. It is important to note that in older, small-breed dogs with no clinical signs, the diagnosis of mitral valve disease is easily made by auscultation.
The severity of heart disease as assessed by clinical signs and heart size is moderately correlated to the degree of NT-proBNP elevation. Dogs with plasma NT-proBNP levels < 900 pmol/L are very unlikely to be affected by clinically significant heart disease. If a dog has mildly elevated concentrations of plasma NT-proBNP levels (900–1800 pmol/L) and the clinical presentation is suspicious for heart disease, further workup, including thoracic radiographs or echocardiography, is recommended. Plasma NT-proBNP levels > 1800 pmol/L are severely elevated and the likelihood of heart failure is high if clinical signs are present.
False-positives and false-negatives can occur and results of NT-proBNP assays should be interpreted in conjunction with history, physical examination findings, and other diagnostic tests. Current diagnostic recommendations for dogs and cats are summarized in the Table.