NT-proBNP Testing: An important tool for veterinary practitioners

Cardiac-specific biomarkers play a crucial role in identifying cardiac perturbations. A biomarker can be objectively measured and evaluated as an indicator of normal or pathological biological processes.¹ Some common biomarkers include pulse and blood pressure, basic chemistries, and more complex laboratory tests utilizing blood and tissue samples. Cardiac biomarkers can provide rapid, accurate information regarding myocardial necrosis/cell injury and hemodynamic stress. The most widely studied cardiac biomarkers in veterinary medicine include N-terminal fragment pro-B type natriuretic peptide (NT-proBNP) and cardiac troponin I.

B-type Natriuretic Peptide

B-type natriuretic peptide (BNP) is a hormone produced and secreted by cardiac muscle cells (cardiomyocytes) in response to excessive cellular stretch.¹ BNP helps to regulate homeostasis of intravascular volume and systemic pressure, and counteracts the effects of the reninangiotensin-aldosterone system (RAAS), which becomes upregulated with heart disease. BNP promotes sodium and water loss via the kidneys and vasodilation, both of which help decrease cardiac stretch and work.² Many cardiac diseases cause excessive cardiomyocyte stretch and increased BNP release. The magnitude of circulating BNP level increase has been correlated to the severity of cardiac disease.^3,4

Cardiomyocytes secrete BNP as a precursor prohormone. The prohormone is cleaved into 2 fragments – a bioactive C-terminal fragment (C-BNP) and an inactive NT-proBNP fragment. C-BNP has a short half-life (approximately 90 seconds) which limits measurement ability.¹ NT-proBNP has a longer half-life (approximately 120 minutes) and has enhanced stability during sample handling making it an ideal biomarker.

Cardiac disease evaluation

Evaluation of heart disease severity can be challenging as clinical signs are variable and often nonspecific. Heart murmur diagnosis may not correlate with cardiac disease severity. Clinical signs that can be attributed to respiratory and cardiac diseases often have overlap. Diagnostic tests such as echocardiography, electrocardiography and thoracic radiography may not be available at the time of initial examination and may not be appropriate in unstable respiratory cases. These tests may not be feasible for all owners. Recent studies have also provided evidence supporting the identification of specific preclinical cardiac disease stages that may benefit from pharmacologic intervention.^5,6

Two of the most commonly acquired cardiac diseases in dogs are myxomatous mitral valve disease (MMVD) and dilated cardiomyopathy (DCM).^7,8 MMVD is characterized by slow progressive myxomatous degeneration of the mitral valve apparatus leading to regurgitation (leakage) of the valve.^7,8 MMVD accounts for approximately 75% of heart disease cases seen by North American veterinary practices.⁵ Progressive valvular regurgitation leads to cardiac remodeling (dilation of the left atrium and left ventricle) and increased cardiac work. Dogs with MMVD often have systolic heart murmurs with a point of maximal intensity localized over the left thorax over the mitral valve region.⁷

DCM is a primary myocardial disease characterized by cardiac enlargement and impaired systolic function (contractility) of one or both ventricles.⁸ DCM is theorized to be the final result of various myocardial insults including genetic, nutritional, viral and toxic processes. There are two stages of disease – the occult (asymptomatic) phase and the overt (symptomatic) phase. The most common physical examination findings are a soft systolic heart murmur centered over the mitral valve and/or a gallop heart sound.

A heart murmur may be the sole finding on physical examination. Additional findings, depending on disease severity can include systolic clicks, arrhythmias, pulse quality changes, ascites, cyanosis, tachypnea, and increased pulmonary sounds and/or crackles.^7,8 Clinical signs are variable – many dogs with mild to moderate cardiac disease are often asymptomatic. Clinical signs can include exercise intolerance, appetite decrease/loss, cough, breathing changes, nighttime restlessness/orthopnea and syncope.

NT-proBNP Testing

NT-proBNP levels are measured in serum and testing can be performed by outside laboratories or with in-clinic assays. An assay recently brought to the market by the Bionote veterinary team is the first of its kind for veterinarians providing in-clinic, quantitative NT-proBNP level measurement in minutes. Adding quantitative NT-proBNP test results to exam findings can help identify dogs with advanced cardiac disease that would benefit from further diagnostics⁹ and can help monitor dogs with known heart disease.^2,3 Bionote’s canine NT-proBNP test is available under its Vcheck branded line of tests and analyzers. It is the first and only in-clinic, quantitative NT-proBNP for the detection of heart disease. It should be noted that other BNP testing in the marketplace must be sent to reference labs for confirmation, taking more time and incurring a higher risk of sample degradation affecting accuracy. Although no one specific finding or test result is adequate or appropriate for diagnosing heart disease, when many pieces of information are combined, a stronger cardiac clinical picture develops.

Utilizing NT-proBNP testing in your clinical practice

Dogs presenting with respiratory signs can be diagnostically challenging. NT-proBNP measurement can further assist with diagnosis. A normal or low NT-proBNP concentration is typically associated with respiratory disease and elevated NT-proBNP levels (>2,500pmol/L) are associated with cardiac disease.³

Additionally, results of NT-proBNP testing (>1500pmol/L) in a dog with historical MMVD^2,3 along with thoracic radiographic changes can detect progressive cardiac disease and predict increased risk for CHF development in the following 3 to 6 months.

NT-proBNP assessment can be combined with other tests for screening purposes.^5,6 A recent study found that utilizing NT-proBNP results with other common clinical values could be used in a predictive model to identify dogs with a higher probability of having stage B2 MMVD.^5,9

NT-proBNP testing can be used during wellness visits for dog breeds predisposed to heart conditions. Elevations are not disease-specific and can’t solely be used to establish a diagnosis or make pharmacologic decisions. False positives can be observed in certain breeds (Labrador retrievers and greyhounds) and patients with kidney disease.^{1, 2}

The newest NT-proBNP testing option from Bionote provides an accurate and extremely cost-effective way to assist with cardiac disease diagnosis while patients are still in the clinic. This enables veterinarians to better determine and promptly communicate follow-up recommendations for treatment, with owners. Identifying and encouraging at-risk patients to seek further evaluation results in a greater proportion of patients receiving appropriate care, and is a win for the entire veterinary team.

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References

1. Viera de Lima G and de Silveira Ferreira F. N-terminal-pro brain natriuretic peptides in dogs and cats: A technical and clinical review. Vet World. 10: 1072-1082 2017.
2. Gordon SG: NT-proBNP Testing in the Dog. Circulations conversations with a cardiologist. Cardiaceducationgroup. org. October 2014 www. cardiaceducationgroup.org/wp-content/ uploads/2015/10/CEG_Circulations_ Canine-Biomarkers_FINAL.pdf
3. Fox PR, Oyama MA, Hezzel MJ, et al. Relationship of Plasma N–terminal Pro– brain Natriuretic Peptide Concentrations to Heart Failure Classification and Cause of Respiratory Distress in Dogs Using a 2nd Generation ELISA Assay. J Vet Intern Med. 29: 171-179 2015.
4. Chetboul V, Serres F, Tissier R, et al. Association of plasma N-terminal pro-Btype natriuretic peptide concentration with mitral regurgitation severity and outcome in dogs with asymptomatic degenerative mitral valve disease. J Vet Intern Med. 23: 984-994 2009.
5. Keene BW, Atkins CE, Bonagura JD, et al. ACVIM consensus guideline for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Intern Med. 33: 1127-1140 2019.
6. Summerfield NJ, Boxwood A, O’Grady MR, et al. Efficacy of Pimobendan in the Prevention of Congestive Heart Failure or Sudden Death in Doberman Pinschers with Preclinical Dilated Cardiomyopathy (The PROTECT Study). J Vet Intern Med. 26: 1337-1349 2012.
7. Ljungvall I and Haggstrom J. Adult-Onset of Valvular Heart Disease. Ettinger SJ Feldman EC Cote E. Textbook of Veterinary Internal Medicine. ed 8 2017 Elsevier St. Louis 1250-1269.
8. Stern JA and Meurs KM. Myocardial Disease. Ettinger SJ Feldman EC Cote E. Textbook of Veterinary Internal Medicine. ed 8 2017 Elsevier St. Louis 1269-1277.
9. Wilshaw J, Rosenthal SL, Wess, G, et al. Accuracy of history, physical examination, cardiac biomarkers, and biochemical variables in identifying dogs with stage B2 degenerative mitral valve disease. J Vet Intern Med. 35: 755-770 2021.