Mark A. Oyama, DVM, DACVIM (Cardiology)
Why Test for Heart Disease Using Blood Tests?
The attraction of blood-testing for heart disease lies in its wide availability, minimal invasiveness, low cost, lack of need of special equipment, and rapid results. To a cardiologist, it seems a bit unfair that other organ systems, such as the liver or kidney, can be evaluated by blood-testing but the heart cannot. Why is this? In order to use blood testing, a biomarker of organ performance and health must be established. For the renal system, such a biomarker is the familiar marker, creatinine. Common to all good biomarkers, creatinine is specific to the renal system, is detected in proportion to disease, offers prognostic value, is stable in circulation, and can be used to assess response to treatment. Heretofore, such biomarkers of cardiac function have been elusive. For many years, the only potential candidates were substances such as creatinine kinase-MB or myoglobin; however these substances lacked in many of the characteristics just described. In 2000, the US Food and Drug Administration approved the use of B-type natriuretic peptide (BNP) assay for the diagnosis of congestive heart failure in people. BNP had long been understood as a peptide released by the heart in response to wall stretch and promoted, as its name suggests, natriuresis. Researchers soon realized that BNP, despite being initially discovered in CNS tissue, and called brain-natriuretic peptide, was only elaborated in significant quantities in the heart, and thus, was largely specific to myocardial tissues. BNP is routinely used in people to help differentiate cardiac vs. non-cardiac causes of heart failure, offer prognosis, and recently, to guide therapy and screen high-risk populations for asymptomatic heart disease. As such, BNP is a valuable and practical biomarker for heart disease and function in humans with heart disease. Over the past few years, there has been increasing amounts of interest in bringing a veterinary version of this test to our patients. BNP is produced from a prohormone, proBNP that is released by the heart and rapidly cleaved to BNP and a largely inactive N-terminal proBNP segment (NT-proBNP). In dogs and cats, NT-proBNP has a longer half-life than BNP and thus is more amenable to conventional diagnostic testing methods, such as ELISA. The currently available BNP test in dogs and cats actually tests for this inactive fragment of NT-proBNP. Its circulating concentration is a direct reflection of how much proBNP, and hence BNP, was released by the heart
How Can One Use The NT-proBNP Test?
A NT-proBNP blood test could be useful in a variety of clinical circumstances in both dogs and cats. A few of the indications are presented below. During the course of the discussion and presentation, we will cover how the NT-proBNP test may or may not help clinicians in each of these situations. We will discuss the results of multiple studies that have looked into these indications and formulate guidelines and critical NT-proBNP values that can help you manage dogs and cats with heart disease. The presentation will concentrate on the clinical utility of the test and emerging guidelines for its use, rather than the biology and pathophysiology of BNP.
Cats with Respiratory Distress
Cats that present with respiratory distress are usually afflicted with either congestive heart failure or primary respiratory disease (i.e., asthma). Often, due to the degree of distress, diagnostics such as thoracic radiography and echocardiography are not feasible. Many cats receive the standard "cat cocktail" of diuretics, bronchodilators, and steroids to cover both diseases. While this empiric therapy can be successful, it is obviously less than ideal. The results of several single-site and multi-centered studies now indicate that plasma or serum NT-proBNP can help differentiate cats with heart failure vs. those with primary respiratory disease. Cats with heart failure have much higher BNP values than cats without, as might be expected if BNP is released due to myocardial stress. The cumulative results of these studies suggest that NT-proBNP can be as much as 95% accurate in differentiating heart vs. respiratory disease in cats. The development of an on-site bedside NT-proBNP test has the potential to make point-of-care testing a reality.
Dogs with Respiratory Distress
Similar to the scenario in cats, NT-proBNP appears able to distinguish cause of respiratory distress in dogs with a moderate to high degree of accuracy. We will discuss several clinical studies which support this statement.
Dogs with Heart Disease
Most adult small breed dogs with heart disease have a murmur (mitral valve disease), so the ability of a blood test to detect heart disease in this population seems redundant; however, the loudness of the murmur does not necessarily reflect the severity of disease, leading one to require further diagnostics, such as chest radiographs. NT-proBNP levels in dogs with heart disease correlate with a variety of traditional indices of disease severity, such as heart size, heart rate, and left atrial size on echocardiography. Thus, NT-proBNP may help clinicians prioritize which dogs should receive further work-up and which ones likely have mild and clinically insignificant disease. We will discuss several studies that provide guidelines regarding clinically important NT-proBNP values and how to use them to help make recommendations to clients.
Cats with Asymptomatic Heart Disease
Unlike dogs, many cats with heart disease are entirely asymptomatic and have a normal physical exam. When murmurs or gallop heart sounds are present, they are often soft or transient. Thus, a potential and very intriguing role for NT-proBNP testing involves its ability to detect occult or asymptomatic disease in cats. Preliminary studies suggest that this is indeed the case. A small two-site study involving 40 cats found that NT-proBNP was extremely accurate at detecting a sub-population with underlying heart disease. On the strength of that study, a larger study is currently underway. We will discuss the results of the preliminary study and investigate how NT-proBNP could possibly be used to screen at-risk feline populations for occult disease.
Dogs with Asymptomatic Dilated Cardiomyopathy
For those practitioners with Doberman pinscher, Boxer, or Great Dane patients, the frustration surrounding detection of occult DCM is all too familiar. Currently Holter monitoring, ECG, and echocardiography are used to help detect cases but is expensive and time consuming. A study involving Doberman pinschers and testing for BNP (as opposed to NT-proBNP) indicated that blood testing for DCM could be done (however, the test utility is somewhat affected by a high rate of false positives). A large multicentered study in Doberman pinschers is currently being conducted and we will discuss the pros and cons of trying to use the more recent NT-proBNP test for this indication.
In summary, blood-based testing for heart disease and for specific indications is quite feasible according to the results of many preliminary studies. Definitive proof of this potential awaits larger studies, but the preliminary results are very encouraging. This presentation is designed to introduce and familiarize attendees with this new test, how to use it in your practice today, and the potential uses for tomorrow.
The author and presenter consults for IDEXX, Portland, ME.