A new study finds that plasma B-type natriuretic peptide (BNP) concentrations can discriminate between normal cats and cats with occult cardiomyopathy and are associated with several echocardiographic markers of disease severity.
The use of biomarkers for large-scale disease screening is an active area of research in human and veterinary medicine. Previous studies have demonstrated that elevated BNP in the blood can indicate cardiac dysfunction since it is secreted from cardiac myocytes in response to stretch, pressure overload, and neurohormonal stimuli.
The goal of this study was to evaluate the efficacy of plasma N terminal-probrain natriuretic peptide (NT-proBNP) concentrations at accurately differentiating cats with occult cardiomyopathy from healthy cats. Additionally, the authors attempted to determine whether NT-proBNP concentrations were correlated with heart size, estimates of left ventricular filling pressure, age, body weight, and blood urea nitrogen (BUN), serum creatinine, serum thyroxine, and cardiac troponin I concentrations or whether concentrations differed between different forms of cardiomyopathy.
This prospective trial included four private practices and eight veterinary medical colleges and universities and involved 18 cardiology specialists; 114 healthy cats and 113 cats with occult cardiomyopathy were enrolled in the study. Normal cats had no history of medical problems, normal physical examination findings, and normal echocardiographic examination results. A systolic murmur was not a criterion for exclusion provided that the valvular insufficiency was minimal or the outflow tract obstruction was mild. Cats with asymptomatic occult cardiomyopathy were recruited through cardiology specialty clinics and were evaluated with standard and Doppler echocardiography.
Plasma NT-proBNP concentration was measured by using a commercially available assay for the quantitative determination of feline NT-proBNP. Three feline samples with known NT-proBNP concentrations were used to calculate inter- and intra-assay coefficients of variation. All other blood tests were performed by a commercial laboratory.
Study results and implications
The researchers found that, compared with healthy cats, cats with occult cardiomyopathy had significantly higher concentrations of NT-proBNP. Age, weight, sex, and creatinine and thyroxine concentrations had no influence.
A cutoff value of 46 pmol/L resulted in a sensitivity of 86% and a specificity of 91% to discriminate between normal cats and those with occult cardiomyopathy. The authors suggest that this value would result in a low rate of false negative results.
Cats with hypertrophic obstructive cardiomyopathy had higher NT-proBNP concentrations than did cats with nonobstructive forms of hypertrophic cardiomyopathy, similar to what is seen in people. The authors also noted a positive correlation between NT-proBNP and left atrium/aortic ratio, left ventricular wall thickness at end-diastole, and left ventricular chamber dimension at end-systole as well as a negative correlation to left ventricular fractional shortening. These findings suggest that NT-proBNP may reflect disease progression or other cardiac structural changes, but the authors caution that these relationships require further study.
Interestingly, 43% of normal cats in this study were found to have a systolic murmur but had normal echocardiographic examination results, indicating one potential use for the NT-proBNP test. The authors suggest that since cats with NT-proBNP concentrations > 46 pmol/L were likely to have occult cardiomyopathy, this information may guide efficient use of further diagnostics in this population and perhaps more effective monitoring and risk stratification in the future.
The researchers point out that the utility of any test is influenced by disease prevalence and that, since cases in this study were referred to cardiology specialists because of a high suspicion of cardiac disease, this population was more likely to benefit from NT-proBNP screening. How well this assay performs when used in the general population will require further study.
Additionally, overlapping results between the groups at the low and moderate NT-proBNP concentrations may have a significant impact on whether a patient is correctly categorized as having occult cardiomyopathy and whether other diagnostic testing may be indicated.
Fox PR, Rush JE, Reynolds, CA, et al. Multicenter evaluation of plasma N-terminal probrain natriuretic peptide (NT-pro BNP) as a biochemical screening test for asymptomatic (occult) cardiomyopathy in cats. J Vet Intern Med 2011;25(5):1010–1016.
Link to abstract: http://onlinelibrary.wiley.com/doi/10.1111/j.1939-1676.2011.00776.x/abstract