01866-A: Enhancing Treatment of Mitral Valve Disease through the Identification of Biological Markers of Disease

Grant Status: Closed

Grant Amount: $12,960
Dr. Ashley B. Saunders, DVM, Texas A&M AgriLife Research
February 1, 2013 - January 31, 2014
Sponsor(s): American Cavalier King Charles Spaniel Club Charitable Trust
Breed(s): Cavalier King Charles Spaniel
Research Program Area: Cardiology

Project Summary

Heart disease, specifically chronic valvular disease (CVD), is a common disease in aging dogs. All dogs can develop this disease, but small breed dogs and especially the Cavalier King Charles Spaniel have a higher risk. Typically, all Cavaliers over the age of 10 years of age are affected. The disease is easy to diagnose, because affected dogs have heart murmurs. However, it can be difficult to determine the risk of heart failure and death in affected dogs. Cardiac biomarkers, troponin and B-type natriuretic peptide, are released from the heart and can be measured in the blood to provide information about the health of a dog's heart. Specifically they can help determine if heart disease is present or progressing. In human patients, the daily and weekly variability of biomarkers have been studied and have been shown to influence the interpretation of these tests. These biomarkers are currently included in many heart disease studies in the dog, however very little is known about their biologic variability. The main objective of this study is to assess biologic variability of these tests in normal dogs and in dogs with various stages of CVD. The data collected in this study has helped us better understand the degree of biologic variability of cardiac biomarkers in dogs. We have learned that there is a clinically relevant amount of biologic variability that occurs in dogs. This will be important both in the clinical assessment of dogs with CVD, as well as in future studies which incorporate cardiac biomarker measurement. Even healthy dogs have a clinically relevant amount of biologic variability that must be considered when studying these dogs. In fact, there are important differences in how much these cardiac biomarkers change in healthy dogs compared to dogs with CVD. For instance, it appears that healthy dogs have a higher inherent variability in one common cardiac biomarker called NTproBNP compared to dogs with CVD. This means that healthy dogs can have a wider range of NTproBNP values than dogs with CVD. Knowing how much these values can change in a healthy dog will be of paramount importance as future studies emphasize these biomarkers. Knowing the biologic variability of these biomarkers will help improve patient evaluation and assessment. For instance, we know how much these biomarker values can change within a given severity level of CVD. This is really important to understand, because these biomarkers are often measured at a dog's annual check-up. If the dog's biomarker value is higher than it should be (i.e. it has increased more than is typical for this patient's previously known disease severity level), then we would worry that the dog's heart disease has gotten worse. This would then prompt further tests, which may help in early diagnosis of disease worsening. Ultimately, using this information may help veterinarians institute helpful medications earlier and therefore help prolong our pet's lives. From this study, we can see that each stage of CVD has differences in how much cardiac biomarkers change. Specifically, dogs with CVD that have heart enlargement but have not had heart failure have the greatest amount of variability in the NTproBNP measured. This means that these dogs as a group have a very wide range of NTproBNP values compared to other groups which have a more narrow range of NTproBNP values. Some of these dogs progress very rapidly towards heart failure, whereas some never progress to heart failure. The information collected in this study suggests that more studies on this particular severity level of CVD may be beneficial. For instance, maybe the levels of NTproBNP and how much they change in any given dog within this severity level of CVD may help predict whether or not they are progressing toward heart failure. This study has helped elucidate the biologic variability of cardiac biomarkers in dogs, and the potential applications of this information in veterinar

Publication(s)

Winter, R. L., Saunders, A. B., Gordon, S. G., Miller, M. W., Fosgate, G. T., Suchodolski, J. S., … Winter, C. R. L. (n.d.). Biologic variability of cardiac troponin I in healthy dogs and dogs with different stages of myxomatous mitral valve disease using standard and high-sensitivity immunoassays. Veterinary Clinical Pathology, n/a-n/a. http://doi.org/10.1111/vcp.12495

Winter, R. L., Saunders, A. B., Gordon, S. G., Buch, J. S., & Miller, M. W. (2017). Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease. Journal of Veterinary Cardiology, 19(2), 124–131. http://doi.org/https://doi.org/10.1016/j.jvc.2016.11.001

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