01365-A: Multifaceted investigation into the characteristics of degenerative mitral valve disease in Norfolk Terriers: biomarkers, pedigree analysis, and DNA banking - PART 1
Grant Status: Closed
Grant Amount: $12,960
Dr. Mark A. Oyama, DVM, University of Pennsylvania
December 1, 2009 - November 30, 2010
Sponsor(s): Friends of Norfolk Terrier, Norfolk Terrier Club
Breed(s): Norfolk Terrier
Project Summary Mitral valve disease (MVD) is a very common disease of adult small breed dogs. MVD results in mitral valve regurgitation (leaks), and if severe, MVD can cause congestive heart failure, poor quality of life, and mortality. In a cohort of 48 overtly healthy dogs, we found a high incidence of heart murmurs (48%) as well as echocardiographic evidence of mild disease in 85% of dogs. The incidence in the study group is likely higher than in the general Norfolk population, nonetheless, MVD appears to be very common in this breed. Interestingly, investigators felt that 12 dogs had enough echocardiographic abnormalities to diagnose MVD despite the absence of a heart murmur. This "silent" form of MVD requires further study, and might carry important implications as to how Norfolks are screened for disease. On echo, Norfolks with MVD had significantly thicker mitral valve leaflets, greater mitral valve leaflet 2D area, and larger left atria. Norfolks with MVD tended to have greater plasma concentration of a cardiac marker called NT-proBNP. This molecule is produced by the heart in response to cardiac stress or stretch, and is a marker of disease severity. Dogs with MVD had a significantly greater serum serotonin concentration. We believe that serotonin is involved in the molecular changes within the valve that lead to and promote MVD. We also found that dogs with more severe mitral valve changes had changes in 6 plasma amino acids. The importance of this finding requires additional study into the role of diet and environment. In summary, our study reveals 1) a relatively high incidence of MVD in overtly healthy Norfolks, 2) that mild MVD can occur in the absence of heart murmur, 3) that echocardiographic exam can be used to quantify the valve thickness and 2D area, 4) that NT-proBNP and serotonin are higher in dogs with MVD, and 5) that further study into the diet and environment are needed to determine impact on disease prevalence or progression. The current study has laid an important foundation on which to build. We would like to follow this cohort of dogs over the next several years to determine how many dogs with echocardiographic changes eventually develop a murmur, to examine changes in NT-proBNP and serotonin, and to perform additional dietary and environmental studies. Finally, DNA from each of the dogs has been successfully banked for future genetic studies.