Background and aim of the study: Myxomatous mitral valve disease (MMVD) is the single most common cardiac disease of the dog, and bears close similarities to chronic degenerative mitral valve disease in humans. However, limited quantitative data are available on cellular and morphological changes in both species. The study aim was to use an image analysis system to examine various morphological changes associated with MMVD, and in particular to measure changes in cell numbers in overtly myxomatous areas of the distal portion of the valve.
Methods: Mitral valve complexes were collected from normal dogs and dogs with varying severity of myxomatous mitral valve disease (veterinary Whitney grades 1-4; a measure of disease severity and age-related disease progression in the dog). An image analysis technique (ImageJ; National Institutes of Health, USA) was used to measure valve leaflet length, thickness, connective tissue content and density, glycosaminoglycan (GAG) content, cell number and shape in normal and myxomatous areas of diseased valves.
Results: There was a change in the valve leaflet anterior/posterior length ratio in the diseased valves, suggestive of valve lengthening. Distinct and statistically significant (p <0.01) changes occurred in the valve thickness ratio for both anterior and

posterior leaflets as the disease progressed, and the posterior leaflet thickness ratios were consistently higher than for the anterior leaflets. There was a statistically significant decrease in cell numbers in overtly myxomatous areas of the distal portion of affected valves compared to similar locations in normal valves, but there was no difference between the different grades of disease. The majority of cells in both diseased and normal valves had a circularity score typical of a spindle (elongated) shape. Connective tissue derangement was clearly seen in the myxomatous areas, and this was associated with a significant reduction in connective tissue density. The reduction in connective tissue density was associated with advancing disease severity (age). There was an increase in GAG expression with disease severity, as shown by the level of Alcian blue staining, but this could not be quantified with ImageJ.
Conclusion: Mitral valve myxomatous degeneration in the dog is associated with lengthening and thickening of valve leaflets, a loss of connective tissue, and a decrease in cell numbers in selected myxomatous areas, but no change in cell circularity. Some of these changes were age- (disease severity-) related.


The Journal of Heart Valve Disease 2010;19:60-70