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I. Ljungvall1
1The Swedish university of agricultural sciences, Sweden
Ingrid Ljungvall
Associate Professor, DVM, PhD
Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science,
Swedish University of Agricultural Sciences, Uppsala, Sweden
Myxomatous mitral valve disease (MMVD) is by far
the most common heart disease in dogs. The disease
is characterized by a slow progressive myxomatous degeneration of the mitral valve apparatus with subsequent left atrial (LA) and ventricular (LV) dilatation. MMVD is encountered in all breeds, but the highest prevalence is seen in small to medium-sized dog breeds. The presentation will review newer aspects/knowledge of MMVD, such as disease terminology, disease etiology and pathogenesis, congestive heart failure (CHF) identification, in addition to disease treatment strategies.
Consistent terminology in the scientific literature is important for defining a disease. Unfortunately, this disease has many names, such as chronic valvular disease, degenerative mitral valve disease, mitral valve disease, endocardiosis, and more recently myxomatous mitral valve disease. The term “myxomatous” describes a characteristic histologic feature of this disease. Conversely, the term “myxomatous” excludes most, if not all, other forms of mitral valve disease. Although the myxomatous degeneration most commonly affects the mitral valve; any of the four intracardiac valves can be affected. However, the most commonly used descriptor “mitral” does not necessarily exclude involvement of other valves. Thus, it is our opinion that ”Myxomatous mitral valve disease” accurately and succinctly defines the pathophenotype of this condition.
Genetic background
The etiology of MMVD has not been ascertained, but heredity has long been suspected to play a major
role owing to the strong association of this disease
with certain small to medium-sized breeds. Studies
in dogs have shown associations between cardiac status in parents and offspring both with regard to murmur intensity and MMVD severity. These studies suggests that the disease have a polygenic inheritance; that is, multiple genes influence the trait and a certain threshold has to be reached before MMVD develops. The polygenic mode of inheritance means that a combination of a sire and a dam that both have an early onset of MMVD will give offspring that have, on average, an early onset of MMVD (and CHF). A combination of dogs with late onset will give offspring that manifest
the disease at old age or never. In a EU funded study (the LUPA project), genome-wide association study (GWAS) was performed to identify loci associated with early onset of MMVD in Cavalier King Charles spaniels (CKCSs) recruited from several countries in Europe. Two loci, located on chromosome 13 and 14, were found
to be associated with early age of onset of MMVD in dogs. This finding is likely to herald causative mutations in the future, and such discovery will clearly increase the knowledge of disease pathways, and may lead to genetic tests, but no such tests are currently available.
Possible influence of the serotonin signaling pathway
One or more primary inciting factors likely increase the risk of disease in predisposed dogs, but little is known about the pathogenesis of the progressive degeneration of the leaflets. An interesting development in the pathophysiology of MMVD is the suggested impact
of increased activity in the serotonin (5-HT) signaling pathway. Studies have demonstrated increased serum 5-HT concentrations in dogs predisposed to MMVD in comparison to other breeds. One of the studies reported that the serum concentrations of 5-HT decreased at more progressed stages. The finding of higher serum 5-HT concentrations in dogs of breeds predisposed
to early onset of MMVD (CKCS) and dogs with mild MMVD suggests that alterations in 5-HT signaling might play a role in progression of early stages of MMVD, and that 5-HT potentially could be genetically linked to the etiologic mechanisms of MMVD in CKCS. Likewise, expression of 5-HT receptors and extracellular matrix signaling molecules have been shown to be altered in diseased mitral leaflets. Possible influence of 5-HT in disease development is currently investigated further by several research groups.
An Urban Experience

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