Abstract:
A number of key questions remain unanswered in the pathogenesis of myxomatous mitral
valve disease (MMVD). As MMVD typically afflicts small-breed dogs, a genetic basis has
been implied. In addition, the fact that not all dogs within a risk group develop MMVD
is still unexplained. Research into the pathogenesis of MMVD typically falls under three
categorical divisions, namely genetic factors, mechanical factors of the valve and systemic
factors. Genetic studies have implicated certain loci in the pathogenesis of MMVD. Of
particular interest is the insulin-like growth factor (IGF)-1 locus, as IGF-1 is also associated
with growth. The mechanical structure and function of the mitral valve have also received
much attention in recent years. What has emerged is the notion of a highly complex dynamic
structure, which has an uneven distribution of stress and strain according to the flow of
blood. Research efforts have also identified a number of systemic factors such as cytokines
and signalling pathways that may contribute to the failure of the valve. Serotonin remains
an area of interest in this field. Taken together, the amalgamation of research efforts in
these three areas will go a long way towards resolving the understanding of this disease.
Another area of focus in MMVD has been the development of clinical tests to diagnose the
onset of congestive heart failure. To this end, echocardiographic indices and biochemical
markers have been investigated. Echocardiographic indices such as left atrial to aortic ratio
and the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) have been
identified as specific risk factors to predict progression. Advanced imaging studies such as
cardiac magnetic resonance imaging have enabled investigators to determine the earliest
remodelling changes that occur in MMVD.
