Advances in the understanding of the pathogenesis, progression and diagnosis of myxomatous mitral valve disease in dogs

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.