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 mitralvalve disease (MMVD). As MMVD typically afflicts small-breed dogs, a genetic basis hasbeen implied. In addition, the fact that not all dogs within a risk group develop MMVDis still unexplained. Research into the pathogenesis of MMVD typically falls under threecategorical divisions, namely genetic factors, mechanical factors of the valve and systemicfactors. Genetic studies have implicated certain loci in the pathogenesis of MMVD. Ofparticular interest is the insulin-like growth factor (IGF)-1 locus, as IGF-1 is also associatedwith growth. The mechanical structure and function of the mitral valve have also receivedmuch attention in recent years. What has emerged is the notion of a highly complex dynamicstructure, which has an uneven distribution of stress and strain according to the flow ofblood. Research efforts have also identified a number of systemic factors such as cytokinesand signalling pathways that may contribute to the failure of the valve. Serotonin remainsan area of interest in this field. Taken together, the amalgamation of research efforts inthese 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 theonset of congestive heart failure. To this end, echocardiographic indices and biochemicalmarkers have been investigated. Echocardiographic indices such as left atrial to aortic ratioand the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) have beenidentified as specific risk factors to predict progression. Advanced imaging studies such ascardiac magnetic resonance imaging have enabled investigators to determine the earliestremodelling changes that occur in MMVD.