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Valvular Heart Disease

Michele Borgarelli, DVM, PhD, DECVIM (Cardiology)

Department of Small Animal Clinical Sciences, Virginia‐Maryland Regional College of Veterinary Medicine, Blacksburg, VA, USA

Canine Degenerative Myxomatous Activation of valvular interstitial cells (VICs) is likely
Mitral Valve Disease to play an important role in the pathogenesis of the dis-
ease. VICs represent the most common cell type in the
Etiology and Pathophysiology cardiac valves and are responsible for extracellular
matrix synthesis, valvular repair, and remodeling. VICs
Canine chronic myxomatous mitral valve disease are commonly present in a quiescent state but can be
(MMVD) is the result of a progressive myxomatous activated by endothelial damage or valvular stress.
degeneration of mitral valve leaflets and chordae tendi- Activated VICs are able to synthesize collagen, fibronec-
nae. Pathologic changes include excessive deposition of tin, elastin, and growth factors and are responsible for
mucopolysaccharide, fragmentation of elastin, and dis- extracellular matrix remodeling through production of
organization and disruption of collagen. matrix metalloproteinases and their inhibitors (tissue
The exact etiology of the disease has not been estab- inhibitors of metalloproteinases [TIMPs]). Eventually,
lished. Because the disease has a high prevalence in some this process leads to decreases in collagen content and
breeds, such as Cavalier King Charles spaniel (CKCS), a deposition of proteoglycan, typical of the myxomatous
genetic predisposition has been hypothesized. Swenson degenerative process. In summary, it can be hypothe-
and co‐workers provided the first evidence of a genetic sized that in dogs with a genetic predisposition for the
predisposition in 1996. These authors reported that disease, mechanic stimuli can activate VICs with valvu-
CKCS dogs with a more severe disease status produced lar remodeling and myxomatous degeneration. This
more offspring with murmurs and with murmurs of hypothesis would support the theory that myxomatous
higher intensity than dogs with a low‐intensity status. degeneration is the end‐result of a continuous process of
They concluded that MMVD is inherited as a polygenic damage and repair as a result of mitral valve stress.
trait. The same etiology has been reported for other The myxomatous degeneration of the valve leaflets
breeds. It has also been reported that the threshold for eventually leads to prolapse and valvular insufficiency.
the expression of the disease is lower in males than in Accordingly, mitral valve prolapse usually precedes
females. This would explain why males present with the mitral valve insufficiency. Mild mitral valve insufficiency
disease at a younger age. is generally well tolerated by dogs and is not associated
Recently, using a genome‐wide association study, with any compensatory response because it is not associ-
two specific loci associated with development of ated with decreased cardiac output. However, if the dis-
MMVD in CKCS have been identified. It is likely that ease progresses and regurgitation through the mitral
other factors might contribute to the development of valve into the left atrial becomes more severe, cardiac
the disease, including the anatomy of the mitral valve, output decreases and activation of compensatory mech-
obesity, and exercise. Recently, serotonin has been anisms occurs. These mechanisms include activation of
hypothesized as playing a role in the pathogenesis of the renin‐angiotensin‐aldosterone system (RAAS) and
MMVD. However, despite similarities in the myxoma- sympathetic nervous system, and increased release of
tous pathology of serotoninergic and degenerative endothelin, vasopressin, and natriuretic hormones. Due
mitral valves, a direct cause–effect relationship between to the chronic nature of the disease, these mechanisms
serotonin and the pathogenesis of MMVD has not are not necessarily activated in the early stages of
been established. MMVD. This consideration has important therapeutic

Clinical Small Animal Internal Medicine Volume I, First Edition. Edited by David S. Bruyette.
© 2020 John Wiley & Sons, Inc. Published 2020 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/bruyette/clinical