Valvular heart disease
Degenerative valve disease

Author: R. Amita, M.D. (see Authors page)

Revised: 19 March 2018, last major update September 2014

Copyright: (c) 2014-2018, PathologyOutlines.com, Inc.

PubMed Search: Degenerative valve disease [title]

Cite this page: Amita, R. Degenerative valve disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/heartdegenerative.html. Accessed March 20th, 2018.
Definition / general
  • Degenerative valve disease occurs due to a pathological weakening / sclerosis of connective tissue
  • Mitral valve prolapse (MVP), Floppy mitral valve, Flail leaflet, Calcific aortic valve disease
  • Prevalence of degenerative valve disease is estimated at 2 - 3% of the population
  • Mitral and aortic valves
  • Degenerative mitral valve disease:
    • Degeneration occurs in conjunction with an accumulation of dermatan sulfate, a glycosaminoglycan, within the connective tissue matrix of the valve but the exact mechanism is not known
  • Calcific aortic valve disease:
    • T lymphocytes and macrophages infiltrate endothelium and release cytokines that act on valvular fibroblasts to promote cellular proliferation and extracellular matrix remodeling
    • A subset of valvular fibroblasts within fibrosa layer differentiates into myofibroblasts that possess characteristics of smooth muscle cells
    • LDL that is taken into the subendothelial layer is oxidatively modified and taken up by macrophages to become foam cells
    • ACE is colocalized with apolipoprotein B (ApoB) and facilitates conversion of angiotensin II (AngII), which acts on angiotensin 1 receptors (AT-1R), expressed on valvular myofibroblasts
    • A subset of valvular myofibroblasts differentiate into osteoblast phenotype that is capable of promoting calcium nodule and bone formation
Diagrams / tables

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Potential pathways

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MVP subtypes

  • Occurs with greater frequency in individuals with Ehlers-Danlos Syndrome, Marfan syndrome or polycystic kidney disease
  • Other risk factors include Graves disease and chest wall deformities such as pectus excavatum
Clinical features
  • Asymptomatic or has a nonspecific clinical presentation
  • Mitral valve prolapse:
    • For unknown reasons, MVP patients tend to have a low body mass index (BMI) and are typically leaner than individuals without MVP
    • May have a syndrome of atypical chest pain, palpitation and dyspnea
    • Patients with sudden worsening of the mitral regurgitation owing to chordal rupture or with the onset of atrial fibrillation may have an abrupt onset of dyspnea and exercise intolerance
  • Non ejection systolic click of the mitral valve and a late systolic murmur
Radiology description
  • Echocardiography is the most useful method of diagnosing a prolapsed mitral valve
  • Two and three dimensional echocardiography are particularly valuable as they allow visualization of the mitral leaflets relative to the mitral annulus
  • This allows measurement of the leaflet thickness and their displacement relative to the annulus
Prognostic factors
  • MVP is benign, but MVP patients with a murmur, not just an isolated click, have an increased mortality rate of 15 - 20%
  • The major predictors of mortality are the severity of mitral regurgitation and the ejection fraction
  • Symptomatic patients may benefit from beta blockers (e.g., propranolol)
  • Patients with prior stroke or atrial fibrillation may require blood thinners such as aspirin or warfarin
  • In rare instances, when mitral valve prolapse is associated with severe mitral regurgitation, mitral valve repair or surgical replacement may be necessary
  • Mitral valve repair is generally considered preferable to replacement
  • Current ACC / AHA guidelines promote repair of mitral valve in patients before symptoms of heart failure develop
  • Symptomatic patients, those with evidence of diminished left ventricular function or those with left ventricular dilatation need urgent attention
Clinical images

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Mitral valve prolapse TEE

Gross description
  • Calcific aortic valve disease:
    • Characterized pathologically by large nodular calcific masses within the aortic cusps that protrude along the aortic surface into the sinuses of Valsalva, interfering with opening of the cusps
    • There is no disease along the ventricular surface
  • Degenerative mitral valve disease:
    • Two forms of mitral valve disease have been described:
    • In the more common, classic form, there are thickened and redundant myxomatous mitral leaflets resulting from abnormal connective tissue
    • In the nonclassic form, the prolapsing mitral leaflets are normal in thickness
    • Patients with Barlow syndrome have diffuse, generalized thickening and billowing of the leaflets; patients with fibroelastic dysplasia have disease localized to isolated regions of the valve
    • The chordae tendineae are frequently elongated and prone to rupture
Gross images

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Left: minimally diseased aortic valve
Right: severely stenotic aortic valve

Microscopic (histologic) description
  • MVP is characterized by myxomatous infiltration, fibroelastic deficiency, collagen alterations, mucopolysaccharide accumulation
  • Myxomatous infiltration is characterised by thickening and proliferation of the spongiosa with pooling of glycosaminoglycans
  • Spongiosa invades fibrosa giving the appearance of cystic spaces and less dense collagen
  • Collagen alterations are characterized by fragmentation of collagenous bundles within the fibrosa
  • Elastic fiber alterations are characterized by disrupted, fragmented and granular elastic fibers that form an amorphous clump
  • The number of elastic fibers is increased in the abnormal area
Microscopic (histologic) images

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Calcific aortic valve: Verhoeff-van Gieson stain