What is the significance of myxomatous degeneration in mitral valve disease?

The Significance of Myxomatous Degeneration in Mitral Valve Disease

Myxomatous degeneration is the fundamental pathological process in mitral valve prolapse (MVP) that weakens valve structure, leading to prolapse, regurgitation, and potential complications including heart failure, arrhythmias, and sudden cardiac death. 1

Pathophysiology of Myxomatous Degeneration

Myxomatous degeneration involves:

• Structural changes: Marked proliferation of the spongiosa layer (the delicate myxomatous connective tissue) between the atrialis and fibrosa layers of the valve leaflets 1
• Biochemical alterations: Accumulation of acid mucopolysaccharides in the spongiosa tissue 1
• Mechanical disruption: Focal interruption of the fibrosa layer, which is the primary structural support of the leaflet 1

These pathological changes result in:

• Leaflet redundancy and thickening (≥5 mm)
• Interchordal hooding affecting both rough and clear zones
• Thinning and/or elongation of chordae tendineae
• Ventricular friction lesions
• Fibrin deposits at the mitral valve-left atrial angle 1

Clinical Significance and Risk Stratification

The significance of myxomatous degeneration in mitral valve disease is multifaceted:

1. Predictor of complications: Leaflet thickness ≥5 mm due to myxomatous degeneration is associated with:

   • Higher risk of endocarditis (3.5% vs 0%) 1
   • Increased incidence of moderate-severe mitral regurgitation (11.9% vs 0%) 1
   • Greater likelihood of requiring mitral valve replacement (6.6% vs 0.7%) 1
   • Higher risk of ruptured chordae 1

2. Mechanical consequences:

   • Myxomatous chordae fail at loads approximately half those of normal chordae 2
   • Reduced tensile strength (6.0 MPa vs 25.7 MPa in normal chordae) 2
   • Significantly lower moduli (40.4 MPa vs 132 MPa) 2
   • These mechanical deficiencies explain why chordal rupture is the main indication for repair of myxoid mitral valves 2

3. Phenotypic variations with prognostic implications:

   • Fibroelastic deficiency (FED): Often with localized myxomatous degeneration
   • Diffuse myxomatous degeneration (Barlow's disease): More extensive involvement 3
   • DMD shows more profound annular degeneration, greater prolapse volume, and abnormal valve dynamics compared to FED 3

Genetic and Systemic Associations

Myxomatous degeneration has important genetic and systemic implications:

• Genetic basis: Familial MVP is transmitted as an autosomal trait with several identified chromosomal loci 1
• Association with connective tissue disorders: Increased frequency in Marfan syndrome and other connective tissue diseases 1
• Systemic manifestations: May represent a generalized disease of connective tissue affecting mesenchymal cell lines 1
• Skeletal abnormalities: Often associated with thoracic skeletal abnormalities such as straight thoracic spine and pectus excavatum 1

Clinical Complications and Mortality Risk

Myxomatous degeneration significantly impacts morbidity and mortality:

• Cardiovascular mortality: The most frequent predictor is moderate to severe mitral regurgitation resulting from myxomatous degeneration 1
• Arrhythmias: Associated with complex ventricular arrhythmias, particularly with leaflet thickness >5 mm 1
• Sudden death: Although rare (fewer than 2% of cases), it's more common in familial forms of MVP 1
• Mitral annular disjunction: A subtype of myxomatous mitral valve disease where the mitral annulus separates from the basal myocardium, associated with serious arrhythmias and LV fibrosis 1

Diagnostic and Management Implications

Understanding myxomatous degeneration is crucial for:

1. Surgical planning: The degree and distribution of myxomatous degeneration determines repair feasibility and technique selection 1

   • Focal prolapse (fibroelastic deficiency) vs. diffuse process (Barlow's syndrome) requires different surgical approaches
   • Common repair techniques include artificial neochordae construction, limited triangular resection, or extensive posterior leaflet resection 1

2. Risk assessment: Patients with significant myxomatous degeneration (leaflet thickness ≥5 mm) require closer monitoring 4

   • Annual follow-up with serial echocardiography for high-risk features
   • Regular clinical evaluation every 3-5 years for those with no/mild mitral regurgitation 4

3. Surgical outcomes: Myxomatous degeneration affects long-term repair durability

   • Despite correction of dilated and displaced mitral annulus and leaflet prolapse, late recurrent regurgitation is common in advanced myxomatous degeneration 5

Rare Manifestations

While myxomatous degeneration commonly affects the mitral valve, it can rarely involve other valves:

• Aortic valve: Can lead to aortic insufficiency and acute decompensated heart failure 6
• Tricuspid valve: May occur in up to 40% of patients with MVP 1
• Pulmonic valve: Occurs in 2-10% of patients with MVP 1

Understanding the significance of myxomatous degeneration is essential for appropriate risk stratification, monitoring, and management decisions in patients with mitral valve disease.