What are the causes and consequences of myxomatous degeneration of the mitral leaflet?

Myxomatous Degeneration of Mitral Leaflet: Causes and Consequences

Primary Etiology

Myxomatous degeneration of the mitral leaflet is a primary degenerative condition characterized by intrinsic structural abnormalities of the valve tissue itself, representing the most common cause of primary mitral regurgitation in developed countries 1.

The pathologic process involves:

• Disruption of collagen fiber microstructure within the leaflet tissue, leading to excessive leaflet extensibility and weakened chordal tissue 2
• Accumulation of proteoglycans in the valve matrix, causing leaflet thickening and redundancy 1
• Progressive weakening of chordae tendineae, with reduced stiffness (23.5 ± 3.6 MPa in myxomatous tissue versus 59.1 ± 11.7 MPa in normal tissue) and lower failure stress 3

Clinical Phenotypes

The ACC/ESC guidelines recognize two distinct presentations 4:

• Barlow disease: Diffuse myxomatous degeneration affecting both leaflets with voluminous, aneurysmal tissue and marked annular dilatation (>40 mm diameter) 5, 2
• Fibroelastic deficiency (FED): Localized myxomatous changes, typically affecting single segments with less extensive tissue involvement 2

Mechanical Consequences Leading to Mitral Regurgitation

The degenerative process causes mitral regurgitation through two primary mechanisms 3, 6:

• Chordal rupture: Results from progressive weakening of chordae, creating flail leaflet segments with acute severe regurgitation 3, 6
• Leaflet prolapse: Excessive leaflet tissue (56.4% ± 7.9% strain versus 42.9% ± 2.7% in normal tissue) billows beyond the mitral annular plane during systole, preventing proper coaptation 3

Important Clinical Distinctions

Myxomatous degeneration must be distinguished from secondary causes of mitral regurgitation 4, 1:

• In myxomatous disease, the valve apparatus itself is pathologic (primary MR), whereas secondary MR involves structurally normal leaflets with dysfunction from ventricular or atrial pathology 4, 1
• When mitral regurgitation jets are directed centrally or anteriorly (rather than posteriorly), or when multiple jets are present, suspect myxomatous degeneration as the underlying cause 4

Age-Related Patterns

Myxomatous degeneration shows distinct age-dependent presentations 4:

• In adults, myxomatous degeneration is the most common cause of chordal rupture, followed by endocarditis, then rheumatic disease 4
• In the pediatric population (<20 years), chordal rupture predominantly occurs with rheumatic carditis rather than myxomatous disease 4
• Standard echocardiographic criteria for mitral valve prolapse (≥2 mm billowing visible in multiple views including parasternal long-axis) apply to degenerative myxomatous disease in adults 4

High-Risk Features for Progression

Patients with flail mitral leaflet from myxomatous disease represent a distinct high-risk subset 3:

• Younger age at presentation (53.7 ± 1.8 years versus 59.3 ± 1.4 years for non-flail prolapse) 3
• More severe mitral regurgitation at diagnosis 3
• Paradoxically less likely to be in NYHA class III-IV heart failure at presentation (5% versus 20%), suggesting sudden decompensation rather than gradual progression 3
• Less likely to have bileaflet involvement (5% versus 38%), indicating focal severe disease 3

Cardiovascular Consequences

Without surgical correction, myxomatous degeneration with severe mitral regurgitation leads to progressive left ventricular dysfunction and increased mortality 1, 3:

• Chronic volume overload causes left ventricular dilatation and eventual systolic dysfunction 1
• Elevated left atrial pressure leads to pulmonary hypertension and right ventricular dysfunction 4
• Survival is significantly impaired without timely surgical intervention 3

Critical Management Principle

Surgery is the only treatment proven to improve symptoms and prevent heart failure in severe mitral regurgitation from myxomatous disease 1:

• Valve repair reduces mortality by approximately 70% compared to medical management alone 1
• Early surgical intervention is advocated given the intrinsic tissue abnormalities and risk of sudden chordal rupture 3
• Emergency surgery is required for acute papillary muscle or chordal rupture presenting with cardiogenic shock or pulmonary edema 1

Common Pitfall

In patients with bicuspid aortic valve regurgitation and aortic root dilatation, isolated aortic valve replacement (without root replacement) carries significantly increased risk of late myxomatous mitral regurgitation (62% versus 0% at 15 years), suggesting a shared connective tissue abnormality 7. Consider this association when planning aortic interventions in BAV patients.