What are the causes of mitral regurgitation?

Causes of Mitral Regurgitation

Mitral regurgitation is fundamentally classified into two major categories: primary (organic/structural) MR caused by intrinsic valve abnormalities, and secondary (functional/non-structural) MR occurring despite a structurally normal valve due to dysfunction of surrounding cardiac structures. 1

Primary (Organic) Mitral Regurgitation

Primary MR results from direct pathology of the mitral valve apparatus itself. The most common causes include: 1

Degenerative Disease (Most Common in Developed Countries)

• Mitral valve prolapse/myxomatous disease - the most common cause in athletic and general populations 1, 2
• Barlow disease 1
• Fibroelastic degeneration 1
• Connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome) 1
• Mitral annular calcification 1

Infectious and Inflammatory Causes

• Infective endocarditis - causing leaflet perforation, vegetations, or chordal/papillary muscle rupture 1, 3, 4
• Rheumatic heart disease - characterized by leaflet thickening and chordal fibrosis, particularly affecting the posterior leaflet 1, 3
• Toxic valvulopathy (including anorectic drugs) 1, 3

Acute Structural Failure

• Chordae tendineae rupture - the most common cause of acute severe MR today, typically in patients with floppy mitral valve 4
• Papillary muscle rupture secondary to myocardial infarction - classified as primary ischemic MR despite ischemic etiology 1, 4
• Leaflet perforation or clefts 1

Secondary (Functional) Mitral Regurgitation

Secondary MR develops despite structurally normal valve leaflets, resulting from dysfunction of surrounding cardiac structures: 1

Ventricular Causes

• Ischemic heart disease - causing LV remodeling, papillary muscle displacement, and leaflet tethering (95% exhibit Type IIIb dysfunction with restrictive systolic motion) 1, 5
• Dilated cardiomyopathy (ischemic or non-ischemic) - leading to symmetric tethering pattern with both leaflets exhibiting reduced systolic motion 1, 5
• Regional wall motion abnormalities, particularly inferobasal or posterobasal segments, can cause severe MR despite preserved global LV function 1

Atrial Causes

• Severe left atrial dilation - causing pure annular dilation, termed "atrial functional MR" 1
• Most commonly seen in persistent or long-standing persistent atrial fibrillation 1
• Also occurs in restrictive cardiomyopathies such as amyloidosis 1

Carpentier's Functional Classification of Mechanisms

Understanding the mechanism helps identify the underlying cause: 1

• Type I (Normal leaflet motion): Annular dilation, endocarditis with perforation, or clefts 1
• Type II (Excessive leaflet motion): Mitral valve prolapse or flail leaflet from chordal rupture 1
• Type IIIa (Restricted motion in systole and diastole): Rheumatic disease, radiation injury, or inflammatory conditions 1
• Type IIIb (Restricted motion in systole only): Ischemic or non-ischemic cardiomyopathy with leaflet tethering 1

Important Clinical Pitfalls

Mixed pathology commonly occurs and should not be overlooked. 1 For example:

• Untreated primary MR may eventually cause irreversible LV dilation where both prolapse and tethering coexist 1
• Patients with long-standing secondary MR may subsequently rupture a chord 1
• Older patients may have calcifications or clefts combined with underlying LV disease 1

Anterior leaflet override in Type IIIb motion should not be mistaken for prolapse - the anterior leaflet overrides the severely tethered posterior leaflet but does not move above the annular plane. 1

The geographic and developmental context matters: Rheumatic disease remains a major cause in developing countries, while degenerative disease predominates in developed nations. 2, 3