Mitral regurgitation can be categorized as organic or functional, depending on the architecture of the valve and remainder of the heart. Organic mitral regurgitation refers to disease of the valves themselves—e.g., after rheumatic heart disease or infective endocarditis. The remainder of the heart is often structurally normal initially; but remodeling then occurs to compensate for the valvular dysfunction. Functional mitral regurgitation is where the valve's architecture is normal, but has been distorted by remodeling of the surrounding heart muscle, resulting in regurgitation. Ischemic heart disease is the most common culprit.

Symptoms of heart failure include exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea, and peripheral edema. In mitral regurgitation, the effective output of the heart is reduced because a proportion of the ejection fraction is expelled back into the left atrium. To maintain the circulating volume, dilation of the left ventricle occurs, in as per Starling's law. Once the left ventricle has dilated beyond a certain point, progressive systolic dysfunction results; this culminates in overt heart failure. Dilation may also worsen the mitral regurgitation by distorting the ventricular architecture.

Atrial fibrillation is often seen as a complication of mitral regurgitation. When it develops it can present as palpitations; an acute reduction in exercise tolerance, due to the switch from sinus rhythm to fibrillation; or as chest pain, due to the increased heart rate causing reduced myocardial perfusion. This is a result of the progressive left atrial remodeling that occurs in chronic mitral regurgitation.

Mitral valve prolapse is a known cause of mitral regurgitation. In this condition, changes in elasticity result in prolapse of one or more valvular leaflets into the left atrium during systole. This can progress into overt mitral regurgitation over time; chordal rupture can also occur. Mitral valve prolapse has been shown to have a genetic component; it is also linked to several connective tissue disorders.

Infective endocarditis involving the mitral valve is a known cause of mitral regurgitation. This tends to occur due to rupture of the chordae tendineae that maintain the valve's structure. Note that most cases tend to present acutely and severely. However, in others, the valve's architecture is altered only slightly; it may be years before symptoms appear.

Ischemic cardiomyopathy can give rise to functional mitral regurgitation and heart failure; this can mimic the signs and symptoms of organic mitral regurgitation. Pointers towards this diagnosis include a previous diagnosis of ischemic heart disease, or signs and symptoms suggestive in this regard. Echocardiography may show signs suggestive of ischemia, include myocardial scarring, wall thinning, and wall motion abnormalities. Definitive diagnosis can be made by coronary angiography showing ≥75% stenosis of the left main stem, proximal left anterior descending artery, or two or more epicardial coronary arteries.

Echocardiography is the key diagnostic study; note that an ECG should be obtained beforehand, as this is important for interpretation. Echocardiography can both confirm the presence of mitral regurgitation, determine the severity of regurgitation, assess the size of the left atrium and ventricle, and visualize the valvular architecture. Echocardiography is also helpful to determine the presence of complications such as systolic heart failure and pulmonary hypertension.

Electrocardiography (ECG) may detect atrial fibrillation, left bundle branch block, and left ventricular hypertrophy.

Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) reduce cardiac remodeling. In the case of organic mitral regurgitation, this slows disease progression and delays the development of complications. In patients with functional mitral regurgitation, the severity of regurgitation may also be reduced.

Diuretics provide symptomatic relief via reducing fluid overload; this is more pronounced in severe cases. The degree of regurgitation seen on echocardiography may also diminish, due to reduction of left-ventricular pressures. Note that the underlying disease process is not affected.

Isolated mitral regurgitation is usually asymptomatic. Most patients presenting with symptoms related to one or more complications, including heart failure, and atrial fibrillation. These conditions should be managed appropriately.

Mitral valve repair involves removal of sections of the valve leaflet; the annulus is sutured to return it to its premorbid dimensions and shape. Currently, this is the preferred surgical technique, due to its lesser morbidity and mortality, and comparable outcomes. Repairing the valve retains the existing anatomy, maintains natural shape and function, and reduces the need for anticoagulation; the native value often has greater durability than a prosthesis. Repair may also be undertaken in combination with other cardiac surgery (e.g., coronary artery bypass grafting). Outcomes are better in patients with organic regurgitation, as they often have a normal ventricular structure. This is as compared to individuals with functional regurgitation, who often have extensive ventricular remodeling which continues postoperatively.