Mitral regurgitation (MR) is characterized by a systolic blood flow reversal from the left ventricle (LV) to the left atrium (LA). MR can be classified based on etiology and mechanisms. The etiology of MR is generally stratified as ischemic that occurs in up to 40 % of patients affected by myocardial infarction [1] and nonischemic. Mechanisms of MR are stratified as functional (mitral valve is structurally normal and MR is due to valve deformation caused by ventricular remodeling) or as organic (intrinsic valve lesions). A further classification of MR, according to Carpentier, is by observation of leaflet movement: type I (normal valve movement such as annular dilatation, perforation), type II (excessive movement), and type III (restrictive movement: IIIa, diastolic restriction such as rheumatic disease; IIIb, systolic restriction as in functional MR) (Table 16.1).

The mitral valve apparatus is made of the leaflets, the annulus, the chordae, the papillary muscles, and the left ventricular wall [2]. When one of these portions of the apparatus becomes abnormal, MR may develop. Also left ventricle dilatation or papillary muscle displacement can provoke the dysfunction of the mitral valve apparatus.

As seen above, the etiology of MR can be stratified into nonischemic and ischemic.

Nonischemic etiologies include:

According to the classification of the mechanisms of MR, it is possible to distinguish two types of pathologies: functional MR and organic MR. While the former includes all forms of MR that are not secondary to alterations of the valve per se, the latter is due to primary mitral valve disease (fusion of commissures, annulus dilatation, leaflet prolapse, chordal elongation, retractile fibrosis, etc.).

Even if etiology and mechanism are not synonymous (a single etiology may generate MR by different mechanisms), the mechanism of ischemic and functional MR is similar; in fact mitral leaflets are intrinsically normal, but their coaptation is incomplete [5] because of annular and left ventricular dilatation due to ischemia, previous myocardial infarction and scarring, aneurysm formation, cardiomyopathy, or myocarditis.

Anatomic malcoaptation of mitral leaflets during systole results in a regurgitant orifice (ERO), which under the influence of the pressure gradient between the LV and LA allows abnormal regurgitant flow into the LA. The systolic pressure gradient between the LV and LA begins when mitral valve closes (S1) and persists after aortic valve closure (S2) up to mitral opening [6]. Thus, regurgitant flow is typically holosystolic. The regurgitant flow throughout systole is the regurgitant volume (RVol) accumulated in the LA, which reenters the LV during the next diastole, causing a volume overload of LA and LV.

Determinants of this volume overload are the area of ERO [7], the regurgitant gradient, and duration of regurgitation. In both organic MR [8] and functional MR [9], ERO increases when afterload increase and decreases with afterload reduction or improved contractility. Its change is independent of rate [8]. The consequences of volume overload of the LA and LV are different depending on the fact that regurgitation is acute or chronic. In acute severe MR, the left ventricle responds to the sudden volume overload with increased sarcomere stretch and augmented left ventricular stroke volume (Frank-Starling mechanism). The larger volume increases left ventricular diastolic pressure, which in turn increases left atrial pressure. However, left atrial compliance is normal in the acute state and the large regurgitant volume markedly increases left atrial pressure. This phenomenon causes pulmonary congestion, edema, and dyspnea. Otherwise, chronic MR progresses slowly, so the LA has enough time to remodel and accommodate the RVol with a near normal LA pressure. As a result, clinical tolerance may be excellent [10]. In these patients, the Frank-Starling mechanism continues to augment total stroke volume. The left atrium dilates, thus increasing its compliance. The blood that reflows from a dilated left ventricle to a dilated atrium provokes only a small rise of filling pressures, with minimal symptoms of pulmonary congestion (chronic compensated stage).

LV dysfunction (chronic decompensated stage) is a frequent complication of severe MR that occurs if the disease is not treated properly during the reversible phase [11, 12]. It is associated with myocardial structural damage as interstitial fibrosis and reduction in myofiber content that provokes decrease in myofiber contractility [13] and increase in left ventricular filling pressures and finally pulmonary congestion. A downward cycle is now activated: increased ventricular pressure further dilates the left ventricle, increasing systolic wall stress and afterload, which in turn reduces ventricular systolic function. The time during which patients progress from compensated to decompensated MR depends on some variables as the severity of the regurgitation, afterload, and ventricular contractility.

In ischemic/functional MR, blood regurgitation is provoked by tethering and tenting of the leaflets and loss of coaptation surface [14, 15] due to localized LV deformation with apical and posterior displacement of the papillary muscles. The RVol in ischemic MR is usually less than in organic MR [16], and LV dilatation and LA dilatation are in excess to the degree of MR [7], due to the presence of a dilatated, poor performant heart.

Chronic MR is a slow process that allows a gradual LA enlargement and a consequent increase in LA compliance that permits to maintain a normal or near normal LA pressure. For this reason, patients may remain asymptomatic for years despite severe MR. However, once symptoms arise, fatigue and generalized weakness predominate early. As left ventricular function deteriorates, exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea become more prominent. Frank pulmonary edema or hemoptysis may also develop and is usually triggered by atrial fibrillation or increase in the degree of MR. Sudden death as the initial presentation of MR is possible [17].