Mitral Regurgitation: Valve Anatomy, Regurgitant Severity, and Timing of Intervention

Embryology and Components of the Mitral Valve

The MV apparatus forms from delamination of the ventricular myocardium after formation of the atrioventricular valves from the endocardial cushions. The MV apparatus includes the mitral annulus, mitral leaflets, chordae tendineae, and PMs. Knowledge of the anatomy of the MV apparatus is important for understanding MV function and the mechanisms of primary and secondary MR.

Mitral Annulus

The mitral annulus is part of the fibrous skeleton of the heart. It is composed of a fibromuscular ring situated between the left atrium (LA) and LV, and it anchors the leaflets. The normal mitral annulus is elliptical and has an area between 5 and 11 cm ² (mean, 7 cm ² ). It also has a bimodal or saddle shape, with the anterior and posterior points superiorly oriented (toward the LA) and the medial and lateral points inferiorly oriented (toward the LV). In vitro testing and computer modeling studies have demonstrated that the bimodal shape is optimal for minimizing stress on the mitral leaflets during opening and closing.

The anteromedial portion of the mitral annulus, which forms the straight edge of the D-shaped aspect, shares a common wall with the aortic annulus at the attachment of noncoronary and left coronary cusps. This shared wall, which is called the intervalvular fibrosa (i.e., aortomitral curtain), is more rigid than the posterior annulus due to fibrous attachments.

The posterior portion of the annulus accounts for a greater circumferential length than the anterior portion. Because the anterior annulus is relatively fixed compared with the posterior annulus, dilation of the mitral annulus predominantly occurs posteriorly. The mitral annular area is dynamic throughout the cardiac cycle and is influenced by LA contraction and filling mechanics.

Mitral Leaflets

The two leaflets of the MV are referred to as anterior and posterior based on their anatomic locations. The broad anterior leaflet has a greater surface area and thickness than the posterior leaflet and accounts for most of the closing surface area of the MV ( Fig. 24.1 ).

The anterior leaflet is attached to the anterior mitral annulus through fibrous continuity with the noncoronary and left aortic cusps. The posterior leaflet is crescent shaped and has overall less surface area than the anterior leaflet, despite having a greater circumferential attachment length to the mitral annulus. The shape of the posterior leaflet forms three scalloped segments separated by thin clefts between each segment.

Both leaflets are attached at the posterior and anterior commissures. The common nomenclature divides each leaflet into three segments or scallops, labeled 1 through 3, indicating the anterolateral, middle, and posteromedial segments, respectively. The anterior leaflet segments are labeled A and the posterior ones B (see Fig. 24.1 ).

Compensatory Leaflet Growth

Cardiac valves were once seen as static structures, but the data suggest that compensatory leaflet growth may result from altered cardiac dimensions. An increase in leaflet area and thickness occurred in response to subvalvular leaflet tethering in sheep. These changes were attributed to endothelial cells coexpressing smooth muscle α-actin more in tethered leaflets, which indicated endothelial-mesenchymal transdifferentiation.

Chordae Tendineae and Papillary Muscles

The mitral chordae tendineae, which typically number 25, are thin, fibrous structures composed of collagen interwoven with elastin fibers that extend from the PMs to attach to the mitral leaflets. The chordae anchor the mitral leaflets during systole, allowing symmetric coaptation and preventing prolapse of the leaflets into the LA.

The chordae are attached to the LV by the PMs. During systole, the PMs contract to facilitate closure of the leaflets by the chordae. The PMs arise from the area between the apical and middle thirds of the LV free wall and are divided into anterolateral and posteromedial PMs. The anterolateral PM is the larger of the two, has a single body but two heads (i.e., anterior and posterior), and is supplied by the first obtuse marginal branch of the circumflex artery and the first diagonal branch of the anterior descending artery. The posteromedial PM is smaller, has two bodies and three heads (i.e., anterior, intermediate, and posterior), and is supplied by the posterior descending artery, a branch of the right coronary artery in 90% of cases and by the circumflex artery in the other 10%, making it much more vulnerable to ischemic episodes.

Equal numbers of chordae come from each PM to insert into each of the leaflets. Chordae originating from the posteromedial PM attach to the medial one half of each leaflet, and chordae from the anterolateral PM attach to the lateral one half of each leaflet.

Primary, secondary, and tertiary chordae exist. The primary chordae (i.e., marginal chordae) extend from the PMs in a branching pattern to attach along the coaptation line (i.e., margin) of the leaflets ( Fig. 24.2 ). The main role of these primary chordae is to maintain coaptation of the leaflets. Rupture or elongation of the primary chordae results in loss of coaptation and development of prolapse or flail leaflet and, invariably, MR.

The secondary chordae (i.e., intermediate or strut chordae) attach at the midbody of the leaflets in the transition area between the rough and smooth zones of the leaflets. Their main function is to provide the basic support from the PM to the leaflet. They prevent the valve leaflet from developing excess tension by distributing tension across the ventricular surface of the leaflets, preventing leaflet billowing and potentially maintaining dynamic ventricular shape and function. Secondary chordae are thicker and longer than primary chordae and do not have a branching pattern. Secondary chordae may rupture without compromising leaflet coaptation.

Basal or tertiary chordae are associated only with the posterior leaflet. They connect the base of the leaflet and the posterior mitral annulus to the PMs.

Primary Mitral Regurgitation

Degenerative MV disease is a common mechanism for primary MR. It includes the mitral valve prolapse (MVP) spectrum and nonspecific calcification and thickening of the leaflets associated with age and comorbidities such as chronic kidney disease, diabetes, and hypertension. Organic MV disease is another commonly used term for primary valvular disease that includes the MVP spectrum.

MVP is a common cause of primary MR. MVP is defined as displacement of the mitral leaflets during systole of at least 2 mm from the annular plane ( Fig. 24.3 ). It can occur with or without MR or leaflet thickening. Leaflet thickening on echocardiography is often associated with myxomatous changes. Some patients have mitral annular disjunction (MAD), which is abnormal atrial displacement of the MV leaflet hinge point. In MAD, the posterior leaflet is often involved. MAD has been associated with MVP and ventricular arrhythmias.

The reported prevalence of MVP is approximately 2.4%, and MR due to MVP accounts for most of the more than 10,000 isolated MV operations performed annually in the United States. MVP has a familial basis, with an autosomal dominant mode of inheritance and variable penetrance influenced by age and sex.

Echocardiographically, MVP encompasses a spectrum from minimal prolapse to flail leaflet. Flail leaflet is an eversion of the leaflet segment with loss of its normal concave shape ( Fig. 24.4 ); as a result, the tip of the leaflet is located in the LA. Flail is almost always associated with severe MR, which results from rupture of the primary chordae. Rarely, elongation of the chordae without frank rupture can also result in flail leaflet ( Fig. 24.5 ).

The MVP spectrum includes two distinct clinical entities: fibroelastic deficiency (FD) and Barlow disease (BD). FD is the more common of the two, and in this entity, the abnormalities of the connective tissue structure or function are localized to a single segmental prolapse or flail leaflet (see Fig. 24.5 ). It is typically diagnosed in patients in their sixth decade with a short, acute history of MR that is likely caused by rupture of a single mitral chord. Patients with FD typically have chordal rupture due to progressive weakening and elongation of the chordae tendineae, usually involving the middle segment of the posterior leaflet. The leaflets and the segments are often normal, with no change in height, size, or tissue properties.

BD is caused by an abnormal accumulation of mucopolysaccharides in the leaflets and chordae, which results in thick, bulky, redundant, billowing leaflets and elongated chordae, leading to prolapse of the leaflets ( Fig. 24.6 ). This condition is typical in younger females and usually remains relatively stable until the fourth decade. In BD, the leaflets have diffuse and complex lesions, with prolapse and myxomatous degeneration of many segments in one or both leaflets caused by excessive leaflet tissue, leaflet thickening, and/or rupture of many chordae tendineae. Patients with BD frequently have a dilated annulus and various degrees of annular and subvalvular apparatus calcification, which often affects the posterior face of the annulus and the anteromedial PM.

Cleft-like indentations are abnormal exaggerations of the normal small indentations that occur between the lateral and middle segments and the medial and middle segments of the posterior leaflet ( Fig. 24.7 ). They are associated with mitral flail leaflet and can be a source of significant MR. In a single-center study, cleft-like indentations occurred in up to one third of patients with degenerative MV disease who underwent surgical repair.

Cleft-like indentations are visualized with three-dimensional (3D) imaging, but they are difficult to diagnose directly by two-dimensional (2D) imaging. Clues to their presence include a central MR jet or MR jet originating at the base of the leaflet rather than at the coaptation line. 3D transesophageal echocardiography (TEE) can improve the diagnosis of cleft-like indentations (see Fig. 24.7A–C ). Features of cleft-like indentations on 3D TEE are the presence of a gap located where normal indentations occur with demonstration of the MR jet originating through this gap. Corroboration of the location of the MR jet through the CLI with color Doppler is important as there can be “drop out” of the acoustic signal, which can be mistaken for a cleft-like indentation. A cleft-like indentation of the posterior mitral leaflet should be distinguished from a congenital cleft of the anterior mitral leaflet and from an abnormal pathologic exaggeration of a normal posterior leaflet indentation.

Other valvular causes of MR include endocarditis manifesting as valvulitis with leaflet thickening, vegetation with leaflet destruction, and leaflet perforation ( Fig. 24.8 ). In developed countries, rheumatic MR is relatively uncommon, and MR usually occurs in conjunction with rheumatic mitral stenosis. Rheumatic MR remains a common cause of MR in developing countries.

In rheumatic MR, leaflet thickening and scarring and/or restricted posterior leaflet motion prevent complete coaptation ( Fig. 24.9 ). This pattern is also seen with MR induced by anorexigens or other drugs. A less common cause of MR is nonbacterial thrombotic endocarditis (NBTE), which encompasses a spectrum of sterile MV vegetations associated with malignancy and collagen vascular disease, radiation exposure, and drug-induced MV disease. Calcific mitral annular disease, in which annular calcification extends onto the leaflet bodies, often results in mixed MV disease with mitral stenosis and MR.

Congenital abnormalities of the MV account for a small percentage of adult patients with MR. The most common congenital abnormality in the pediatric population that causes MR is MVP. Cleft of the anterior mitral leaflet is a congenital abnormality that occurs most commonly as part of an endocardial cushion defect complex and less commonly as an isolated cleft of the MV caused by failure of the common anterior leaflet to fuse. Other congenital MV abnormalities include double-orifice MV and parachute MV, which can often result in mixed mitral disease with stenosis and regurgitation.

Secondary Mitral Regurgitation

Secondary MR results from nonvalvular pathology, typically in the setting of chamber dilation due to coronary artery disease, non-ischemic cardiomyopathy, or congestive heart failure. It has also been referred to as functional MR , indicating MR that occurs in the absence of any structural abnormality of the MV leaflets or chordal apparatus. Secondary MR is the most common mechanism of MR because ischemic heart disease is more prevalent than primary mitral valvular disorders. Secondary MR is associated with an adverse prognosis.

Geometric changes and remodeling of the LV and/or LA occur, distorting the normal spatial relationship of the valve apparatus and tethering the leaflets. Leaflet morphology is initially normal in secondary MR, but structural changes in leaflet architecture can occur over time, worsening coaptation. The mechanism of secondary MR in most cases is dilation or ischemic distortion of the myocardium underlying the PMs. The resulting lateral displacement of the PMs leads to tethering of the mitral leaflets and incomplete leaflet coaptation. Closing forces from LV contraction work to counteract the tethering forces. In secondary MR, the tethering forces overcome the closing forces and prevent the leaflets from closing properly ( Fig. 24.10 ).

The estimated prevalence of mild or greater MR after myocardial infarction (MI) is as much as 50%, and the MR is associated with a worse prognosis. ^{, ,} Patients who present with congestive heart failure due to systolic dysfunction have an approximately 50% incidence of moderate or greater MR.

Ischemic MR and functional MR are types of secondary MR. Ischemic MR is related to MR that results from coronary artery disease. PM rupture is an uncommon but dramatic type of ischemic MR. Up to 1% of patients with MI can develop PM rupture. Ischemic MR can also develop from acute myocardial ischemia. This type of MR is usually transient, resolving after the acute ischemia subsides.

A more common type of ischemic MR results from chronic LV remodeling after MI that causes geometric distortion of the MV apparatus. Development of akinesis, scar, or aneurysm of the infarcted or ischemic myocardium underlying the PMs results in lateral displacement of the affected PMs, which leads to tethering of the mitral leaflets and incomplete closure ( Fig. 24.11 ).

Echocardiographic features include apical tenting of the mitral leaflets, which are best imaged in the apical 4-chamber view in mid-systole. Often, the anterior mitral leaflet has a bend caused by tethering of the midportion of the anterior leaflet from a secondary (strut) chord ( Fig. 24.12 ). Secondary MR can result in a centrally directed jet, which typically occurs in diffusely dilated LVs and results in symmetric tethering, or a posteriorly directed MR jet due to asymmetric tethering, in which the posterior mitral leaflet is more tethered than the anterior leaflet (see Fig. 24.12C and D ).

Because the PMs are located along the inferior posterolateral walls, the incidence of ischemic MR is greater for inferior MIs than for anterior MIs. However, inferior MR can develop with any large MI that results in significant LV dilation and remodeling and affects MV geometry.

An uncommon but often catastrophic form of secondary MR due to MI is PM rupture. MI can cause tissue necrosis of the PM head, which can result in a flail leaflet. Compared with the lateral PM with its dual coronary artery blood supply (i.e., left anterior descending and/or left circumflex artery), the medial PM is more susceptible to rupture due to its single coronary artery supply (i.e., right coronary artery). This results in acute and severe MR into the LA, which has not had time to adapt to the sudden increase in LA pressure, leading to pulmonary edema. The absence of prior LV remodeling and dilation underlies the inability to maintain forward stroke volume and possible cardiogenic shock.

Atrial Functional Mitral Regurgitation

Atrial functional MR is a type of secondary MR that can occur in the setting of atrial fibrillation and a rate control strategy. It is often marked by heart failure with a preserved ejection fraction and a dilated mitral annulus. Structurally, there is minimal to no apical tethering of the leaflets. Instead, there is incomplete closure of structurally normal MV leaflets in the setting of mitral annular dilation relative to leaflet length, annular flattening (i.e., loss of the nonplanar saddle shape), and insufficient atrial or annular dynamics to enhance leaflet coaptation ( Fig. 24.13 ). Posterior leaflet tethering can sometimes be observed in atrial functional MR. It has been hypothesized that this is related to outward displacement of the posterior mitral annulus, leading to iatrogenic leaflet tethering.

Restoration of sinus rhythm decreases the severity of MR. The data suggest that compensatory mitral leaflet area adaptation may occur in patients with persistent atrial fibrillation. The valve may grow, but adaptation may be limited by atrial fibrillation and a concomitant increase in annular area.

Management aims to optimize heart failure therapy because atrial functional MR is frequently associated with heart failure with a preserved ejection fraction and diastolic dysfunction. A rhythm control strategy for atrial fibrillation in patients with significant atrial functional MR may be preferred over rate control. MV intervention can be pursued if medical management and rhythm control strategies are not successful.

Carpentier Classification

An MR classification used predominantly by the cardiac surgery community is one proposed by Alain Carpentier, based on motion of the mitral leaflets ( Fig. 24.14 ). In type I, mitral leaflet motion is normal, and MR results from annular dilation. Type II MR results from excessive leaflet motion such as prolapse or flail leaflet. Type III is caused by restricted leaflet motion and is subdivided into types IIIa and IIIb MR. In type IIIa, leaflets have restricted motion in systole and diastole; rheumatic MR is an example. Ischemic MR and functional MR are grouped as type IIIb MR, for which there is restricted motion during systole. Atrial functional MR is type 1.