Summary
Congenital malformations of the mitral valve may be encountered in isolation or in association with other congenital heart defects. Each level of the mitral valve complex may be affected, according to the embryological development, explaining the fact that these lesions are sometimes associated with each other. As a perfect preoperative assessment is of importance, good knowledge of both normal and abnormal anatomy is required in order to guide the surgeon accurately. This review presents the different embryological, anatomical and echocardiographic aspects of the congenital mitral anomalies.
Résumé
Les malformations congénitales de la valve mitrale peuvent être rencontrées isolément ou en association avec d’autres cardiopathies congénitales. Ainsi que le montre l’embryologie, chaque étage du complexe valvulaire mitral peut être atteint. Cela explique le fait que ces lésions peuvent parfois s’associer entre elles. Une parfaite évaluation préopératoire étant cruciale, une bonne connaissance de l’anatomie normale et des malformations est requise afin de pouvoir guider précisément le chirurgien dans son geste. Cette revue présente les différents aspects embryologiques, anatomiques et échocardiographiques des anomalies congénitales de la valve mitrale.
Background
Congenital anomalies of the mitral valve represent a wide spectrum of lesions that are often associated with other congenital heart anomalies. In an echocardiographic study, congenital malformations of the mitral valve were detected in almost 0.5% of the 13,400 subjects . These lesions can have a variable impact on valve function. When necessary, surgical repair provides good long-term results . Although mitral valve replacement appears to provide acceptable mid- and long-term results , mitral valve repair is always preferable when possible. Because suboptimal primary repair is a significant predictor for reoperation, the successful management of congenital mitral valve disease is closely dependent on the preoperative assessment of the anatomical substrate . An accurate description of the malformations can be achieved through echocardiography but requires prior knowledge of these lesions. Thus, the mitral valve should be analysed as an entire complex, including the valvar leaflets, tensor apparatus and papillary muscles. This review will discuss the different congenital malformations that can affect the mitral valve.
Normal anatomy
The mitral valve, so named because of its resemblance to the episcopal mitre, is bicuspid and marks the left atrioventricular junction. The mitral valve is better understood as a complex that comprises the annulus, the anterior and posterior leaflets, the chordae tendinae and the papillary muscles. The annulus is surgically defined as the level of visible transition between the left atrial myocardium and the whitish leaflet. According to its anatomical definition, it is considered as the fibrous hingeline of the valvar leaflets . Due to the fibrous continuity between the aortic valve and the anterior (or aortic) mitral leaflet, defining its exact limits is extremely difficult . The annulus is saddle-shaped (or D-shaped) ( Fig. 1 ) ; it is a dynamic structure that contracts and reduces its size during systole .
The mitral leaflets are uninterrupted structures, which vary in shape and in circumferential length. They are usually divided into anterior and posterior segments ( Fig. 1 ). At present, many authors have separated them into aortic (anterior) and mural (posterior) leaflets because of their connection with the aortic valve and the posterior wall of the left ventricle. Unlike the tricuspid valve, the mitral valve leaflets have no attachments to the septum. During systole, when the leaflets meet to close the ventricle, the line of coaptation, also called the commissure, looks like a smile. The terms anterolateral and posteromedial commissures, sometimes used to designate each end of the closure line, are unsuitable because a bifoliate valve can have only one zone of apposition between the two leaflets . Coaptation occurs along the leaflet edge in the rough zone. According to the classification by Carpentier et al. , the free edge of the posterior leaflet is divided into three scallops: P1 (lateral); P2 (middle); and P3 (medial). The anterior leaflet is subdivided into A1, A2 and A3 regions that are opposite the scallops of the posterior leaflet.
The subvalvular apparatus is composed of chordae tendinae and papillary muscles ( Fig. 1 ). Chordae tendinae connect all parts of the leaflets to two ventricular papillary muscles. Leaflet cords have several shapes and are attached to the leaflets at various sites. Thus, marginal cords (attached to the free edge), rough zone cords (attached to the rough zone) and strut cords (attached to the basal portion of the posterior leaflet) have been identified . In most cases, papillary muscles are organized as two groups of closed papillary muscles as opposed to two distinct muscles, which arise from the apical and two thirds of the left ventricular wall. The tendinous cords extend from their tips. Papillary muscles are in anterolateral and posteromedial positions. All these structures can be analysed accurately by transthoracic echocardiography ( Fig. 2 ).
Embryology
Mitral valve formation begins during the fourth week of gestation. Knowledge of its embryology is very useful for understanding the various anomalies that can affect it. During the sixth week, fusion of the endocardial cushions divides the atrioventricular canal into right and left atrioventricular junctions ( Fig. 3 ) . Failure of fusion of the superior and inferior cushions, presumably secondary to a deficiency of the vestibular spine, is responsible for producing AVSD. Normally, the lateral cushion forms the posterior mitral leaflet while the anterior leaflet derives from the apposition of the left part of the superior and inferior cushions. At the eighth week, the shape of the orifice looks like a crescent, the two ends of which are connected to compacting columns in the trabecular muscle of the left ventricle. These columns form a muscular ridge, the anterior and posterior parts of which become the papillary muscles . The transformation of the ridge into papillary muscles implies a gradual loosening of muscle, which is called delamination ( Fig. 3 ). The abnormal compaction of the ventricular trabecular myocardium is responsible for producing the PMV. Simultaneously, as for the tricuspid valve, the cushion tissue loses contact with the myocardium of the ridge, except at the insertion of the future tendinous cords. The very rare Ebstein’s malformation of the mitral valve results from a failure of excavation of the posterior leaflet from the parietal ventricular wall. The chordae can be individualized between the eleventh and thirteenth week of development by the appearance of defects in the cushion tissue at the place where the tips of the papillary muscles are attached to the leaflets. As proved by their having the same immunohistochemical characteristics, both leaflets and chordae originate from the cushion tissue , whereas papillary muscles are derived from the ventricular myocardium. A lack of development of the tendinous cords results in hammock or arcade mitral valve. The more severe anomaly of the leaflet is represented by the imperforate mitral valve. Finally, as each stage of this embryological development may be abnormal, the different malformations of the mitral valve can be either isolated or associated.
Anomalies of the leaflets
Mitral valve prolapse
MVP occurs when the leaflets extend above the plane of the mitral annulus during ventricular systole. It is the most common cardiac valvular anomaly in developed countries. Myxomatous degeneration is the main aetiology of prolapsing valvar leaflets, explaining the fact that MVP is uncommon before adolescence. Indeed, the prevalence of MVP was 0.7% in a population of healthy teenagers . In comparison, the Framingham study revealed that 2.4% of adult subjects had an MVP . When MVP occurs during childhood, it generally integrates into a congenital disorder affecting the connective tissue, such as Marfan syndrome, Ehler-Danlos syndrome, osteogenesis imperfecta, dominant cutis laxa or pseudoxanthoma elasticum.
As previously pointed out, the mitral valvar annulus is not perfectly circular but appears more like a saddle that has high and low points. The high points are represented by the anterior and posterior parts of the annulus, while the medial and lateral parts correspond to the low points. This particular morphology explains the fact that, in the past, MVP was broadly overestimated. Indeed, the normal leaflets can falsely appear to prolapse in certain echocardiographic views, especially in the apical two- and four-chamber views. New echocardiographic criteria have consequently been established based on the understanding of the three-dimensional non-planar shape of the mitral annulus. Since then, echographical MVP has been defined as a single or bileaflet prolapse located at least 2 mm beyond the long-axis annular plane, with or without a thickening of leaflets ( Fig. 4 ) . It has been clearly proven that only prolapses shown in the parasternal long-axis view are true MVPs. Prolapses simply observed in the four-chamber view do not satisfy the diagnosis . A classic prolapse is defined as a leaflet thickening exceeding 5 mm, whereas a prolapse with a lesser degree of leaflet thickening is referred to as non-classic.
In children, MVP may be secondary to a distortion of the left ventricular geometry, as seen in unrepaired atrial septal defects (right ventricular volume overloading and left ventricular size reduction). In this case, the mitral valve is histologically normal and the prolapse usually resolves postoperatively. MVP is also observed in cases of connective tissue disorders . The percentage of MVPs associated with Marfan syndrome ranges from 40 to 91% . Marfan syndrome is associated with mutations in fibrillin-1 on chromosome 15q21.1 and with mutations in TGF-β receptor 2 on chromosome 3p24.2-p25 . Fibrillin-1 is involved in the activation of TGF-β. Several studies have suggested that abnormalities in the TGF-β signalling pathway represent a common pathway for the development of the Marfan phenotype. It is a diffuse disease process, probably due to structural protein defects in cardiac tissues (fibrillin 1), which explains the concomitant illness of the aortic root and mitral valve. MVP most commonly involves both leaflets and is symmetrical in Marfan syndrome, whereas it more frequently affects one leaflet (posterior) in myxomatous degeneration .
The most serious complication is severe mitral valve regurgitation, although it is uncommon . Vasodilator therapy is not recommended for the treatment of asymptomatic patients with severe mitral regurgitation and normal left ventricular function, as this may increase the risk of paradoxical worsening in mitral regurgitation . Mitral valve repair is recommended in patients with symptomatic severe mitral regurgitation or in asymptomatic patients with ventricular enlargement or dysfunction. Surgical technique consists of resection of the prolapsed part of the leaflet, with or without an annuloplasty. The risk of endocarditis is higher for patients with MVP than for the general population, especially if the valve has thickened leaflets , but antibiotic prophylaxis is not strictly recommended according to the current American College of Cardiology/American Heart Association guidelines .
Isolated cleft
Isolated cleft of the anterior mitral valve leaflet is a rare but well-known finding, the origin of which is under debate. Indeed, some authors have considered isolated cleft to be a ‘forme fruste’ of AVSD whereas others have supposed it to be a distinct morphological entity. The definition of a mitral cleft is a division of one of the leaflets (usually the anterior leaflet) of the mitral valve. This must not be mistaken with the so-called ‘cleft’ in AVSD . AVSD is characterized by a five-leaflet valve guarding a common atrioventricular junction: superior bridging leaflet; inferior bridging leaflet; left mural leaflet; right inferior leaflet; and right anterosuperior leaflet . AVSD can be separated into complete and partial forms, depending on the degree of attachment of the superior and inferior bridging leaflets to the crest of the ventricular septum and to the inferior rim of the atrial septum. In complete AVSD, there is a single common orifice. The partial form is also defined by a common valve annulus but with the existence of two separate orifices due to a tongue of tissue joining the free margins of the superior and inferior bridging leaflets . A characteristic finding of AVSD is the shorter inlet dimension of the left ventricular septal surface compared with its outlet dimension, whereas in a normal heart, inlet and outlet lengths are nearly equal. AVSD is believed to be the consequence of a deficiency in the development of the vestibular spine. In their large autopsic series, Van Praagh et al. stated that isolated cleft may be classified into two distinct groups: cleft with normally related great arteries, which would be a milder variation of the abnormal development of the atrioventricular canal; and cleft with abnormal conus associated with transposition of the great arteries or double outlet right ventricle . Supporting the hypothesis of a common origin with AVSD, another series reported cases of isolated clefts with intact septal structures but with characteristics of AVSD . Opposing this theory, some surgical studies did not find any feature of AVSD, such as the position of the papillary muscle, in all cases of isolated mitral cleft . Kohl et al. clearly demonstrated that in AVSD, the positions of both papillary muscles were rotated counterclockwise ( Fig. 5 ), whereas in isolated cleft, the position of the papillary muscles was similar to that in normal children . Indeed, in AVSD, the posteromedial papillary muscle is more rotated than the anterolateral one, making it a good marker of this lesion. Moreover, in AVSD, the cleft points towards the ventricular inlet septum, whereas in isolated cleft, it is usually more directed towards the aortic root ( Fig. 5 ). On transthoracic echocardiography, it looks like a slit-like hole in the anterior mitral leaflet ( Fig. 6 ). Chordal attachments may connect the edges of the cleft to the ventricular septum and subsequently create a subaortic obstruction . More rarely, isolated cleft may be seen in the posterior leaflet of the mitral valve ( Fig. 6 ) . Although it may occur at any segment of the posterior leaflet, the predominant localization of the cleft is within scallop P2 . Cleft of the posterior mitral leaflet has been reported in association with counterclockwise malrotation of the papillary muscles that may, again, lead one to suspect a common embryological origin with AVSD . Mitral regurgitation, which is severe in 50% of cases, seems to be well analysed using three-dimensional echocardiography .
