This chapter details the echocardiographic assessment of congenital mitral valve abnormalities that might be encountered during the evaluation of primary mitral valve pathology or, more frequently, mitral valve pathology in association with other forms of congenital heart disease. It must be stated that congenital mitral valve abnormalities are rare, unlike their rheumatic counterpart. Also, when assessing a patient with suspected mitral valve pathology, it is important to pay attention to associated hemodynamic abnormalities that influence the interpretation of Doppler physiology.
With the recent advent of three-dimensional techniques, our understanding of mitral valve morphology and function as assessed by echocardiography is fundamentally changing. This technique in conjunction with its two-dimensional counterpart is currently becoming the reference standard for surgical or medical intervention.
This chapter will address both the two- and three-dimensional approach to the assessment of mitral valve abnormalities and their hemodynamic consequence.
MITRAL VALVE DEVELOPMENT
The atrioventricular junction comes into prominence following rightward looping of the heart tube after the 25th day of gestation. By the end of the fifth week, the developing ventricles are visible, with the future left ventricle supporting a large portion of the atrioventricular canal. The lumen of the atrioventricular canal is occupied by the inferior and superior endocardial cushions. Initially unfused, these cushions eventually fuse during the sixth week and form the right and left atrioventricular junctions, to which the developing leaflets of the mitral valve will be anchored. Parts of these fused cushions remain on the left side of the septal crest and form the aortic leaflet, often referred to as the anterior leaflet, of the mitral valve.
Formation of the normal mitral valve can only proceed when the aorta becomes committed to the left ventricle, resulting in fibrous continuity between the two leaflets; hence the name the aortic leaflet is given, which distinguishes it from its mural counterpart, often referred to as the posterior leaflet. Initially, there is still a cleft at the parietal margins of the fusion of the superior and inferior cushions. The mural leaflet of the mitral valve develops from the lateral cushion tissue of the atrioventricular canal myocardium that protrudes into the ventricular lumen. The myocardium disappears via apoptosis, and therefore the entire leaflets are derived from cushion mesenchyme that is endocardial in origin. This provides an explanation as to why persistence of the myocardium results in the mitral arcade. Although the tricuspid septal leaflet delaminates from the ventricular myocardium, the aortic leaflet is never attached to or supported by the myocardium, except at its cranial and caudal margins, which represent chordal and papillary muscle attachments. Expansion of the inferior quadrants of the left atrioventricular junction involves growth of the parietal wall of the left ventricle, with comparable growth of the lateral cushion. This eventually results in the lateral cushion occupying two-thirds of the circumference of the developing mitral valve.
This expanded crescent, which represents the developing mitral valve, is associated with compacting columns in the spongy layer of the ventricular muscle, which eventually form the papillary muscles. Excessive or abnormal compaction of the trabecular layer of the developing ventricular myocardium is responsible for the parachute mitral valve. Failure of the formation of the tendinous chords from the myocardial primordium results in the mitral arcade lesion, with muscle extending from the tips of the leaflets to the papillary muscles. When Ebstein’s malformation of the mitral valve occurs, it is the mural leaflet that is involved, as this is the leaflet that excavates from the parietal ventricular wall.
GENETICS OF MITRAL VALVE DEVELOPMENT
Reciprocal signaling between the endocardial and myocardial cell layers in the cushion is mediated in part by transforming growth factor (TGF) family members and induces a transformation of endocardial cells into mesenchymal cells. This is induced by BMP-2 signals that are derived from adjacent myocardial cells. Sox9 is activated when myocardial cells undergo mesenchymal transformation and Sox9-deficient mesenchymal cells fail to express ErbB3, which is required for cushion cell proliferation. The mesenchymal cells migrate into the cushions and differentiate into the fibrous tissue of the valves. Several genes play a role in heart valve formation, including calcineurin with signaling and downstream activation of the NFAT (nuclear factor of activated T cells) family of transcription factors, with an absence of these resulting in fatal defects of valve formation.
ANATOMY OF THE MITRAL VALVE
About two-thirds of the annulus of the mitral valve is supported by a fibroareolar junction, which serves also to separate the parietal portion of the left atrial myocardium from the ventricular myocardium. The remaining third of the ring is part of an extensive sheet of fibrous continuity with the leaflets of the aortic valve, strengthened at its ends by the left and right fibrous trigones. There are two so-called commissural areas within the valve, corresponding more or less to the areas of the fibrous trigones. The zone of apposition between these areas delineates the two primary valvar leaflets. The more extensive leaflet is attached to the parietal part of the annulus. It is more accurate to describe this as the mural leaflet, rather than posterior. It has relatively little depth; consequently, when the valve is closed, it is seen as a long rectangular structure that is usually divided into scallops. There are usually three scallops, with a large central and then smaller lateral and medial structures. The second major leaflet of the valve is attached along the area of aortomitral fibrous continuity. Although its overall shape is semicircular, it is much squarer and more boxlike than the long, rectangular mural leaflet. Often termed the “anterior” leaflet, it is not strictly anterior in position. That is why we prefer to describe it as the aortic leaflet.
The tension apparatus of the valve consists of the tendinous cords and the papillary muscles. The important cords are those supporting the free edge of the leaflets (notably the commissural fan-shaped cords) and those supporting the rough zone (particularly the thick strut cords) of the aortic leaflet and the basal cords. The cords supporting the free edge are much more significant in support of the mural leaflet. In contrast, the rough zone and strut cords are more significant in support of the aortic leaflet. A study by Becker and de Wit showed considerable variation of the free edge chords in normal hearts. The papillary muscles of the mitral valve are relatively constant in position, although they, too, show marked variation in their detailed anatomy. They are sited beneath the ends of the zone of apposition between the leaflets in posteromedial and anterolateral position and have a typical paired appearance. The axis of opening of the valve subtends a considerable angle relative to the inlet septum. Unlike the septal leaflet of the tricuspid valve, the leaflets are never attached by tendinous cords directly to the inlet component of the muscular ventricular septum.
Mitral Annular Shape and Function
The shape of the mitral annulus was initially thought to be planar, which resulted in a gross overdiagnosis of mitral valve prolapse. With the advent of three-dimensional echocardiography, this was recognized as being incorrect, as the mitral annulus has both high and low points, appearing with a shape like a saddle (Figs. 9.1 and 9.2). The anterior and posterior aspects represent the high points, while the medial and lateral represent the low points. Therefore, unless severe, mitral valve prolapse should be confidently diagnosed only in the long-axis view.
The saddle shape of the valve is most likely responsible for reducing leaflet stress, which is important when designing prosthetic valve rings or performing other surgical procedures that impact normal annular function.
Previous animal and human studies demonstrated that mitral annular motion is very heterogeneous. The reported expansion of anterior mitral annulus and aortic root during ventricular systole corresponds with segmental diameter changes observed from previous data. The commissure-to-commissure (C–C) direction of the mitral annulus, which is muscular on both sides, moves dynamically throughout the cardiac cycle; however, the anteroposterior direction moves differently due to the sites of fibrous continuity with the aortic valve. In early systole, the mitral annular segments in the C–C direction start to contract, followed by diameter reduction in the anteroposterior direction with a slight expansion in the C–C direction in mid-systole, which continues on during late systole. This shape change is thought to permit maximal expansion of the aortic root to facilitate ejection and good coaptation of the mitral valve leaflets.
Figure 9.1. Three-dimensional image of the mitral valve as seen from the left atrium. Note the annular shape. The aortic and mural leaflets can be seen. Also, note the nomenclature used for assessing the individual components of the leaflets (A1–A3 for the aortic or anterior leaflet, and P1–P3 for the posterior or mural leaflet). AO, aorta; AL, aortic leaflet; ML, mural leaflet.
Figure 9.2. Mitral annular shape in the normal heart. Note the high points at the anterior and posterior parts of the annulus. The maximum bending of the annulus occurs along the commissures between the aortic and mural leaflets. A, anterior; AL, anterolateral; AO, aortic leaflet; P, posterior; PM, posteromedial.
Left atrial contraction contributes to area reduction of the mitral annulus before the ejection phase, contributing to 89% of area reduction in adult sheep. The contribution of atrial contraction to annular diameter reduction is most prominent in the anterolateral–posteromedial direction (i.e., the C–C direction for mitral valve) in children. This result was different from data in adult sheep for the mitral annulus, which showed a more prominent diameter reduction in the anteroposterior direction during atrial contraction. This difference might be due to the difference in species, the maturity of myocardial tissue, and the fact that the human control subjects were not under general anesthesia.
When measured as C–C, the mitral annulus starts to bend in mid-systole, becoming most acute during the isovolumic relaxation phase of the mitral annulus (Fig. 9.3). After this, the annulus flattens, which may have a role in early diastolic filling. There appears to be a positive correlation between the bending angle of the mitral annulus and global left ventricular systolic function, which corresponds with the finding that the mitral annulus becomes planar after myocardial ischemia.
Mitral Valve Leaflets
It is generally accepted that the mitral leaflets move closer together, after opening widely at the beginning of the E wave, with leaflet separation being maximal at the second left atrial/left ventricular pressure crossover, a pattern that corresponds exactly to the E wave as described in the use of Doppler echocardiography.
The line of closure of the mitral valve is on the atrial aspect of the valve and is about one-third of the distance from the free edge of the leaflets to their annular attachment. It is important to note, therefore, that the valve does not close at its free edge. This aspect of valve closure is much better viewed by three- rather than two-dimensional echocardiography (see Fig. 9.1).
Figure 9.3. Graph demonstrating the bending angle in the normal mitral annulus in a pediatric case. Note the annulus starts to bend in late systole, becoming maximal during isovolumic relaxation, and subsequently becomes flatter. AVO, aortic valve opening; AVC, aortic valve closure; DF, diastolic phase; EF, ejection phase; MVC, mitral valve closure; IC, isovolumic contraction; IR, isovolumic relaxation; MVO, mitral valve opening.
Papillary Muscle Location
It is well accepted that in patients with ischemic mitral regurgitation, leaflet tethering due to papillary muscle displacement is responsible for restricted diastolic excursion that is independent of inflow volume. In addition, this mechanism is responsible for poor systolic coaptation and the ensuing regurgitation. Therefore, there is an important and definite relationship between the mitral valve papillary muscles, leaflets, and supporting chordae to maintain normal valve function. Three-dimensional echocardiography provides a unique opportunity to image these relationships (Fig. 9.4), providing views that cannot be obtained with two-dimensional echocardiography.
It is also possible to see the chordal apparatus in three dimensions, which may have future implications with regard to their importance in mitral valve tethering (Fig. 9.5). More intriguing is the finding that the mitral aortic leaflet is able to adapt to increased mechanical stress by expanding, with associated thickening and lengthening of the chordal apparatus. The histological changes noted were those of altered endothelial protein expression, which suggests possible reactivation of embryonic developmental pathways.
Figure 9.4. Three-dimensional image of a normal mitral valve. Top left: Aortic leaflet, which is inserted into the anterior papillary muscle. Top right: Posterior papillary muscle. Bottom left: Two papillary muscles. Bottom right: Apex of the left ventricle. APM, anterior papillary muscle; LA, left atrium; LV, left ventricle; PPM, posterior papillary muscle.
Figure 9.5. Three-dimensional images of the mitral chordal apparatus. The upper two images are from the same full volume data set seen in the lower right-hand panel. These demonstrate two-dimensional images of specific chordal components of the mitral valve. The lower right-hand panel shows the chords inserting onto the aortic leaflet, as well as the supporting two papillary muscles. The lower left-hand panel is a specimen which shows a strut chord as indicated by the upper right-hand arrow, and rough zone chords by the second lower black arrow. AO, aorta; LA, left atrium; LV, left ventricle; PM, papillary muscles; RZ, rough zone.
INCIDENCE OF CONGENITAL MITRAL VALVE ABNORMALITIES
Congenital deformities of the mitral valve are rare, with mitral stenosis occurring in 0.6% of postmortem studies and in 0.21% to 0.42% of clinical series. Congenital mitral incompetence is rarer. There is a male-to-female ratio of around 1.5:1 to 2.2:1. The fully developed syndrome of “Shone syndrome” includes four obstructions within the left heart: the valvar lesion itself, supravalvar mitral ring, subaortic stenosis, and aortic coarctation. Any of these obstructions may coexist with any congenital lesion afflicting the mitral valve, particularly coarctation. Annular hypoplasia of the mitral valve is almost always associated with hypoplasia of the left ventricle and aortic stenosis or atresia. This may also be seen in association with ventricular septal defect or double-outlet right ventricle and tetralogy of Fallot. When the mitral valve is imperforate, left ventricular hypoplasia is inevitable unless there is an associated ventricular septal defect.
SPECIFIC MITRAL VALVE PATHOLOGY
At the outset, it should be stated that although in some cases there is pure mitral valve stenosis or regurgitation, in many other cases there is a combination.
Mitral Valve Dysplasia and Hypoplasia
With mitral valve dysplasia, the leaflets are thickened, the interchordal spaces often are obliterated, and the papillary muscles are deformed, the last frequently extending as muscular strands directly into the leaflets. Usually such a valve shows global hypoplasia and is the most common lesion associated with isolated congenital mitral stenosis. When the free edges of the dysplastic leaflets are thickened and rolled, the valve may be incompetent as well as stenotic. This appearance can be viewed in the parasternal long-axis, short-axis, and four-chamber views by two-dimensional echocardiography, with evidence of thickened leaflets and reduced mobility (Fig. 9.6A). Of note, it is often difficult to differentiate between the edge of the leaflets, the chordal apparatus, and the papillary muscles.
Color flow Doppler demonstrates the flow acceleration just proximal to the mitral annulus, followed by variance as the blood exits the restrictive orifice. In many cases, there are multiple exits due to the fused nature of the chordal apparatus (Fig. 9.7). In some cases, there is laminar flow through the orifice into the center of the valve, with more distal exits (Fig. 9.8).
Three-dimensional echocardiography provides an en face view of the mitral valve. The valve can be seen from the left ventricular aspect, providing full anatomical details of the valve. The advantage of the “looking up” view from the left ventricular cavity is that exquisite detail regarding the commissures can be viewed (Fig. 9.6B). Although the surgical en face view is good, it is often difficult to appreciate the commissural detail due to the normal curved closure line of the mitral valve. To overcome this, it is possible to provide a slightly lower cut plane, which allows visualization of the commissures as well as the valve-supporting apparatus. It is also possible to remove the front of the left ventricle, such that the anterior aspect of the mitral valve and its tension apparatus can be seen. Three-dimensional color flow Doppler remains at a somewhat primitive stage and at present does not provide much added diagnostic information in congenital mitral valve stenosis (Fig. 9.7). Part of the problem is that, unlike rheumatic mitral valve stenosis, there are frequently multiple small eccentric jets, which make vena contracta summation difficult (see Fig. 9.8).
Figure 9.6. Patient with dysplastic mitral valve stenosis. A. Two-dimensional four-chamber view showing a small associated mitral valve ring (left) and the thickened mitral leaflets and subvalvar apparatus (right). AO, aorta; LA, left atrium; LV, left ventricle; RV, right ventricle. B. Three-dimensional echocardiogram from the same patient as in A. Left: Images from above the mitral valve. The supramitral ring is well seen. Right: Thickened mitral valve leaflets as well as tethering of the mural leaflet. ANT, anterior; CS, coronary sinus; INF, inferior; LA, left atrium; LVOT, left ventricular outflow tract; MV, mitral valve; PM, papillary muscle; RV, right ventricle; SUP, superior.
Figure 9.7. Color flow Doppler in the same patient as Figure 9.6. The two-dimensional color flow Doppler shows that the acceleration is occurring just above the annulus, which is consistent with the supramitral ring. Note the narrow inflow orifice. Upper right: Three-dimensional color flow data. Bottom right: En face view of the stenotic jet. LA, left atrium; LV, left ventricle; RV, right ventricle.
Figure 9.8. Mitral valve stenosis with multiple exit points and laminar flow centrally. Note in both the short- and long-axis views, there is no flow acceleration centrally. The M-mode shows a prolonged E-F slope. LA, left atrium; LV, left ventricle; RV, right ventricle.
Occasionally, mitral stenosis may occur when the valve is miniaturized in its entirety but does not show dysplastic features. Of more significance is the arrangement when only part of the valve is hypoplastic. This is typically seen when one papillary muscle, usually the anterolateral muscle, is grossly reduced in size or even totally absent. Then the anterolateral commissure either inserts directly on to the left ventricular free wall or is supported on the wall by a small papillary muscle (Fig. 9.9).
The tension apparatus then has a grossly eccentric appearance, effectively inserting into a solitary papillary muscle. This arrangement was illustrated by Shone and colleagues as a “parachute mitral valve.” This is different from those cases where the two papillary muscles are fused into a solid solitary structure that supports the tension apparatus from the entire valve. In addition, an echocardiographic/morphologic correlation noted that many patients with aortic coarctation have altered positions of the left ventricular papillary muscles and narrowing of the interpapillary valley.
A supravalvar stenosing ring was described by Shone and his colleagues as part of the complex including the parachute valve. The supravalvar ring in this setting was a concentric thickening of the left atrial endocardium immediately above the atrioventricular junction. In the clinical setting, in contrast, it seems that the so-called stenosing supravalvar ring is formed on the atrial aspect of the valvar leaflets (Fig. 9.10). This is best seen in the parasternal long-axis view by two-dimensional echocardiography, as the beam is perpendicular to the ring in the axial plane where the resolution is best. Although it can be imaged in the four-chamber view, depth and lateral resolution may make differentiation from the annulus and leaflets difficult. Color flow Doppler is very helpful in this setting, as the flow acceleration seen proximal to the stenosis occurs well above the mitral annulus, with the variance seen at the annular level (see Fig. 9.7).
One of the advantages of three-dimensional echocardiography is that the ring can be seen in its entirety, unlike that seen by two-dimensional echocardiography. In the majority of cases the supravalvar ring does not occur in isolation but is seen in association with valve dysplasia. In some instances, there is the appearance of a membrane-like structure below the annulus that traverses the orifice of the valve. Whether this represents a component of valve dysplasia or is related to the supravalvar ring is unclear.
Figure 9.9. Two-dimensional image in a patient with a dominant anterior papillary muscle. LA, left atrium; LV, left ventricle; RV, right ventricle.
Anomalies of the Mitral Valve Leaflets
The most extreme anomaly is an imperforate mitral valve. This usually coexists with aortic atresia, forming part of the “hypoplastic left heart syndrome.” An imperforate mitral valve can also be found without aortic atresia and is then part of the combination termed “mitral atresia with patent aortic root.” Often, the ventriculoarterial connection is double-outlet right ventricle; however, in a significant number of cases, the patent aorta arises from a good-sized left ventricle that is connected via a ventricular septal defect. The ventricular septal defect can be of varying morphology.
Ebstein’s malformation can rarely affect the morphologically mitral valve. The characteristic feature of Ebstein’s malformation of the mitral valve is that the mural leaflet is plastered down onto the ventricular wall; consequently, its hinge is below the atrioventricular junction but there is no thinning of the atrialized inlet portion as is usually seen when it is the morphologically tricuspid valve that is involved.
Figure 9.10. Two- and three-dimensional images from a patient with a supramitral ring. The left-hand panel is a three-dimensional image of the complete supramitral ring, as seen from the left atrial view and outlined by the black arrows. The middle and right-hand panel show parts of the ring as seen by two-dimensional echo. LA, left atrium; LV, left ventricle.
An isolated cleft of the mitral valve is also an anomaly confined to the leaflet, and one that primarily produces mitral incompetence. The affected leaflet tends to be dysplastic, and its edges are usually rolled and thickened. It is important to distinguish an isolated cleft of the aortic leaflet of the mitral valve in hearts with a separate atrioventricular junction from a “cleft” in the left valve of atrioventricular septal defects with a common atrioventricular junction. The isolated cleft “points” into the aortic outflow tract, often in association with a ventricular septal defect, and the aortic leaflet is readily reconstituted by suture of its edges (Fig. 9.11).
In contrast, the so-called cleft in atrioventricular septal defects points to the septum and represents the space between the bridging leaflets. Closure of the bridging leaflets cannot produce a left atrioventricular valve that in any way resembles a normal mitral valve. These features, as well as differentiation from the cleft of an atrioventricular septal defect, are well viewed by both two- and three-dimensional echocardiography. One advantage of the latter technique is that the precise length of the cleft can be viewed and measured (Figs. 9.12 and 9.13).
Figure 9.11. Isolated cleft of the mitral valve with significant regurgitation. Note the edges of the cleft are thickened and unsupported. LA, left atrium; LV, left ventricle; RV, right ventricle.
Figure 9.12. Isolated cleft of the mitral valve in a patient who had associated transposition of the great arteries and a ventricular septal defect. The left-hand panel is from the left atrial view, and the right-hand one from the left ventricular aspect. Note that in this case the cleft (black arrow) is eccentric, which is common in this setting. AO, aorta; AL, aortic leaflet; ML, mural leaflet; MV, mitral valve; PM, papillary muscle.
In addition, the location and extent of the regurgitation are better viewed with three-dimensional echocardiography. A significant problem with imaging color flow jets by two-dimensional echocardiography is that it is frequently difficult to appreciate multiple jets when imaging in one plane. Jets change direction, which provides additional confusion when changing from one imaging plane to another. Likewise, the presence of central and lateral commissural jets is best seen with three-dimensional echocardiography (Fig. 9.14).
Double-Orifice Mitral Valve
The most common anatomical presentation is that in which a tongue of valvar tissue extends between the mural and aortic leaflets, dividing the valvar orifice into two components. Such an arrangement is frequently encountered in the left valve seen in an atrioventricular septal defect. The rarer variant, involving the otherwise normal mitral valve, shows duplication of the entire valvar structure. As a result, the left atrium is connected to the left ventricle by two valves, each with its own annulus, leaflets, cords, and papillary muscles (Fig. 9.15). This anomaly can exist in otherwise normal hearts where it is often discovered coincidentally, as well as in more complex anomalies such as tricuspid atresia or double-inlet ventricle.
Figure 9.13. Cleft anterior mitral valve leaflet, which is only partial. Note that the two-dimensional appearance is similar to Figure 9.12, where the cleft extends toward the aortic valve. The three-dimensional image clearly demonstrates the extent of the cleft. AO, aortic valve; LV, left ventricle; RV, right ventricle.
When a double-orifice mitral valve is associated with exact duplication of the leaflets, tension apparatus, and papillary muscles, it is readily viewed with two-dimensional echocardiography, being best imaged in the parasternal long- and short-axis views (see Fig. 9.15). Color flow Doppler usually demonstrates a competent valve, although occasionally stenosis and regurgitation are present. Three-dimensional echocardiography provides a more complete picture, as the whole valve from annulus to papillary muscle can be appreciated in one view. In addition, imaging the precise area of each orifice is possible with this technique.
Figure 9.14. Three-dimensional enface surgical view of a regurgitant mitral valve, with a the view seen by the surgeon at the time of operation, and saline testing. Note the regurgitant jet extends from the center of the valve orifice into the posteromedial commissure. AL, aortic leaflet; ML, mural leaflet.
It is more difficult with two-dimensional echocardiography to appreciate a double orifice when seen in the setting of an atrioventricular septal defect, particularly when there is a common atrioventricular valve. Although there are no studies available at present, there is the potential that three-dimensional echocardiography will overcome this limitation, mainly because of the ability of this modality to obtain a perception of depth.
A rarer abnormality that can result in congenital mitral valve regurgitation is hypoplasia of the mural leaflet such that the valve leaflets cannot coapt normally during systole. This can be viewed with two-dimensional echocardiography from the parasternal long-axis and apical four-chamber views, where the leaflet appears to be relatively splinted during systole (Fig. 9.16A).
Three-dimensional echocardiography permits the evaluation of the extent of leaflet immobility, which can be best seen from either the “looking up” or the en face views (Fig. 9.16B). These views also allow a detailed assessment of the extent of the regurgitant jet. For example, if the whole valve is involved, then the regurgitant jet extends from commissure to commissure. This is helpful to the surgeon when planning mitral valve repair, invariably through the use of leaflet extension and annuloplasty.
Anomalies of the Tension Apparatus
Anomalies of the tension apparatus include the lesions variously referred to as mitral arcade or hammock valve. This abnormality is characterized by papillary muscles extending directly to the edges of the leaflets (Fig. 9.17). In the most severe form, the muscles fuse on the leading edge of the aortic leaflet, forming the muscular arcade observed by the pathologist or echocardiographer. This type of lesion is frequently associated with significant mitral valve regurgitation (Fig 9.18).
Figure 9.15. Two-dimensional echocardiogram in a double-orifice mitral valve. Note the smaller anterior orifice is regurgitant, unlike its larger counterpart. AO, aorta; LA, left atrium; LV, left ventricle; OR1, orifice 1; OR2, orifice 2.
Straddling Mitral Valve
Mitral valve straddling occurs through an anterior ventricular septal defect, involving the anterior leaflet. It occurs more frequently in hearts where there is an abnormal ventriculoarterial connection, such as transposition with ventricular septal defect, or double-outlet right ventricle. There is invariably an associated cleft in the aortic leaflet, with the free edges being supported by the chordal apparatus. As a result, mitral valve regurgitation is uncommon, unlike the scenario of an isolated cleft in the absence of a ventricular septal defect. The tension apparatus may be inserted into the crest of the interventricular septum, just to its right side, or to a major papillary muscle group situated more toward the apex of the right ventricle (Fig. 9.19). This entity is best viewed in the parasternal long- and short-axis views, where the extent of the straddling and the associated cleft can be appreciated.
Mitral Valve Prolapse
Mitral valve prolapse is encountered less frequently in the pediatric age range in the absence of syndromes, such as Marfan syndrome. In the past, M-mode provided a gross overestimation of the true frequency, which was in part resolved by two-dimensional echocardiography. Even this did not completely resolve the issue, until three-dimensional techniques demonstrated that the mitral annulus was saddle-shaped, with the four-chamber view again resulting in an overdiagnosis of this entity because it demonstrated the low points of the saddle. Therefore, mitral valve prolapse should be diagnosed confidently only in the long-axis view. Using such criteria, a report from the Framingham study demonstrated an incidence of 2.4% in an adult population.
Figure 9.16. The upper four panels display two-dimensional echocardiographic images in the four-chamber and long-axis projections from a patient with a tethered mural leaflet and significant mitral valve regurgitation. Note the relatively fixed position of the mural leaflet. The lower four panels are three-dimensional images of the mitral valve from the same case. Bottom right: The “looking up” view of the mitral valve as seen from the left ventricle. Note the tethering of the mural leaflet. Bottom left: Three-dimensional vena contracta, which extends from one commissure to the other. Note the improved visualization of the regurgitant jet, compared with the two-dimensional image. Top left: Surgical en face view, with the arrow pointing to the tethered mural leaflet. Top right: Two separate papillary muscles within the ventricular cavity. ANT, anterior; ANT COMM, anterior commissure; ANT PAP, anterior papillary muscle; LA, left atrium; LV, left ventricle; LVOT, left ventricular outflow tract; POST COMM, posterior commissure; POST, posterior; POST PAP, posterior papillary muscle; RA, right atrium.
Figure 9.17. Two-dimensional echocardiogram and anatomic specimen (right) from the same patient with a form of mitral arcade. Note the complete fusion of the papillary muscles to the supporting tension apparatus and leaflets. This patient had severe mitral valve stenosis. AO, aorta; LA, left atrium; LV, left ventricle; PM, papillary muscle; RV, right ventricle.
Figure 9.18. This set of images are from a patient with a mitral arcade and severe mitral valve regurgitation. Note the extent of the regurgitant jet, as seen in the lower right-hand panel. As well, the lower left-hand image shows the muscularization of the subvalvar apparatus. AL, aortic leaflet; AO, aorta; APM, anterolateral papillary muscle; LA, left atrium; LV, left ventricle; ML, mural leaflet; PPM, posteromedial papillary muscle; RV, right ventricle.
It is the mural leaflet that is most commonly involved in floppy leaflets. The lesion may affect only one of its scallops, or the entire leaflet may be involved. It has been suggested that the mural leaflet of the mitral valve is less well supported at its free edges than its aortic counterpart, which may predispose it to prolapse.
The affected leaflets are grossly thickened with myxomatous transformation of their atrial aspect, with evidence of annular dilatation that is seen mostly on the atrial aspect of the leaflet. When studied microscopically, this is reflected by obvious myxomatous proliferation of the spongy layer of the leaflet. There is an increase in the spongiosa layer, including altered collagen and an increase in glycosaminoglycans and a disrupted fibrous backbone. Myxomatous valves show disorganized collagen and elastin fibers with pools of proteoglycans from the spongiosa layer present in the load-bearing fibrosa layer. Myxomatous chordae contain significantly more glycosaminoglycans than controls, specifically chondroitin dermatin-6-sulfate and hyaluronan, which binds more water, contributing to the enlarged gelatinous nature of chordae and leaflets. The end result is destruction of the fibrous core of the valve as the essence of the lesion.
Nonsyndromal mitral valve prolapse is most likely autosomal dominant with variable penetrance, as there is clinical heterogeneity in families. It is well recognized that mitral valve prolapse is associated with Marfan syndrome. The recent ability to understand the three-dimensional nature of the mitral valve has provided greater diagnostic specificity, which has aided in an improved understanding of the genetics of nonsyndromal mitral valve prolapse. Based on this new understanding, there has been a linkage of myxomatous mitral valve prolapse to chromosome 16 (MMVP1) in some families, with an autosomal dominant form in others linked to MMVP2 on chromosome 11p15.4 and on 13q31.3–q32.1 in another. Some of the family studies have led to a prodromal form with no actual mitral valve prolapse but with anteriorly shifted leaflet coaptation, indicating posterior leaflet elongation. Others have studied an X-linked valvular dystrophy that has been linked to filament A mutations. Therefore, mitral valve prolapse may be similar to hypertrophic cardiomyopathy with multiple genetic abnormalities responsible for a common phenotype.
Figure 9.19. This montage is from a patient with a straddling mitral valve. The left-hand two-dimensional image shows the chords from the aortic leaflet inserting on a papillary muscle on the anterior free wall of the right ventricle (black arrow). The right-hand panel is the three-dimensional image from the same patient and shows the large anterior muscular VSD through which the mitral valve straddles. LV, left ventricle; RV, right ventricle; IVS, intraventricular septum.
Echocardiographic Assessment of Mitral Valve Prolapse
Two-dimensional echocardiography improves the diagnosis of prolapse by enhancing the spatial configuration of the valvar leaflets. During diastole, the leaflets of the normal valve lie widely open and are more or less parallel, as seen in long-axis sections. With the onset of systole, the two leaflets coapt to give a funnel-shaped appearance. As systole continues, the line of coaptation moves anteriorly and lags behind the aortic root. The entire valvar apparatus then moves anteriorly and inferiorly. Both leaflets frequently arch slightly toward each other and become more horizontal, but no part of the leaflets appears above the atrioventricular junction. Volume overload of the left ventricle from a ventricular septal defect results in an increase in the total excursion of the mitral valve and an even more horizontal position of the leaflets during ventricular systole.
In prolapsing valves the mural, or less often the aortic leaflet (or both), arch toward each other to an excessive degree and pass above the plane of the atrioventricular junction into the left atrium (Fig. 9.20). Either an individual component of the valve is involved, or there is pansystolic hammocking. If records of motion are made from the body of the leaflets rather than from their free edges, about one in six normal patients will have pseudo-prolapse owing to holosystolic hammocking. Even mid-systolic buckling can be artifactually produced in patients with ventricular septal defect and normal mitral valves.
Figure 9.20. Parasternal long-axis view in mitral valve prolapse of the aortic leaflet. Note the significant regurgitation seen (right). LA, left atrium; LV, left ventricle.
Figure 9.21. Mitral valve prolapse. This montage shows a transesophageal two-dimensional view of mitral valve prolapse and then the value of three-dimensional echocardiography, as seen in the middle and right-hand panels. Note that there is significant prolapse of A1 and A2. AO, aorta; LV, left ventricle; A1-A3, aortic leaflet; P1-P3, mural leaflet; LA, left atrium.
Transesophageal multiplane echocardiography has been a useful tool to identify specific leaflet prolapse. At 20 degrees, scallops A3–P1 are seen; at 60 degrees, scallops P3–A2–P1 are demonstrated; at 90 degrees, scallops P3–A1 are visualized; and at 120 to 160 degrees, scallops A2–P2 are seen. Even though this description has been helpful to the cardiologist and surgeon, this is being replaced by three-dimensional echocardiography to aid in the diagnosis and surgical planning of patients with mitral valve prolapse (Fig. 9.21). Indeed, en face surgical views can be obtained from either the transthoracic approach using real-time three-dimensional echocardiography or, until recently, by transesophageal echocardiography using a matrix transducer. This also permits a quantitative approach to the assessment of mitral valve prolapse using software packages that are online (Fig. 9.22). There is good evidence emerging that this technique is superior to either transthoracic or transesophageal two-dimensional echocardiography with regard to specific leaflet pathology, as well as commissural abnormalities. There are few data on the use of three-dimensional echocardiography in the pediatric population. Recent reports, however, using the transesophageal rotation device have demonstrated additive value to standard two-dimensional assessment.
More recently, real-time three-dimensional transesophageal echocardiography has become available, although its application is limited to older children and adults. Indeed, current real-time three-dimensional TEE probes are slightly larger than the standard biplane probes, which limits their use to children who are about 18 kg and greater. Despite the size limitation, three-dimensional TEE provides superior images of the mitral valve. In a real-time mode it can be used to guide catheter interventions, although at the expense of frame rate.
ASSESSMENT OF STENOSIS AND REGURGITATION: QUALITATIVE OR QUANTITATIVE?
Mitral Valve Stenosis
A detailed assessment of mitral valve morphology is important, as this, in conjunction with the hemodynamic effects, determines not only the timing but also the type of intervention. For example, classic dysplastic mitral valve stenosis, without an associated supramitral ring, appears to respond more favorably to balloon dilatation. In adults, the pressure half-time provides an accurate assessment of mitral valve area, independent of cardiac output. This same technique can be applied to children, although absolute valve areas calculated in this way are of little value because of the wide variation in body surface area. Mean gradients across the mitral valve have traditionally been used in assessment of congenital heart disease, despite the limitation of its dependency on cardiac output (Fig. 9.23). Left atrial size is of value, although in some cases the presence of endocardial fibroelastosis of the left atrium prevents dilatation. In addition, the presence of an associated patent foramen ovale or atrial septal defect reduces the value of Doppler mitral inflow assessment. As congenital mitral valve stenosis rarely occurs in isolation, increased inflow from an associated left-to-right shunt at the ventricular or great vessel level provides additional confusion. An assessment of pulmonary arterial pressure, resulting from either tricuspid regurgitation or pulmonary insufficiency, is of value, as invariably the greater the stenosis, the more likely there is to be associated pulmonary hypertension.
Figure 9.22. Mitral valve prolapse. This montage shows four images of mitral valve prolapse, the two upper being two-dimensional images, the lower right as seen by RT3D echocardiography, and the lower left a quantitative approach in the same patient. A, anterior; LA, left atrium; P, posterior.
Figure 9.23. Continuous-wave and color Doppler in congenital mitral valve stenosis. Note that it is only possible to obtain a mean Doppler gradient and not a pressure half-time. LA, left atrium; RA, right atrium; RV, right ventricle.
Mitral Valve Regurgitation
Left Atrial and Left Ventricular Size
In general, there is left atrial and ventricular enlargement in chronic mitral valve regurgitation. These are good indicators of the severity of regurgitation, and indeed both left ventricular end-systolic and end-diastolic dimensions are used to determine optimal timing for surgical intervention. In children, these measurements, as a true representation of the effect of the mitral regurgitation, are less subject to other variables that influence dimensions in an adult population. For example, diastolic dysfunction secondary to aging and ischemic regurgitation is rarely an issue in the pediatric population. The one potential problem that might be encountered is in the patient with an underlying dilated cardiomyopathy who has associated mitral regurgitation.
Primary mitral valve regurgitation is uncommon in the infant and toddler and, if seen, the echocardiographer should pay particular attention to the status of the coronary arteries to exclude an anomalous left coronary artery from the pulmonary artery. In this setting, the right coronary artery is usually dilated and provides an initial clue, with color Doppler permitting the identification of the abnormal origin, as well as the collateral flow.
Pulmonary Venous Doppler Flow Pattern
In general, systolic flow reversal in the pulmonary veins is a useful sign of significant mitral valve regurgitation. Care must be taken to sample all pulmonary veins, as a regurgitant jet may be directed toward one particular vein. Limitations of this technique relate to those patients with diastolic dysfunction, when the systolic pulmonary venous Doppler profile is blunted due to the raised left atrial pressure (Fig. 9.24).
Continuous-Wave Doppler Regurgitant Jet Profile
In general, the more severe the regurgitation, the denser the continuous-wave Doppler profile (see Fig. 9.24).
Mitral E Velocity Dominance
In general, patients with more severe regurgitation have a dominant Doppler E profile through the mitral valve (see Fig. 9.24). Again, the main limitation here is in those cases with associated diastolic dysfunction.
Quantitative Assessment of Mitral Regurgitation
Doppler Assessment of Regurgitant Fraction and Volume
This technique measures the stroke volume through the mitral valve and aorta, the difference of which represents the volume of regurgitation:
SV = CSA × VTI = πd2/4 × VTI = 0.785d2 × VTI
where SV is stroke volume, CSA is cross-sectional area, d is annular diameter, and VTI is velocity-time integral. Therefore,
Regurgitant volume (mL) = SVMV – SVLVOT
Regurgitant fraction = (SVMV – SVLVOT)/SVMV
where MV is mitral valve and LVOT is left ventricular outflow tract. Limitations relate to cross-sectional area measurements, as any measurement errors are squared. Measurement errors can also be caused by poor Doppler alignment and failure to properly trace the modal velocity. Similar measurements can be made by calculating the left ventricular stroke volume with the use of biplane Simpson’s rule and subtracting the left ventricular outflow stroke volume determined with Doppler. The main problem with this methodology relates to obtaining accurate and reproducible stroke volume measurements by Simpson’s biplane rule. Three-dimensional echocardiography will play an increasingly important role in the assessment of left ventricular volumes for stroke volume measurements, as it is more accurate and reproducible than two-dimensional biplane calculations.
Figure 9.24. Doppler profiles from a child with significant mitral valve regurgitation. Top left: Dominant “E” wave. Bottom left: Blunted systolic forward flow in the pulmonary veins. Top right: Normal mitral annular tissue Doppler. Bottom right: Dense continuous-wave Doppler profile of mitral regurgitation.
Contribution of Color Flow Doppler
Color Doppler is essential to identify the presence of mitral regurgitation and to pinpoint the site of insufficiency. This has been enhanced with the advent of three-dimensional echocardiography. It is important to understand some of the limitations of two-dimensional color flow mapping. Color flow mapping measures velocity and not volume, so it is very gain sensitive. In addition, it is affected by adjacent boundaries, with the Coanda affect having an impact on apparent jet size when the regurgitation is not central. For all these reasons, there has been a concerted effort to provide a volumetric assessment of regurgitation. Unlike its two-dimensional counterpart, this three-dimensional technique permits the construction of en face views, as seen by the surgeon, or “looking up” views from the left ventricle, as seen by the echocardiographer. These views permit a detailed assessment of the site of the regurgitant jet(s) (see Figs. 9.14 and 9.18), as well as of the size of the vena contracta (the width of the jet origin).
There is good evidence that the vena contracta size is an accurate representation of the volume of regurgitant flow (see Fig. 9.14). Thus, by summating the vena contractas, a semiquantitative assessment of regurgitant volume can be assessed. This helps to overcome the limitations of color flow mapping by two-dimensional echocardiography. Although it is possible to measure vena contracta diameter by this method, it does not take shape into consideration. When imaged by three-dimensional echocardiography, it is clear that many vena contractas are irregular in shape, hence the potential for underestimation or overestimation of size using two-dimensional echocardiography alone. In addition, identifying multiple jets and those involving the commissures is problematic by two-dimensional echocardiography. Three-dimensional color flow Doppler is becoming increasingly useful in measuring vena contracta area, especially in the presence of multiple jets. Vena contracta area provides a reliable and accurate assessment of regurgitant orifice area compared to current two-dimensional standard measures for assessing mitral regurgitation severity. However, current vena contracta assessment is usually done during one phase of systole, which does not take the dynamic variation of regurgitation into consideration.
Proximal Isovelocity Surface Area or Flow Convergence
Proximal isovelocity surface area (PISA) is based on the principle that as blood approaches an orifice, it forms a series of concentric, roughly hemispheric shells that increase in velocity but decrease in area (Fig. 9.25A). In practical terms, the color Doppler Nyquist limit is set to a value at which aliasing occurs near the regurgitant orifice. From this the regurgitant flow is calculated as:
2πr2 × Va
where r is radius of aliasing velocity and Va is velocity at which aliasing occurs. From this, effective regurgitant orifice area (EROA) can be calculated as: Regurgitant flow/Peak velocity of regurgitation (Fig. 9.25B). Limitations of this technique are related to (a) the shape of the PISA shell, which may not be a hemisphere, (b) multiple jets, and (c) the effect of adjacent boundaries, as well as in determining the precise location of the regurgitant orifice. A recent study comparing two-dimensional PISA calculation of regurgitant volume to that measured by real-time three-dimensional echocardiography showed that the former method significantly underestimated the true volume.
Transesophageal echocardiography has provided an additional tool for the evaluation of the congenitally abnormal mitral valve. Fortunately, apart from the older child or obese patient, this technique is unnecessary in the majority of cases. It is also apparent that transesophageal color flow mapping appears to be more sensitive than transthoracic assessment. Systematic overestimation of the severity of regurgitation is found when it is compared with standard transthoracic assessment.
Figure 9.25. Proximal isovelocity surface area (PISA). A: Anatomy of a regurgitant color flow jet. Note the PISA (asterisk) and the vena contracta (outlined by arrow). LV, left ventricle. B: cartoon demonstrating PISA and the measurements that are made in the PISA calculation (B, courtesy of Dr. Brian Sonnenberg).
Three-Dimensional Echocardiography in Mitral Valve Disease
Despite the excellent information provided by two-dimensional echocardiography of the mitral valve, there is increasing evidence in adults and now in children that three-dimensional echocardiography provides new and complementary anatomical and pathological information. Three-dimensional echocardiography has been vital in demonstrating the saddle shape of the annulus as well as the dynamic annular changes seen throughout the cardiac cycle. Recent guidelines for the use of three-dimensional echocardiography have highlighted its advantages for quantification of left ventricular volumes and function which are important for assessment of the severity of mitral valve disease. When used clinically, three-dimensional echocardiography increases the diagnostic accuracy, particularly in pathology affecting the commissural and the subvalve regions. It may improve localization of pathology or regurgitant jets. Three-dimensional echocardiography can aid communication of anatomical and pathological findings with the surgical team when intervention is required.
What is needed to optimally assess mitral regurgitation is a true volumetric assessment of regurgitant volume by three-dimensional echocardiography. Early, preclinical use of matrix-array technology has provided encouraging results. Using broad-beam spectral Doppler on a matrix probe, it has been possible to measure a power velocity integral (PVI), which represents volume flow. The strength of this technique is that it takes into consideration variations of the regurgitant volume throughout systole. The current limitation is that it is a prototype and still has a limited window; hence, it is applicable to single, more central jets. Assessment of flow through the regurgitant orifice allows estimation of regurgitant volume and regurgitant fraction. Similarly, measurement of stroke volume through the aortic and mitral valve provides an indirect measurement of regurgitant volume and regurgitant fraction. These direct and indirect measurements have proved accurate and reproducible in the adult population when compared to cardiac magnetic resonance imaging as the reference standard. Unfortunately, this has not been repeated in the pediatric age group, and indeed a multicenter study was unable to demonstrate any benefit of the volumetric approach to quantitative mitral regurgitant assessment.
SURGICAL INTERVENTION: TIMING AND TECHNIQUE
Briefly, surgical techniques for mitral valve disease vary with the presenting valvar pathology. Accepted practice at most centers is to attempt repair, indeed often repeatedly, prior to replacing the valve with a tissue or mechanical prostheses.
There is little data in children demonstrating robust, evidence-based criteria for intervention for mitral stenosis. Most adult data is based on rheumatic mitral valve disease. Based on adult recommendations, mitral valve area less than 1 cm2, mean gradient greater than 10 mm Hg, and pulmonary artery pressure greater than 50 mm Hg are considered severe. In practice, serial assessments of patient symptoms and growth, combined with the above echocardiographic parameters, will probably provide the most useful information to assist in the timing of interventions.
In recent case series of surgical repair of mitral stenosis, the predominant abnormalities included supravalvar mitral ring, parachute mitral valve, and isolated congenital mitral stenosis with valve dysplasia, hypoplasia, and fused commissures and chords. Surgical repair of a supravalvar ring involves resection of the ring in its entirety from the valve. This is often successful but recurrent resection is often required. Parachute mitral valves may require surgical “splitting” of the single papillary muscle to produce two papillary muscles, and often also includes commissurotomy or leaflet-splitting. Mitral valve dysplasia/hypoplasia will often require commissurotomy and/or papillary muscle-splitting to increase valvar orifice and leaflet mobility. Balloon mitral valvuloplasty has been demonstrated to effectively relieve mitral stenosis due to congenital mitral stenosis without supravalvar ring or rheumatic mitral stenosis, with slightly higher risk of re-intervention and postprocedure mitral regurgitation compared to surgical valvotomy.
It is currently unclear whether an increase in the size of the left ventricle represents deterioration in ventricular function or just an alteration to accommodate an increase in regurgitant volume. The “Holy Grail” of echocardiography is to match reproducible and accurate volume changes with alterations in left ventricular function, which then predict timing for intervention. Currently echocardiographers of the adult population struggle with this, so in the pediatric population, congenital echocardiographers are at an even greater disadvantage due to the smaller measurements that are being made.
What is probably safer is an extrapolation from adult data using an indexed end-systolic diameter of greater than 4.5 cm or an ejection fraction by volumetric assessment of less than 60% as echocardiographic indications for valve surgery in those with predominant mitral valve regurgitation. Of course, patient growth, symptoms, and pulmonary artery pressure have to be factored into the equation. In addition, it is unclear whether this extrapolation is an accurate one or whether the pediatric left ventricle is more robust than its adult counterpart. In the adult population a left atrial volume index of >60mLs/m2 has been factored in as a class 2B indication; however, there is no pediatric data that corresponds with this.
Pathology associated with mitral regurgitation includes an isolated mitral valve cleft, annular dilatation, leaflet prolapse or restriction, and valve dysplasia. The majority of surgical interventions involve multiple techniques to improve leaflet coaptation. Closure of the isolated cleft, where present, often achieves good results without any additional procedure involving the mitral valve apparatus. For other MV pathology, annuloplasty is invariably required, ranging from a placement of a complete annuloplasty ring, to partial or complete posterior annuloplasty. In younger children, partial annuloplasty may allow for more growth with time. For prolapsing leaflets, surgery to the chordae, including shortening or transfer, has been used to limit leaflet excursion.
Agricols E, Oppizzi M, De Bonis M, et al. Multiplane transesophageal echocardiography performed according to the guidelines of the American Society of Echocardiography in patients with mitral valve prolapse, flail, and endocarditis: diagnostic accuracy in the identification of mitral regurgitant defects by correlation with surgical findings. J Am Soc Echocardiogr. 2003;16:61–66.
Arora R, Mukhopadhyay S, Yusuf J, et al. Technique, results, and follow-up of interventional treatment of rheumatic mitral stenosis in children. Cardiol Young. 2007;17:3–11.
Asante-Korang A, O’Leary PO, Anderson RH. Anatomy and echo of the normal and abnormal mitral valve. Cardiol Young. 2006;16:27–34.
Banerjee A, Kohl T, Silverman NH. Echocardiographic evaluation of congenital mitral valve anomalies in children. Am J Cardiol. 1995;76:1284–1291.
Barrea C, Levasseur S, Roman K, et al. Three-dimensional echocardiography improves the understanding of left atrioventricular valve morphology and function in atrioventricular septal defects undergoing patch augmentation. J Thorac Cardiovasc Surg. 2005;129:746–753.
Baumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. J Am Soc Echocardiogr. 2009;22:1–23.
Becker AE. Valve pathology in the paediatric age group. In: Anderson RH, MaCartney FJ, Shinebourne EA, Tynan M, eds. Paediatric cardiology, vol 5. Edinburgh: Churchill Livingstone, 1983:345–360.
Becker AE, de Wit APM. Mitral valve apparatus. A spectrum of normality relevant to mitral valve prolapse. Br Heart J. 1979;42:690.
Bini RM, Pellegrino PA, Mazzucco A, et al. Tricuspid atresia with double-outlet left atrium. Chest. 1980;78:109–111.
Bonow RO, Carabello BA, Chatterjee K, et al. Writing Committee Members. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: executive summary. J Am Coll Cardiol. 2006;114:450–527.
Bonow RO. Chronic mitral regurgitation and aortic regurgitation. J Am Coll Cardiol. 2013;61:693–701.
Borer JS, Bonow RO. Contemporary approach to aortic and mitral regurgitation. Circulation. 2003;108:2432–2438.
Buck T, Plicht P, Hunold P, et al. Broad beam spectral Doppler sonification of the vena contracta using matrix-array technology. J Am Coll Cardiol. 2005;45:770–779.
Carlhall C, Wigstrom L, Heiberg E, et al. Contribution of mitral annular excursion and shape dynamics to total left ventricular volume change. Am J Physiol Heart Circ Physiol. 2004;287:H1836–H1841.
Carpentier A, Branchini B, Cour JC, et al. Congenital malformations of the mitral valve in children. Pathology and surgical treatment. J Thorac Cardiovasc Surg. 1976;72:854–866.
Castello R, Lenzen P, Aguire F, et al. Variability in the quantitation of mitral regurgitation by Doppler color flow mapping: comparison of transthoracic and transesophageal studies. J Am Coll Cardiol. 1992;20:433–438.
Chao K, Moises VA, Shandas R, et al. Influence of the Coanda effect on color Doppler jet area and color encoding. In vitro studies using color Doppler flow mapping. Circulation. 1992;85:333–341.
Cheitlin MD. Valvular heart disease: management and intervention. Circulation. 1991;84(suppl I):I-259–I-264.
Collins-Nakai RL, Rosenthal A, Castaneda AR, et al. Congenital mitral stenosis. A review of 20 years’ experience. Circulation. 1977;56:1039–1046.
Coto EO, Jimenez MQ, Deverall PB, et al. Anomalous mitral “cleft” with abnormal ventriculoarterial connection: anatomical findings and surgical implications. Pediatr Cardiol. 1984;5:1–6.
Dal-Bianco JP, Aikawa E, Bischoff J, Guerrero JL, Handschumacher MD, Sullivan S, Johnson B, Titus JS, Iwamoto Y, Wylie-Sears J, Levine RA, Carpentier A. Active adaptation of the tethered mitral valve: insights into a compensatory mechanism for functional mitral regurgitation. Circulation.2009;120:334–342.
Daliento L, Thiene G, Chirillo F, et al. Congenital mitral valve malformations: clinical and morphological aspects. Ital J Cardiol. 1991;21:1205–1216.
de Lange FJ, Moorman AFM, Anderson RH, et al. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004;95:645–654.
Enriquez-Sarano M, Bailey KR, Seward JB, et al. Quantitative Doppler assessment of valvular regurgitation. Circulation. 1993;87:841–848.
Feigenbaum H. Echocardiography in the management of mitral valve prolapse. Austral NZ J Med. 1992;22:550–555.
Fernex M, Fernex C. La dégénérescence mucoide des valvules mitrales. Ses repercussions functionelles. Helv Med Acta. 1958;25:694–705.
Freed LA, Levy D, Levine RA, et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med. 1999;341:41–47.
García-Orta R, Moreno E, Vidal M, et al. Three-dimensional versus two-dimensional transesophageal echocardiography in mitral valve repair. J Am Soc Echocardiogr. 2007;20:4–12.
Glasson JR, Komeda M, Daughters GT, et al. Most ovine mitral annular three-dimensional size reduction occurs before ventricular systole and is abolished with ventricular pacing. Circulation. 1997;96(9 suppl):II-22.
Goldberg SJ, Gerlis LM, Ho SY, et al. Location of the left papillary muscles in juxtaductal aortic coarctation. Am J Cardiol. 1995;75:746–750.
Grande-Allen KJ, Griffin BP, Calabro A, et al. Myxomatous mitral valve chordae. II: selective elevation of glycosaminoglycan content. J Heart Valve Dis. 2001;10:325–332; discussion 332–323.
Hatle L, Brubakk A, Tromsdal A, et al. Noninvasive assessment of pressure drop in mitral stenosis by Doppler ultrasound. Br Heart J. 1978;40:131–140.
Hoashi T, Bove EL, Devaney EJ, et al. Mitral valve repair for congenital mitral valve stenosis in the pediatric population. Ann Thorac Surg. 2010;90:26–41.
Kanani M, Moorman AFM, Cook AC, et al. Development of the atrioventricular valves: clinicomorphologic correlations. Ann Thorac Surg. 2005;79:1797–1804.
Karlsson MO, Glasson JR, Bolger AF, et al. Mitral valve opening in the ovine heart. Am J Physiol. 1998;274(2 Pt 2):H552–H563.
Karr SS, Parness IA, Spevak PJ, et al. Diagnosis of anomalous left coronary artery by Doppler color flow mapping: distinction from other causes of dilated cardiomyopathy. J Am Coll Cardiol. 1992;19:1271–1275.
Kohl T, Silverman N. Comparison of cleft and papillary muscle position in cleft mitral valve and atrioventricular septal defect. Am J Cardiol. 1996;77:164–169.
Koike K, Musewe NM, Smallhorn JF, et al. Distinguishing between anomalous origin of the left coronary artery from the pulmonary trunk and dilated cardiomyopathy: role of echocardiographic measurement of the right coronary artery diameter. Br Heart J. 1989;61:192–197.
Kwan J, Qin JX, Popovic ZB, et al. Geometric changes of mitral annulus assessed by real-time 3-dimensional echocardiography: becoming enlarged and less nonplanar in the anteroposterior direction during systole in proportion to global left ventricular systolic function. J Am Soc Echocardiogr.2004;17:1179–1184.
Lang RM, Badano LP, Tsang W, et al. EAE/ASE recommendations for image acquisition and display using three-dimensional echocardiography. J Am Soc Echocardiogr. 2012;25:3–46.
Lansac E, Lim KH, Shomura Y, et al. Dynamic balance of the aortomitral junction. J Thorac Cardiovasc Surg. 2002;123:911–918.
Layman TE, Edwards JE. Anomalous mitral arcade. A type of congenital mitral insufficiency. Circulation. 1967;35:389–395.
Lee C, Lee CH, Kwak JG, et al. Long-term results after mitral valve repair in children. Eur J Cardiothorac Surg. 2010;37:267–272.
Leung M, Rigby ML, Anderson RH, et al. Reversed offsetting of the septal attachments of the atrioventricular valves and Ebstein’s malformation of the morphologically mitral valve. Br Heart J. 1987;57:184–187.
Levine RA, Slaugenhaupt SA. Molecular genetics of mitral valve prolapse. Curr Opin Cardiol. 2007;22:171–175.
Levine RA, Triulzi MO, Harrigan P, et al. The relationship of mitral annular shape to the diagnosis of mitral valve prolapse. Circulation. 1987;75:756–767.
Little SH, Igo SR, Pirat B, et al. In vitro validation of real-time three-dimensional color Doppler echocardiography for direct measurement of proximal isovelocity surface area in mitral regurgitation. Am J Cardiol. 2007;99:1440–1447.
Malkowski MJ, Boudoulas H, Wooley CF, et al. Spectrum of structural abnormalities in floppy mitral valve echocardiographic evaluation. Am Heart J. 1996;132:145–151.
McElhinney DB, Sherwood MC, Keane JF, et al. Current management of severe congenital mitral stenosis, outcomes of transcatheter and surgical therapy in 108 infants and children. Circulation. 2005;112:707–714.
Mele D, Soukhomovskaia O, Pacchioni E, et al. Proximal flow convergence region as assessed by real-time three-dimensional echocardiography: challenging the hemispheric assumption. J Am Soc Echocardiogr. 2007;20:389–396.
Mickell JJ, Mathews RA, Anderson RH, et al. The anatomical heterogeneity of hearts lacking a patent communication between the left atrium and the ventricular mass (‘mitral atresia’) in presence of a patent aortic valve. Eur Heart J. 1983;4:477–486.
Moreno F, Quero M, Diaz LP. Mitral atresia with normal aortic valve. A study of eighteen cases and a review of the literature. Circulation. 1976;53:1004–1010.
Müller S, Müller L, Laufer G, et al. Comparison of three-dimensional imaging to transesophageal echocardiography for preoperative evaluation in mitral valve prolapse. Am J Cardiol. 2006;98;243–248.
Nii M, Roman KS, Macgowan CK, et al. Insight into normal mitral and tricuspid annular dynamics in pediatrics: a real-time three-dimensional echocardiographic study. J Am Soc Echocardiogr. 2005 Aug;18(8):805–814.
Oberhansli I, Baldovinos A, Beghetti M, et al. Hypoplasia of the posterior leaflet as a rare cause of congenital mitral insufficiency. J Card Surg. 1997;12:339–342.
Otsuji Y, Gilon D, Jiang L, et al. Restricted diastolic opening of the mitral leaflets in patients with left ventricular dysfunction: evidence for increased valve tethering. J Am Coll Cardiol. 1998;32:398–404.
Padang R, Bagnall RD, Semsarian C. Genetic basis of familial valvular heart disease. Circ Cardiovasc Genetics. 2012;5:569–580.
Passafini A, Shiota T, Depp M, et al. Factors influencing pulmonary venous flow velocity patterns in mitral regurgitation: an in vitro study. J Am Coll Cardiol. 1995;26:1333–1339.
Patel V, Hsiung MC, Nanda NC, et al. Usefulness of live/real time three-dimensional transthoracic echocardiography in the identification of individual segment/scallop prolapse of the mitral valve. Echocardiography. 2006;23:513–518.
Pepi M, Tamborini G, Maltagliati A, et al. Head-to head comparison of two- and three-dimensional transthoracic and transesophageal echocardiography in the localization of mitral valve. J Am Coll Cardiol. 2006;48:2524–2530.
Prakash A, Lacro RV, Sleeper LA, et al. Challenges in echocardiographic assessment of mitral regurgitation after repair of atrioventricular septal defect. Pediatr Cardiol. 2012;33:205–214.
Ruckman RN, Van Praagh R. Anatomic types of congenital mitral stenosis: report of 49 autopsy cases with consideration of diagnosis and surgical implications. Am J Cardiol. 1978;42:592–601.
Salgo IS, Gorman JH 3rd, Gorman RC, et al. Effect of annular shape on leaflet curvature in reducing mitral leaflet stress. Circulation. 2002;106:711–717.
Shone JD, Sellers RD, Anderson RC, et al. The developmental complex of “parachute mitral valve”, supravalvular ring of left atrium, subaortic stenosis, and coarctation of aorta. Am J Cardiol. 1963;11:714–725.
Sigfusson G, Ettedgui JA, Silverman NH, et al. Is a cleft in the anterior leaflet of an otherwise normal mitral valve an atrioventricular canal malformation? J Am Coll Cardiol. 1995;26:508–515.
Sittiwangkul R, Ma RY, McCrindle BW, et al. The echocardiographic assessment of obstructive lesions in atrioventricular septal defect. J Am Coll Cardiol. 2001;38:253–261.
Smallhorn JF, De Leval M, Stark J, et al. Isolated anterior mitral cleft. Two-dimensional echocardiographic assessment and differentiation from ‘clefts’ associated with atrioventricular septal defect. Br Heart J. 1982;48:109–116.
Smallhorn JF, Sutherland GR, Anderson RH, et al. Cross-sectional echocardiographic assessment of conditions with atrioventricular valve leaflets attached to the atrial septum at the same level. Br Heart J. 1982;48:331–341.
Stellin G, Padalino MA, Vida VL, et al. Surgical repair of congenital mitral valve malformations in infancy and childhood: a single-center 36-year experience. J Thorac Cardiovasc Surg. 2010;140:1238–1244.
Sugeng L, Shernan SK, Salgo IS, et al. Live three-dimensional transesophageal echocardiography: initial experience using a full-sampled matrix array probe. J Am Coll Cardiol. 2008;52: 446–449.
Sugeng L, Shernan SK, Weinert L, et al. Real-time three-dimensional transesophageal echocardiography in valve disease: comparison with surgical findings and evaluation of prosthetic valves. J Am Soc Echocardiogr. 2008;21:1347–1354.
Sugeng L, Weinert BS, Lang RM. Real time three-dimensional color Doppler flow of mitral and tricuspid valve regurgitation: feasibility and initial quantitative comparison with 2-dimensional methods. J Am Soc Echocardiogr. 2007;20:1050–1057.
Sullivan ID, Robinson PJ, de Leval M, et al. Membranous supravalvular mitral stenosis: a treatable form of congenital heart disease. J Am Coll Cardiol. 1986;8:159–164.
Takahashi K, Guerra V, Roman KS, et al. Three-dimensional echocardiography improves the understanding of the mechanisms and site of left atrioventricular valve regurgitation in atrioventricular septal defect. J Am Soc Echocardiogr. 2006;19:1502–1510.
Takahashi K, Mackie AS, Rebeyka IM, et al. Two-dimensional versus transthoracic real-time three-dimensional echocardiography in the evaluation of the mechanisms and sites of atrioventricular valve regurgitation in a congenital heart disease population. J Am Soc Echocardiogr.2010;23:26–34.
Tamura M, Menahem S, Brizard C. Clinical features and management of isolated cleft mitral valve in childhood. J Am Coll Cardiol. 2000;35:764–770.
Thavendiranathan P, Liu S, Datta S, et al. Automated quantification of mitral inflow and aortic outflow stroke volumes by three-dimensional real-time volume color-flow Doppler transthoracic echocardiography: comparison with pulsed-wave Doppler and cardiac magnetic resonance imaging. J Am Soc Echocardiogr. 2012;25:56–65.
Thavendiranathan P, Phelan D, Collier P, et al. Quantitative assessment of mitral regurgitation: how best to do it. J Am Coll Cardiol Img. 2012;5:1161–1175.
Timòteo A, Galrinho A, Fiarresga A, et al. Isolated cleft of the anterior mitral valve leaflet. Eur J Echocardiogr. 2005;8: 59–62.
Tsakiris AG, Von Bernuth G, Rastelli C, et al. Size and motion of the mitral valve annulus in anesthetized dog hearts. J Appl Physiol. 1971;30:611–618.
Tsang W, Weinert L, Sugeng L, et al. The value of three-dimensional echocardiography derived mitral valve parametric maps and the role of experience in the diagnosis of pathology. J Am Soc Echocardiogr. 2011;24:860–867.
Van der Bel Kahn J, Duren DR, Becker AE. Isolated mitral valve prolapse: chordal architecture as an anatomic basis in older patients. J Am Coll Cardiol. 1985;5:1335–1340.
Watson DG, Rowe RD, Coren PE, et al. Mitral atresia with normal aortic valve. Report of 11 cases and review of the literature. Pediatrics. 1960;25:450–467.
Wenink ACG, Goot GD, Brom AG. Developmental considerations of mitral valve anomalies. Int J Cardiol. 1986;11:85–98.
Yellin EL, Peskin C, Yoran C, et al. Mechanisms of mitral valve motion during diastole. Am J Physiol Heart Circ Physiol. 1981;241:H389–H400.
Zeng X, Levine R, Hua L, et al. Diagnostic value of vena contracta area in the quantification of mitral regurgitation severity by color Doppler 3D echocardiography. Circ Cardiovasc Imaging. 2011;4:506–513.
Zoghbi WA, Enriquez-Sarano M, Foster E, et al. Recommendations for evaluation of the severity of native valvar regurgitation with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr. 2003;16:777–802.
1.Abnormal apoptosis of myocardial tissue from the mitral valve leaflets is associated with which of the following echocardiographic findings:
A.Elongated chordal tissue
B.Prolonged mitral valve inflow pressure half-time
C.Left atrial dilatation
D.Single papillary muscle
2.A child has mitral valve pathology related to incomplete fusion of the superior and inferior endocardial cushions. Which of the following echocardiographic features suggests that surgical repair is warranted:
A.Dilated left ventricle (LV end-systolic diameter 4 cm / m2)
B.Ejection fraction of 50%
C.Thickened leaflet edges
D.Systolic flow reversal in the pulmonary veins on pulsed wave Doppler
3.In children, atrial contraction contributes to mitral valve annular function by its effect on:
A.increasing mitral valve annular bending angle.
B.improving leaflet coaptation.
C.annular dilatation in early diastole.
D.reducing commissure-commissure diameter.
4.A mitral valve cleft without significant regurgitation is most likely to be associated with the following echocardiographic findings:
A.Closely spaced papillary muscles
B.Mitral valve cleft angled towards the left-ventricular outflow tract
C.Ventricular septal defect seen in the apical four-chamber view at the level of the mitral and tricuspid valves
D.Double-outlet right ventricle
5.The cause of mitral valve dysfunction related to abnormal papillary muscle position in children is associated with which of the following echocardiographic findings:
A.Dilated right coronary artery
B.Closely spaced papillary muscles
C.Prolapse of mural leaflet
D.Ventricular septal defect
6.Delamination defects affecting the mitral valve differ from those affecting the tricuspid valve in that:
A.atrioventricular valve regurgitation is uncommon.
B.atrialization of the ventricle does not occur.
C.it affects leaflets formed by fusion of the inferior and superior endocardial cushions.
D.associated atrial septal defects are more common.
7.Abnormal growth of the left ventricular parietal wall is best seen in which trans-thoracic echocardiographic view:
A.Parasternal short-axis at the apical level
B.Apical four-chamber view
C.Parasternal long-axis view of the left ventricular inflow and outflow
D.Parasternal short-axis view at the level of the papillary muscles
8.Mitral valve disease caused by destruction of the fibrous core is best imaged in which trans-esophageal view?
A.Mid-esophageal 0-20 degrees
B.Mid-esophageal 90 degrees
C.Mid-esophageal 120-140 degrees
D.Trans-gastric 0-30 degrees
9.Which of the following cardiac lesions does NOT have a confounding effect on assessment of mitral valve stenosis:
A.Atrial septal defect
B.Ventricular septal defect
C.Mitral valve regurgitation
10.Which of the mitral valve pathologies described by Shone and colleagues is due to abnormal compaction of ventricular myocardium:
A.Mitral valve arcade
C.Parachute mitral valve
D.Mitral valve dysplasia
1.Answer: C. Persistence of myocardium in leaflet tissue results in mitral arcade, which is associated with significant regurgitation and left atrial dilatation, rather than stenosis.
2.Answer: B. Indications are not entirely clear, but LV dysfunction (EF, 60%) is considered an indication for surgery in the context of significant MR.
3.Answer: D. Atrial contraction causes annular area reduction in the commissure-commissure direction.
4.Answer: D. A cleft mitral valve is more common in the context of straddling mitral valve with abnormal atrioventricular connections. The free edges of the cleft are well supported by chordal tissue, and thus regurgitation is uncommon.
5.Answer: A. Abnormal papillary muscle position is associated with ischemia, as seen in anomalous left coronary artery from pulmonary artery. The right coronary artery is often dilated in this condition.
6.Answer: A. Ebstein anomaly of the mitral valve affects the mural leaflet, causing significant regurgitation but not atrialization of the left ventricle.
7.Answer: D. Abnormal growth of the LV parietal wall is seen in atrioventricular septal defects. It is seen in the short-axis views at the level of the papillary muscles as closely-spaced papillary muscles, or a rotated posterior-medial papillary muscle counter-clockwise.
8.Answer: C. Mitral valve prolapse is caused by myxomatous proliferation of the spongy layer of the leaflet, disrupting the fibrous backbone. Viewing the valve in the parasternal long-axis view is the accepted way to diagnose this condition. The TEE mid-esophageal 120 degree view is an equivalent long-axis view.
9.Answer: D. Mitral regurgitation and ventricular septal defects are associated with increased flow through the mitral valve affecting estimation of mitral inflow gradient. Atrial septal defects reduce mitral valve inflow, and thus reduce the velocity of mitral valve inflow Doppler.
10.Answer: C. Papillary muscles are formed from columns of ventricular myocardium via compaction of the trabecular layer. Abnormal compaction is associated with formation of a parachute mitral valve.