In this chapter, we discuss those lesions than afflict the morphologically mitral valve, the likeness to the episcopal mitre of this valve in the normal heart first being emphasised by Andreas Vesalius, the Belgian morphologist, who worked in Padova, the birthplace of cardiac morphology, in the 15th century. As with the episcopal headwear, the feature of the normally constructed mitral valve is the solitary zone of apposition between its component parts, the leaflets, this feature producing a bifoliate pattern of closure. The pattern of closure, in turn, distinguishes the normally structured left valve from the left half of the common valve seen in the setting of atrioventricular septal defect with common atrioventricular junction. Although similar lesions can affect the left-sided heart when there are separate or common atrioventricular junctions, the anomalies involving the left half of the common valve will be discussed in Chapter 27 . We also reserve discussion of anomalies of the left-sided valves in hearts with double inlet ventricle for Chapter 31 , despite the fact that, when there is double inlet to a dominant left ventricle, it is usual for both atrioventricular valves to resemble the morphologically mitral valve. Either the right-sided or left-sided valve, nonetheless, can be deformed in this setting. In this chapter, therefore, we confine our attention to the valve guarding the inlet to the morphologically left ventricle in hearts with separate right and left atrioventricular junctions. The lesions to be described that involve the morphologically mitral valve, therefore, can also involve this valve when both the atrioventricular and ventriculo-arterial connections are discordant. The latter malformation, best described as congenitally corrected transposition, will receive its own coverage in Chapter 39 .
MORPHOLOGY
It is convenient, albeit not always entirely accurate, to describe the abnormal morphology in terms of malformation of the various components of the mitral valve, remembering that, in functional terms, such derangement can result in stenosis, incompetence, or both.1–3 In terms of anatomy, we will discuss anomalies of the leaflets, the tension apparatus, and the papillary muscles, all of these components working in harmony when the valve is normal ( Fig. 35-1 ). The leaflets are hinged from the annulus, but this is far from a constant structure in the mitral valve. Furthermore, as far as we are aware, there are no specific congenital lesions that afflict only the annulus. The hinges of the aortic and mural leaflets are markedly different in their structure. The hinge, or annulus, of the anterior leaflet of the valve is the area of its fibrous continuity with the leaflets of the aortic valve, hence our preference to describe this leaflet of the valve as being aortic. The two ends of the region of fibrous continuity between the leaflets of the atrioventricular and arterial valves are themselves thickened as the right and left fibrous trigones. It is the anchorage of these trigones to the basal surface of the ventricular mass that secures the combined unit of the inlet and outlet valves within the left ventricle ( Fig. 35-2 ). The part of the mitral valvar circumference formed by the aortic leaflet, therefore, is strong. It is much less likely to dilate under abnormal circumstances than the remaining part of the valve. This second part of the valve, the mural or posterior leaflet, is anchored along the parietal part of the left atrioventricular junction. There is marked variation in the arrangement of the mural annulus itself. 4 In places, it is a firm fibrous cord that fits well with the notion of a ring ( Fig. 35-3 ). It is unusual, nonetheless, for such a fibrous ring to support the entirety of the leaflet throughout the mural part of the valvar perimeter. In places, the cord is replaced by a longer fibrous sheet, or else the fibrous tissue becomes deficient, with the atrial and ventricular musculatures separated by fibroadipose tissue rather than a true annulus. 4 Because of this variation, and the frequent lack of a complete fibrous ring, it is this part of the valvar circumference that dilates in the setting of valvar disease. In such cases of acquired change, it is often the case that all parts of the valve are abnormal. We commence our account of morphology, therefore, by considering anomalies of the entire valvar apparatus.
Mitral Valvar Dysplasia and Hypoplasia
All components of the complex are malformed when the valve is dysplastic and hypoplastic. The leaflets are thickened, the intercordal spaces often obliterated and the papillary muscles 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 underscoring congenital mitral stenosis, be this isolated or as seen most frequently in the setting of hypoplasia of the left heart ( Fig. 35-4 ).
When the free edges of the dysplastic valve leaflets are thickened and rolled, the valve may be incompetent as well as stenotic. Occasionally, mitral stenosis may be produced when the valve is hypoplastic and dysplastic.
Anomalies of the Leaflets
The most extreme anomaly involving the leaflets is an imperforate valve ( Fig. 35-5 ). Such imperforate valves are seen most frequently in combination with aortic atresia, when they form part an integral part of the hypoplastic left ventricle syndrome (see Chapter 29 ). In this setting, from the stance of anatomy, the imperforate valve is distinguished from absence of the left atrioventricular connection ( Fig. 35-6 ), since both produce atrioventricular valvar atresia. In the setting of left heart hypoplasia, of course, this morphological distinction is rarely, if ever, of clinical significance. In hypoplasia of the left heart, when the left atrioventricular connection is absent, the right atrium is connected to a dominant right ventricle. The left atrioventricular connection can also be absent when the right atrium is connected to a dominant left ventricle ( Fig. 35-7 ). This lesion is best considered in the setting of the functionally univentricular heart (see Chapter 31 ). Imperforate mitral valves, of course, can also be found without aortic atresia (see Fig. 35-5 ), and are then part of the combination termed mitral atresia with patent aortic root. 5 The ventriculo-arterial connection is often double outlet from the right ventricle, but in a significant number of cases, the patent aorta arises from a good-sized left ventricle. The ventricle is then filled through a ventricular septal defect.
Ebstein’s malformation can rarely affect the morphologically mitral valve. 6 When this is the case, the mural leaflet is plastered down onto the ventricular wall, with its hinge below the atrioventricular junction ( Fig. 35-8 , left panel). In this setting, there is no thinning of the atrialised inlet portion, as is usually seen when it is the morphologically tricuspid valve that is deformed in the setting of concordant atrioventricular connections ( Fig. 35-8 , middle panel). Such lack of morphologic atrialisation is also a feature of Ebstein’s malformation of the left-sided atrioventricular valve in the setting of congenitally corrected transposition, but then, of course, the valve itself is of tricuspid morphology ( Fig. 35-8 , right panel; see Chapter 39 ).
The isolated cleft is another anomaly confined to the leaflet, usually involving the leaflet in fibrous continuity with the leaflets of the aortic valve ( Fig. 35-9 ). Well explained on the basis of failure of fusion between the left ventricular components of the superior and inferior atrioventricular cushions, 7 the space between the cleft components of the leaflet creates the substrate for valvar incompetence. Both parts of the cleft leaflet tend to be dysplastic, and the edges are usually rolled and thickened (see Fig. 35-9 ). The cleft valve often co-exists with deficient ventricular septation, and the edges of the cleft are then frequently tethered to the crest of the ventricular septum by tendinous cords. The essence of these so-called isolated clefts of the aortic leaflet is that they are found in hearts with separate atrioventricular junction. 8,9 The space between the edges of the cleft then points towards the subaortic outflow tract ( Fig. 35-10 ), or to the antero-superiorly located interventricular communication when seen in the setting of the Taussig-Bing malformation. The lesion must be distinguished from the so-called cleft found in the left half of the atrioventricular valve of patients having atrioventricular septal defects with common atrioventricular junction (see Chapter 27 ). In the setting of the common junction, the so-called cleft is the zone of apposition between the left ventricular components of the leaflets that bridge the ventricular septum. This space points at the ventricular septum. Although the space between the leaflets is nowadays readily reconstituted by suture of its edges in both settings, it is only when there is a separate left atrioventricular junction that the surgical maneuver restores the morphology of a relatively normal mitral valve.
Another isolated anomaly of the valvar leaflets is the so-called funnel-shaped valve. 10 This entity is characterised by thickening and retraction of the leaflets, with fused tendinous cords, but in the presence of normal papillary muscles. The funnel produces mitral stenosis. It is rare in postmortem collections. More common are valves with dual orifices. The dual orifices are produced by a tongue of valvar tissue that extends between the mural and aortic leaflets, dividing the valvar orifice into two components, with each orifice then supported by one of the papillary muscles ( Fig. 35-11 ). Dual orifices are more common within the left half of the atrioventricular valve of patients having atrioventricular septal defects with common atrioventricular junction ( Chapter 27 ). As with the so-called cleft, these malformations should again be distinguished from those afflicting the bifoliate and otherwise normally structured mitral valve.
A rarer abnormality that can result in congenital mitral valvar regurgitation is hypoplasia of the mural leaflet, such that the valve leaflets cannot coapt normally during systole. 11 More frequent is straddling and overriding of the valvar leaflets. These anomalies can affect either the tricuspid or the mitral valve. Bridging of leaflets is also, of course, a common feature of the common atrioventricular valve, albeit that a common valve can be exclusively connected to one or other of the ventricles. It is the spectrum between the commitment of straddling valves to one or other ventricle, underscoring the difference between functionally univentricular and biventricular arrangements, which forms the focus of our chapter devoted specifically to straddling and overriding (see Chapter 33 ). When the morphologically mitral valve straddles and overrides, the valve always straddles through an antero-superior interventricular communication and is found with either discordant or double outlet ventriculo-arterial connections—the so-called Taussig-Bing malformation ( Fig. 35-12 ).
When discussing malformations of the leaflets, we should also pay attention to a fibrous ridge that anchors together the aortic and mural components, narrowing the valvar orifice. Although usually described as a supravalvar structure, the abnormal fibrous shelf is an integral part of the atrial surface of the leaflets, 12 and can readily be removed at surgery. Shelves can, indeed, exist within the left atrium, and produce true supravalvar rings, but these are much rarer than the variant attached to the atrial aspect of the leaflets ( Fig. 35-13 ).
Without question, the commonest lesion afflicting the leaflets of the mitral valve is prolapse. The problems concerning the pathology of prolapse of the mitral valve, however, are as numerous as those concerning its clinical features. There is no unanimity concerning nomenclature or aetiology and, perhaps more important, no standard definition of what precisely constitutes prolapse of the leaflets. The morphologist is under considerable constraint in this respect, since of necessity, in autopsy studies, the valve is viewed only in its fixed state. The morphologist can only speculate on what might have happened as the valvar leaflets moved from their open diastolic position to the closed systolic pattern, unless the heart is fixed with pressure in the left ventricle so that the leaflets assume their systolic position (see Fig. 35-1 ). Much can be learnt concerning the mechanics of prolapse, nonetheless, by comparing the morphology of the prolapsing valve with the normal arrangement. The pathologist usually describes the prolapsing variant as being floppy. Several pathological processes can produce a prolapsed leaflet as their end-point, such as ruptured tendinous cords secondary to ischaemic heart disease. The particular process producing the floppy valve is the one associated with the so-called click/murmur syndrome, this being the essence of the commonest form of mitral valvar prolapse. It is the mural leaflet that is most usually involved when the valve is floppy. The lesion may affect only one of its scallops ( Fig. 35-14 ), but in severe cases the aortic leaflet may also be involved ( Fig. 35-15 ). The affected leaflets are hooded, with their convexity to the left atrium. When the whole leaflet is involved, as is seen mostly in adults, the arrangement of the domed leaflets with their elongated cords takes on a parachute-like appearance, particularly when surgically removed (see Fig. 35-15 ). Pathologists dealing with disease of the adult population have described the valve in this fashion, but the choice of parachute is perhaps unfortunate in the setting of congenital cardiac malformations, since as we will see, the term is more usually used to described malformations of the papillary muscles. Irrespective of the descriptions, when the leaflets are grossly prolapsed, there is little difficulty in recognition. Most floppy valves, nonetheless, are seen in adult patients, and in this setting it can be difficult to distinguish minimal prolapse from the normal arrangement. This may well be significant, since Becker and de Wit 13 have pointed out that, in some normal valves, parts of the leading edge of the mural leaflet are less well supported by tendinous cords than other parts. They suggested that such an arrangement might predispose to prolapse, and subsequent observations confirmed that prolapsed segments of an affected leaflet are, indeed, less well supported than the non-prolapsed parts. 14 The affected leaflets are markedly thickened, with myxomatous transformation of their atrial aspect. When the prolapse is marked, there is also dilation of the annulus, involving the attachment of the mural rather than the aortic leaflet. Part and parcel of the myxomatous proliferation of the spongy layer of the leaflet is an increased proliferation of acid mucopolysaccharides. These then impinge on the fibrous layer, with focal interruption. The end result is destruction of the fibrous core of the valve, some considering this to be the essence of the lesion. 15,16 Histological studies of the abnormal leaflets, however, reveal no appreciable inflammatory reaction. It is the accumulation of acid mucopolysaccharides, with weakening of the fibrous core of the valve, along with the inequality of cordal support to the free edge of the affected valvar leaflet, therefore, which most probably account for the pathogenesis of prolapse. A myocardial factor has been proposed by many authors but is probably not of significance. The accumulation of acid mucopolysaccharide with weakening of the fibrous tissue and impaired collagen formation is seen typically in Marfan’s syndrome, and it is no coincidence that prolapsed valvar leaflets are a well-recognised feature of this syndrome. Indeed, it has been suggested that isolated prolapse is an atypical form of Marfan’s syndrome. 17 As with so many controversies, the truth may well prove to lie between the two extremes, with disorders of both biochemical make-up and cordal support contributing to production of the floppy leaflets.
Anomalies of the Tension Apparatus
Anomalies of the tension apparatus include the lesions variously referred to as mitral arcade 18 or hammock 10 valve. These terms likely describe the same lesion, in which the papillary muscles extend directly to the edges of the leaflets ( Fig. 35-16 ). In the most severe form, the muscles fuse on the leading edge of the aortic leaflet, forming the muscular arcade observed by the pathologist. When viewed from the atrial aspect, with the valve intact as seen by the surgeon, the intermixing of cords attached to the enlarged papillary muscle gives the appearance of a hammock. The abnormal attachments produce mitral valvar insufficiency, but the morphologic appearance suggests that the valve would also be stenotic.
Anomalies of the Papillary Muscles
It is anomalies of the papillary muscles that produce the lesion most usually described by paediatric cardiologists and surgeons as being the parachute lesion, although it must be admitted that the valve malformed in this fashion bears appreciably less similarity to a parachute than the prolapsing valve (compare Figs. 35-17 and 35-15 ). There is also lack of agreement as to what produces the parachute malformation when the term is applied to the papillary muscles. The situation most closely resembling the parachute is seen when the two muscles are fused to produce a solitary mass (see Fig. 35-17 ). The alternative arrangement that has been likened to the parachute is seen when one papillary muscle, usually the anterolateral muscle, is grossly reduced in size or even, on occasions, totally absent. The tension apparatus then has a grossly eccentric appearance, effectively inserting into a solitary papillary muscle ( Fig. 35-18 ). It was the latter arrangement, with a solitary papillary muscle, which was illustrated by Shone and colleagues 19 when they introduced the term parachute mitral valve. This confusing situation was highlighted by Rosenquist, 20 who preferred to use the term to account for the arrangement with fused muscles. Furthermore, Carpentier and colleagues 10 described fused papillary muscles as producing parachute valves. In the detailed study of Ruckman and Van Praagh, 21 however, such cases were specifically excluded, since they did not fit the original illustration of Shone and his colleagues. 19 The form with fused papillary muscles, nonetheless, is more likely to be chosen by clinicians as their paradigm for the parachute malformation. For the morphologist, an absent or hypoplastic papillary muscle is readily recognised and described as such. Similar precision can also be provided by cross sectional echocardiography. 22 So as to remove any confusion, when we speak of parachute valves, we will specify whether we are discussing the variant produced by fusion of the papillary muscles into a solid mass, often additionally dysplastic, or whether there is hypoplasia or absence of one or other of the papillary muscles.
Stenosis versus Incompetence
It is often difficult for the morphologist to predict from a specimen whether the observed pathology would have produced stenosis or incompetence. A much better appreciation is obtained by the surgeon. 2,3,10 When insufficiency is the primary lesion, then this is most frequently the consequence of problems with the leaflets, exacerbated by dilation of the annulus. Alternatively, insufficiency as a primary feature can be caused by subvalvar problems, such as cordal retraction or elongation, or hypoplasia or agenesis of the papillary muscles. Prolapse is obviously the major substrate for many patients with mitral valvar problems. When stenosis is the major problem, this is likely to be a result of fusion along the ends of the zone of apposition between the leaflets of a dysplastic valve, a hammock lesion, a parachute deformity, or a funnel-shaped valve. Combined stenosis and insufficiency are related to fusion of the ends of the zone of apposition between the leaflets, a hammock valve, a parachute deformity, or papillary muscular hypertrophy.
Effect on the Heart
Valvar pathology always affects the cardiac pump and, despite compensatory mechanisms, may lead to serious side effects in the myocardium and endocardium. It should always be remembered that valvar pathology can also affect the pulmonary vascular bed, with pulmonary hypertension as a possible consequence. 23
DEVELOPMENT OF THE MORPHOLOGICALLY MITRAL VALVE
The atrioventricular junction comes into prominence following the rightward looping of the heart tube after the 25th day of gestation. 7 By the end of the fifth week, the developing apical parts of the ventricles are visible, with the future left ventricle supporting the larger part of the circumference of the atrioventricular canal. The lumen of the atrioventricular canal is occupied by the inferior and superior endocardial cushions. Initially separate and discrete, these cushions eventually fuse during the sixth week, producing the right and left atrioventricular junctions, to which will be anchored the developing leaflets of the mitral and tricuspid valves. Parts of these fused cushions remain to the left side of the crest of the muscular ventricular septum, forming the scaffold of the aortic leaflet of the mitral valve.
Formation of the normal mitral valve can proceed only when the aorta becomes committed to the left ventricle, permitting the development of fibrous continuity between one of the leaflets of the mitral valve and two of the leaflets of the aortic valve, hence the name of aortic leaflet for the mitral component, which distinguishes it from its mural counterpart. Initially, there is still a cleft at the parietal margins of the site of fusion of the superior and inferior cushions within the left ventricle. The mural leaflet of the mitral valve is formed by protrusion and growth of a sheet of atrioventricular myocardium into the ventricular lumen, with subsequent formation of valvar mesenchyme on its surface, rather than by delamination of the lateral cushion from the ventricular myocardium, as was previously thought. The myocardial layer is then removed by apoptosis. 24 The aortic leaflet of the mitral valve, along with parts of the septal leaflet of the tricuspid valve, develops from mesenchyme of the superior and inferior atrioventricular cushions. Whereas the septal leaflet of the tricuspid valve 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 develop with cordal and papillary muscular attachments to the left ventricular wall. 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 valvar orifice.
This expanded crescent is associated with compacting columns in the trabecular layer of the ventricular muscle, which eventually form the papillary muscles. Excessive or abnormal compaction of this 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 primordiums 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.
Reciprocal signaling between the endocardial and myocardial cell layers in the cushion is mediated in part by members of the TGF-β family, and induces a transformation of endocardial cells into mesenchymal cells. Sox 9 is activated when myocardial cells undergo mesenchymal transformation. Sox 9 deficient mesenchymal cells fail to express ErbB3, which is required for proliferation of the cells within the endocardial cushions. The mesenchymal cells migrate into the cushions, and differentiate into the fibrous tissue of the valves. Several genes play a role in formation of the valvar leaflets, including calcineurin, with signalling and downstream activation dependent on the NFAT family of transcription factors. Absence of any of these genes results in fatal defects of valvar formation. 25
INCIDENCE AND AETIOLOGY
Congenital deformities of the mitral valve are rare, if those involving the left valve in hearts with common atrioventricular junction are excluded, with mitral stenosis occurring in 0.6% of postmortems and in 0.21% to 0.42% of clinical series. 26 Congenital mitral incompetence is even rarer. There is a male to female ratio of around 1.5 to 1 to 2.2 to 1. 26,27 Congenital mitral valvar anomalies are rarely isolated. The fully developed syndrome of so-called parachute mitral valve, 19 for example, includes four obstructions within the left heart, namely the valvar lesion itself, supravalvar mitral ring, subaortic stenosis and aortic coarctation. Any of these obstructions may co-exist with any congenital lesion afflicting the mitral valve, particularly coarctation. In a clinical series of patients with congenital mitral stenosis, excluding hypoplasia of the left heart, almost three-quarters had additional anomalies. 26 It is tempting to imagine that development of one abnormality upstream may, during morphogenesis, result in a series of more distal abnormalities owing to disturbance in the patterns of flow. Annular hypoplasia of the mitral valve is almost always associated with hypoplasia of the left ventricle and aortic stenosis or atresia. Ventricular septal defect is quite common in this setting, and double outlet right ventricle and tetralogy of Fallot occasionally occur. When the mitral valve is imperforate, left ventricular hypoplasia is inevitable unless there is an associated ventricular septal defect. 21
PATHOPHYSIOLOGY
Supravalvar mitral ring and congenital mitral stenosis are, by and large, indistinguishable in their effects. Unless specific differences are mentioned, they may be assumed to behave in the same way. Pure mitral stenosis, or imperforate mitral valve, results in a diastolic pressure difference between the left atrium and left ventricle with a consequent elevation of left atrial pressure. Patients in sinus rhythm, the great majority, have a tall a wave in the left atrial trace. Co-existence of an interatrial communication results in decompression of the left atrium. This may be so profound as to obscure or eliminate the transmitral pressure difference, even when the mitral valve is imperforate. By contrast, excessive flow through the mitral valve, as may result from an associated ventricular septal defect, will exaggerate the transmitral diastolic pressure difference. Elevation of the left atrial pressure usually results in reflex pulmonary vasoconstriction, particularly if the development of pulmonary oedema results in mismatch between ventilation and perfusion, and pulmonary venous hypoxaemia. The combined effect is to produce pulmonary hypertension. In the presence of associated patency of the arterial duct, or a ventricular septal defect, this can result in right-to-left shunting at an earlier age than would be expected were mitral obstruction not present. The rise in pulmonary vascular resistance, and consequent fall in pulmonary blood flow, means that, on sequential cardiac catheterisations in individuals with mitral stenosis, the gradient is frequently found to fall. This finding is similar to medical intervention using nitric oxide in patients with congenital mitral stenosis, 28 where it was observed that the pulmonary vasoreactivity was greater than previously reported in adults. In the absence of pulmonary stenosis, and without any communication at great arterial or ventricular level, the pulmonary arterial systolic pressure may exceed systemic pressure. Right heart failure may then ensue. By contrast, severe pulmonary stenosis in the setting of a ventricular septal defect may mask entirely the effects of the valvar obstruction by reducing the flow of blood to the lungs. Left atrial pressure is bound to be lower than pulmonary arterial pressure, irrespective of the severity of the mitral obstruction. Pure mitral insufficiency may cause left atrial hypertension with all the consequences already described. More commonly, considerable left atrial dilation occurs, with the result that left atrial hypertension is modest or non-existent. Cardiac output is maintained with a normal left ventricular ejection fraction by a modest increase in left ventricular end-systolic volume and a marked increase in left ventricular end-diastolic volume. This is not as striking as the increase in left atrial volume. The regurgitant fraction may be as high as 83%. Associated obstructive lesions downstream obviously increase the severity of the mitral regurgitation. In contrast to rheumatic mitral disease, the congenitally malformed mitral valve is usually either obstructed or regurgitant. An intermediate situation is produced in the rare case of mixed stenosis and incompetence.
CLINICAL PRESENTATION AND SYMPTOMATOLOGY
Congenital disease of the mitral valve usually presents as a result of the associated abnormalities, such as coarctation or ventricular septal defect. In these lesions, the symptoms are exacerbated by the presence of the mitral valvar problem, but this may be too subtle to detect. As already mentioned, the effects of the valvar anomaly are more or less neutralised by pulmonary stenosis and an interventricular communication. So, whatever the associated anomaly, the result tends to be that mitral disease is masked, and will not be recognised unless specially looked for. The presentation of isolated mitral valvar disease is largely determined by the height of the left atrial pressure. If this is normal, there are usually no symptoms at all. At most, there will be fatigue after severe exertion. A high left atrial pressure is likely to result in poor feeding, sweating in infancy, and failure to thrive. Patients with severe obstruction are likely to present in intractable cardiac failure in the first month or so of life. Orthopnoea is extremely rare, but patients frequently complain of a dry nocturnal cough. Wheezing and respiratory infections are frequent. Syncope, haemoptysis, or aphonia owing to compression of the recurrent laryngeal nerve by an enlarged left atrium, have occasionally been described. Pure mitral stenosis is characterised by poor nourishment, tachypnoea, and intercostal recession. There are normal-to-small peripheral arterial pulses, and the jugular venous pulse is also usually normal. If pulmonary hypertension is severe, a prominent a wave will reflect the raised right ventricular end-diastolic pressure. A systolic wave will demonstrate secondary tricuspid incompetence. Palpation of the heart will reveal either a normal impulse or right ventricular hypertrophy, and there may be an apical diastolic thrill. Pulmonary valvar closure will be palpable if pulmonary hypertension is severe. The first heart sound is either normal or loud and, in contrast to rheumatic mitral stenosis, an opening snap is only occasionally audible. Closure of the pulmonary valve is accentuated in patients with pulmonary hypertension. There is a loud low-pitched mid-diastolic murmur at the apex, usually with presystolic accentuation. Occasionally, no diastolic murmur is heard. In severe untreated disease, an early diastolic murmur of pulmonary incompetence and a pan-systolic murmur of tricuspid incompetence may be heard, both resulting from pulmonary hypertension. Crepitations may be heard in the lung fields, but these are usually clear. Cyanosis is not seen unless there is severe pulmonary venous desaturation, or a right-to-left shunt through an associated defect.
PURE MITRAL INSUFFICIENCY
Most children are well nourished and in no distress. The peripheral pulses are usually normal, though sometimes jerky because of the predominant ejection of blood in early, rather than late, systole. The jugular venous pulse is normally not elevated. On palpation of the heart, left rather than right hypertrophy is usually discovered. On auscultation, the first and second heart sounds are usually normal, except in the relatively rare case of pulmonary hypertension. There is a blowing pan-systolic murmur at the apex. The pan-systolic murmur of ventricular septal defect is much rougher, is maximal at the left sternal border, and does not radiate to the axilla. If mitral regurgitation is more than mild to moderate, an apical third heart sound will be heard, followed in severe cases by a diastolic flow murmur. This diastolic murmur, particularly if it is accompanied by a third sound, does not necessarily indicate stenosis. When congenital mitral anomalies are associated with other cardiac defects, the physical signs are usually dominated by the other lesions. In particular, an imperforate mitral valve generates no direct physical signs, though evidence of pulmonary hypertension is almost invariable. The main clue to the presence of mitral stenosis in association with other defects is an inappropriately prominent mid-diastolic murmur. A typical example would be that of a 6-month-old child who, in earlier life, had typical signs of ventricular septal defect and yet who now has all the signs of Eisenmenger’s syndrome except an unexpected loud mid-diastolic murmur, often with presystolic accentuation. Care has to be taken with many children with aortic coarctation, and a few with discrete subaortic stenosis. Such patients may have short apical mid-diastolic murmurs, which, for reasons that are not obvious, disappear after resection of the obstruction.
INVESTIGATIONS
Electrocardiography
Sinus rhythm is the rule in children, though first-degree heart block is common, particularly when the left atrium is greatly enlarged. Left atrial hypertrophy occurs in about nine-tenths of patients, and right atrial hypertrophy is the rule in patients with pulmonary hypertension. In mitral stenosis, the mean frontal QRS axis is usually normal, or to the right and inferior, whereas it is generally normal in mitral incompetence. The pattern of ventricular hypertrophy reflects the underlying haemodynamics. Consequently, patients with mitral stenosis tend to have right ventricular hypertrophy, while those with mitral incompetence have left ventricular hypertrophy. All of these findings are modified by associated abnormalities. In patients with the physical signs of mitral regurgitation, the electrocardiogram provides important clues to the presence of atrioventricular septal defects with common atrioventricular junction, when there is a superior counter-clockwise QRS loop, and discordant atrioventricular connections, characterised by Q waves in the right and inferior precordial leads. Mitral regurgitation secondary to anomalous origin of the left coronary artery from the pulmonary trunk is suggested by a pattern of anterolateral infarction.
Chest Radiography
Whatever the nature of the mitral abnormality, cardiac enlargement tends to be considerable. Splaying of the bronchuses by the enlarged left atrium is particularly prominent. Infants with imperforate mitral valve, or severe mitral stenosis, very occasionally show the ground-glass appearance of pulmonary oedema. More commonly, left atrial hypertension is manifested in older children by Kerley B lines and diversion of blood to the upper lobes. In infants, the pulmonary trunk and left atrial appendage do not form discrete bulges on the upper left cardiac border, which is consequently straighter than normal. In older children, prominence of the left atrial appendage is the rule and, in patients with pulmonary hypertension, the pulmonary trunk is prominent. These appearances may be profoundly modified by associated abnormalities. If the ascending aorta is seen on the left upper cardiac border and the patient has clinical features of mitral incompetence, then congenitally corrected transposition with tricuspid rather than mitral incompetence is the most likely diagnosis.
Echocardiography
M-mode echocardiography provides non-specific evidence as to enlargement of the left ventricle, left atrium, and right ventricle. It is unhelpful in diagnosing mitral incompetence. A number of features are suggestive of mitral stenosis, but none of them is invariably present. These include anterior movement of the mural leaflet in diastole, a prolonged time to reach one-fifth of the peak rate in change of left ventricular dimensions, and a reduced peak rate of these changes in dimension. 29 A flattening of the E-F slope is again suggestive, but difficult to recognise in infants with tachycardia ( Fig. 35-19 ). The time from closure of the aortic to opening of the mitral valve, and from left ventricular minimum dimension to mitral opening, have proved unhelpful as indicators of congenital mitral stenosis, 30 though they are useful in assessment of acquired mitral valvar disease.
