The most common congenital malformations afflicting the tricuspid valve are Ebstein’s malformation and tricuspid valvar dysplasia. We will primarily consider Ebstein’s malfor mation in this chapter. Isolated dysplasia of the tricuspid valvar leaflets, and other right ventricular abnormalities frequently mistaken for Ebstein’s malformation, will be briefly described. Tricuspid valvar abnormalities or abnormalities of the morphologically right atrioventricular valve are also often associated with atrioventricular septal defects with common atrioventricular junction ( Chapter 27 ), ventricular septal defect with straddling valve ( Chapter 33 ), or pulmonary atresia with intact septum ( Chapter 30 ). These lesions are described in detail in the appropriate chapters of our book.
NAMING OF THE TRICUSPID VALVAR APPARATUS
We have chosen to adopt an anatomically unambiguous system of names to describe the components of the tricuspid valvar apparatus. This will create some differences between the descriptions contained within this chapter and many previous publications. It seems best concretely to define this system to avoid potential confusion. The three valvar leaflets will be referred to as the anterosuperior, the septal, and the mural leaflets. The designation of the septal leaflet is already clear. The anterosuperior leaflet has most commonly been referred to as the anterior leaflet. The mural leaflet has often been called the posterior leaflet. This designation is anatomically incorrect. The mural leaflet is positioned inferiorly within the ventricular cavity, lying adjacent to the diaphragm in the normal heart. We recognise that abnormal valves often display rotation of their components away from the normal position. We prefer, therefore, to refer to this leaflet as mural, since it will invariably be more closely associated with the ventricular free wall than its counterparts.
EBSTEIN’S MALFORMATION
Ebstein’s malformation has an extremely variable natural history depending on the degree of abnormality of the right ventricle and the tricuspid valvar apparatus, which may range from mild to severe. If the deformity of the tricuspid valve is severe, it may result in profound congestive heart failure in the neonatal period, or even in intrauterine death. At the other end of the spectrum, patients with mild degrees of displacement and dysfunction may remain asymptomatic until late adult life or may remain symptomless throughout life.
Ebstein’s own description 1 of the malformation in 1866, with illustrations by Dr Weiss ( Fig. 34-1 ), was based upon the anatomical findings relating to the heart of Joseph Prescher, a 19-year-old labourer with cyanosis, who had been troubled with dyspnoea and palpitations since childhood. The premortem diagnosis had been congenital cardiac defect. The first case described in the English literature was not published until 1900. 2 It was not until 1951 that the diagnosis was made during life, using angiocardiography. 3 In the 1950s, successful surgical palliation was achieved, and the association with Wolff-Parkinson-White syndrome had been recognised. In the 1960s came the first attempts at corrective surgery, including valvar replacement 4 and repair. 5 The malformation accounts for no more than 0.3% to 0.5% of congenital heart disease. 6,7 Equal numbers of male and female patients with Ebstein’s malformation are usually observed. 8,9
With the advent of cross sectional echocardiography, 10 it became much easier to make the diagnosis, even in fetal life. 8 The malformation is now known to be more common than previously appreciated, and there has been a marked change in the spectrum of disease seen by paediatric cardiologists. In the era of echocardiographic diagnosis, review of a series of over 200 cases collected from hospitals in southeast England revealed an appreciable increase in the number of diagnosed cases, with more than half of the patients aged less than 1 year at diagnosis. 9 Surgical correction, with repair or replacement of the malformed valve and closure of the atrial septal defect, is known to produce excellent results. 11–17 Conversion to the Fontan circulation or cardiac transplantation are reserved for extreme situations. 11,12
We will limit our discussions in this chapter to Ebstein’s malformation as found in hearts with concordant atrioventricular connections, with or without associated defects. The lesion, of course, is well recognised as being part of the substrate of congenitally corrected transposition, when it typically afflicts the left-sided morphologically tricuspid valve subserving a systemic function. This combination is considered in Chapter 39 .
Definition and Anatomy
Ebstein’s malformation is often thought of as a primary disorder of the tricuspid valve. In reality, it is a manifestation of a more global aberration in myocardial development. Those afflicted with Ebstein’s malformation invariably display abnormalities in both myocardial structure and function, as well as the characteristic valvar deformities. The right ventricle and tricuspid valve are universally involved, while changes in the left heart are less common. 13
The hallmark of Ebstein’s malformation is displacement of the points of attachment, or the hinges, of the septal and mural leaflets into the right ventricle, away from the atrioventricular junction. This results from failure of these leaflets fully to separate from the ventricular wall during cardiac development. The anterosuperior leaflet, in contrast, has a different developmental origin. 14 Because of this, its junctional hinge usually retains a normal position. It had already been recognised late in the 19th century that formation of the valvar leaflets was a relatively late embryologic event. 15 At the time of closure of the embryonic interventricular communication, the septal and mural leaflets of the tricuspid valve have not begun to develop. These are produced subsequently by delamination of the superficial layer of the ventricular myocardium. 14,16
In hearts with Ebstein’s malformation, this failure to delaminate results in the tricuspid valvar leaflets remaining variably adherent to the underlying right ventricular and septal myocardium. Such failure to delaminate creates the characteristic displacement of the annular attachments of the valve and its functional orifice. This displacement is not linear, but spiral in nature. The effect is to move the tricuspid apparatus both anteriorly and towards the right ventricular apex ( Fig. 34-2 ). The valvar hinge points are shifted into the body of the ventricle, and the functional orifice of the tricuspid valve moves to the junction between the inlet and the remaining apical trabecular and outlet components of the right ventricle, shown as the dotted line in Figure 34-2A . In the most severe cases, the functional leaflets may be positioned within the outlet itself. The adherent portions of the valvar leaflets usually have little or no motion. This typically leads to tricuspid regurgitation, or more rarely to stenosis.
In hearts studied in the autopsy room, mild cases can be encountered in which only the hinge of the septal leaflet is displaced away from the atrioventricular junction. Such cases are found most frequently in the setting of pulmonary atresia with an intact ventricular septum ( Fig. 34-3 ). Cases with pulmonary atresia and an intact ventricular septum, of course, are not diagnosed primarily as Ebstein’s malformation. It is certainly unusual to find such mild examples at autopsy in patients diagnosed clinically with Ebstein’s malformation. 17 In the absence of pulmonary atresia, it is unlikely that such minimal changes would produce the typical, if indeed any, symptomatology.
Problems also exist during life in distinguishing such minimal displacement of the septal leaflet from the typical valvar off-setting found in the normal heart ( Fig. 34-4 ). In those cases coming to clinical attention, the entirety of the tricuspid valvar apparatus is malformed, and obviously so. In almost all cases, nonetheless, it is only the septal and mural leaflets that have their annular attachment displaced from the atrioventricular junction, with sparing of the proximal attachment of the anterosuperior leaflet. 17–19
A major problem for the morphologist in analysing these cases coming to clinical attention is precisely to distinguish, in the abnormal valve, the boundaries between the mural and anterosuperior leaflets. In fact, the essence of the malformation is that the leaflets adopt a bifoliate configuration, with a plane of closure at the junction of the inlet and the remaining components of the right ventricle ( Figs. 34-5 and 34-6 ).
It is the appreciation of this abnormal position and structure of the valve that is the key to subsequent analysis and, arguably, to selection of appropriate treatment.
The abnormal, displaced location of the valve represents a rotational or spiral deformity ( Figs. 34-2 and 34-7 ) rather than a linear, downward or apical, displacement that has received attention in the past.
There is, nonetheless, marked variation from patient to patient. The variability reflects the degree of formation of the septal leaflet, the nature of the distal attachments of the anterosuperior and mural leaflets, and the amount of mobility/tethering of the anterosuperior leaflet. In the typical diseased valve as seen in the postmortem room, the septal leaflet is either represented by an array of verrucous remnants adherent to the septum towards the ventricular apex (see Fig. 34-5 ), part of a tongue that becomes continuous with the anterosuperior leaflet, or a circular remnant on the septum ( Fig. 34-8 ). It was the latter arrangement that was seen in the initial heart described by Ebstein. 1 In either event, the septal leaflet may seem to be absent when attention is directed to the ventricular inlet component ( Fig. 34-9 ). It is when assessment is redirected at the junction between the inlet component and the functional right ventricle that the valvar leaflets are seen, forming a bifoliate valvar mechanism ( Fig. 34-10 ).
The functional part of the ventricle, therefore, is made up of the apical trabecular and outlet components beyond the plane of coaptation of the leaflets. As already indicated, the mural and anterosuperior leaflets themselves tend to be combined as an abnormal curtain, which forms the parietal part of the abnormal bifoliate valve (see Fig. 34-5 ). The part formed by the anterosuperior leaflet usually retains its normal hinge from the atrioventricular junction along the supraventricular crest, but the hinges of the valve move increasingly away from the junction as attention is directed to the attachments along the diaphragmatic surface of the ventricular mass. When seen in the postmortem room, this arrangement can give the impression of forming a potentially competent valve. In other cases, nonetheless, the valvar mechanism is clearly seen to be incompetent, due to either inadequate leaflet size, mobility, or fenestrations in the body of the leaflet itself ( Fig. 34-11 ). Relative to the mass of the atrialised right ventricle, the functional valvar orifice is frequently judged to be stenotic. In this setting, the upstream components of the right side of the heart, both the atrium and the right ventricular inlet, are dilated and thin walled. This produces anatomic atrialisation.
Further variation is then seen in the nature of the distal attachments of the mural and anterosuperior components of the valvar curtain, which are almost always additionally dysplastic. 20 In some cases, the anterosuperior leaflet retains its focal attachment to the medial and anterior papillary muscles (see Fig. 34-8 ). In the most florid cases, the entire leading edge of the anterosuperior leaflet is attached linearly to a muscular shelf formed between the inlet and apical trabecular components of the ventricle ( Fig. 34-12 ). Between these extremes are found hearts in which the edge of the leaflet is attached in hyphenated fashion along the muscular shelf ( Fig. 34-13 ). Further abnormal tetherings can be found between the ventricular aspect of the abnormal leaflets and the parietal ventricular wall ( Fig. 34-14 ). Such tetherings serve to constrain still further the motion of the abnormal sail produced by the combined mural and anterosuperior leaflets. 21,22 When the valvar mechanism is arranged as a bifoliate structure, then its opening is adjacent to the septum and is directed towards the ventricular outlet component. This keyhole can become increasingly restricted and stenotic. Should the leaflets fuse along the edges of the keyhole, the result is tricuspid atresia in the setting of Ebstein’s malformation ( Fig. 34-15 ).
The essence of symptomatic Ebstein’s malformation, therefore, is formation of an abnormal bifoliate valvar mechanism, with septal and parietal components, at the junction between the atrialised inlet part of the right ventricle and the functional right ventricle, the latter comprising the apical and outlet components. Although the annular attachments of the septal leaflet of the valve are displaced from the atrioventricular junction, the triangle of Koch continues to be the landmark for the atrial components of the atrioventricular conduction tissue axis. Right bundle branch block is commonly found and may be caused by fibrosis in the distal conduction tissue. The frequent presence of accessory muscular pathways across the atrioventricular junctions results in a high incidence of preexcitation, this feature being found in up to one quarter of patients. 7 The accessory pathways are often multiple and are usually found to the right of the inferior paraseptal space or in the parietal part of the junction. 23 When found laterally, they frequently arise from a remnant of atrioventricular ring tissue and produce the so-called Mahaim variant of pre-excitation. 24
As we have already discussed, the abnormally located line of attachment of the valvar leaflets divides the right ventricle into proximal atrialised and distal functional portions. The proximal portion lies between the atrioventricular junction and the displaced attachments of the leaflets. This atrialised portion has walls of ventricular myocardium but in severely affected patients tends to be smooth, thin-walled, and dilated, with a high content of fibrous tissue. When very thin, it moves paradoxically during ventricular systole, and it may also expand during atrial systole. Its electrical potentials are ventricular, but its pressure pulse shows an atrial waveform.
The cavitary portion of the functional right ventricle is usually smaller than the normal ventricle. This feature, however, may be modified by dilation, which is a frequent finding. The functional portion consists of the infundibulum, the apical trabecular component, and that portion of the ventricle beneath the distal attachments of the combined mural and anterosuperior leaflets. The walls of this functional ventricle, particularly when dilated, are also usually thinner than normal. They contain fewer than normal myocytes and more fibrous tissue. 25 Left ventricular abnormalities are frequent. They can sometimes simply be the consequence of the gross dilation of the right-sided chambers. In severe cases, the left ventricular free wall also has an abnormally high content of fibrous tissue, although its thickness is usually normal. 25 The mitral valve is frequently nodular and thickened, and prolapse of the leaflets is common.
Associated cardiac defects are also common, particularly in the patients diagnosed in fetal or neonatal life. Almost all patients have a co-existing interatrial communication at the oval fossa, usually a patent foramen. Any type of communication, nonetheless, may be present, including atrioventricular septal defects in the setting of a common atrioventricular junction. A large spectrum of other lesions has been described in addition to atrioventricular septal defects, including ventricular septal defects, tetralogy of Fallot, aortic coarctation, and persistent patency of the arterial duct. The most common associated defect is pulmonary stenosis or atresia, which is found in up to one third of those presenting in infancy. 26 Obstruction of the right ventricular outflow tract is commonly associated with Ebstein’s malformation when diagnosed in fetal life. 8 In this setting, it may be difficult to distinguish structural from functional pulmonary atresia using echocardiography, especially in the presence of severe tricuspid regurgitation. In either case, the pulmonary valvar abnormality is probably secondary to the malformation of the tricuspid valve, with hypoplasia of the outflow tract resulting from low anterograde flow through the right heart. When severe Ebstein’s malformation is associated with fetal and neonatal distress or death, both lungs are usually hypoplastic but otherwise normal. The hypoplasia is secondary to the gross cardiomegaly, itself caused by dilation of the right heart. 27
In the setting of gross dilation of the heart because of severe tricuspid valvar incompetence, whether the consequence of Ebstein’s malformation or dysplasia of the valvar leaflets, the overall ventricular myocardium can become particularly thin. This should not be described as Uhl’s malformation. In the lesion described by Uhl, 28 the tricuspid and pulmonary valves were both normal. The essence of Uhl’s malformation is congenital absence of the parietal myocardium, histological analysis showing that the epicardial and endocardial layers of the wall lie edge-to-edge. 29 It is also a mistake to correlate fibro-fatty replacement of the right ventricular parietal walls with either Ebstein’s malformation or Uhl’s malformation. Fibro-fatty replacement is the essence of arrhythmogenic right ventricular cardiomyopathy, now recognised as a cardiomyopathy in its own right, with various genetic causes (see Chapter 54A , Chapter 54B ). While dysplasia of the valvar leaflets is often an integral part of Ebstein’s malformation, dysplastic leaflets can also be found when retaining their normal hinges at the atrioventricular junction ( Fig. 34-16 ). Such dysplasia of normally hinged leaflets can produce just as much valvar incompetence as Ebstein’s malformation. Isolated dysplasia can produce the same wall-to-wall heart, 30 with the same consequences for pulmonary problems in the neonatal period. 27
Causation and Genetics
No specific cause has been consistently associated with Ebstein’s malformation. Based on retrospective case reporting, treatment with lithium during the first trimester of pregnancy was thought to be strongly associated, producing a 400 fold relative risk, with the occurrence of Ebstein’s malformation in the fetus. 31 More recent cohort and case-control epidemiologic studies have not confirmed these initial findings. 32 In contrast, these more rigorous studies found that, while the frequency of all congenital malformations was increased with gestational exposure to lithium, the relative risk for any malformation, not only cardiac, was only two to three times that of non-treated mothers. More importantly, although the frequency of all congenital cardiac malformations was greater in pregnancies exposed to lithium, there was no increase in the frequency of Ebstein’s malformation relative to controls. Given the rarity of Ebstein’s malformation, these studies did not have the power completely to exclude a connection between lithium and the development of Ebstein’s malformation. They do conclusively demonstrate that the relative risk of treatment with lithium during pregnancy is much less than was originally estimated from the retrospective case reports. The decision to continue or discontinue such treatment during pregnancy must now be made by weighing the relative risk of teratogenicity against the risks of relapse of manic/depressive disease in the mother. 32 The majority of cases of Ebstein’s malformation are sporadic, but some familial cases have been reported. There continues to be a difference of opinion as to whether there is a major hereditary basis for transgenerational transmission in Ebstein’s malformation. 33,34
PATHOPHYSIOLOGY AND CLINICAL ASPECTS OF EBSTEIN’S MALFORMATION
The broad range of anatomic severity seen in Ebstein’s malformation, combined with the variable myopathy, produce a wide spectrum of clinical and haemodynamic manifestations. The pathophysiologic changes are related to several factors. These include the functional state of the tricuspid valve in terms of the degree of regurgitation or more rarely, stenosis, the presence, or absence, and size of the interatrial communication or other congenital cardiovascular malformations, the degree of right ventricular dysfunction, and the amount of left ventricular dysfunction. To a lesser degree, the pathologic substrates predisposing to tachyarrhythmias produce an additional dimension contributing to the pathophysiology.
The dysfunctional nature of the right ventricular myocardium, and the co-existing abnormalities of the tricuspid valve, impair flow through the right heart and the pulmonary circulation. The interaction between the dilated right atrium and the atrialised segment of the right ventricle are perhaps just as important in the creation of ineffective patterns of flow within the right heart. During ventricular systole, the atrialised right ventricular myocardium is contracting. There is no valvar tissue separating this area from the true atrial chamber and the great veins. This results in increased venous pressure, and effectively increases resistance to forward flow. This decreases the ability of the great veins to empty into the anatomic right atrium while its myocytes are relaxed. The increase in resistance to flow out of the atrium will also augment the amount of right-to-left shunting through any co-existing interatrial communication.
When the atrialised portion of the right ventricle relaxes, it will expand, and can even balloon outwards during true atrial contraction. This creates a reservoir for venous blood, and decreases the amount of effective forward flow that crosses the abnormal tricuspid valve. This to and fro flow pattern between the right atrium and the atrialised right ventricle not only decreases effective output from the right heart, but also provides an ongoing stimulus for atrial dilation and atrial arrhythmias, even when there is little transvalvar regurgitation. The degree of functional impairment experienced by patients with Ebstein’s malformation has been directly related to these anatomic and physiologic abnormalities. Shiina and colleagues 10 found that a small functional right ventricle and large atrialised right ventricle, extreme displacement or absence of the septal leaflet, the degree of displacement or tethering of the anterosuperior leaflet, and the aneurysmal dilation of the right ventricular outflow tract were all associated with reduced functional state as measured using the categorisation prepared by the New York Heart Association.
Although the primary focus in patients with Ebstein’s malformation has been on right-sided structures, there have been an increasing number of reports of left-sided abnormalities, specifically in left ventricular size, shape, and function. 35–37 In the past, these have been attributed to the degree of enlargement of the right heart compromising the left ventricle, and to leftward diastolic bowing of the interventricular septum. Radionuclide scans and cineangiograms have shown impaired left ventricular function at rest in unoperated patients. During formal exercise testing, most unoperated patients show an appropriate increase in left ventricular ejection fraction due to a reduced end-systolic volume and unchanged end-diastolic volume. 37 Recently, however, Attenhofer and colleagues 13,38 reported that one-fifth of their cohort of patients with Ebstein’s malformation had a markedly abnormal echocardiographic appearance of the left ventricular myocardium. These patients displayed segments of left ventricular myocardium with multiple layers and deep intratrabecular recesses, consistent with myocardial noncompaction. An additional one-tenth had hypertrabeculated segments of left ventricular myocardium reminiscent, but not diagnostic, of noncompacted myocardium. Although most patients had satisfactory left ventricular function, a small percentage showed severe systolic and diastolic dysfunction, even contributing to the need for transplantation in one young patient. 38 These left-sided myocardial abnormalities, although seen in only a fraction of patients, support the concept that Ebstein malformation is actually a global myocardial disorder that primarily manifests itself within the right ventricle and its derivative, the tricuspid valve.
The infant with Ebstein’s malformation poses an especially difficult clinical problem. Pulmonary vascular resistance is always high immediately after birth, and usually decreases fairly rapidly in the first days of life. The infant with severe Ebstein’s malformation is poorly prepared to deal with the transition to the neonatal circulation. The combination of right ventricular myopathy, tricuspid regurgitation, and elevated pulmonary resistance can lead to poor pulmonary perfusion when the arterial duct constricts or closes. Venous pressures rise, leading to right-heart failure and cyanosis due to right-to-left shunting across the oval foramen. Until the pulmonary resistance decreases, and the pulmonary flow increases, these infants present a diagnostic and therapeutic dilemma. Patency of the pulmonary outflow tract and valve must be confirmed. This can be done by demonstrating opening of the pulmonary valvar leaflets by cross sectional echocardiographic scans, or by documenting either forward, or more commonly regurgitant, flow across the valve using Doppler techniques.
In the rare case where echocardiographic findings are inconclusive, an angiogram demonstrating pulmonary regurgitation following injection of contrast into the arterial duct, or the ability to advance a catheter across the valvar orifice, are other methods that can confirm patency of the right ventricular outflow tract. When the outflow tract is open, infusions of prostaglandin to maintain ductal patency, with or without mechanical ventilation, will often allow the baby to transition to the postnatal circulation without the need for palliative surgery.
Clinical Presentation
Patients with Ebstein’s malformation may present at any age. The most severe cases present prenatally, or as newborns. Prenatal diagnosis is dependent upon ultrasonic screening examinations. Fetal presentation is accompanied by increased heart size, a significant incidence of fetal hydrops and, in the most severe cases, pulmonary parenchymal hypoplasia secondary to marked cardiac enlargement. Prenatal arrhythmia is not common. Newborns most often present with cyanosis, while slightly older infants present with a combination of desaturation and symptoms of cardiac failure. Murmurs and arrhythmias are more frequently encountered as presenting complaints in older patients. Although some patients remain asymptomatic, most will have some cardiovascular symptoms. Beyond infancy, the majority will display abnormal fatigueability, dyspneoa, or cyanosis with exertion or palpitations. Palpitations in a cyanotic child should raise the possibility of Ebstein’s malformation ( Table 34-1 ). 9,39,40
| Prenatal ( N = 21) | Neonate ( N = 88) | Infant ( N = 23) | Child ( N = 50) | Adolescent ( N = 15) | Adult ( N = 23) | All (%) | |
|---|---|---|---|---|---|---|---|
| Cyanosis | 0 | 65 | 8 | 7 | 2 | 1 | 83 (38) |
| Heart failure | 0 | 9 | 10 | 4 | 2 | 6 | 31 (14) |
| Murmur | 0 | 8 | 3 | 33 | 5 | 3 | 52 (24) |
| Arrhythmia | 1 | 5 | 1 | 6 | 6 | 10 | 29 (13) |
| Abnormal prenatal ultrasound | 18 | 0 | 0 | 0 | 0 | 0 | 18 (8) |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
