Part 1

Primary Cause of Right Heart Dilation in the Fetus: Abnormal Tricuspid Valve

Introduction

One of the etiologies for right heart enlargement in the fetus is severe tricuspid insufficiency secondary to an anatomically abnormal tricuspid valve. There are 3 primary tricuspid valve abnormalities which include Ebstein’s anomaly of the tricuspid valve (EA), tricuspid valve dysplasia, (TVD) and unguarded tricuspid valve orifice (UTO). Tricuspid valve insufficiency ranges from mild to severe: fetuses with severe insufficiency can be recognized as early as 15 weeks due to the right heart, especially right atrial, enlargement. Both pre-and postnatal prognosis for the fetus with severe tricuspid is poor due to development of hydrops and functional pulmonary atresia. Functional pulmonary atresia occurs because of reduced antegrade flow to the higher pressure pulmonary artery and preferential regurgitant flow to the low pressure right atrium.

Tricuspid insufficiency and right heart enlargement (Figures 1a and 1b) are progressive throughout gestation.

Figures 1a and 1b. Tricuspid insufficiency and right heart enlargement at 20 weeks and 34 weeks.

Unguarded tricuspid orifice

Although they present with similar findings, EA, TVD and UTO are anatomically distinct. There is no demonstrable tricuspid valve at all in UTO (Figures 2a and 2b). In the absence of a tricuspid valve, the flow pattern from atrium to ventricle is very characteristic: antegrade systolic flow (atrium to ventricle) and retrograde diastolic flow (Figure 2c and d). This defect is exceedingly rare.

Ebstein’s anomaly and tricuspid valve dysplasia

The differences between EA and TVD relate to insertion of the 3 tricuspid valve leaflets (Figure 3).

All 3 leaflets of the tricuspid valve insert normally in the fetus with TVD, but they are thickened and dysplastic and often fail to coapt resulting in severe tricuspid insufficiency (Figure 4a and b)

Figure 4. Tricuspid insufficiency resulting from failure of leaflet coaptation

There are abnormal distal and proximal attachments of the valve leaflets from the AV valve ring in EA; the diagnostic feature is inferior displacement of the septal tricuspid valve leaflet (Figure 5a). The area between the tricuspid valve ring and the tricuspid valve is called the “atrialized” right ventricle. Sometimes the tricuspid valve insertions are so inferior you cannot see the valve unless you look carefully (Figure 5b). Other features of EA are RV” dysplasia”: either the RV wall thickness is < 2 standard deviations or the RV size is > 2 standard deviations above the mean. It is the degree of tricuspid insufficiency, not the degree of valve displacement, that determines the prognosis of fetuses with EA.

Figure 5a. Inferior displacement of the septal tricuspid valve leaflet Figure 5b. Atrialized RV

Associated features of Ebstein’s anomaly

There are several unique associated findings with EA. One is a high (about 10%) incidence of accessory connections resulting in ventricular pre-excitation and the predisposition to supraventricular tachycardia. This condition is called Wolf-Parkinson-White syndrome. Another associated finding with EA is L-transposition of the great vessels (also known as congenitally corrected transposition of the great vessels or atrioventricular and ventriculoarterial discordance) (Figure 6).

Figure 6. Transposition of the great vessels

Ironically, because of the abnormal atrioventricular connections, fetuses with L-transposition are at risk for atrioventricular block and bradycardia.

Figure 7. AV and VA connections in L-transposition (also known as congenitally corrected transposition)

Because of the association of EA with L-transposition, it is important to carefully evaluate the atrioventricular and the ventriculoarterial relationships and remember that the AV valve always follows its ventricle. A third, albeit uncommon association with EA is pulmonary atresia and intact atrial septum. In this case, the valve is deep in the ventricle and not insufficient. Although tricuspid valve tissue is present, the systolic retrograde flow and diastolic antegrade flow is like the flow characteristics of UTO.

Functional perturbations in Ebstein’s anomaly and tricuspid valve dysplasia

There are also functional perturbations associated with the hemodynamics of EA and TVD. We have previously alluded to functional pulmonary atresia, which develops because of the high regurgitant volume in both EA and TVD. Besides functional pulmonary atresia, true pulmonary atresia or stenosis, and pulmonary insufficiency can also develop and be diagnosed by fetal echocardiography. The hallmark of pulmonary atresia, be it functional and true pulmonary atresia, is a reverse or “cyanotic” ductus. The cyanotic ductus arises from the underside of the aortic arch. Blood is shunted in the opposite direction from normal: from the aorta to the pulmonary arteries, rather than from the pulmonary arteries to the aorta. Thus the “ductal arch” cannot be visualized in these cases. The cyanotic ductus is not limited to EA and TVD, but is also seen in Uhls anomaly and RV cardiomyopathy, and any congenital defect with severe pulmonary artery obstruction including tetralogy of Fallot with severe pulmonary stenosis or atresia and pulmonary atresia with intact ventricular septum.

The significance of pulmonary insufficiency in Ebstein’s anomaly and tricuspid valve dysplasia: the circular shunt

The most severe cases of EA and TVD occur when not only is there pulmonary atresia, but also pulmonary insufficiency. The pulmonary valve can be normal with antegrade flow early in pregnancy and progress to functional or true pulmonary atresia (no antegrade flow from RV to PA) with insufficiency.

The reason pulmonary insufficiency is such an ominous finding in EA and TVD is that a circular shunt can develop (Figure 8).

Figure 8. Circular shunting in Ebstein’s Anomaly

In the circular shunt, blood enters the right atrium from the superior and inferior vena cavae, as in the normal fetus. However, due to the tricuspid insufficiency, more blood enters the right atrium than normal. If there is pulmonary atresia (no forward flow across the pulmonary valve) and pulmonary insufficiency, blood from the ductus arteriosus enters the main pulmonary artery, then the right ventricle (though the pulmonary insufficiency) and back again to the right atrium through the abnormal tricuspid valve tand tricuspid insufficiency. With increased right atrial volume, the normal right to left shunt across the patent foramen ovale is increased, resulting in a greater volume of blood entering the left heart. Because of the reversed ductal shunt (left to right), this means that a greater volume of blood traverses the ductus arteriousus to the pulmonary artery only to return ultimately to the right atrium. This vicious cycle known as the “circular shunt”. The effect of the circular shunt on the fetus is shown in Figure 8. Management of these patients after birth frequently involves ductal closure to reduce the effects of the circular shunt.

Table 1. Poor Prognostic Signs for Fetal/Neonatal Tricuspid Valve Disease.

Incidence and outcome of Ebstein’s anomaly and tricuspid valve dysplasia

In a 6 year retrospective case matched study of fetal demise among 1584 fetuses with structural or functional cardiac defects (Table 2, below), 74 (5%) had Ebstein’s anomaly, which was the second highest cause of demise (Macoll, 2014).

Table 2. Demise Among Fetuses With Congenital Heart Disease

Because of the right risk of fetal demise, EA is more common in fetal life than after birth. EA comprises 3-7% of all fetal congenital heart disease but only 0.5-1% of postnatal congenital heart disease. There is equal distribution between males and females. About 20% have non-cardiac anomalies. Risk factors for EA include a family history of cardiac defects (including defects other than EA), maternal exposure to solvents, a history of poor pregnancy outcomes and maternal exposure to marajuna and benzodiazepines. In the Baltimore-Washington Infant Study Group report, there was not sufficient power to link fetal lithium exposure with EA.

Unlike EA, TVD does not have a strong association between chromosome or non-cardiac defects. TVD is commonly seen with atrial septal defects. Because it is so unusual, there is no data in prevalence and associated findings with UTO.

Fetal Right Heart Enlargement

Part 1: Prenatal Tricuspid Valve Disease