Part 2

Primary Causes of Right Heart Dilation in the Fetus with a Structurally Normal Tricuspid Valve

Introduction

There are 4 causes of an enlarged right heart in the fetus with a normal tricuspid valve. Some of these defects can result in tricuspid insufficiency due to RV dysfunction or dilation, rather than a primary abnormality of the tricuspid valve. The causes are: 1. an intrinsic congenital abnormality of the right ventricle or right atrium; 2. Increased afterload faced by the right ventricle; 3. Right ventricular volume load and 4. Abnormal intracardiac connections.

Intrinsic RA or RV abnormality

The first cause of an enlarged right heart is a primary problem in the right atrial or ventricular muscle.

Idiopathic dilatation of the right atrium is usually an incidental finding which may be associated with atrial arrhythmias. It is progressive during fetal life (Figure 1) but can stabilize after birth.

Figure 1A, 1B. Dilated RA associated with atrial arrythmia

Uhl’s anomaly has a very poor prognosis if identified in fetal life. Diagnosed pre or postnatally, the only treatment is cardiac transplantation. In this disorder of unknown etiology, the right ventricular muscle is replaced by fibrous-fatty tissue and the ventricle becomes parchment-thin (Figure 2). The thinning of the RV usually begins with the anterior wall just distal to the tricuspid valve and extends to the apex. The intraventricular septum is spared. An important consequence of the poor RV function and severe dilation is development of functional pulmonary atresia, similar to what occurs in severe Ebstein’s anomaly and tricuspid valve dysplasia. Figure 3A shows a 20-week fetus with Uhl’s anomaly and a very small main and branch pulmonary arteries. The pulmonary valve is very thick, and its mobility is restricted. In figure 3B, retrograde flow is seen in the main pulmonary artery due to reverse (left to right) flow in the ductus arteriosus. This fetus was still-born at 23 weeks.

Figure 2. Thinned RV wall in Uhl’s anomaly

Figure 3 Uhl’s anomaly - Pulmonary atresia with thick, restricted PV.

Right ventricular diverticulum or aneurysms can cause heart failure, isolated ventricular ectopy or sustained ventricular arrhythmias. Ventricular diverticulum and aneurysms are categorized as ventricular wall defects. The differences between them are based on the components of the right ventricular free-wall that are present and movement characteristics of the defect. For example, an aneurysm does not have all 3 layers of the ventricle and moves paradoxically when compared to the rest of the ventricle. A diverticulum is comprised of all 3 layers: epicardium, myocardium and endocardium, and can be dyskinetic or akinetic (Figure 4 and b). Both defects can spontaneously regress or fail to grow with the rest of the heart. Left ventricular wall defects occur in a 5:1 ration with RV wall defects. Most fetuses do well: in a literature review of 46 subjects, 12 were still born at 26-39 weeks, there were 7 pregnancy interruptions, and 27 were liveborn and clinically well. Ventricular arrhythmias can both regress or progress after birth.

Figure 4 A and B. Right ventricular diverticulum

Increased afterload

The second cause of a dilated right heart is increased afterload due to downstream obstruction (pulmonary stenosis or ductal constriction). The right ventricle initially hypertrophies in response to increased afterload; if the obstruction is not relieved, the ventricle then dilates and becomes dysfunctional.

Constriction of the ductus arteriosus

Constriction of the ductus arteriosus usually occurs after indomethacin treatment for tocolysis, maternal consumption of non-steroidal anti-inflammatories or excessive phenols from berries or green tea. Ductal constriction can also be idiopathic. Some cases of ductal constriction occur acutely, for example after indomethacin administration during open meningomyelocele repair (Figure 5). The hallmark of ductal constriction is increased systolic and diastolic flow in the ductus arteriosus (Figure 5A). Ductal constriction is said to be present if the pulsatility index (PI), (calculated as peak systolic velocity – peak diastolic velocity divided by mean velocity) is <1.94. Color can be seen to alias in the constricted DA (Figure 5A, B). Right ventricular function will be preserved, in the initial stages of ductal constriction.

Figure 5 A-C. 22 week fetus following indomethacin administration

Like fetuses with severe ductal constriction, fetuses with an absent ductus arteriosus and an otherwise structurally normal heart will have signs of increased afterload including right ventricular hypertrophy, dysfunction and dilation (Figure 8A). The echogenic chordae of the tricuspid valve are typical for ductal constriction or absent ductus arteriosus (Figures 6B, 7A, 8A).

Figure 6. Echogenic tricuspid valve chordae at (A) 24 weeks and (B) 32 weeks

On the other hand, chronic ductal constriction can be mistaken for hypoplastic left heart syndrome or coarctation of the aorta because the left ventricle is compressed by the dilated and hypertrophied right ventricle (Figure 6). Findings of continuous antegrade flow In the ductus arteriosus clinches the diagnosis of ductal constriction. Often, there is at least moderate tricuspid insufficiency (Figure 7A) of high velocity indicating elevated RV peak systolic pressure. In contrast to acute constriction, when the ductus is normal in size, but flow is accelerated, in chronic constriction, the DA is tiny and serpiginous (Figure 7b and c).

Figure 7 A. Tricuspic insufficiency B and C. Tiny and serpiginous ductus arteriosus

However, in contrast to the tiny twig-like ductus arteriosus seen with severe chronic constriction, these fetuses will have no ductus arteriosus at all. Sweeping from “ductal arch” to aortic arch (Figure 8B) and in the 3-vessel tracheal view (Figure 8C), no ductus arteriosus is visualized.

Figure 8A-C. Absent ductus arteriosus

The hemodynamics of DA constriction or absence are shown in Figure 9.

Figure 9a shows the holosystolic jet of tricuspid insufficiency (above baseline). The peak velocity is about 4 m/s, suggesting a RV systolic pressure of about 70 mm Hg (64 mm Hg+ estimated RA mean pressure of 6 mm Hg). Normally, the RV systolic pressure should be equal to the gestational age; hence RV pressure is more than 2x normal in this 30 week fetus. Figure 9 b shows monophasic filling of tricuspid inflow (below baseline). The filling time of 83 ms is markedly reduced indicating very abnormal diastolic function. In constrast, LV filling was bi-phasic and filling time was normal (~150 ms).

Figure 9C shows flow in the ductus venousus, which is normally all antegrade (above baseline). Flow below baseline during atrial systole is indicative of reduced RV complaince. Figure 9D demonstrates flow in the left pulmonary artery. Flow is antegrade during systole (above baseline) but retrograde during diastole, indicating that diastolic pressure in the lungs is higher than diastolic pressure in the heart.

If the foramen ovale is widely patent in the setting of chronic ductal constriction or absent ductus arteriosus, cardiac output is re-distributed, and the fetus will not develop hydrops. Occasionally, a very redundant fossa ovalis aneurysm and a dilated coronary sinus can occur with ductal constriction or absent ductus arteriosus, which may restrict filling of the left heart, and result in fetal hydrops.

Timing of delivery can be challenging with ductal constriction or absent ductus. The fetus should be monitored carefully with non-stress tests and biophysical profile scores. If mature, the fetus should be delivered. Delivery of a mature fetus usually results in a good outcome, but occasionally pulmonary vasodilators (nitric oxide) and rarely, extracorporeal membrane oxygenation (ECMO) is necessary to treat severe pulmonary hypertension. The right heart slowly normalizes weeks to months after birth.

Pulmonary stenosis

Another cardiac anomaly causing increased afterload to the right ventricle is valvar pulmonary stenosis (Figure 10). The echo findings can be quite mild initially, even limited to abnormal doming motion of a thickened valve or post-stenotic dilation of the main pulmonary artery. As the obstruction progresses the right ventricle becomes hypertrophied, dilated and dysfunctional, and tricuspid insufficiency can develop (Figure 10a). The pulmonary valve can be relatively immobile, and retrograde flow can be seen in the main pulmonary artery due to a left to right ductal shunt (Figure 10b). In the Baltimore-Washington Infant Study, 9% of newborns with valvar pulmonary stenosis had non-cardiac anomalies, the most common being Noonan’s syndrome. The prevalence among live-born infants was 3.8/10,000. Pulmonary stenosis can also be seen in the recipient twin in twin to twin transfusion syndrome. In these cases, the pulmonary stenosis is often functional and due to poor systolic performance of the right ventricle. Pulmonary obstruction can improve and even reverse with a selective fetoscopic laser procedure (SFLP).

Figure 10 A. Tricuspid insuficiency B. Left to right shunt

“Critical “pulmonary stenosis refers to valvar pulmonary stenosis that will require treatment in the newborn period. In cases of critical pulmonary stenosis, the ductus arteriosus in kept open after birth with prostaglandin infusion to help unload the right ventricle. The treatment of choice for critical pulmonary stenosis is a pulmonary balloon valvuloplasty which has an excellent outcome and is often the only intervention the patient will ever need. The hemodynamic findings are the same as for valvar pulmonary stenosis as for ductal constriction (Figure 9 9a-c): monophasic filling of the right ventricle, tricuspid insufficiency, a hypertrophied ventricle with poor systolic function and abnormal flow in the ductus venosus. The peak velocity of the tricuspid insufficiency or systolic flow velocity across the pulmonary valve can be used to predict the peak RV pressure but cannot determine the severity of the pulmonary stenosis without knowing the ventricular function. If the ventricular function is poor, the RV cannot generate sufficient pressure to eject blood backwards (tricuspid insufficiency) or forward (pulmonary systolic flow) at an increased velocity.

Peripheral pulmonary artery stenosis (PPS) is difficult to diagnose prenatally unless you recognize the branch pulmonary artery measurements are more than -2.5 Z-scores for gestational age (Figure 11). PPS, especially left pulmonary artery stenosis, can be seen with DA constriction. The right ventricle will generally not be enlarged, but PPS is important to recognize because of its association with Williams syndrome and Alagille syndrome.

Figure 11. Peripheral pulmonary artery stenosis

Volume loading of the RV

Volume loading of the RV is due to moderate to severe pulmonary insufficiency from a dysplastic or “absent “pulmonary valve. There are 3 types of absent pulmonary valve syndromes: Tetralogy of Fallot (ToF) with absent pulmonary valve (APV) with no ductus arteriosus; ToF, APV and a patent ductus arteriosus, and pulmonary valve dysplasia with intact ventricular septum.

Of fetuses with absent pulmonary valve syndromes, 93% have ToF and APV. In the late 1st and early 2nd trimester, about a 3rd of patients with absent pulmonary valve present with an enlarged nuchal translucency and/or hydrops. The dilated pulmonary arteries so characteristic of this syndrome tend to be seen at 15 weeks or later. Fetuses with Tof , APV and a patent ductus arteriosus are rarely seen for 2 reasons. First, there is a high incidence of miscarriage due to concomitant chromosome anomalies. Second, the presence of both the ductus arteriosus and pulmonary insufficiency results in massive bi-ventricular volume loading and heart failure.

However, even if the ductus arteriosus is absent, fetal losses are high in ToF with APV, which represent 15-20% of fetal ToF and 1% of all prenatal congenital cardiac anomalies, but only 3-6% of postnatal ToF and 0.2-0.4% of all congenital cardiac anomalies in liveborns. In utero mortality correlates not with size of the pulmonary arteries or the right ventricle, but similar to prognostic indicators for Ebstein’s anomaly or tricuspid valve dysplasia, mortality correlates with the degree of LV dysfunction. There is a high (45%) incidence of associated anomalies including the 22q11 deletion and non-cardiac anomalies.

In contrast to ToF with pulmonary stenosis or pulmonary atresia, in ToF with APV

The pulmonary arteries are enlarged and pulsatile. In fact, fetuses are often referred because of a pulsatile chest mass not recognized to be the pulmonary arteries. Common to all types of ToF are: levorotation, an aorta which overrides a malalignment VSD with anterior deviation of the conal septum (Figure 12A, B), right ventricular dilation and sometimes hypertrophy, severe dilation and pulsatility of the main and branch pulmonary arteries (Figure 12C) with to- fro flow across the “pulmonary valve” seen best by color flow Doppler (Figure 12D). In fact, before 18 weeks, most patients are identified by the to-fro color flow in the main pulmonary atery. About 20% of the time the aortic arch will be right sided.

Figure 12. Tetralogy of Fallot (see text for descriptions)

Figure 12A-B

Figure 12C-D

We recently had a case of a 22-week fetus with Tof and APV with a suspected RV diverticulum (Figure 13). FISH for the 22q11 deletion was positive. Note the levorotation at the beginning of the clip, how small the aorta is compared to the pulmonary arteries and the severe dysfunction of the right ventricle.

Figure 13. Tetralogy of Fallot and absent PV

The outcome of fetal ToF APV was recently evaluated (Figure 14A,B). Survival was bleak, and almost half of the cohort had chromosome anomalies

Figure 14A.

Figure 14B.

Figure 14C.

The final absent pulmonary valve syndrome is a dysplastic pulmonary valve with an intact ventricular septum. In these fetuses, volume loading is restricted to the RV because there is no VSD. However, they still need vigilant follow-up especially after 30 weeks because the dilated right ventricle can impair left ventricular function, thus increasing the risk of hydrops and fetal demise.

Abnormal AV or VA connections

Structural heart disease with increased inflow or outflow from the RV can cause RV enlargement with a normal tricuspid valve. We will discuss double outlet right ventricle (DORV).

DORV is a common congenital cardiac defect. It is mostly seen with abdominal and atrial situs solitus and levocardia. In all but one type (DORV with mitral atresia) there is a large ventricular septal defect (VSD) with an unrestricted left to right shunt. The location of the VSD (sub-pulmonic, sub-aortic, doubly committed or uncommitted) the relationship of the great vessels (malposed or normally related, Figure 15) and the presence of aortic or pulmonic outflow tract obstruction determine the hemodynamics of this defect.

One way to recognize DORV is to note the great vessels arise in parallel, as they do in transposition of the great vessels. However, this does not mean the vessels in DORV are transposed. To be transposed both great vessels would arise solely from their ventricles, even in the presence of a VSD. In DORV, one vessel is committed to 2 ventricles (Figure 16).

It can be difficult to distinguish between “DORV with normally related great vessels and pulmonary stenosis” and “ToF”. One approach is to say that Tof describes the infundibular morphology and DORV describes the VA connection, and diagnose the fetus with “DORV of tetralogy type”.

Clues to the echo diagnosis of fetal DORV are: 1. The right ventricle is larger than the left ventricle; 2. There is a VSD (Figure 17A-C) (unless the mitral valve is atretic); 3. The great vessels arise in parallel; 4. Only one great vessel is seen on the 3-vessel tracheal view (Figure 17D).

Variants of DORV are shown in Figure 17.

Figure 17A, 17B

Figure 17C, 17D

Figure 17E, 17F

Figure 17G

Figure 17 DORV variants

Figure 17 A-C. Malposition and hypoplastic pulmonary artery

Figure 17 D-F. Malposition and coarctation of the aorta (Taussig-Bing)

Figure 17 G. Subaortic VSC and normally related great vessels

DORV with mitral atresia (MA) is sometimes incorrectly referred to as “hypoplastic left heart” (HLHS). In true HLHS, there is VA concordance, that is the stenotic or atretic aorta arises from the left ventricle and the pulmonary artery arises from the right ventricle. There is not VA concordance in DORV with MA, nor is there a VSD as there is in other forms of DORV. Either the pulmonary artery or the aorta can be hypoplastic, and the great vessels either malposed (anterior aorta) or normally related (pulmonary artery anterior. FIGURE 19 shows a fetus with DORV and MA and a hypoplastic pulmonary artery which is anterior to the aorta.

The tables in figures 18-20 below describe the incidence of DORV compared to other types of congenital heart disease. The number of fetuses and infants with DORV and either syndromes or chromosome anomalies is significant, thus a careful targeted ultrasound and amniocentesis should be strongly considered.

Figure 18. Incidence of cardiac defects in liveborn infants

Figure 19. Distribution of non-cardiac malformations

Figure 20. Frequency of extracardiac and chromosome anomalies in fetuses with CHD

Fetal Right Heart Enlargement

Part 2: Idiopathic Dilation of the Right Atrium and Uhl’s Anomaly