Part 3

Secondary Causes of Right Heart Enlargement in the Fetus

Introduction

Secondary causes of right heart enlargement occur with volume or volume and pressure loading of a structurally and functionally normal right heart, or decreased volume to the left heart. Etiologies include fetal growth restriction, anemia, an absent ductus venosus, hepatic or cerebral arterial venous malformations, vascular tumors, and left sided obstructive lesions such as a restrictive foramen ovale, aortic or mitral stenosis, coarctation of the aorta or Shone’s syndrome.

Growth restriction or anemia

In response to hypoxia, more blood from the umbilical vein is shunted to the ductus venosus and across the PFO to the left heart and then to the brain. Increased flow to the brain means increased venous return to the superior vena cava and a volume load on the right heart. Anemia can further increase the volume loading of the right side. Figure1 shows a severely growth restricted (<3rd% for gestational age) fetus with a hematocrit of 7. A: The entire heart is enlarged, but the right side more so than the left. Brain sparing is noted by the retrograde flow in the transverse aortic arch (B) and heart sparing is seen with flow in the right coronary artery (C).

Figure 1A, 1B

Figure 1 Severely growth restricted fetus A. Enlarged heart B. Retrograde flow in the transverse aortic arch C. RCA flow

In the presence of a large ventricular septal defect, right heart enlargement may not be obvious. Rather, the entire heart, as measured by the CT ratio, may be enlarged (Figure 2A). In this fetus with growth restriction and an atrioventricular septal defect, heart sparing was noted by flow in the coronary arteries and brain sparing was diagnosed by retrograde flow in the ductus arteriosus to the transverse arch and ascending aorta (Figure 2B).

Figure 2 Growth restricted fetus with ASD A. Mild heart enlargement with normal systolic function B. Retrograde DA flow

Absent ductus venosus

In the fetal venous circulation oxygen and nutrients from the placenta enter the liver from the umbilical vein. Normally, 25-30% are diverted to the ductus venousus, but this number can increase depending on gestational age and the oxygen levels in the fetus.

If the ductus venosus is absent, the umbilical vein becomes very dilated (Figure 3A) and all the blood returning to the fetus from the umbilical vein enters the inferior vena cava so the IVC also enlarges (Figure 3B) This result is a dilated right atrium and right ventricle (Figure 3C). Thus, a greater volume of blood returns to the right heart since preferential flow across the PFO to the left atrium from the ductus venosus does not occur. There is a substantial co-occurrence of chromosome anomalies and non-cardiac defects that accompany absent ductus venosus; thus, a targeted ultrasound and amniocentesis are recommended. These fetuses should be followed serially especially after 30 weeks because of the risk of hydrops.

Figure 3 Absent DA A. Dilated umbilical vein B. Enlarged IVC C. Dilated RA and RV

Twin to twin transfusion syndrome

In some monochorionic diamniotic twin pregnancies, vasoreactive substances such as renin-angiotensin and endothelin 1 and volume transferred from donor to recipient twin via placental anastomosis. In 8-10% of monochorionic twins, twin to twin transfusion syndrome (TTTS) can develop in response to the pressure and volume load on the recipient twin. There is a very high perinatal mortality in TTTS: presentation before 25 weeks is associated with a 90% mortality without treatment. Characteristics of TTTS are: 1. A single placenta; 2. Same gender fetuses; 3. Significant amniotic fluid discordance; 4. Weight discordance (usually ≥10%).The recipient twin heart hypertrophies and function decreases (Figure 4A, B). In about 10% of cases, right ventricular function is so poor, there is no antegrade flow from the RV to the PA, and functional pulmonary atresia results with retrograde (left to right) flow in the DA (Figure 4C) and the typical cyanotic ductus arising from the underside of the aortic arch (Figure 4D). Pulmonary insufficiency can also develop (Figure 4E). These findings can be reversed in some cases and improved in most, after SFLP.

Figure 4. Twin to Twin Transfusion Syndrome

Figure 4A, 4B

Figure 4C, 4D, 4E

Figure 5 shows typical Doppler changes that occur in the recipient twin with TTTS. In the normal fetus, both left and right ventricular filling is biphasic. Thus, both the mitral and tricuspid valve Doppler will have 2 distinct peaks: and “e-wave” (passive filling of the ventricle) followed by an “a-wave” (active filling from atrial contraction). One of the early changes in the recipient is partial fusion of the “e” and “a” waves until they become monophasic. As the duration of mitral and tricuspid valve inflows correspond to ventricular filling time, a monophasic inflow corresponds to decreased ventricular filling time. As TTTS progresses, the “a-wave” of the ductus venosus falls to baseline and then becomes retrograde.

Figure 5. Doppler changes in twin to twin transfusion syndrome

A common way to characterize the cardiac dysfunction in TTTS is by measuring the left and right myocardial performance indices (MPI), also known as the Tei index (Figure 6) The MPI compares the time the heart is filling and ejecting with isovolumic times (contraction and relaxation). The greater the isovolumic times, the higher the MPI and the greater the cardiac dysfunction. The right and left MPIs are measured separately: the left MPI by simultaneous mitral and aortic valve Dopplers (Figure 6A) and the right by separate pulmonary valve and tricuspid valve Dopplers (Figure 6B, C). The heart rates for the right sided samples must be within 5 beats per minute of one another to be accurate. The MPI is calculated as isovolumic times divided by ejection time. Normal MPI values are: (LV) 0.36±0.6 and (RV) 0.35±0.5.

Figure 6. Measurement of the myocardial performance index

Figure 6A. Left MPI as measured with simultaneous mitral and aortic valve Dopplers

Cerebral and Hepatic Arteriovenous Malformations

Cerebral arteriovenous malformations are uncommon but devastating. Fetuses typically present with ventriculomegaly and cardiomegaly, signs of high output failure, dilated carotid arteries and an enlarged superior vena cava and innominate vein. Early prenatal diagnosis is unusual unless the turbulent flow of the arteriovenous malformation is seen by turbulent color Doppler in the fetal brain. Cerebral arteriovenous malformations usually involve the vein of Galen which is often dilated. A cerebral arteriovenous malformation is often termed a “Vein of Galen Aneurysm because of the dilation.

Figures 7-9 demonstrate the typical findings of a cerebral arteriovenous malformation in a newborn. This mother did not receive prenatal care, and upon delivery the infant was found to be cyanotic and in respiratory distress with significant cardiomegaly on chest x-ray. Figure 7A shows the very dilated right atrium and right ventricle. There is moderate tricuspid insufficiency with a peak Doppler flow velocity suggesting systemic right ventricular pressure (~70 mmHg in Figure 7B). As seen in Figure 7C, the left ventricle is pancaked by the high-pressure right ventricle. The right ventricular systolic and diastolic pressures in this newborn were so elevated that the atrial shunt was right to left (not shown; normally in the newborn it is left to right). Figure 8A-C shows the typical findings of a cerebral arteriovenous in the aortic arch and superior vena cava. Figure 9 shows the flow in the ascending aorta to be only systolic (A), while flow in the transverse aortic arch is continuous in systole and diastole (B). Evaluation of the brain through the anterior fontanelle demonstrates turbulence involving the vein of Galen and clinches the diagnosis of a cerebral arteriovenous malformation (C).

Figures 7-9. Fetal cerebral arteriovenous malformations (see text description above)

Figure 7A ,7B

Figure 7C, 7D

Figure 8A, 8B, 8C

Figure 9C.

The findings of a hepatic arteriovenous malformation are similar except there is no dilation and abnormal flow in the cerebral vessels, and the inferior vena cava, not the superior vena cava, is dilated. Color Doppler will turbulent flow in the liver.

Large vascular tumors such as sacrococcygeal tumors will also cause a high output state, but the cardiac dilation is not specific to the right ventricle.

Decreased flow to the left heart

Restriction to the right to left atrial shunt can occur if the patent foramen ovale (PFO) is restrictive (Figure 10A). This can be demonstrated by color flow Doppler. Reduced flow to the mitral valve can occur if there is a prominent aneurysm of the fossa ovalis (Figure 10B), regardless of the size of the PFO. The combination of a large aneurysm of the fossa ovalis and a dilated coronary sinus (which receives a left superior vena cava) can further reduce blood flow from the left atrium to the mitral valve resulting in a small left heart (Figure 10C) and concerns for coarctation or mitral stenosis. An increased mitral valve diameter and left heart area following a maternal hyperoxia challenge (asking the mother to breathe 100% oxygen through a rebreathing mask for 10 minutes) is reassurance that the left side is normal in size. After birth the PFO closes, flow is increased through the left heart and the disproportion between the right and left sides decreases.

Figure 10 A. Restrictive PFO B. Fossa ovalis aneurysm C. Large fossa ovalis aneurysm and dilated coronary sinus

Aortic coarctation (see below) is one of the most difficult lesions to diagnose with certainty in the prenatal period. Findings consistent with coarctation are:

1. A larger right atrium and ventricle than left atrium and ventricle
2. A larger (> 2.5 mm difference) pulmonary artery than aorta
3. Distance between the left carotid and left subclavian arteries.

At times, this right/left disproportion can be seen in the early to mid-2nd trimester, but at other times it is not detected until the 3rd trimester. At other times the great vessel disproportion or arch characteristics are more obvious than the ventricular disproportion. Figures 11 and 12 show the progression of coarctation development in a fetus referred for an early echo due to hypoplastic left heart in a sibling. The ventricular disproportion is not seen in the earlier scans (11a and 11b), but is noticeable by 27 weeks (11c). While the aortic arch already looked unusual at 14 weeks and at 28-weeks, the coarctation was clearly seen (Figure 12). On the other hand, in Figure 13, both the ventricular and great vessel disproportion are obvious at 20-weeks (a and b) and more so at 32-weeks (c and d). Figure 14 nicely demonstrates the difference in caliber between the pulmonary artery and the aorta as seen from the 3-vessel tracheal view.

Figures 11-13. Findings in aortic coarctation

Figure 11-C. Ventricular disproportion becoming evident by 27 weeks (C)

Figure 12A-C. Visible coarctation becoming clearer with progression of pregnancy

Figure 13A,B. Disproportion of ventricles (A) and great vessels (B) at 20 weeks

Figure 13C,D. Disproportion of ventricles (A) and great vessels (B) at 32 weeks

A common brachiocephalic trunk (also known as a bovine arch) can sometimes be mistaken for a coarctation. This is because the common trunk consists of the right subclavian artery and the right and left carotid arteries. Thus, there is more distance than normal between the trunk and the left subclavian artery, and transverse arch can be smaller than normal (Figure 15A and B). However, sometimes a coarctation is present with a common brachiocephalic trunk, and the key is to evaluate the other features of a coarctation (ventricular and great vessel disproportion). Sometimes the only way to diagnose coarctation with certainty is viewing the isthmus after the ductus arteriosus has closed.

Other findings reported in coarctation include a predominantly left to right (rather than a right to left) shunt across the patent foramen ovale. Comparison of the ductal arch and the transverse aortic arch is also helpful, this can be done from the long axis views of the arches (Figure 13 B and D) and by the 3-vessel tracheal view (Figure 14).

Chromosome anomalies have been detected in as many as 30% of fetuses with coarctation, the most common being Turner syndrome.

Figure 14. Left to right shunt found by comparison of the ductal and transverse aortic arches in the 3-vessel tracheal view

Figure 15-B. Common brachiocephalic trunk appearing as a coarctation

Five (Not so Easy) Cases

Using the decision tree below, diagnose the 5 cases shown in Figures 16-20. Answers are provided below each case for easy review. Don’t peek!

Case 1 (Figure 16)

Figure 16A, 16B

Figure 16C, 16D

Answer Case-1

(A) shows right/left disproportion at the ventricular level. (B) shows the ventricular disproportion, but also great vessel disproportion. However, the right ventricle is hypertrophied, and the apex of the left ventricle collapses in systole, suggesting the RV pressure may be elevated. The atrial shunt is purely right to left, not bidirectional or left to right (C). In the long axis of the aortic arch, the ductal ampulla is prominent, but the head vessels are normally spaced, and the isthmus and transverse arch do not appear smaller than the ascending aorta D).

This fetus had trisomy 21, pulmonary hypertension and a structurally normal heart.

Case 2 (Figure 17)

Figure 17A, 17B, 17C

Answer-Case 2

This fetus had a normal targeted ultrasound at 20-weeks. The right/left ventricular disproportion is easily noticed in (A) and (B). In contrast to Figure 16, the left ventricular apex does not collapse in systole. Once the long axis of the aortic arch is visualized, the narrow transverse arch, hypoplastic isthmus and distance between the left carotid and left subclavian are well seen (C).

This fetus had isolated coarctation of the aorta which was repaired on day 2 after birth.

Case 3 (Figure 18)

Figure 18A, 18B, 18C

Answer-Case 3

As with the other fetuses in this series, there is right/left disproportion at the ventricular level (A and B). However, different from the previous fetuses the left atrium is smaller, and the mitral valve barely opens. The transverse arch and isthmus are hypoplastic with retrograde flow seen by color Doppler (blue flow in the in the distal transverse arch) (C).

This fetus had mitral stenosis, coarctation of the aorta, and a bicuspid aortic valve with normal function (no stenosis or insufficiency). Because of the hypoplastic and stenotic mitral valve, he underwent Stage 1 Norwood palliation for hypoplastic left heart syndrome.

Case 4 (Figure 19)

Figure 19A, 19B

Figure 19C, 19D

Answer- Case 4

Ventricular and great vessel disproportion are seen in (A) and (B). Also noted is the incomplete excursion of the mitral valve leaflets, especially in (A). The aortic arch is unusually elongated, but only the isthmus (C), not the transverse arch is hypoplastic. There is also retrograde flow in the isthmus. The postnatal 4-chamber view shows a mitral arcade is responsible for the reduced mobility of the valve leaflets (D). An arcade occurs when the papillary muscles connect directly to the mitral valve leaflets

This fetus had a mitral arcade, mild mitral stenosis, a well-functioning bi-cuspid aortic valve, but no coarctation. He has not had any surgery at this time

Case 5 (Figure 20)

Figure 20A, 20B, 20C

Answer- Case 5

In contrast to the other 4 fetuses, this fetus has no right/left disproportion at the ventricular level (A). However, in both (B) and (C), this transverse arch taper at the isthmus, suggesting a coarctation

This fetus had a muscular VSD diagnosed after birth and no left sided pathology.

Fetal Right Heart Enlargement

Part 3: Ductal Constriction