H Chapter 3

39

H ypoplastic left heart syndrome encompasses a spectrum of lesions affecting the left heart, the main features of which are hypoplasia of the left ventricle, together with atresia or stenosis of its inlet and outlet. The positional relationship of the great arterial trunks in these cases is normal. Such a syndrome, involving underdevelopment of the left atrium, left ven- tricle and ascending aorta, was already recognised in the 1800s.

These early investigators noted that the right side of the heart and the pulmonary trunk were dispro- portionately large, although the heart itself was of normal size, and that the cavity of the left ventricle was unnaturally small. In 1952, Lev

used the term

“hypoplasia of the aortic tract complex” to describe a group of abnormalities with inflow and outflow obstruc- tion of the left heart. Then, in 1958, the term

“hypoplastic left heart syndrome” was proposed by Noonan and Nadas

to include obstructive lesions on the left side of the heart associated with a hypoplastic left ventricle and right ventricular hypertrophy. In 1968, Sinha et al.

argued that the constellation would better be called the hypoplastic left ventricle syndrome, thus excluding all cases of primary coarctation and inter- rupted aortic arch. Despite the wisdom of this sugges- tion, the term “hypoplastic left heart syndrome” has persisted, albeit that there is still controversy as to pre- cisely which lesions should be included.

Most commonly, it is accepted that the syndrome consists of aortic atresia with or without mitral atresia, although some cases will have mitral atresia with a patent aortic valve and the aorta arising concordantly from the left ventricle. In a minority of cases, the mitral and aortic valves may both be patent, but the left heart structures are very hypoplastic. Those placed in this latter group fall into the severe end of the spectrum of coarctation of the aorta as seen during fetal life.

The incidence of the syndrome is reported to vary from 4.8% to 9%, and the prevalence is between 0.1 and 0.27 cases in every 1000 live births.

Babies born with this condition appear normal and healthy at birth, and develop signs of heart failure as the arterial duct starts to close. When this happens, the systemic circulation is inadequate, and the baby develops circula- tory collapse, presenting in a shock-like state. Early diagnosis of this condition thus has potential benefits, and antenatal diagnosis can be made as early as 14 weeks of pregnancy.

FETAL SPECTRUM AND DIAGNOSIS

Hypoplastic left heart syndrome is one of the common- est forms of cardiac abnormality encountered in fetal life.

It accounts for almost one-fifth of structural cardiac abnormalities in the large series of fetuses scanned at Guy’s Hospital (Fig. 3.1). The reason for this high incidence is that fetuses with the syndrome are readily detectable by examination of the four-chamber view of the heart during routine obstetric ultrasonic examination.

In the majority of cases referred to our unit, such an abnormality in the four chamber view had been noted at the time of the routine obstetric scan. In a smaller proportion of cases, there was a different reason for referral (Fig. 3.2). Although this type of cardiac abnormality can be detected from 13 to 14 weeks of pregnancy, the majority of cases are detected at between 20 and 22 weeks, coinciding with the timing of the obstetric scan seeking congenital anomalies (Fig. 3.3). Some cases, however, are not detected and referred until the third trimester of pregnancy (Fig. 3.3).

Unfortunately, there are still some cases that remain undetected until after birth.

Chapter 3

A NTENATAL D IAGNOSIS OF H YPOPLASTIC L EFT H EART

S YNDROME

Gurleen Sharland

The fetal echocardiographic findings are those of an abnormal left ventricle and aorta. The left ventricle is small, although there is some variation in this depend- ing on the patency of the mitral valve, and whether there is an associated ventricular septal defect. In cases of aortic and mitral atresia, the left ventricle is tiny.

Indeed, oftentimes it is not discernible (Fig. 3.4). In this setting, the components of the left heart are so under- developed that, in the four-chamber view, the impres- sion may be of only one atrium, one atrioventricular valve, and one ventricle. In cases of aortic atresia asso- ciated with a patent mitral valve and an intact interven- tricular septum, the left ventricular cavity is more easily recognised, but it is often echogenic, globular, and dys- functional (Fig. 3.5A). In these cases the normal inflow of the left ventricle cannot be demonstrated, even though the mitral valve is patent (Fig. 3.5B). The echogenicity of the left ventricle correlates well with the finding of endocardial fibroelastosis at postmortem examination of the heart. The prerequisite for the pres- ence of endocardial fibroelastosis is severe obstruction to the egress of blood from the left ventricle in the pres- ence of an intact ventricular septum, but with a route for ingress of mitral flow.

If there is aortic atresia, then the ascending aorta is usually tiny, measuring around 1 mm in the middle- trimester fetus. This makes it difficult to demonstrate, but careful searching usually allows identification of the hypoplastic vessel compared to the larger pulmonary trunk (Fig. 3.6). No forward flow is detectable across the aortic valve, and only retrograde flow from the duct is detected in the hypoplastic aortic arch (Fig. 3.7). In some cases, the aortic valve may be patent, as in the setting of mitral atresia with a ventricular septal defect and the aorta arising concordantly from the left ventri- cle. In these instances, the aortic root may be normal in size, or only slightly hypoplastic. Forward flow will then usually be detected in the ascending aorta. A minority of cases fall in the severe end of the spectrum of coarcta- Proportion of cases of hypoplastic left heart in fetal series

(Total with congenital cardiac malformations =2521)

19%

81%

HLH Other CHD

Proportion of cases of hypoplastic left heart in fetal series (Total with congenital cardiac malformations =2521)

19%

81%

HLH Other CHD

Proportion of cases of hypoplastic left heart in fetal series (Total with congenital cardiac malformations =2521)

19%

81%

HLH Other CHD

FIGURE 3.1. The proportion of cases with hypoplastic left heart (HLH) syndrome in the series of 2521 fetuses with congenital heart disease (CHD) seen in the fetal cardiology unit at Guy’s Hospital.

0 100 200 300 400 500

?chd FH

Hypoplastic Left Heart Gestational age at referral

0 20 40 60 80 100 120 140

13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38

FIGURE 3.2. Reasons for referral in 471 cases of hypoplastic left heart syndrome diagnosed during fetal life. ?chd, abnormality sus- pected during routine screening; FH, family history of congenital heart disease; F Abn, extracardiac fetal abnormality; F Arr, fetal arrhythmia;

F Hyd, non immune fetal hydrops; NO, increased nuchal translucency.

FIGURE 3.3. The gestational age at referral in 471 fetuses with hypoplastic left heart syndrome.

RA

RA LA

FIGURE3.4. The four-chamber view of the fetal heart in a baby with mitral and aortic atresia. The left ventricle (arrow) is slit like and hypoplas- tic. LA, left atrium; RA, right atrium; RV, right ventricle.

RV

LV RV

LV RA RA

A

B

FIGURE3.5. The four-chamber appearance in aortic atresia with a patent but hypoplastic mitral valve. The left ventricle appears echogenic and globular (A). It was poorly contractile on the moving image. Colour flow demonstrates flow across the tricuspid valve into the right ventricle, but no flow is seen across the mitral valve into the left ventricle (B). LV, left ventricle; RA, right atrium; RV, right ventricle.

tion of the aorta, where there is marked hypoplasia of all the components of the left heart, but the mitral and aortic valves are still patent (Fig. 3.8).

Premature closure of the oval foramen has been sug- gested as a cause of the syndrome, but in the majority of fetuses diagnosed with this lesion, the foramen is usually patent.

In these instances, the blood usually shunts from left to right atriums, which is the reverse of the normal situation (Fig. 3.9). In a minority of cases, the foramen can be restrictive, or more rarely intact. A clue to the presence of a restrictive atrial septum can be the finding of an abnormal pulsed Doppler pattern of pulmonary venous flow.

An increase in the reverse flow wave into the pulmonary veins during atrial systole correlates with restriction of the foramen.

ASSOCIATED SYNDROMES

Those with the syndrome can occasionally have chro- mosomal anomalies, particularly Turner’s syndrome, but also trisomy 18 and 13.

It has also been reported to be associated with duplication of the short arm of chromosome 12.

Extracardiac structural mal- formations can also occur, and in some instances this increases the surgical risk. Brackley et al.

reported karyotypic anomalies in one-eighth of their cases, and associated extracardiac anomalies in one-fifth. In the fetuses we have seen at Guy’s Hospital, from 3% to 4%

had an associated karyotypic anomaly, and a further 7%

had an extracardiac anomaly in association with a normal karyotype.

Small AAo

LV RV

A

B

FIGURE3.6. The pulmonary trunk (A) is significantly larger than the ascending aorta (B) in this example. The aorta is seen arising from a fibrotic and hypoplastic left ventricle in B. AAo, ascending aorta; PT, pulmonary trunk; LV, left ventricle; RV, right ventricle.

MANAGEMENT

Hypoplastic left heart syndrome lies at the severe end of the spectrum of cardiac malformations. When the diag- nosis is made in the middle trimester of pregnancy or earlier, the parents have the option of either interrupt- ing the pregnancy or proceeding to term. The thera- peutic options that are available after birth include no treatment, cardiac transplantation, or palliative surgery.

The option of no treatment, allowing nature to take its course, is a complex decision made between physicians and parents. If transplantation is being considered, then the major limiting factor is the availability of a donor heart.

Such an organ may become available within hours, but may take weeks or months. Most of the time, it may not become available at all. Palliative surgery involves progression through the stages of the Norwood

procedure,

which is described in detail in other chapters of this book. The Norwood strategy has now become the preferred treatment option for this condi- tion in the United Kingdom. In the United States, sur- vival from the first stage now exceeds 80% in some centres,

with even better results reported elsewhere in this book (see Chapter 7). Current results of this strat- egy in the United Kingdom are now beginning to approach those achieved in the United States. Some studies have reported that the outcome for babies with a prenatal diagnosis is worse, with the mortality follow- ing the first stage of the Norwood procedure being in the range of 50% to 55%, with some babies not even reaching the operating room.

Other studies, in con- trast, have reported an improved outcome in babies with a prenatal diagnosis,

as well as finding a reduc- tion in early neurological morbidity compared with cases

A

B

FIGURE3.7. A very hypoplastic aortic arch (A), with reversed flow only in the arch, shown in red (B).

presenting postnatally.

If antenatal data are analysed on an “intention to treat” basis, the results are different compared with looking at surgical mortality alone.

This is because some pregnancies may result in a spon- taneous intrauterine loss, and some infants may die postnatally prior to surgery. These factors have to be taken into account, in addition to the surgical mortality, when counselling parents antenatally.

It is now apparent that, with a properly organised programme, it is possible to achieve satisfactory results in the early and medium term. Uncertainty remains, however, as to what will happen to the systemic right ventricular function over the long term. Whether a significant proportion of the survivors of the staged Norwood approach will eventually require cardiac trans-

plantation also remains unknown. Thus, when dis- cussing the options following prenatal diagnosis, a real- istic view must be given about the outcome, not just in terms of surgical mortality, but also in terms of longer- term development and survival. As yet, there is little information about the long-term survival for these chil- dren. Despite the uncertainty of the long-term outlook for the Norwood procedure, many parents are now electing to choose this option. Since the introduction of the Norwood procedure in the United Kingdom, there has been a change in the proportion of pregnancies resulting in termination. Overall, however, the majority of parents still choose the option of termination of preg- nancy following prenatal diagnosis. The overall outcome of pregnancy following prenatal diagnosis in

Spine

PT Ao

C

FIGURE3.7. (cont.) In a transverse view of the pulmonary trunk and aortic arch (C), there is forward flow in the pulmonary trunk (PT), seen in blue heading toward the spine, and retrograde flow in the aortic arch (Ao), seen in red heading away from the spine.

LV RV

RA LA

RV

LV RA

A B

PT

Ao Spine

C

FIGURE3.8. An example of a four-chamber view in severe coarctation falling into the pattern of hypoplastic left heart syndrome. The left atrium (LA) and left ventricle (LV) are significantly smaller than the right atrium (RA) and right ventricle, respectively (RV) (A). Colour flow mapping reveals that the mitral valve is patent (B). A view of the great arteries in the same baby is shown in C. Although the aorta (Ao) is significantly smaller than the pulmonary trunk (PT), there is still forward flow in the arch.

the fetuses with the syndrome seen at Guy’s Hospital is shown in Figure 3.10. It is worth noting that the per- centage of parents electing to choose termination has fallen from 78% in 1994, prior to the introduction of the Norwood strategy at our unit, to 63% in 2001. In comparison, the percentage of parents choosing to interrupt the pregnancy following prenatal diagnosis of congenital cardiac disease in general is currently between 35% and 40%.

CONCLUSION

Hypoplastic left heart syndrome can be diagnosed with a high degree of accuracy from 13 to 14 weeks of pregnancy. Antenatal diagnosis gives parents time to understand, and come to terms with, the problem in the heart of their baby. It also gives them the opportunity to

make informed choices, and to be prepared for events postnatally.

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FIGURE3.9. The interatrial flow in this example is left to right, which is the reversal of the normal pattern. LA, left atrium; RA, right atrium.

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Hypoplastic Left Heart Outcome in 471 cases

0 50 100 150 200 250 300 350

TOP IUD NND INFD Alive

FIGURE3.10. The outcome in 471 cases of hypoplastic left heart syndrome diagnosed during fetal life. TOP, termination of pregnancy;

IUD, intrauterine death; NND, neonatal death; INFD, infant death.