Management and outcome in hypoplastic left heart syndrome

ARTICLE IN PRESS Current Paediatrics (2004) 14, 26–32

www.elsevierhealth.com/journals/cuoe

Management and outcome in hypoplastic left heart syndrome W.J. Brawn*, D.J. Barron Birmingham’s Children’s Hospital NHS Trust, Diana, Princess of Wales Children’s Hospital, Steelhouse Lane, Birmingham B4 6NH, UK

KEYWORDS Hypoplastic left heart syndrome; Norwood procedure; Fontan operation; Neurodevelopmental outcome; Neonatal and infant cardiac transplantation; Left Heart Matters group

Summary Hypoplastic left heart syndrome is a common cause of cardiac death in the first few weeks of life. It comprises atresia or underdevelopment of the left-sided heart structures. Over the past 20 years, Norwood and his co-workers have developed a three-stage complex palliative correction of this lesion. The first and second stages are performed within the first few months of life; the third stage, or Fontan procedure, whereby the right ventricle is connected to the systemic circulation and the systemic venous return is connected directly to the lungs without an intervening ventricle, is performed in the second to fifth year of life. Results have improved, the survival rate for stages I and II now being of the order of 70% and actuarial survival at 2–5 years being around 60%. Recent modifications of the technique comprise a right ventricle to pulmonary artery shunt rather than the modified Blalock–Taussig shunt. This is likely to impact positively on the outcome, with survival rates of 80–90% for stages I and II and actuarial survival greater than 80% at 5 years. The long-term outlook for this group of patients is likely to be that of the normal Fontan population, most or all perhaps requiring a heart transplantation later in life. & 2003 Elsevier Ltd. All rights reserved.

Practice points *

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Hypoplastic left heart syndrome is a congenital heart condition in which there is failure of development of the mitral valve, aortic valve, left ventricle and ascending aorta. The cause of hypoplastic left heart syndrome is unknown Hypoplastic left heart syndrome is uniformly fatal without treatment and accounts for 25% of cardiac deaths in the first week of life

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*Corresponding author. Tel.: þ 44(0)121 333 9435; fax: þ 44(0)121 333 9441. E-mail address: [email protected] (W.J. Brawn). 0957-5839/$ - see front matter & 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.cupe.2003.09.004

Norwood developed a complex reconstructive procedure to palliate children with hypoplastic left heart syndrome. This culminates in the Fontan procedure, in which the right ventricle supports the systemic circulation and the systemic venous return is directly connected to the pulmonary arteries without a ventricular pump The survival rates for Norwood-type programmes for hypoplastic left heart syndrome are currently 70% plus 30 day mortality and an actuarial survival of about 60% over the first 2–5 years of life Owing to the paucity of donors, transplantation is not a viable option for the majority of patients with hypoplastic left

ARTICLE IN PRESS Management and outcome in hypoplastic left heart syndrome

heart syndrome although a few centres where this has been carried out have achieved 80% survival in the first 5 years

Introduction The management of congenital heart disease has evolved tremendously over the past 50 years since Alfred Blalock and Helen Taussig introduced the Blalock–Taussig shunt for cyanotic children at the John Hopkins Hospital in the USA in 1944.1 Complex surgical reconstruction became possible with the improvement in surgical techniques, the introduction and sophistication of cardiopulmonary bypass technology and then the introduction of hypothermia together with cardioplegia to protect the brain and heart. The past 20 years have seen a major improvement in surgical outcome for infants with congenital heart disease. In the 1970s, the Fontan procedure2 was introduced for the complex palliation of children with only one effective ventricle, which opened up new possibilities for children with otherwise inoperable lesions. The Fontan physiology depends on normal pulmonary artery size, and distribution and low pulmonary vascular resistance so that when the systemic veins are connected to the pulmonary arteries, a slightly higher venous pressure than normal, approximately 14 mmHg, can ‘push the blood around the pulmonary circulation’. The single ventricle is then utilized as the systemic pump. Norwood and his colleagues used these techniques to develop the three-stage Norwood repair of hypoplastic left heart syndrome,3 first in Boston Children’s Hospital and then in Philadelphia Children’s Hospital in the 1980s and 1990s. Over the past 10 years in particular, there has been an explosion in the number of children with hypoplastic left heart syndrome undergoing surgical palliation.

Definition Hypoplastic left heart syndrome is a condition in which the left side of the heart is underdeveloped. The left ventricle and ascending aorta are usually diminutive, and this is associated with severe stenosis or atresia of the mitral and aortic valve (Fig. 1). Blood flow through the left heart is therefore not possible, and the systemic circulation is maintained by patency of the ductus arteriosus feeding blood from the right ventricle and pulmonary arteries into the aorta.

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Diminutive ascending aorta

Ao

Ductus arteriosus

RPA

SVC

LPA PV Patent foramen ovale

RV

TV

IVC

WJ B

Fig. 1 Hypoplastic left heart syndrome

The condition was recognized by Lev4 in 1952 and named hypoplastic left heart syndrome by Noonan and Nadas in 1958.5 The cause is unknown. The condition occurs in 0.2 per 1000 live births, accounts for 2.5% of all congenital heart defects and is a major cause of death in the first week of life, accounting for 25% of cardiac deaths. In more then 90%, of cases, hypoplastic left heart syndrome exists in its classic form. Hypoplasia of the left ventricle can, however, occur with isolated aortic valve stenosis, atrioventricular septal defect, double-outlet right ventricle and truncus arteriosus. Shone’s syndrome,6 whereby there are multiple obstructions on the left side of the heart (coarctation of the aorta, aortic valve stenosis, subaortic stenosis and mitral valve stenosis) is often associated with a small left ventricle. These conditions in which the left ventricle is small are usually also managed by the Norwood procedure. Naturally, babies with hypoplastic left heart syndrome do not survive more than the first few hours or days of life, and this was the normal course of events until Norwood introduced a surgical management for this condition.

Norwood procedure The Norwood programme comprises three distinct and separate stages. Stage I is performed in the first week of life (Fig. 2). In this operation,

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W.J. Brawn, D.J. Barron

Homograft patch

SVC Ao

Blalock-Taussig shunt

Ao

SVC

LPA

RPA

LPA

RV

RV

PV

TV

PV TV WJ B

IVC

WJ B

IVC

Fig. 2 Norwood I procedure with modified Blalock– Taussig shunt

performed under hypothermic cardiopulmonary bypass with varying amounts of circulatory arrest, the patient’s native pulmonary artery is connected to the aorta with a patch of pulmonary homograft material (human pulmonary valve tissue donated after death and stored in liquid nitrogen). In this way, the right ventricle is connected to the systemic circulation. The patient’s oxygenation is achieved by a modified Blalock–Taussig shunt, usually a 3.5 mm Goretex tube connected between the innominate and pulmonary arteries. The interatrial septum between the left and the right atria is also excised to allow unobstructed pulmonary venous return. The second stage of the Norwood procedure is performed at 4–6 months of age. This comprises removal of the Goretex tube, which is replaced by a venous shunt. The venous shunt involves a direct connection of the superior vena cava to the pulmonary artery, the so-called bi-directional Glenn procedure (Fig. 3). The superior vena cava can also be connected to the pulmonary artery via a baffle in the right atrium, the hemi-Fontan procedure (Fig. 4). A venous shunt is possible in the child at 4–6 months of age because the pulmonary vascular resistance has fallen from its high neonatal level to a normal level. After both stages I and II, the systemic oxygen saturation is usually between 70% and 80%.

Fig. 3 Stage II NorwoodFsuperior cavopulmonary shunt (bidirectional Glenn procedure).

SVC

Ao

LPA RPA

Baffle

RV PV TV

WJ B

IVC

Fig. 4 Stage II NorwoodFhemi-Fontan procedure. Arrows show the direction of blood flow.

The third stage of the Norwood programme, i.e. the completion of the Fontan procedure, is performed between the second and fifth year of life depending on institutional preference. In many

ARTICLE IN PRESS Management and outcome in hypoplastic left heart syndrome

SVC Ao

LPA RPA

Fenestration RV External conduit TV

WJ B

IVC

Fig. 5 Norwood stage IIIFFontan procedure with external conduit.

North American centres, the Fontan procedure is completed in the second year of life; our local preference is for the Fontan to be completed in the fourth or fifth year. In the Norwood III procedure, the inferior vena cava is connected to the pulmonary arteries either via a baffle in the atrial chambers or via an external Goretex tube connecting the inferior vena cava directly outside the heart to the lungs (Fig. 5). Many units leave a small communication or fenestration between the pulmonary and systemic venous atria; this is to allow some admixture of desaturated blood with oxygenated blood in order to try to lower the pulmonary artery pressure and therefore reduce the incidence and chronicity of pleural effusions, which are usually associated with the postoperative period in the Fontan procedure. The three stages of the Norwood programme thus create a pulmonary circulation without a ventricular pump and a systemic circulation that is dependent on a right ventricular systemic pump.

Patient management with the Norwood procedure In all centres and published series, it is clear that the risk of death for patients with hypoplastic left heart syndrome is concentrated in the first few weeks around the Norwood I procedure.7–9 Stage II

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and the final Fontan procedure are currently associated with a very low risk of less than 5%. Since the major risk of death occurs around the time of the Norwood I procedure, much effort has been put into trying to improve the outcome by attempting to identify the risk factors that are important in determining survival. As in all patients with a congenital heart anomaly undergoing surgery, a stable child with good ventricular function and stable haemodynamic parameters, together with preserved renal, hepatic and respiratory function, is an essential prerequisite for a good outcome. Thus, if the child has deteriorated, collapsed and become acidotic, careful resuscitation and stabilization are essential before surgery. In hypoplastic left heart syndrome, this can usually be achieved over a few hours with the introduction of a prostaglandin infusion to open the ductus arteriosus and re-perfuse the systemic organs, together with the reversal of acidosis by administering sodium bicarbonate. Ventilatory support may be necessary, together with intravenous inotropes. Resuscitation may be prolonged if the collapse is complicated by infection such as necrotizing enterocolitis or respiratory infection. Prolonged resuscitation over several days or even a week or two may be necessary, but successful resuscitation with stabilization must be achieved before embarking upon surgery. The diagnosis of hypoplastic left heart syndrome is increasingly being made antenatally, and in these situations, circulatory collapse can be prevented by the introduction of a prostaglandin infusion immediately after birth to prevent the closure of the ductus arteriosus. Thus, the child need not go through the stress of circulatory collapse and acidosis before coming to surgery. These antenatally diagnosed patients can often be supported with minimal intervention and without ventilation before the Norwood I procedure. If the diagnosis can be made antenatally, consideration should be given to transferring the mother and fetus close to the congenital heart centre where intervention is planned so that delivery and transfer can be carried out with minimal risk to the infant. During the initial preoperative management and subsequent perioperative care after the Norwood I procedure, the relative pulmonary and systemic blood flows, which are dependent on the pulmonary and systemic vascular resistance, seem to be crucial to the patient’s stability. Thus, any intervention that alters pulmonary vascular resistance and increases lung flow may cause a fall in systemic cardiac output and hence perfusion of the systemic organs, with the onset of acidosis. In general, high pulmonary vascular resistance and hence a

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W.J. Brawn, D.J. Barron

Homograft patch

Ao

SVC LPA

RV to PA shunt

RV

PV

TV

WJ B

IVC

Fig. 6 Norwood I procedure with right ventricle-topulmonary artery shunt.

restriction to pulmonary blood flow may be advantageous in optimizing systemic cardiac output in the pre and perioperative period. Inspired oxygen is usually kept at a normal atmospheric level, and the arterial carbon dioxide level is maintained near normal. Some institutions add carbon dioxide or nitrogen to the inspired gases to alter the arterial partial pressures of oxygen and carbon dioxide (PO2 and CO2) in order to manipulate the pulmonary vascular resistance. This has not been our own practice; we do, however, aim to use as low an inspired oxygen concentration as is practicable in order to maintain the aortic oxygen saturation at 70–80% and the arterial PCO2 level at normal. In the past few years, Tweddell et al. have improved results by continuously monitoring superior vena cava oxygen saturations.10 Sudden death in seemingly well infants has been a cause for concern after the Norwood I procedure. One possibility is that there can be reduced coronary blood flow during diastole because of run-off via the shunt to the low-resistance pulmonary arteries.11 This could cause myocardial ischaemia and then possibly cardiac arrythmias and cardiac arrest. Over the past few years, this problem has been addressed by placing a smaller shunt of 3.5 or 3.0 mm from the systemic to the pulmonary arteries. More significantly over the past

2 years, however, there has been a reintroduction by the Japanese group led by Sano et al.12 of a technique initially used by Norwood: instead of using a modified Blalock–Taussig shunt, the shunt is taken from the right ventricle to the pulmonary artery (Fig. 6). This technique maintains the diastolic filling pressures for the coronary arteries without run-off in the low resistance pulmonary arteries.13 Many centres, including our own and Norwood’s (W. Norwood, personal communication, 2002) units, have changed to this shunt, with a marked improvement in the early results after the Norwood I procedure. In our own unit, there has only been one death in the past 16 cases in which we have used the right ventricle to pulmonary shunt procedure.

Results of the Norwood procedure Survival rates consistently above 70% have been difficult to achieve, our own 30 day mortality over our 10 year programme being 30%.9 These results are similar to those of other large published series.7,8 Over the past 5 years, however, a few centres have managed to achieve a survival rate of over 85%.10,14 At this time, we think there is little doubt that the right ventricular to pulmonary artery shunt will impact greatly on the survival rate following the Norwood I procedure, with a much improved survival rate for stage I. Stage II and the Fontan procedure or Stage III already have very low mortality and morbidity rates. The survival of Fontan patients at 10 years and coming up to 20 years is good, whether they have a right ventricular-or a left ventricular-dependent circulation.15 Since we know that the patient with a Fontan circulation never reaches a normal actuarial survival curve, it is likely that many of these patients will need to be considered for cardiac transplantation in the years ahead.

Transplantation In a small number of units worldwide, neonatal transplantation has met with success. This can be seen particularly at the Loma Linda Medical Centre, California, led by Leonard L. Bailey, where an 80% 1-year survival has been achieved for neonatal transplantation.16 As with all transplantation programmes, however, the limitation is the paucity of suitable donors, especially for neonatal recipients.17 Most units would therefore reserve transplantation for patients who are not suitable to

ARTICLE IN PRESS Management and outcome in hypoplastic left heart syndrome

progression to stage II or stage III of the Norwood programme and for those in whom there is early failure of the Fontan circulation. Advances in mechanical hearts and xeno-transplantation may well, however, open up the field for neonatal transplantation in the years ahead.

Social considerations When we commenced our hypoplastic left heart programme at Birmingham Children’s Hospital in the early 1990s, we had concerns about how it would be received by other health professionals and by parents, and what the outcome would be for the children. We were gratified early on to receive tremendous support from all quarters, in particular the parents and families, who developed a very active support group, the Left Heart Matters group.18 This has been a very vigorous support group and a model for other groups throughout Europe and the USA. We are also concerned about the quality of the children’s lives and their neurodevelopmental outcome. Although the quality of the children’s lives is good when one sees them with their families, neurodevelopmental outcome has been satisfactory but not perfect. In our own group, a small cohort of patients (20) were assessed by our neurodevelopmental psychologist, Dr. J Blyth,19 who reported that the hypoplastic left heart group who had had a Fontan procedure were no different in terms of neurodevelopmental outcome from other patients who had undergone a Fontan procedure for another single ventricle situation, such as tricuspid atresia. Their motor skills were, however, significantly impaired compared with those of their normal siblings. Similarly, Bove’s group, in an analysis of patients who had undergone a Fontan procedure, showed that neurodevelopmental outcome was satisfactory, although verbal and communication skills were significantly better than motor and performance skills.20 A more detailed analysis of a larger number of patients is certainly necessary to provide a true picture of neurodevelopmental outcome in these patients. In parallel with the increased success of surgery for these very complex lesions has come the ability to diagnose these lesions in utero early on in the antenatal period. There has thus been a tension between whether these patients, having been diagnosed, should go down the route of termination or whether they should then continue to full term and undergo complex reconstructive, palliative surgery. Attitudes vary of course according to

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religion, social group and geography. However, in our own region, some 40% of parents with an antenatal diagnosis of hypoplastic left heart syndrome opt for termination of pregnancy. In the USA, however, termination rates for all conditions are much lower because of social and religious considerations. Conversely, the termination rate is much higher in parts of Europe. It remains to be seen what impact a possibly earlier antenatal diagnosis might have on management of this complex form of heart disease.

Conclusions The evolution over the past 20 years of complex palliative surgery for hypoplastic left heart syndrome has had a major impact on not only this group of patients, but also other patients with complex congenital heart disease. Results have improved over time and have in some centres been outstanding. The more recently introduced, newer shunt procedures are likely to impact positively on outcome, the projected actuarial survival rate over the first 5 years of life being likely to improve from around about 55–60% to 80–90%. This is, however, still a complex palliation with a right ventriculardependent systemic circulation, and many if not all patients will require some form of cardiac transplantation later on. It seems as if the challenge to achieve good, early survival in these patients may be being overcome, but the future challenge is likely to be achieving a good, long-term outcome and quality of life with the Fontan procedure, with the possibility of cardiac transplantation in the future.

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