Hypoplastic left heart syndrome (HLHS) occurs in 0.16 to 0.36 per 1000 live births and accounts for 1.4%–3.8% of congenital heart defects. It is responsible for 23% of all cardiac deaths occurring in the first week of life.1 The term HLHS is used to cover a wide spectrum of lesions characterized by underdevelopment of the left heart structures, which in extreme cases manifest with aortic and/or mitral atresia or severe stenosis and hypoplasia or virtual absence of the left ventricle (LV) (Fig. 1).

Figure 1.

Schematic representation of hypoplastic left heart syndrome. Note the underdevelopment of the structures of the left side of the heart.

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In the 1970s, a multitude of articles in the surgical literature described various ingenious procedures that could allow survival of neonates with underdevelopment of left heart structures. However, there were no reports of successful stage 1 palliation (S1P) leading to a Fontan completion until William I. Norwood and colleagues described performance of an anastomosis connecting the proximal main pulmonary artery (PA) and the aorta at Boston Children’s Hospital in 1983.2 This revolutionary surgery using the right ventricle (RV) as the main pumping chamber for the systemic circulation became known as the Norwood procedure. In subsequent operations, the systemic and pulmonary circulations are separated by connecting the venae cavae directly to the pulmonary vasculature, also known as Fontan physiology.

Several technical and management modifications have been introduced overtime and have led to an increased survival of S1P to up to 90% in many institutions,3 but there are still controversial aspects and substantial peri-S1P and interstage morbidity and mortality.4 In this review, we describe the currently available surgical options for newborns with HLHS and their outcomes.

During intrauterine life, in which the physiological pulmonary vascular resistance (PVR) of the foetus is high and the systemic vascular resistance (SVR) low, the RV functions as the systemic ventricle and HLHS is well tolerated. Affected foetuses are usually born at term with adequate birth weights. Moreover, in the first hours of life there is a “honeymoon period” with minimal or no symptoms of haemodynamic instability. In this transitional situation, after the pulmonary venous return reaches the left atrium, while a small proportion of blood may reach the hypoplastic LV through the mitral valve, most of it enters the right atrium through a defect in the interatrial septum. Thus, oxygenated blood from the pulmonary veins is mixed with deoxygenated blood from the systemic venous return in the right atrium and then pumped to the RV and PA. From the pulmonary trunk, there are 3 “outlets” for the blood flow: the PAs and the ductus arteriosus (DA). In the absence of anatomical obstruction, the distribution of the flow depends on the relationship between the PVR and the SVR. Through the DA, the blood reaches the systemic circulation going into the descending aorta and retrogradely to the supra-aortic branches and coronary arteries (Fig. 2). There may also be a marginal anterograde flow contribution from the hypoplastic LV to the systemic circulation.

Figure 2.

Preoperative echocardiogram in a newborn with hypoplastic left heart syndrome. Note the retrograde flow into the aortic arch and ascending aorta.

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Closure of the DA and the resulting fall in the PVR leads to systemic hypoperfusion and pulmonary overcirculation, which rapidly progresses to haemodynamic shock. Therefore, the initial management of newborns with HLHS requires maintenance of ductal permeability with prostaglandins, balancing the systemic and pulmonary circulations mainly thorough manipulation of the PVR and ensuring adequate mixing at the atrial level. In the ideal preoperative situation, blood flow from the RV is distributed equally between both the pulmonary and the systemic circulations, maximizing oxygen delivery to the tissues and minimizing cardiac work. Preoperative stabilization of critically ill HLHS neonates with ECMO has also been described.5 Nevertheless, the need for mechanical circulatory support before or after the Norwood operation remains a major risk factor for mortality.6

The specific perioperative management of these patients is beyond the scope of this manuscript. In Spain, these complex patients are referred to one of six specific hospitals across the country accredited by The Ministry of Health as reference centres, departments and units, which include ours.

At present, many infants with HLHS receive a prenatal diagnosis, which allows planning of delivery and treatment (Fig. 3). The impact of prenatal diagnosis on surgical outcomes remains controversial. Most reports do not show a reduction in mortality with prenatal diagnosis.7,8 However, there is consistent evidence on improvements in morbidity following prenatal diagnosis of HLHS, including lower lactate levels and a better preoperative renal function, as well as a reduction in post-S1P seizures.7,9 The ability to detect the evolving hypoplastic LV (critical aortic stenosis) in mid-gestation makes it possible to perform aortic valvuloplasty in select foetuses. In 1991, Maxwell et al described their experience with dilatation of the aortic valve in 2 foetuses with severe aortic stenosis.10 Since this report, an increasing number of hospitals are attempting foetal cardiac interventions worldwide, and an International Fetal Cardiac Interventions Registry was established in 2010.11 In 2014, the foetal cardic intervention team at Boston Children’s Hospital reported the initial postnatal outcomes and survival in 100 patients that underwent foetal aortic valvuloplasty, of who 88 survived to birth and 38 achieved a biventricular circulation.12

Figure 3.

Prenatal echocardiogram at 31 weeks of gestation revealing a severely underdeveloped left ventricle.

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Presence of an intact or highly restrictive intact atrial septum is associated with a high mortality. The mortality for S1P in patients with HLHS with a prenatal diagnosis of restrictive atrial septum is of approximately 50%.13 Attempts to open the atrial septum in utero have been associated with no change in outcome. This is in part due to the inability to ensure maintenance of the patency of the septum even after septoplasty.14

In 1992, Gibbs and colleagues proposed stenting of the arterial duct for palliation, which they performed in 2 neonates with pulmonary atresia.31 One year later, Ruiz et al. used ductal stenting in 6 patients with HLHS as a bridge to HT.32 The same year, Gibbs et al. reported performance of ductal stenting and bilateral PA banding in 4 newborns with HLHS.33 This hybrid approach achieves the same goals as the Norwood procedure: the ductal stent establishes the systemic blood flow and bilateral banding restricts pulmonary blood flow, thus reducing the potential coronary steal. Cerebral and coronary perfusion is achieved through the aortic arch in a retrograde fashion, contrary to the surgical S1P (Fig. 7). Stenosis or obstruction of the connection between the descending aorta and aortic arch (retrograde aortic arch obstruction) is a significant complication that has been reported in up to 25% of patients.34 The use of a “reverse Blalock-Taussig shunt” from the main PA to the innominate artery has been proposed to avoid the complications of retrograde arch obstruction in hybrid palliation.35 Moreover, avoiding cardiopulmonary bypass could have important benefits in newborns. A recent comparison of 49 patients managed with the classic Norwood surgery and 13 with the hybrid procedure after completion of the Fontan surgery showed that patients treated with the hybrid procedure had poorer weight gain before establishing the superior cavopulmonary connection which, although recovered by Fontan completion, could be a risk factor for morbidity and poorer neurodevelopmental outcomes.36

Figure 7.

Schematic representation of the hybrid approach for treatment of hypoplastic left heart syndrome.

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Over the last decade, the hybrid approach has been applied to many patients with HLHS. Galantowicz et al. and more recently Yerebekan et al. have reported 90% and 97.5% survival in 40 and 182 patients with HLHS undergoing a hybrid procedure, respectively.37,38 Nevertheless, there is evidence that bilateral banding is associated with an increase in the number of branch PA interventions with a significant proportion of patients failing to progress through palliation at this point or after the comprehensive stage 2 procedure.38

A study from the Congenital Heart Surgeons Society evaluated hybrid procedures as an alternative to the classic S1P in 564 neonates managed with the Norwood operation with either a MBT shunt or RVPA shunt or a hybrid procedure. The risk-adjusted 4-year survival was better in patients managed with a RVPA shunt compared to the MBT shunt or the hybrid procedure (76% vs 60% vs 61%).39 A recent meta-analysis reported a lower early survival for the hybrid procedure compared to the classic S1P approach.40 Consequently, most centres currently rely on the surgical Norwood operation and reserve the use of the hybrid approach for the most fragile patients (low birth weight or restrictive atrial septum) or those presenting in shock.

Despite significant improvements in the outcomes of patients with HLHS, there is still substantial morbidity and mortality through staged palliation,30 and recent large care series suggest that the survival after the Norwood procedure has plateaued.41 A recent meta-analysis comparing the long-term outcomes of HLHS palliation with either a MBT shunt or an RVPA shunt found that the 1-, 4- and 6-year HT-free survivals for the MBT shunt were 67%, 64% and 63%, respectively, compared to 75%, 67%, and 61% for the RVPA shunt. Thus, the observed survival differed significantly between the 2 shunts was significant at 1 year but was comparable thereafter.42

The use of orthotopic HT for initial palliation of neonates with HLHS was first described by L. Bailey.43 This group reported the outcomes of HT in 28 neonates with HLHS between 1985 and 1989. Early mortality rate was 18%. However, an 89% operative survival was achieved in the last 19 patients of the series. An update on the pioneering Loma Linda University experience on 111 HLHS patients entering the transplant protocol showed a 5-year survival of 81%, which reflected recent improvements in anti-rejection protocols.44 Given the long waiting times for neonatal HT and the progressive improvements in the multistage palliation strategy, heart transplant is rarely offered as first-line treatment to HLHS patients at present. Attempts have also been made to increase the donor pool through the use of ABO-incompatible donors.

Transplantation is also offered to HLHS patients who fail to progress through staged palliation or develop complications of the Fontan circulation. An analysis of risk factors for being placed in the HT waitlist and associated outcomes after the Norwood procedure was made with data from the SVRT, in which 33 patients were listed and 18 underwent HT. The mortality was 39% in the waiting list and 33% after HT. Nevertheless, HT for rescue following the Norwood operation in the first year of life still carries a significant risk of death. Another study in 253 children that underwent HT after palliation with the Norwood procedure found that survival was not affected by last palliation stage or sensitization.45

Prior to the original breakthrough described by William I. Norwood and colleagues in 1983, unoperated patients born with HLHS had almost no chance for survival. Since the first description of successful surgical palliation, there have been major improvements in the management of these patients, with many centres reporting survival rates of 90% for S1P. Moreover, completion of staged palliation and survival into adulthood is now possible. However, the long-term morbidity and mortality in HLHS patients remain disturbingly high. The outcomes of HT in both unoperated and operated patients have been improving. Nonetheless, just as important advances in medical and surgical care have improved outcomes for HLHS this far, we are confident that they will continue to improve the long-term outcomes of patients born with this challenging disease.

There is no conflict of interest to disclose.