I will simply take this opportunity to point out the virtues of an alternative therapy for hypoplastic left heart syndrome among selected patients, specifically cardiac transplantation. I will go so far as to say that, on a case-by-case basis, there is no way that the Norwood reconstructive procedures are the best treatment for hypoplastic left heart syndrome. The reason, of course, is that it is impossible to repair anatomy that does not exist! Rearranging existing structures does not produce anything like normal anatomy, or normal physiology. I will concede, however, that as a broad strategy for management of all the infants born with hypoplastic left heart syndrome, staged reconstruction for all but a few is, indeed, a more rational modality of treatment. The reasons for this are that there are far too few donors, palliation does produce survival of many infants, and the quality of that survival can be astonishingly good for some. In reality, both strategies of management have the same objectives. Those objectives include an acceptable quality of life, prolonged survival, and the potential for education, employment, and creation of a family. It seems really incredible that we've reached a time in history, thanks to Bill Norwood and to transplantation, and to the work of many, many excellent investigators, that these objectives apply, in any way, to infants with hypoplastic left heart syndrome.

Surgical repair is really a euphemism for what is, and has always been, a continuously evolving palliation of this complex malformation. In other words, Norwood's procedure is a strategy that is based on eventual Fontan physiology, it is based on a functionally single, passively loaded, right ventricle, and it is based on the well-recognized late attrition of the Fontan procedure. Neonatal cardiac transplantation for these patients, in contrast, is surgically corrective for all, and perhaps even curative for many. The strategy is based on normal cardiac anatomy, near normal cardiovascular physiology, and somewhat less chronic attrition. Despite these virtues, donor-dependent transplantation remains an exceptional, rather than a practical, option for treatment.

Recent reports, which cover experience with the Norwood reconstructive strategy for hypoplastic left heart syndrome during the decade of the 90s, are of interest. The report from Boston,¹ which included 131 subjects with hypoplastic left heart syndrome undergoing staged palliative reconstruction between 1990 and 1998, revealed a survival of just over half at one year. A report from the group at Columbia University in New York² also had a survival of just over half at five years among 106 babies managed with the Norwood strategy between 1990 and 1999. And the Indiana group reported their most recent experience with 48 babies subjected to staged reconstructive surgery between 1994 and 1999.³ They observed survival for seven-tenths at 5 years.

Perhaps the most revealing report appeared in November of 2000. Bill Mahle and his colleagues,⁴ of the Children's Hospital of Philadelphia, examined the total experience of that center with multistage reconstruction of infants with hypoplastic left heart syndrome between 1984 and 1999 (Fig. 1). Survival at 1 year was 51%, had dropped to 43% at 2 years, and then remained relatively flat, at nearly 40%, for the period from 5 to 15 years. This report obviously covered the evolutionary phases of reconstructive surgery at their center. While the percentage of children surviving at two and five years is relatively modest, the impressive thing about this report is the flatness of the survival curve beyond five years after the initial intervention and up to 15 years. The important message of this report is that, if you do get these babies through the several stages of intervention, they enjoy remarkably durable survival, at least to 15 years.

Figure 1. Outcomes of multistage reconstruction of infants with hypoplastic left heart syndrome as drawn from the total institutional experience of Children's Hospital of Philadelphia between 1984 and 1999 (see reference #4). Note how durable survival remains between 5 and 15 years subsequent to reconstruction.

In 1999, Paul Checchia, at Loma Linda University Children's Hospital, developed a protocol that involved a scoring system for selection of candidates for palliative treatment of hypoplastic left heart syndrome.⁵ The scoring system was based on six variables at presentation that included ventricular function, presence or absence of tricuspid valvar regurgitation, the diameter of the ascending aorta, characteristics of the atrial septal defect, blood type, and age at surgery. Each variable was assigned points, and recommendations to the parents were based on the accumulation of these points. With 8 or more points, our experience indicated that a patient might expect a favorable outcome with surgical palliation, in other words the first stage of the Norwood protocol, and a recommendation for reconstructive surgery was made to the parents. With 7 or fewer points, we anticipated a less favorable outcome employing the Norwood procedure. Hence, a recommendation for transplantation was made to the parents. Between August of 1999 and April of 2002, 18 babies with hypoplastic left heart syndrome were referred to Loma Linda University Children's Hospital. Using the scoring system, 12 of the referred infants were thought to be at higher risk for the Norwood operation, and transplantation was the primary recommendation. Despite the primary recommendation, parents of 9 of these 12 infants chose the Norwood palliative procedure. Survival at 1 year among this group of 9 babies was 33%. We transplanted 3 of the 12 in this group deemed to be at higher risk, and survival was 66% at 1 year. The remaining 6 of the babies referred were considered lower risk candidates, and the parents were counseled to choose primary palliative reconstruction. One set of parents, nonetheless, chose transplantation, and their baby survives. Of the 5 candidates deemed to be at lower risk, and who agreed to the first stage of the Norwood cascade, four were alive at the age of 1 year.

The strategy of primary transplantation also has limitations, the greatest of these being an inadequate supply of donor hearts. At Loma Linda, babies listed for transplantation between 1985 and 2002 had an attrition of 28% prior to transplantation. Those that were transplanted experienced an 8% operative mortality, leaving only 64% of babies listed for transplantation completing and surviving the protocol. Thereafter, these babies experienced continuing attrition at a rate of 2% per year. If we just focus on the 79 babies with hypoplastic left heart syndrome who were transplanted as newborns, that is during their first 30 days of life, overall actuarial survival is 74% at 16 years.

Contrasting the outcomes of transplantation between these newborn recipients and all other age groups in the international registry, newborns enjoy a survival advantage of about 40% at 15 years over all other age groups (Fig. 2). It seems quite likely that many of them enjoy some form of graft-specific tolerance, and hence, transplantation may represent a cure for many of them. Mean follow-up of babies transplanted during neonatal life is 8.7 years, and nearly half the babies have survived 10 or more years since transplantation. Among the long-term survivors of those transplanted as neonates, there has been an incidence of lympho-proliferative disease of 4%. Freedom from coronary arterial disease subsequent to transplantation is 74% at 15 years. Some of these children have required re-transplantation, but freedom from re-transplantation is also 74% at 15 years. It appears that, if a neonatal recipient of heart transplantation survives 10 years, that recipient has a 94% chance of surviving to 15 years. Among babies with hypoplastic left heart syndrome who are transplanted during neonatal life, 82% are felt to be functioning within neurodevelopmentally normal limits, and 87% are in the appropriate grade level at school. Physiologic response to exercise is not significantly different from normal controls.

Figure 2. Actuarial survival of 79 infants with hypoplastic left heart syndrome treated at Loma Linda University (LLU) and others who had heart transplantation during the first 30 days of life as drawn from the data of the Registry of the International Society of Heart and Lung Transplantation (ISHLT). Survival is 74% at 16 years. Compared to heart recipients of all ages, newborn recipients have a distinct advantage in terms of survival.