Florida is the fourth largest state in the United States of America, and the Congenital Heart Institute of Florida is the largest programme providing services for congenital cardiac surgery in Florida. Our Institute is very grateful to Bob Anderson, and the team at Cardiology in the Young, for their support of our programme, and for the opportunity to publish this Supplement. Bob Anderson was a valued faculty member, and tremendous supporter, of our third annual symposium, held at the All Children's Hospital and The University of South Florida, and devoted to echocardiographic, anatomic, surgical, and pathologic correlations of congenital cardiac disease. Our Symposium to be held in 2004, coinciding with the appearance of this supplement, will mark the third consecutive year that Bob Anderson has traveled to Saint Petersburg, Florida as a Featured Guest Speaker. In 2002, at our Second Annual Symposium, the focus of our four-day meeting was the abnormalities of the ventricular inlets and atrioventricular valves, with a full day devoted to echocardiography, followed by three single days spent discussing the tricuspid valve, the mitral valve, and the common atrioventricular valve. In 2003, at our third annual symposium, the focus of our four-day meeting was controversies concerning the hypoplastic left heart syndrome, again beginning with a full day devoted to echocardiography, followed by three single days this time discussing staged palliation by means of the Norwood sequence, replacement by cardiac transplantation, and biventricular repair. A feature of the symposium was the numerous debates. In 2003, our featured guest speakers, in addition to Bob Anderson, were Leonard L. Bailey and his wife Nancy, from Loma Linda University Medical Center, Loma Linda, California. Bob Anderson will again return in 2004, when our other featured guest speaker will also be from Great Ormond Street, namely Martin J. Elliott. The focus of our meeting in 2004 will be controversies concerning the arterial switch, the Ross procedure, and reconstructions of the right ventricular outflow tract, again beginning with a full day devoted to echocardiography, followed by three single days discussing the pulmonary valve, the aortic valve and the Ross procedure, and the arterial switch procedure, with daily debates.

Of all the complex malformations that affect the heart, those that have produced the greatest difficulty, over the years, in terms of logical description and classification are the ones with the circulations supported by a functionally univentricular mass. The problems in description stem from the fact that, although the ventricular mass functions as a singular entity, the majority of lesions falling within this category, from the stance of morphology, possess two ventricular chambers. For many years, and indeed, even now in many centres, the hearts are described as being “univentricular”, or alternatively as “single ventricles”. There is still no consensus as to which particular lesions should be included within this “univentricular” category. The paradigm of the group is usually taken as double inlet left ventricle.1 In this lesion, the dominant left ventricle is accompanied by a rudimentary second chamber, albeit that arguments continue as to whether the second chamber is an incomplete right ventricle,2 or simply an infundibulum.3 Further arguments raged as to whether tricuspid atresia should be included within the univentricular category.4,5 The debate is rationalised when we recognise that all the potentially univentricular hearts are treated nowadays by constructing the Fontan circulation,6 or one of its variants,7 as indeed are some unequivocally biventricular hearts.8 Clarification and simplification of the anatomical arrangement in this functionally univentricular category, as we will show in this review, is provided by rigorous application of the crucial philosophic principle of analysis called the “Morphological Method”,9 coupled with separate analysis of the ventricular mass and the atrioventricular junctions.10,11

The lesion that, nowadays, is most usually described as “hypoplastic left heart syndrome”, was initially described in terms of “hypoplasia of the aortic outflow tract complex”.1 Sporadic cases with aortic atresia, an intact ventricular septum, and gross hypoplasia of the left ventricle, had been described long before, but it was Noonan and Nadas, in a landmark study, who coined the term “hypoplastic left heart syndrome”.2 The paediatric cardiac community has now accepted this term uniformly, although as we will see, problems remain with regard to precisely which malformations should be included within the “syndrome”. The term itself, nonetheless, is not beyond criticism. This is because, for those working in the genetic community, a “syndrome”, by definition, is a constellation of anomalies afflicting multiple systems of organs. The so-called “hypoplastic left heart syndrome”, however, almost always involves only the heart and the great arteries. Thus, according to the geneticists, it should not strictly be described as a “syndrome”, although the Nomenclature committee of the International Coding Project have marshalled arguments in favour of the term. In this review, nonetheless, we will skirt these problems with the use of “syndrome”, and simply describe the morphology as seen in patients unified because they have hypoplasia of the left heart.

The neonate with hypoplastic left heart syndrome presents a challenge for clinical diagnosis and management. Three diagnostic goals must be met. First, it is necessary to make an etiologic cardiac diagnosis so as to rule out any genetic abnormality. Second, the anatomic cardiac diagnosis is made by segmental echocardiographic analysis, including details of the atrial arrangement, venous return, the patency of the arterial duct, atrial anatomy, and the arrangement of the aortic arch. Finally, the physiologic cardiac diagnosis is made by Doppler evaluation. In some patients, the diagnosis of hypoplastic left heart syndrome is not synonymous with functionally univentricular physiology, and a bi-ventricular repair can be achieved.1

Hypoplastic left heart syndrome has provided the pediatric cardiology community one of its largest challenges. Until the mid-1980s, the mortality for this lesion was close to 100%. Through the pioneering work of Bill Norwood,1 Len Bailey,2 and the continued work of many pediatric cardiologists and surgeons, the current five-year survival for staged Norwood palliation and cardiac transplantation is now approximately 75%.3,4

Evolution of staged surgical management

Among the earliest reported attempts at palliation of hypoplastic left heart syndrome were those described by Cayler et al. in 1970,1 and Freedom et al. in 1977.2 Each case involved separate banding of the right and left pulmonary arteries, together with the construction of a direct aortopulmonary shunt. These two babies, one with critical aortic stenosis, and one with aortic atresia and ventricular septal defect, survived initial palliation but died without more definitive surgery. The separate banding of the pulmonary arteries had resulted in distortion of the distal pulmonary arterial branches and abnormal distribution of flow. Litwin et al.,3 in 1972, performed an operation for interrupted aortic arch in which a non-valved conduit was placed from the pulmonary trunk proximally to the descending thoracic aorta, and the pulmonary trunk was banded distal to the conduit. The one survivor again manifested severe distortion of the pulmonary arteries, and developed pulmonary vascular obstructive disease. An operation fundamentally similar to this, nonetheless, was subsequently used by several surgeons in an attempt to treat neonates with hypoplastic left heart syndrome. These included Albert et al. in 1978, and Mohri in 1979.

Recently, the well-known American political commentator, Robert Kagan, reapplied an existing populist statement in describing Americans as being from Mars, and Europeans from Venus.1 He said “they agree on little and understand one another less and less”. In general, it would be churlish to say that this applied to the medical fraternity, but it has great resonance with intercontinental differences in the management of hypoplastic left heart syndrome. In this review, I offer a personal view of those differences, potential explanations for them, and consider how the situation may change in coming years.

Although Norwood's first stage palliative procedure has been adopted by most proponents of reconstructive surgery for hypoplastic left heart syndrome, several technical modifications have recently been introduced. Some are intended primarily to minimize the adverse effects of cardiopulmonary bypass, hypothermic circulatory arrest, or both. Some are intended to simplify the technical performance of the initial palliative procedure. As the number of patients surviving staged reconstructive surgery for hypoplastic left heart syndrome grows steadily, there is a shift in emphasis toward investigation of methods to minimize morbidity. Specifically, the quality of life after staged reconstructive surgery may be affected by the potential for neurologic injury associated with bypass, deep hypothermia, and circulatory arrest. The pathology of cerebral injury includes ischemic cerebral necrosis, periventricular leukomalacia, necrosis of the brain stem, and intracranial hemorrhage. Neurologic injury associated with cardiac surgery during infancy is undoubtedly multi-factorial, and as yet is poorly and incompletely understood. Several surgical teams, nonetheless, have revised the technical aspects of the palliative operations with a goal of minimizing the duration of hypothermic circulatory arrest.

The term “functionally single ventricle” includes a variety of congenital cardiac anomalies where there is only one ventricle pumping blood to the systemic and pulmonary circulations. The physiology in this arrangement is a considerable challenge for the cardiac specialist, because the complexity encountered in patients with these lesions necessitates particularly specialized medical and surgical management. Patients with such functionally univentricular physiology often respond to common interventions, such as supplemental oxygen, mechanical ventilation, and vasoactive drugs, differently than patients with conventional circulations.1 Furthermore, these patients tend to be encountered more frequently by pediatricians and cardiologists because they undergo multiple operations, may be more adversely affected by intercurrent illnesses, or have chronic cardiac problems requiring frequent attention. A thorough understanding of the complexities of the physiology encountered is thus imperative for the pediatric cardiologist. In this review, we will address important physiologic and anatomic principles that influence care of neonates with functionally univentricular hearts. Although the anatomy and physiology of each reconstructive stage of palliation are unique, we will focus upon the pre- and post-operative physiology as encountered in the neonate.

Surgical treatment of hypoplastic left heart syndrome has generated substantial interest and attention amongst cardiac surgeons since the initial reports from Norwood and his colleagues in 1980.1,2 Initial efforts at most programmes were to create reproducible results, and mortality rates remained high at several institutions throughout the 1980s and 1990s. A recent multi-institutional review demonstrates that the hospital mortality still remains high in numerous centers at the current time.3 Nevertheless, several advances over recent years have led to improved outcomes, and in the best centers, hospital survival now approaches 90%. Survival in successful centers is claimed to relate to the ability of the team to help the patient balance the systemic and pulmonary flows of blood. This ability to balance flow has been enhanced, over recent years, by numerous contributions, including decreasing the size of shunt ordinarily used,4 the use of alpha blockade,5 the rapid deployment of extracorporeal membrane oxygenation,6–8 and various forms of ventilatory manipulation.

The technique of deep hypothermia with circulatory arrest has been important in the history of the evolution of cardiac surgery. Wilfred G. Bigelow, working in Toronto in the late 1940s, performed pioneering research on hypothermia, and developed a workable technique of hypothermia in human cardiac surgery.1 Based upon Bigelow's experimental premises, F. John Lewis, at the University of Minnesota, also conducted a number of experiments utilizing hypothermia. On September 2, 1942, Lewis operated on a 5-year-old girl with an atrial septal defect under general hypothermia with inflow occlusion. He was assisted by Richard Varco, Mansur Taufic, and C. Walton Lillehei. Rubberized refrigerated blankets were used to cool the patient to 28°C. The septal defect was closed during five and a half minutes of inflow occlusion. This was the world's first successful open operation on the human heart performed under direct vision, and marked the beginning of the era of open heart surgery. Now, as amazing and as primitive as that methodology may seem, those of you who read Life magazine, or watch the Discovery Channel on television, are aware that, in parts of the Soviet Union, a large fraction of today's open heart surgery is performed not using the technique of cardiopulmonary bypass, but rather using the methodology of immersion hypothermia from the 1950s, with surprisingly good results.

A quiet and bloodless field providing optimal surgical conditions has been a crucial prerequisite for the performance of complex cardiac repairs in early life. The use of deep hypothermic circulatory arrest has fulfilled this role, and has been a catalyst for the development of neonatal and infant cardiac surgery. The recently increased awareness of possibly increased incidence of adverse neurological events and developmental outcome associated with this technique,1–5 however, has led to a general trend away from its use. In its place, techniques have been developed to provide cerebral perfusion during reconstruction of the aortic arch and the Norwood operation. Some have described the techniques as regional low-flow perfusion. In our opinion, they are described more accurately as antegrade regional cerebral perfusion. In this review, we discuss the recently described techniques for such antegrade regional cerebral perfusion during surgery on the aortic arch, with emphasis both on the Norwood operation and the observed physiological changes in the cerebral and systemic circulations. The neurologic and developmental outcomes following the use of the technique are still unknown.

In 1995, Miami Children's Hospital recognized an institutional problem with its programme providing surgical treatment for congenital cardiac malformations. There was a high rate of mortality for neonatal surgery, and no patients had survived attempted first stage palliation for hypoplastic left heart syndrome. The hospital enlisted nationally recognized consultants in congenital cardiac surgery and cardiology to review the existing programme, and to make recommendations for improvement. Based on these recommendations, a new team was recruited. The recruits were a young attending surgeon, an interventional cardiologist, and a cardiac intensivist, attracted from recognized centers of excellence in Boston and Toronto.

Cardiac transplantation is now a therapeutic option with good outcomes for infants and children with end-stage cardiac failure or inoperable congenital cardiac defects.1 In 2000, 356 procedures in children aged up to 18 years were reported to the United Network for Organ Sharing – International Society of Heart and Lung Transplantation Registry.2 Congenital cardiac disease was the most common indication in children less than 1 year of age, and overall was the most common diagnosis leading to cardiac transplantation in children. As a result of the groundbreaking contributions of Bailey et al.,3 transplantation is now an option for primary treatment of infants with hypoplastic left heart syndrome born in the United States of America. The availability of donor organs, however, both limits the number of children with hypoplastic left heart syndrome who can be realistically offered transplantation, and contributes significantly to morbidity, mortality, and costs. Current limitations in the identification and availability of donors would not allow transplantation to be the primary option for all children born with hypoplastic left heart syndrome. Analyses of the database of the Registry, however, indicated that only about half of donations resulted in transplantation of the heart.4 These observations provide compelling evidence of significant opportunities to improve rates of donation, and to utilize better the existing donations, with emphasis on optimizing identification of donors, expanding the number of potential donors, and better distribution of the available organs.

Transplantation of the heart remains a viable option not only as primary treatment for hypoplastic left heart syndrome, but also for end-stage problems after the Norwood sequence of palliations. In this review, I discuss the pre-operative, intra-operative, and post-operative echocardiographic evaluation of these patients, with special emphasis on hemodynamic and functional assessment as well as surveillance for rejection and coronary arterial disease.

Transplantation is an effective treatment modality for infants1 and children2 with end-stage cardiac diseases. Rejection remains a major complication (Figure 1), even in newborn infants.3 Acute rejection can best be operationally defined by clinical findings, histopathology, and/or abnormalities of ventricular function of new origin that require, and respond to, intensified immunosuppression. Mechanistically, the ability to detect acute rejection is critically dependent on the detection of significant new myocytic injury, damage, and/or death. Surveillance for rejection is critically important in determining both long and short-term outcomes following cardiac transplantation. The ideal strategy for surveillance should have a high negative predictive value, correctly identifying the absence of myocytic injury, with high specificity, such that it does not falsely predict such injury.4

The hypoplastic left heart syndrome constitutes a wide spectrum of cardiac malformations, characterized by varying degrees of underdevelopment of the structures of the left heart and aortic arch. At the severe end of the spectrum, there is aortic and mitral atresia, and the left ventricle is vestigial. In contrast, at the mild end, there is hypoplasia of the left ventricle in the absence of overt stenosis of either the aortic or mitral valves, the combination we have described as hypoplastic left heart complex.1 Until recently, debate with regard to the optimal surgical approach has centered on the choice between the Norwood operation and neonatal cardiac transplantation. In the last several years, nonetheless, it has been shown that of biventricular repair can be achieved in those patients at the favorable end of the spectrum that we designated as having the complex rather than the syndrome.1,2 It is well recognized that an ongoing difficulty is the inconsistent and imprecise definition of hypoplastic left heart syndrome. In this presentation, I summarize our own criterions, and our principles for biventricular repair, as based on our experience at the Montreal Children's Hospital, for those patients we judge to have the hypoplastic left heart complex.

Hypoplastic left heart syndrome is the term introduced by Noonan and Nadas1 to describe a spectrum of cardiac anomalies characterized by varying degrees of significant underdevelopment of the left heart and aortic arch. These cardiac anomalies include mitral valvar disease, left ventricular hypoplasia, aortic stenosis at subvalvar, valvar, and supravalvar levels, hypoplasia of the ascending aorta and aortic arch, and aortic coarctation. Although descriptive, hypoplastic left heart syndrome suffers from being a very unspecific term, since it encompasses multiple degrees and combinations of abnormalities involving the left sided structures. In an attempt to provide gradings of severity, Kirklin and Barratt-Boyes2 categorized these patients falling into the syndrome into four classes, according to whether obstruction was found at one, two, or more levels, or whether there is aortic atresia. Then, in 1998, Tchervenkov and colleagues3 introduced the term hypoplastic left heart complex to describe a set of patients falling within the spectrum of hypoplasia of the left heart, but in the absence of intrinsic aortic or mitral valvar stenosis, this concept subsequently being endorsed by the International Committee established by the Society of Thoracic Surgeons, together with the European Association of Cardiothoracic Surgery, to rationalize the approach to nomenclature and databases.4 The analysis offered by Tchervenkov et al.3 showed that, in certain circumstances, there are potentially patients considered to have hypoplasia of the left heart who might be candidates for biventricular repair. If this is the case, then it is important to establish how this subset can be recognized, and how they are best treated.

I am grateful for the opportunity to participate in this debate forum, and for the honor of exchanging concepts with Len Bailey. This debate, fortunately, represents a “win-win” situation. The innovations and evolution of both replacement of the heart and reconstructive surgery for hypoplastic left heart syndrome are stories with lots of winners. The entire field of transplantation biology, the entire scope of management of the newborn with complex congenital heart disease, including both medical and supportive therapy and surgical strategies, has each been advanced tremendously as a consequence of the introduction and refinement of these two very different therapies for hypoplastic left heart syndrome. So, it is a debate that cannot be lost.

Thank you for asking me to make the case for cardiac transplantation in this debate. Marshall, that was a truly comprehensive and spectacular defense of the value of reconstructive surgery in babies born with hypoplastic left heart syndrome. It is clear that the potential for babies born with this complex and lethal malformation has improved dramatically over the past 2 decades. The improvement in outcome is a direct result of complementary surgical strategies. Marshall Jacobs has constructed a stellar review outlining the important issues relating to the ever-evolving staged palliative reconstruction for hypoplastic left heart syndrome. And, he appealed to those present at the Symposium with some images of extraordinary children who represent the most favorable outcomes seen today after staged reconstructive surgery. It would be inappropriate for me to criticize or condemn any feature of these favorable outcomes.