Historical perspectives on nomenclature for the hypoplastic left heart syndrome

As far as we can establish, the initial description of the pathophysiology of hypoplastic left heart syndrome, describing the combination of severe mitral and left ventricular hypoplasia along with aortic atresia, was elegantly written in German by Bardeleben in 1851. This contribution has recently been translated into English by Gehrmann et al.⁸ A century later, in 1952, the tendency of hypoplastic and obstructive lesions of the left heart and aorta to occur together was emphasized by Maurice Lev.⁹ He used the term “hypoplasia of the aortic tract complexes” to describe these heterogeneous malformations. The anatomic features attracting his attention were:

• the ascending and transverse portions of the aorta and the aortic orifice were small;
• the pulmonary trunk and its orifice were large;
• there was no transposition of the arterial trunks.

In terms of physiology, he emphasized the decrease of flow through the components of the left heart and the aorta, with concomitant increase in right ventricular flow. Based on the examination of 40 pathologic hearts, he classified his suggested complexes as follows:

• isolated hypoplasia of the aorta;
• hypoplasia of the aorta with septal defects;
• hypoplasia of the aorta with aortic atresia or stenosis without mitral atresia;
• hypoplasia of the aorta with aortic atresia or stenosis with mitral atresia.

In 1966,¹⁰ he narrowed his classification to, on the one hand, severe aortic stenosis or atresia with a patent mitral valve, and on the other hand, the combination of aortic and mitral atresia. After a further extensive period of review, and having examined 230 hearts, Bharati and Lev¹¹ maintained this classification of hypoplasia of the aortic tract complexes.

In the meantime, however, in 1958, the term “hypoplastic left heart syndrome” had been suggested by Noonan and Nadas¹² to include anomalies with an obstructive lesion on the left side of the heart. Their original definition was broad, including lesions ranging from aortic and mitral atresia with a vestigial left ventricle, to milder forms of left ventricular underdevelopment. They noted that the clinical syndrome could be caused by several pathological complexes. Based on the analysis of 101 postmortem hearts, they subclassified five groups, specifically

• aortic valvar atresia;
• mitral atresia;
• mitral stenosis;
• atresia of the aortic arch;
• hypoplasia of the aortic arch.

Interestingly, the last group was by far the largest, and included 71 cases. All these cases shared similarities in their clinical presentation. Noonan and Nadas¹² suggested that diagnosis of the syndrome should be suspected in the presence of sudden onset of biventricular congestive heart failure in a young infant with mild cyanosis, a nonspecific heart murmur, and either weak pulses in all extremities, or relative hypertension in the arm. Although the clinical recognition of the syndrome, in most cases, was not difficult, the precise pre-mortem anatomic diagnosis was usually impossible because of the limited modalities for cardiac imaging existing at that time.

Shortly after the appearance of the stellar review from Noonan and Nadas,¹² Currarino and associates,¹³ in 1959, used the term “hypoplasia of the left heart complex” to describe the pathologic findings in two neonates who exhibited aortic and mitral stenosis, hypoplasia of the left ventricle with endocardial fibroelastosis, and a hypoplastic aorta from its origin until the insertion of the arterial duct. Both patients, who had died in the first week of life, exhibited differential cyanosis, with a pink right upper quadrant of the trunk, the right side of the head and neck and the right arm, with the rest of the body being cyanotic. Both patients had complete obliteration of the oval foramen, believed by some to be implicated in the aetiology of this complex by causing deranged patterns of flow during fetal life.

Over the ensuing decades, despite its lack of specificity and consistent definition, the term “hypoplastic left heart syndrome” has become the one most widely accepted and currently used in the English language. This reality could be explained by the fact that Norwood et al.,^{14, 15} along with Doty et al.,¹⁶ used this term in their early reports proposing options for surgical treatment. From the beginning, nonetheless, there has been controversy as to what makes up the hypoplastic left heart syndrome. For some, the syndrome was defined in narrow terms, such as atresia of the aortic or mitral valve, or both, with normally related great arteries and intact ventricular septum, and was held to include only cases with a small left ventricle clearly incapable of supporting the systemic circulation.¹⁷ Others preferred a more general definition of underdevelopment, such as atresia or hypoplasia of the left atrial outlet, left ventricle, aortic valve, and aortic arch.¹⁸ Their argument was to avoid focusing attention on the hopeless forms of hypoplastic left heart syndrome, but rather to emphasize that nearly one half of the cases were salvageable by intensive medical management and surgical palliation.

It was the search for a suitable surgical treatment that culminated, in the 1980s, in the development of both the Norwood operation and neonatal transplantation of the heart. Unfortunately, in the early days, the term “Norwood operation” tended to be used as a synonym for the syndrome itself, implying the inability of the left heart to support the systemic circulation. The more recent application of the Norwood operation for lesions such as tricuspid atresia with discordant ventriculo-arterial connections, or hearts with two well-developed ventricles in which biventricular repair is either difficult or impossible, such as some forms of double outlet right ventricle with non-committed ventricular septal defect, hearts with straddling atrioventricular valves, and severely unbalanced atrioventricular septal defects, has shown that use of the term “Norwood operation” no longer implies the diagnosis of hypoplastic left heart syndrome.^19–21 The diagnosis of the syndrome, therefore, should not be defined by the use of the Norwood operation to repair it.

It was, perhaps, the resulting lack of specificity for the syndrome that led Kirklin and Barratt-Boyes²² to use the term with a still wider meaning. They proposed a classification based on the number of obstructions in the left heart and aorta. Their first and second classes were made up of patients with one and two obstructions, respectively. Their third class included those with more than two obstructions together with left ventricular hypoplasia, while their fourth class was made up of the patients with aortic atresia. The use of this classification of hypoplastic left heart syndrome as defined by Kirklin and Barratt-Boyes, however, is impractical, since it lacks specificity, requiring a further specific definition in each individual case. This requirement defeats the purpose of the diagnosis. Furthermore, many would not routinely use the term hypoplastic left heart syndrome to describe those patients making up the first two classes, but rather prefer the specific diagnoses, such as aortic stenosis, coarctation of the aorta, or interruption of the aortic arch. On the other hand, when dealing with the severe form, the opposite is true, with the term hypoplastic left heart syndrome being used frequently to lump together several diagnoses that have in common a right ventricular-dependent systemic circulation, such as aortic atresia, mitral atresia with aortic stenosis, or mitral stenosis with severe left ventricular hypoplasia. Even though the classification proposed by Kirklin and Barratt-Boyes²² is impractical, and has not gained widespread use and acceptance, it does convey the crucial concept that hypoplastic left heart syndrome is a spectrum of malformations.

It is also a fact that, although the term “hypoplastic left heart syndrome” was originally used by Noonan and Nadas¹² to describe a range of anomalies including multiple levels of obstruction within the left heart and the aortic pathways, patients with hypoplasia of the left ventricle with aortic and mitral valves which are hypoplastic but not intrinsically stenotic have been inadequately and inconsistently described within the currently existing terminology.^23–28 For this reason, in 1998, Tchervenkov and associates²⁹ introduced the term “hypoplastic left heart complex” to describe the patients with significant hypoplasia of the structures of the left heart and aorta, but in the absence of intrinsic stenosis or atresia of the aortic and mitral valves. Although Currarino and associates¹³ had previously used the similar, but slightly different, term “hypoplasia of the left heart complex”, they had used it for patients with valvar aortic stenosis, and not for the cardiac phenotype of hypoplasia of the left heart without intrinsic valvar stenosis or atresia as described by Tchervenkov and associates.^{1, 29} The term, “hypoplastic left heart complex”, was accepted and incorporated into the nomenclature published by the International Congenital Heart Surgery Nomenclature and Database Project in 2000, being used to account for the cardiac phenotype at the milder end of the spectrum of hypoplastic left heart syndrome, but without intrinsic aortic or mitral valvar stenosis or atresia.¹ In this respect, it is also of note that, in the review made by Noonan and Nadas,¹² their largest group of patients was made up of those with isolated hypoplasia of the aortic arch. These patients had a small but functioning left ventricle. It is likely that many of the patients in this group would nowadays fall within the diagnosis of the hypoplastic left heart complex. Although patients with the complex also bear some similarities to another developmental complex, namely that described by Shone and associates,³⁰ the two diagnoses are distinct, and should not be used interchangeably. The report of Shone et al.,³⁰ based on analysis of 8 autopsied cases, described the tendency for four obstructive, or potentially obstructive, conditions to coexist. These were:

• supravalvar ring of the left atrium;
• a parachute deformity of the mitral valve;
• subaortic stenosis;
• aortic coarctation.

Only 2 of the 8 cases exhibited all four conditions, with the other cases exhibiting only two or three of the anomalies. Hypoplasia of the various components of the left heart and aorta, a fundamental feature of hypoplastic left heart complex, was not present in the patients described in the account of Shone et al.³⁰ Hypoplastic left heart complex, therefore, is part of the spectrum of hypoplastic left heart syndrome, whereas Shone's complex is not.

The overwhelming majority of patients with hypoplastic left heart syndrome have an intact ventricular septum. If there is a ventricular septal defect, it is usually small. When a large ventricular septal defect co-exists with aortic atresia, the left ventricle is usually well-developed. In a review of 172 patients with aortic atresia,³¹ 12 patients (7%) were found to have a large ventricular septal defect with a well-developed left ventricle. These patients obviously should not be classified as part of the hypoplastic left heart syndrome. In his classic report on palliative surgery for hypoplastic left heart syndrome, describing the management of three patients, Norwood and associates used the term “aortic atresia with intact ventricular septum” to distinguish the common forms of hypoplastic left heart syndrome from their one case of aortic atresia with ventricular septal defect.¹⁴ Unfortunately the terms “aortic atresia with intact ventricular septum”, and “aortic atresia with ventricular septal defect”, have not found favour to the same extent as “pulmonary atresia with intact ventricular septum” and “pulmonary atresia with ventricular septal defect”, probably due to the rarity of the patients with aortic atresia and a large ventricular septal defect. Nevertheless, in the system of nomenclature prepared by the International Congenital Heart Surgery Nomenclature and Database Project, cases with aortic atresia and ventricular septal defect were included under the grouping for hypoplastic left heart syndrome because of the inability to group them with any other congenital lesion. Recognising the potential deficiency in this approach, the chosen grouping is discussed further in the last paragraph in the next section of this manuscript titled “Definition of Hypoplastic Left Heart Syndrome”. In the International Pediatric and Congenital Cardiac Code, the lesion “aortic atresia with ventricular septal defect and a well-developed mitral valve and left ventricle” is not classified as hypoplastic left heart syndrome, but rather as a “hypoplastic left heart syndrome-related malformation”, specifically because the problematic lesion does not include significant hypoplasia of the left ventricle, this being an essential element of hypoplastic left heart syndrome.

We should then note that the term “hypoplastic left heart physiology” was introduced in 2003, in the third edition³² of the textbook devoted to cardiac surgery initially written by Kirklin and Barratt-Boyes. This proposed entity was defined as “the inability of the left heart to sustain an adequate cardiac output following birth because of underdevelopment of one or more left heart structures despite surgical or medical intervention”.³² Although the editors of the textbook chose the term “hypoplastic left heart physiology”, rather than the more common and entrenched term “hypoplastic left heart syndrome”, they pointed out important limitations of both terms when applied in the clinical setting because “tests designed to define morphologic and physiologic characteristics are limited in their ability”. A problem with putting the emphasis on physiology, however, is that physiology can change over a short period of time through a multitude of factors. On the other hand, if classification is based on anatomic and morphologic features, these factors change much more slowly.

Definition of hypoplastic left heart syndrome

Before proceeding further, we consider it useful to provide definitions³³ of several terms pertinent to the ongoing discussion of the term “hypoplastic left heart syndrome”. These are

• atresia
• stenosis
• hypoplasia
• obstruction
• syndrome
• complex

“Atresia” is defined as the congenital absence or closure of a normal body orifice or tubular organ. It is derived from the Greek and Latin bases, where “a” means without, and “tresis” is the word for perforation. Thus, aortic valvar atresia can be defined as either absence or closure of the orifice of the aortic root.

“Stenosis” is narrowing or stricture of a duct or a canal. Aortic stenosis, for example, is a broad term encompassing the supravalvar, valvar or subvalvar variants. More specifically, aortic valvar stenosis is a narrowing of the orifice of the aortic valve due to fusion of the zones of apposition between the leaflets, or the inability of the valve to open adequately because of thickening or calcification of the leaflets, causing obstruction to the flow of blood.

“Hypoplasia” is the incomplete development or underdevelopment of an organ or tissue. For example, a hypoplastic aortic valve can cause obstruction to the flow of blood simply because of its inadequate size.

“Obstruction” is the act of blocking or clogging, or the state or condition of being blocked or clogged. Obstruction to the flow of blood, therefore, may be caused by atresia, stenosis, or hypoplasia of a given structure.

We consider it particularly important to differentiate the meaning of the terms “stenosis” and “hypoplasia”. Although atresia and stenosis are mutually exclusive terms, hypoplasia may be present with atresia or stenosis, or can exist in isolation. Hypoplasia implies that the organ or tissue is less than its normal size. The terms “aortic stenosis” and “left ventricular outflow tract obstruction”, for example, are not synonymous, although they have been used interchangeably in the past. In the setting of obstruction to the left ventricular outflow tract, the obstruction to the flow of blood may be caused by either aortic atresia, aortic stenosis, or because of hypoplasia of the aortic valve.

A “syndrome” is a group of signs and symptoms that occur together, and characterize a particular abnormality.

A “complex” is a whole, being made up of interrelated parts.

During its many meetings, the members of the International Congenital Heart Surgery Nomenclature and Database Project thoroughly debated the term and definition of “hypoplastic left heart syndrome”. Initially, enthusiasm existed for not using the term “hypoplastic left heart syndrome”. Arguments were made to discard the term in favour of specific definitions of the exact anatomy. Thought was given to utilization of the terms “Aortic atresia with ventricular septal defect” and “Aortic atresia with intact ventricular septum”, as well as the descriptive terms:

• Aortic atresia and mitral atresia
• Aortic atresia and mitral stenosis
• Aortic stenosis and mitral atresia
• Aortic stenosis and mitral stenosis
• Combined aortic and mitral valvar hypoplasia

Initial thoughts to discard the term “hypoplastic left heart syndrome” eventually gave way to a consensus to retain the term, but then to define it. This decision was reached after many hours of debate for multiple reasons:

• The descriptive terms listed above fail to convey that the common denominator of this lesion is hypoplasia of the left heart and ventricle.
• The term “hypoplastic left heart syndrome” has widespread use and acceptance in the medical community, as emphasized by its appearance in no less than 1109 articles in a PubMed MedLine Search with the United States National Library of Medicine from November 1958 through November 2005.
• It seems unlikely that this term will disappear because of the work of the International Congenital Heart Surgery Nomenclature and Database Project, the Nomenclature Working Group, or any other governing body.
• Given that the term will still be used, a unifying definition and subclassification should be proposed. Otherwise, it will continue to be used without a common definition.
• It is useful to group together the subtypes of lesions considered to represent the “hypoplastic left heart syndrome”. This grouping can facilitate the analysis of outcomes, and does not prohibit further anatomic description of the subtypes.
• Description and definition of the subtypes is still possible and desirable, even with retention of the term “hypoplastic left heart syndrome”.

Thus, when their work was published in the supplement of Annals of Thoracic Surgery appearing in April, 2000,¹ the International Congenital Heart Surgery Nomenclature and Database Project retained, defined, and subclassified the term “hypoplastic left heart syndrome”. It is a modification of this definition that is suggested currently by the Nomenclature Working Group, as will be shown below.

We may also argue, however, as why to use the word “syndrome” at all. For example, in the French language, the term in common use is “hypoplasie du coeur gauche”, a phrase that avoids the use of “syndrome”. On this basis, an alternative would be to replace the term “hypoplastic left heart syndrome” with “hypoplasia of the left heart”. This proposal is further strengthened by the belief that the genetic community defines a “syndrome” as a constellation of anomalies afflicting multiple systems of organs. There are, nonetheless, several other definitions of “syndrome”, even within the genetic community. According to Dorland's Illustrated Medical Dictionary,³³ a syndrome is “in genetics, a pattern of multiple malformations thought to be pathogenetically related”. This definition, in a very respectable and well-read medical dictionary, makes no mention of the concept that a syndrome should involve multiple systems of organs. Furthermore, Dorland's Illustrated Medical Dictionary then goes on to list and define several pages of a variety of medical syndromes, some of which involve multiple systems of organs, but others which involve only a single system of organs. Thus, even the genetic definition of “syndrome” is not universally accepted.

In the light of their discussions, the Nomenclature Working Group took the stance that the terms “hypoplastic left heart syndrome” and “hypoplasia of the left heart” would better be used as synonyms, since there is no scientific justification exclusively to use one term and eliminate the other. On this basis, therefore, the Nomenclature Working Group offers the following definition for the term “hypoplastic left heart syndrome” or “hypoplasia of the left heart”:

“Hypoplastic left heart syndrome is synonymous with the term hypoplasia of the left heart and is defined as a spectrum of cardiac malformations with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle including atresia, stenosis, or hypoplasia of the aortic or mitral valve, or both valves, and hypoplasia of the ascending aorta and aortic arch.”

Hypoplastic left heart syndrome, therefore, is made up of several pathological cardiac phenotypes. At the severe end of the spectrum are found those patients with aortic and mitral atresia with a virtually nonexistent left ventricle. The heart with a truly non-existent ventricle is extremely rare, and indeed may not exist, as typically it is possible at autopsy to identify some small, incomplete, and hypoplastic ventricle that lacks an atrioventricular connection. At the milder end of the spectrum are those patients with hypoplastic left heart syndrome without intrinsic valvar stenosis or atresia, this representing the hypoplastic left heart complex as defined by Tchervenkov et al.,²⁹ or those patients with critical aortic stenosis and left ventricular hypoplasia.^{34, 35} Patients with critical aortic stenosis with left ventricles and mitral valves of normal size, however, are not considered as comprising part of the hypoplastic left heart syndrome.

On this basis, we offer a definition of hypoplastic left heart syndrome without intrinsic valvar stenosis or atresia as follows:

“Hypoplastic left heart syndrome without intrinsic valvar stenosis or atresia is synonymous with the term hypoplastic left heart complex and is defined as a cardiac malformation at the milder end of the spectrum of hypoplastic left heart syndrome with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle and hypoplasia of the aortic or mitral valve, or both valves, in the absence of intrinsic valvar stenosis or atresia, and with hypoplasia of the ascending aorta and aortic arch.”

In other words, hypoplastic left heart complex is a cardiac malformation at the milder end of the spectrum of hypoplastic left heart syndrome without intrinsic stenosis or atresia of the aortic or mitral valve. We recognize that the term “hypoplastic left heart complex” has not yet gained widespread acceptance, and has been found confusing by some. Because of this, other terms have been suggested to describe patients with hypoplasia of the left heart without intrinsic aortic or mitral valve stenosis or atresia, such as “hypoplastic left heart syndrome without intrinsic valvar stenosis or atresia” and “hypoplasia of the left heart without intrinsic valvar stenosis or atresia”.

The differentiation of the proposed complex from the other subtypes of hypoplastic left heart syndrome is based on identification of hypoplasia of the left heart in absence of intrinsic aortic or mitral valvar stenosis or atresia.²⁹ It remains the case that differentiation between patients to be grouped within the complex as opposed to the other cardiac phenotypes within the syndrome itself can be difficult. The terms “Aortic stenosis” and “Mitral stenosis” infer that there is fusion between the zones of apposition of the valvar leaflets, and hence true valvar stenosis. Hypoplasia of the aortic valve, mitral valve and the left ventricle, in contrast, indicates that the valves are small, but not intrinsically stenotic. This differentiation has therapeutic considerations and potential consequences if one considers biventricular repair. While aortic valvotomy is essential in patients with critical valvar aortic stenosis and left ventricular hypoplasia that are candidates for biventricular repair, it is not required in patients appropriately diagnosed as having hypoplastic left heart complex, because the aortic valve in the setting of the complex, whilst hypoplastic, is not intrinsically stenotic.

Another area of potential controversy regards the relationship between the hypoplastic left heart complex as defined by us, and totally anomalous pulmonary venous connection. In this respect, it should be remembered that, just as hypoplastic left heart syndrome with aortic atresia can coexist with totally anomalous pulmonary venous connection, so can totally anomalous pulmonary venous connection coexist with the so-called “hypoplastic left heart complex”. In most cases of totally anomalous pulmonary venous connection, the components of the left heart appear small as they are compressed by the hypertensive right ventricle, with the ventricular septum bowing severely to the left. In some patients with totally anomalous pulmonary venous connection, however, the left ventricle, aortic and mitral valves are truly structurally small. It is very possible that some of the patients dying after attempted surgical repair of totally anomalous pulmonary venous connection may also have exhibited the so-called “hypoplastic left heart complex”. This phenotype is certainly an area that needs further study and elucidation.

Initially, the members of the coding committee of the Association for European Paediatric Cardiology, whilst endorsing and supporting retention of the term hypoplastic left heart syndrome for all the reasons discussed above, were reticent to create a separate code for the hypoplastic left heart complex within the European Paediatric Cardiac Code. The coding committee was not convinced that this relatively newly defined entity could be objectively distinguished on anatomical or physiological criterions as a distinct and separate lesion, and thus warrant an independent term. They preferred initially to list the various component parts of the complex with appropriate qualifiers, as will be shown below. This approach is in keeping with the overall underlying “atomic” structure to be found within the European Paediatric Cardiac Code, and the wish to avoid conglomerate terms. Part of the remit of the Nomenclature Working Group, however, is to be inclusive of all terms used by a substantial body of those in the field of paediatric cardiology and surgery, unless these terms are known to be scientifically incorrect. The Nomenclature Working Group, therefore, determined that the three terms “hypoplastic left heart syndrome without intrinsic valvar stenosis or atresia”, “hypoplasia of the left heart without intrinsic valvar stenosis or atresia”, and “hypoplastic left heart complex”, should be used as synonyms and mapped between the two nomenclature systems, as will be detailed below.

In coding for hypoplastic left heart syndrome, the European Paediatric Cardiac Code has one code, specifically 01.01.09. Further description of the details of the lesion is achieved by selecting the specific codes related to every abnormal segment or structure, following the overall atomic approach, as will be discussed in more detail below. When using the system of coding established by the International Congenital Heart Surgery and Database Project, in contrast, the global term of “hypoplastic left heart syndrome” or “hypoplastic left heart syndrome-related malformation” is selected, followed by choice from the combination of lesions which best describes the problem at hand. This is the molecular approach, also to be discussed below.

The reader using the list of names in the International Paediatric and Congenital Cardiac Code derived from the earlier collaborations between the group established by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons is advised that several anomalies, such as severely unbalanced atrioventricular septal defect, double outlet right ventricle with left ventricular hypoplasia, tricuspid atresia with transposition, double inlet left ventricle with transposition, and other functionally univentricular hearts with a dominant right ventricle, with or without obstruction of the aortic arch, are not considered under the umbrella of “hypoplastic left heart syndrome”, but should be classified within the group of lesions termed “hypoplastic left heart syndrome-related malformation.” For those using the version of the International Code derived from the original European Paediatric Cardiology Code, these lesions would be coded individually, without using the code 01.01.09 for “hypoplastic left heart syndrome”, also as we discuss later in this review.

We should also re-emphasise that, previously, the International Congenital Heart Surgery Nomenclature and Database Project classified “aortic atresia with ventricular septal defect and a well-developed mitral valve and left ventricle” as a type of hypoplastic left heart syndrome. Even these rare cases with a ventricular septal defect show at least some degree of left or right ventricular hypoplasia. Measurements in autopsied specimens of the lengths of the ventricular inlets has revealed that the left ventricle is smaller than the right; even in cases with ventricular septal defect, the ratio between the ventricular lengths is always less than 1.³⁶ This lesion, nonetheless, has since been reclassified as a “hypoplastic left heart syndrome-related malformation” because it does not include significant left ventricular hypoplasia, which is considered an essential element of hypoplastic left heart syndrome. Thus, hearts with “aortic atresia with ventricular septal defect and a well-developed mitral valve and left ventricle” are now classified in the version of the International Code derived from the International Congenital Heart Surgery Nomenclature and Database Project as a “hypoplastic left heart syndrome-related malformation”, because they are not truly part of the hypoplastic left heart syndrome.

Pathophysiology

The variable pathophysiology of patients diagnosed with hypoplastic left heart syndrome becomes important because of the implications as to whether it is possible successfully to achieve biventricular as opposed to functionally univentricular repair. At the severe end of the spectrum of patients classified within the syndrome, the systemic circulation is completely dependent on the right ventricle and flow through the arterial duct, with flow in the aortic arch and the ascending aorta being retrograde. This pathophysiology is seen in the setting of aortic atresia with mitral atresia or stenosis. At the mild end of the spectrum, the systemic circulation may only be partially dependent on the right ventricle and flow through the arterial duct, as seen in some patients with aortic stenosis and mitral stenosis, those with aortic stenosis with left ventricular hypoplasia, or in those diagnosed with the hypoplastic left heart complex. In this setting, the flow to the descending aorta is dependent on the right ventricle and arterial duct, while flow to the ascending aorta and various portions of the aortic arch and branches are supplied by antegrade flow from the left ventricle. In a very few patients with the complex, the systemic circulation may be entirely dependent on the left ventricle in the presence of lesser degrees of obstruction within the left heart, although such patients are usually in severe congestive cardiac failure, and require surgical correction.

In the greater majority of patients with hypoplastic left heart syndrome, the only surgical reconstruction possible is the functionally univentricular approach using the Norwood, or Norwood-like, operation in the neonatal period, transferring the systemic circulation so that it exits directly from the right ventricle, followed eventually by a Fontan-type operation. Biventricular repair may be possible, however, for some patients at the milder end of the syndrome. The potential exists for left ventricular growth after birth^{23, 25, 28} and after biventricular repair.²⁹ Accurate understanding of the pathophysiology in each patient is important, as it may help to determine whether biventricular repair should be considered.

The atrial septum in hypoplastic left heart syndrome

As our understanding of hypoplastic left heart syndrome has improved, it has become increasingly apparent that the morphology of the atrial septum at the time of birth will influence significantly the pathophysiology and haemodynamic state of the neonate. These variants of atrial septal morphology may be of particular importance during fetal development.³⁷ Furthermore, some variants of atrial septal morphology can be fatal if untreated or improperly treated, and can be quite difficult to treat with balloon septostomy.

The normal atrial septum

The flap valve of the oval foramen, or the foramen ovale, representing the primary atrial septum, or septum primum, normally has an attachment of its half-moon-shaped superior margin to the left side of the infolded superior muscular rim of the foramen, called the secondary septum, or septum secundum. Dissection of any normal heart will demonstrate that this superior limbic band is the deep infolding between the attachments of the right pulmonary veins to the left atrium, and the caval veins to the right atrium (Fig. 1). In hypoplastic left heart syndrome, as in the normal newborn, the space between the half-moon-shaped superior margin of the flap valve and the superior rim of the oval foramen is usually patent. Postnatal bulging of the flap valve resulting from increased pulmonary venous return usually stretches the flap valve, with further opening of the oval foramen (Fig. 2).

Figure 1. The cartoon shows a coronal view of the atrial chambers, illustrating how the superior and inferior caval veins enter the right atrium, and the pulmonary veins enter the left atrium. The normal attachment of the flap valve of the atrial septum, the primary septum, or septum primum, is shown to the left atrial side of infolded superior rim of the oval foramen, usually called the septum secundum.

Figure 2. The cartoon demonstrates the stretched oval foramen (foramen ovale) with postnatal increased pulmonary venous return in the presence of normal attachment of the primary atrial septum (septum primum) to the infolded superior rim of the oval foramen, the septum secundum.

Leftward displacement of flap valve, or septum primum

In a large number of cases of hypoplastic left heart syndrome, most often those with mitral and aortic atresia, the superior aspect of the flap valve or “septum primum” is attached to the roof of the left atrium to the left, and posterior, relative to the infolded “septum secundum”. Thus, there is a gap of at least 4 millimetres in the newborn between the superior rim and the flap valve. In some, however, the gap can be much larger, with the flap valve being attached as far left as the origin of the left atrial appendage. Sufficient lateral displacement can give the false impression of a large atrial septal defect, because the flap valve is not found in its expected location adjacent to the superior margin or septum secundum (Fig. 3). Furthermore, in the most extreme cases of leftward displacement, postnatal rightward bulging of the flap valve may result in a restrictive oval foramen, as the flap valve is pushed up against the roof of the left atrium (Fig. 4). With the normal attachment of the flap valve to the superior rim, postnatal bulging usually results in stretching of the flap valve and further opening of the oval foramen, as discussed above (Fig. 2). The essence of the malformation is that the posterior aspect of the atrial septum is normally located, but the anterior aspect is laterally displaced. In this way, the flap valve forms a hood over the right pulmonary veins, which is sometimes responsible for the appearance of turbulence on Doppler echocardiography without other evidence of pulmonary venous obstruction.

Figure 3. This cartoon shows leftward displacement of the primary atrial septum, flap valve, or septum primum. The arrow passes through the oval foramen. Note the appearance of a large pseudo-defect beneath the persisting infolding marking the septum secundum.

Figure 4. This cartoon shows bulging of the displaced flap valve formed by the primary atrial septum, or septum primum, due to increased postnatal pulmonary venous return, with the oval foramen partially obstructed as it apposes the roof of left atrium. The arrow shows the pathway of flow from the left atrium.

Therapeutic options for patients with the hypoplastic left heart syndrome

Three surgical approaches have evolved over the years and are available today:

• multistage reconstructive surgery based on a single ventricle physiology, popularized by Norwood et al.³⁸
• cardiac replacement championed by Bailey and associates³⁹
• biventricular repair, as used for the patients at the mild end of the spectrum of hypoplastic left heart syndrome,²⁹ as well as for the patients with aortic atresia with ventricular septal defect and a well-developed left ventricle, technically a “hypoplastic left heart syndrome-related malformation”.^{40, 41}

While the first two approaches can be applied to any patient with hypoplastic left heart syndrome, the biventricular approach can be used in very few patients, and requires an extremely careful process of evaluation and selection. Much of the debate over the last 15 years has been centered on the advantages and disadvantages of the Norwood operation as opposed to neonatal cardiac transplantation. Both approaches are based on entirely different surgical philosophies. Different centres tend to favour one or the other of these approaches, while some offer both, and leave the final decision to the parents.⁴² It is possible for a suitably mature programme to obtain excellent results by selectively offering staged palliation, transplantation, and in suitable cases, biventricular repair.⁴³ Some centres, of course, continue to offer the fourth, non-surgical, option of supportive care, called by some compassionate care,⁴⁴ and by others passive euthanasia.⁴⁵ Considerations of this last option raise a number of ethical issues, but these are beyond the scope of our present purpose, and will not be further discussed.

Nomenclature and crossmap for diagnoses and procedures related to hypoplastic left heart syndrome

Thus far, we have summarized the historical aspects of terminology, and the development of surgical treatment for hypoplastic left heart syndrome. Although we have suggested a common definition for hypoplastic left heart syndrome, the term does not provide the details necessary to describe in full the patients afflicted with the syndrome. Since Noonan and Nadas first coined the term in 1958, there have been dramatic developments in invasive and non-invasive imaging that now allow for precise diagnoses. Moreover, since the early 1980s, the development of surgical procedures has offered the prospect of survival from these once-lethal anomalies. Hence, a more detailed, comprehensive, and universal scheme of classification is required for description of cases, and collection of data, in the 21st century.

In 2000, two extensive nomenclatures were published almost simultaneously. These were the European Paediatric Cardiac Code, prepared on behalf of the Association for European Paediatric Cardiology^{73, 74} and the International Congenital Heart Surgery Nomenclature and Database Project, undertaken at the behest of the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons.⁷⁵ Both reflected the need for a more detailed description of anomalies, such as those included in the term hypoplastic left heart syndrome, but the resulting solutions differed significantly. The European Paediatric Cardiac Code lists all individual malformations in a segmental and sequential fashion. The surgical tree for nomenclature, in contrast, is presented as a listing of both individual lesions and formalized groupings, representing lesions that may be found together. The surgical list may also be accessed in a segmental and sequential fashion. The structural difference between the two systems is analogous to the difference between atoms and molecules. The European Paediatric Cardiac Code utilizes an atomic approach, using mostly basic diagnostic terminology, but not formally grouping together the terms. Thus, in the European Paediatric Cardiac Code, under the heading “left ventricular anomalies”, there exists an entry for hypoplastic left heart syndrome. The various details, or “atoms”, of the associated anomalies of the left heart are coded separately within the lists available for the appropriate cardiac segment. The International Congenital Heart Surgery Nomenclature and Database Project, in contrast, uses a molecular approach, with formalized groupings of terms to represent the various lesions that may be found together. The latter nomenclature, therefore, contains an entire section entitled “hypoplastic left heart syndrome”. The version of the International Code derived from the International Congenital Heart Surgery Nomenclature and Database Project, therefore, offers a listing of the various possible combinations of hypoplasia, stenosis, and atresia within the left heart and aorta. The advantage of the molecular approach is that a single selection may be made to code a group of several lesions found together. The disadvantage of the molecular approach is that the list of names is longer, and potentially more challenging to navigate without computerized navigational assistance. Both approaches, nonetheless, be they atomic or molecular, will allow proper coding of the diagnoses and procedures of congenital cardiac disease.

Faced with two complete but different lists of names, the Nomenclature Working Group was formed in 2001 with the remit to cross-map the existing systems, and hence create the International Paediatric and Congenital Cardiac Code.^2–7 In the subsequent pages, we present the work of the group in cross-mapping the names for the parts making up the hypoplastic left heart syndrome.

Nomenclature crossmap for diagnoses related to hypoplastic left heart syndrome

In Table 1, we show the names for diagnoses related to hypoplastic left heart syndrome from the version of the International Code derived from the nomenclature of the International Congenital Heart Surgery Nomenclature and Database Project of the Society of Thoracic Surgeons and the European Association of Cardio-Thoracic Surgery. In Table 2, we show the equivalent and crossmapped terms from the version of the International Code derived from the nomenclature of the European Paediatric Cardiac Code of the Association for European Paediatric Cardiology.

Table 1. The European Association for Cardiothoracic Surgery – Society of Thoracic Surgeons derived version of the International Paediatric and Congenital Cardiac Code for Diagnoses related to Hypoplastic Left Heart Syndrome.

Table 2. The Association for European Paediatric Cardiology derived version of the International Paediatric and Congenital Cardiac Code for the Diagnoses related to Hypoplastic Left Heart Syndrome.

As we have discussed previously, the approach utilized by the Association for European Paediatric Cardiology necessitates that combinations of individual codes are used to describe the possible variants of hypoplastic left heart syndrome. There was initially no separate code for the hypoplastic left heart complex in the European Pediatric Cardiac Code, but a simile has now been created, despite this remaining a somewhat controversial term. For the most part, the version of the International Code derived from the European Paediatric Cardiac Code lists the various diagnostic parts with appropriate qualifiers, as shown in Table 2.

In Table 1, after giving the list of diagnostic terms for the classification of hypoplastic left heart syndrome, we also provide a listing of the diagnostic terms for the so-called “Hypoplastic left heart syndrome (HLHS)-related malformation”, and finally a listing of a group of terms called the “Hypoplastic left heart syndrome (HLHS)-modifier”. The latter is a list of terms that may be used to modify the different types of hypoplastic left heart syndrome and hypoplastic left heart syndrome-related malformations.

In the version of the International Code derived from the initial efforts of the Association for European Paediatric Cardiology (Table 2), there is no separation or grouping of the so-called “Hypoplastic left heart syndrome (HLHS)-related malformation”. The individual conditions are listed as mutually exclusive diagnoses purely on their own merit.

The structure of the version of the International Code derived from the European Paediatric Cardiac Code also differs from the other version in the use of terms as modifiers or qualifiers. The version of the International Code derived from the International Congenital Heart Surgery Nomenclature and Database Project uses the concept of modifiers to list any additional diagnosis, which may be linked to their parent diagnosis. This surgical version of the International Code explicitly lists these modifiers with a formal linkage with the parent diagnosis, incorporating both diagnoses into the same multidiagnostic chain, as illustrated in Table 1. In contrast, although the version derived from the European Paediatric Cardiac Code has all of these diagnoses listed in its system, it does not explicitly link them to the primary diagnosis. The user is encouraged by linkages in the underlying structure of the hierarchy to go to the section dealing with, for example, coronary arterial anomalies, and then list the additional pathology present as part of the total diagnostic description. For the most part, each diagnosis is mutually exclusive, and stands alone. There are a few exceptions, where such linkages have become embedded in the accepted nomenclature of paediatric cardiologists, such as “pulmonary atresia with ventricular septal defect, including the Fallot type”.⁶ Qualifiers, or terms with numerical codes beginning with a “Q” (Qx.xx.xx), exclusively give additional fine detail to a single or multiple diagnoses. As with the modifiers, more than one qualifier can be attached to such an individual term.⁷⁴ These qualifiers cannot, in any part, be used on their own as individual terms. They are divided broadly into those adding diagnostic information, such as which leaflet of the tricuspid valve is involved in an abnormality, or the severity of aortic regurgitation; and those adding surgical information, such as the size of an interposition shunt, conduit, or device.

Nomenclature for therapeutic options for hypoplastic left heart syndrome

The nomenclature for therapeutic options must cover the following procedures:

• Norwood operation
• Transplantation
• Biventricular repair without prior Norwood operation
• Biventricular repair after the Norwood operation
• Transcatheter palliation

Crossmap for therapeutic options related to hypoplastic left heart syndrome

As we showed in the diagnostic section of the crossmap, what follows is the crossmap of the names for procedures related to the hypoplastic left heart syndrome. In Table 3, we show the names emerging from the version of the International Code derived from the nomenclature of the International Congenital Heart Surgery Nomenclature and Database Project, while in Table 4 we show the equivalent and crossmapped terms using the version of the International Code derived from the nomenclature of the European Paediatric Cardiac Code.

Table 3. The European Association for Cardiothoracic Surgery – Society of Thoracic Surgeons derived version of the International Paediatric and Congenital Cardiac Code for Procedures related to Hypoplastic Left Heart Syndrome.

Table 4. The Association for European Paediatric Cardiology derived version of the International Paediatric and Congenital Cardiac Code for the Procedures related to Hypoplastic Left Heart Syndrome.

Summary

During the process of creation of a bidirectional crossmap between the system emerging, on the one hand, from the initiative sponsored by the Congenital Heart Committees of the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons,⁷⁵ and on the other hand, from that formulated by the Coding Committee of the European Association for Paediatric Cardiology,^{73, 74} the Nomenclature Working Group has successfully created the International Paediatric and Congenital Cardiac Code. As would be expected, during the process of crossmapping it became clear that, for most lesions, the European Paediatric Cardiac Code was more complete in its description of the diagnoses, while the International Congenital Heart Surgery Nomenclature and Database Project was more complete in its description of the procedures. Interestingly, for hypoplastic left heart syndrome, the surgical nomenclature proved suboptimal in its description of therapeutic options, in part because a huge amount of time had been spent by the surgical committees debating the diagnostic definition and classification of hypoplastic left heart syndrome. During the meetings of the International Congenital Heart Surgery Nomenclature and Database Project, a separate session was arranged specifically to establish the nomenclature for the syndrome. This session focused on debating the diagnostic definitions and existing classifications. The recent additional debates by the Nomenclature Working Group have allowed for further clarification of these diagnostic definitions and classifications, and have resulted in provision of a more comprehensive and accurate nomenclature for the diagnoses and procedures related to patients born with the hypoplastic left heart syndrome. This process ^2–7 of crossmapping major nomenclature systems for the multiple lesions making up the hypoplastic left heart syndrome exemplifies the entire efforts of the Nomenclature Working Group to create a comprehensive and all-inclusive international system for the naming of paediatric and congenital cardiac disease, the International Paediatric and Congenital Cardiac Code.

The comprehensive nomenclature now offered by the Nomenclature Working Group for the diagnoses and procedures related to hypoplastic left heart syndrome and related malformations demonstrates the value of The International Paediatric and Congenital Cardiac Code produced by this committee. Although names and classification for paediatric and congenital cardiac disease will continue to evolve over time, we are now closer than ever to reaching uniform international agreement and standardization. The International Paediatric and Congenital Cardiac Code can be downloaded from the Internet, free of charge, at www.ipccc.net.