Discussion

This case report highlights a unique case of hypoplastic left heart syndrome with a four-leaflet and four-sinus pulmonary valve. Dysplastic pulmonary valves in the setting of hypoplastic left heart syndrome are exceedingly rare, with less than 0.5% of children with hypoplastic left heart syndrome having significant pulmonary dysplasia or dysfunction. ^{Reference Aggarwal, Delius, Walters and Natarajan3–Reference Kurtz, Alsoufi, Wilkens and Kim7} A four-leaflet pulmonary valve has only been described once before. ^{Reference Bharati, Nordenberg, Brock and Lev4}

In previously reported cases, dysplastic pulmonary valves have been associated with poor outcomes, and in some of these cases, a primary heart transplant was pursued rather than attempting stage I palliation. In the current case, the pulmonary valve was dysplastic and developed haemodynamically significant insufficiency. The central nature of the neo-aortic insufficiency does make it likely that the insufficiency could be secondary to alterations in coaptation of the valve leaflets. The clinical concern for high pulmonary blood flow may lend insight into the mechanism of this potential alteration in coaptation, with dilation of the pulmonary valve leading to worse central coaptation in times of higher pulmonary blood flow. The decrease in neo-aortic insufficiency with clinically decreased pulmonary blood flow also highlights this as a possible mechanism. Concurrently at the time of the increase in the neo-aortic insufficiency, there was also a decrease in the systemic right ventricular dysfunction. Whether or not there is a causal relationship between the two cannot be ascertained, but it is plausible that volume overload due to neo-aortic insufficiency and high pulmonary blood flow could have contributed to the decrease in systemic ventricular function.

As mentioned previously, a four-leaflet pulmonary valve in the setting of hypoplastic left heart syndrome has only been described once before by Bharati and colleagues. They described necroscopy findings of a heart from a child who died at 1 day of life. This heart had hypoplastic left heart syndrome with mitral atresia and aortic atresia. There was an atrial septal defect, although it was small. The pulmonary valve was described as being stenotic, incompletely formed, markedly thickened, and nodular, with four leaflets and with four sinuses. The authors hypothesised that in fetal life a small atrial septal defect may lead to most of the flow from the inferior caval vein going through the tricuspid valve and into the pulmonary valve. They postulated that this increased flow may lead to turbulent flow and promote abnormal tricuspid and pulmonary valve development. ^{Reference Bharati, Nordenberg, Brock and Lev4} This has not been supported by any objective data and, for the current case, could not be the mechanism of abnormal pulmonary valve development, as the atrial septal defect was adequate throughout fetal and postnatal life.

Insights into the more likely mechanism of the formation of a four-leaflet pulmonary valve can be more accurately inferred with a review of the development of the pulmonary and aortic valves. The pulmonary valve and aortic valve form similarly to one another. The right and left leaflets of both these valves are derived from the endocardial cushions, while the posterior leaflet of the aortic valve and the anterior leaflet of the pulmonary valve are derived from the intercalated valve swellings, sometimes referred to as the intercalated cushions. The intercalated valve swellings may appear externally similar to the endocardial cushions at times but are cellularly different, and thus the developmental origins of the valve leaflets in the same valve are also different. The leaflets all enlarge into the lumen of the developing outflow tract, ensuring unidirectional blood flow. Through incompletely understood flow-triggered mechanisms, the endocardial cushions and the intercalated valve swellings become smaller, producing the leaflets themselves through a process of valvar sculpting. As the endocardial cushions and the intercalated valve swellings already abut each other and the valve leaflets are produced by sculpting of already present tissue, the valve leaflets themselves do not elongate during development, contrary to long-held belief. This results in a trifoliate, trisinuate aortic, and pulmonary valve. It is important to remember that these valves both consist of their sinuses, the valvar leaflets themselves, and the interleaflet triangles. Each leaflet attaches in semilunar fashion from its nadir at the plane of the virtual basal ring (referred to as the annulus clinically although it is not the true annulus) to its peak at the sinotubular junction. The resulting valves are often described based on the number of “cusps,” which is problematic as this term is used interchangeably to describe leaflets and/or sinuses without discrimination. This is why in the current description the valve has been specifically described with attention paid to the leaflets and sinuses. ^{Reference Anderson, Lamers, Hikspoors, Mohun, Bamforth and Chaudhry8}

With these developmental considerations in mind, the four-leaflet pulmonary valve can be better explained. It is possible that the intercalated swelling giving rise to the anterior leaflet of the pulmonary valve is divided or duplicated, resulting in a four-leaflet and four-sinus pulmonary valve. The other possibility is that the endocardial cushions contributing to the right and left pulmonary valve leaflets divided or duplicated, resulting in the fourth leaflet and fourth sinus. It is unlikely that this developmental abnormality is related to the developmental aberrations underpinning hypoplastic left heart syndrome but rather that two unlikely developmental abnormalities occurred in the same individual.