Discussion

The sequence of events that lead to semilunar valve atresia and ventricular hypoplasia needs better understanding, as to which is the primary pathology, and the mechanisms involved. More evidence is available for the left ventricle and outflow tracts; similar influences might be valid for the right ventricle and outflow tract.

Outflow obstruction results in complex secondary responses with disturbed flow dynamics and shear stresses, leading to impaired and disorganised ventricular growth and development. Genetic modifiers might impact subsequent remodelling, including intrinsic myocardial growth signalling pathways. Furthermore, during the latter stages of gestation, cardiomyocytes switch their myogenic capacities and become incapable of mitosis: ventricular hyperplasia cannot occur therefore, and remodelling becomes limited to ventricular hypertrophy. ^{Reference Hickey, Caldarone and McCrindle10}

Sub-aortic membranes are well known to recur in a subset of patients after surgical removal; this proposes that an underlying pathology is present and not merely the anatomical condition restored by surgery. Gewillig and colleagues in 1992 studied patients with discrete sub-aortic membranes by echocardiography and showed abnormal flow patterns in these cases and suggested that these chronic flow disturbances trigger endothelial transformation and growth, leading to the development and recurrence of the anatomical stenosis. ^{Reference Gewillig, Daenen and Dumoulin11} It has also been reported that minor changes in the left ventricular outflow anatomy, including the aorto-septal angle, ^{Reference Shar, Brown, Keswani, Grande-Allen and Sucosky9} can produce significant alterations in the dynamic forces and septal shear stress, and thus influencing the development and the progression of sub-aortic obstruction, which is much faster in infants than in older children. ^{Reference Mohan, Shukla, Mohan and Sethi12,Reference Silbiger, Lee, Christia and Perk13} These mechanical theories, however, could not explain the increased familial recurrence rate that is also well-identified in cases with sub-aortic membranes; an underlying genetic factors must therefore be co-existent. ^{Reference Foker8,Reference Gale, Cartmill and Bernstein14-Reference Richardson, Menahem and Wilkinson16}

A theory that combines both the mechanical and the genetic hypothesis states that the disturbed flow dynamics might induce the expression of a number of genes responsible for endothelial and smooth muscle cell proliferation, similar to the mechanisms involved in atherosclerosis. ^{Reference Chiu and Chien17} It is important to remember that discrete sub-aortic membrane can occur following a repair of underlying CHD. Irrespective of the gross appearance, the stenosing lesions exhibit five tissue layers beginning from the luminal aspect: endothelium, acid mucopolysaccharide-rich sub-endothelial layer, collagen-rich fibrous layer, fibro-elastotic layer and a smooth muscle layer. ^{Reference Butany, Vaideeswar and David18}

Fibrous sub-aortic or sub-pulmonary stenosis is in direct fibrous continuity with the overlying semilunar valve, indicating that this sub-valvar ring-like stenosis really is valvar, not infundibular or conal. If the obstruction becomes muscular, then most probably the origin is infundibular and not valvar. ^{Reference Tomar, Radhakrishnan and Sharma4} Anderson thinks that this is not a “membrane” and appears to look more like a fibrous shelf, is almost certainly an acquired lesion and is a fibrous accretion exacerbating the narrowing at the mouth of the sub-pulmonary infundibulum. Anderson and colleagues have illustrated such fibrous accretions in their studies on tetralogy of Fallot, albeit not specifically commenting on the structure. ^{Reference Anderson and Jacobs5}

In our statement, we are suggesting that the sub-pulmonary membrane that was not present before the first intervention might have developed later due to anatomical disturbance such as a long infundibulum forming the right ventricular outflow tract or due to malalignment of the septum in the right ventricular outflow tract reaching the sub-valvular area, either anatomic abnormality resulting in disturbed flow dynamics. Another postulation is that the sub-pulmonary membrane represents a response of the right ventricular outflow tract endothelium to the mechanical trauma during the initial intervention. This, however, does not explain fully the annular nature of the membrane but would have rather resulted in a shelf-like obstruction.

On echocardiography, it is important to differentiate this anomaly from valvar pulmonary stenosis with intact ventricular septum for the management plan. For valvar pulmonary stenosis, balloon pulmonary valvotomy is the treatment of choice with excellent results, while for sub-valvar pulmonary stenosis, surgery is the only option. We have excised the sub-pulmonary membrane in only one patient that had severe obstruction, another has mild right ventricular outflow tract obstruction and the other patients have no significant obstruction either by echocardiography or cardiac MRI. It is time and close follow-up that will show if the sub-pulmonary membrane will act in a similar manner as a sub-aortic membrane and progress into hemodynamic obstruction and recur after surgical excision or not. The rarity of the condition limits the extraction of sold conclusions; however, with the advancement and popularity of interventional treatment for pulmonary atresia with intact interventricular septum, the future might bare more insights.