A potentially curative fetal intervention for hypoplastic left heart syndrome

Hypoplastic left heart syndrome (HLHS) encapsulates a spectrum of complex congenital cardiovascular malformations involving varying degrees of underdevelopment of the left-sided heart structures. However, despite improved survival rates since the introduction of staged surgical reconstruction, treatment options for HLHS remain palliative rather than curative. A major limiting factor in the development of definitive curative therapy for HLHS is an incomplete understanding of its pathogenesis. Currently, the aetiology HLHS is best conceptualised by the 'flow theory' of cardiogenesis, which states that normal cardiac development is reliant on the interrelationship of normal flow patterns of blood through the developing heart, and appropriate growth of the cardiac valves and myocardium. Thus, congenital cardiac malformations, such as HLHS, are thought to arise when these two processes are incorrectly coupled in utero. The rationale for the hypothesis proposed herein rests upon the flow theory of cardiogenesis. Morphological studies of HLHS indicate that, although underdeveloped, all left-sided cardiac structures are present and anatomically correct. Further, of the various structural abnormalities that can occur within the spectrum of HLHS, the presence of a ventricular septal defect (VSD) is rare. The rarity of a VSD within the morphological spectrum of HLHS suggests the syndrome may not develop in the presence of a functionally significant VSD. Presumably, the presence of a functional VSD establishes a communication between the two ventricles during cardiac development, and preserves the normal pressure-flow-dependent growth of the left ventricular (LV) myocardium, despite inflow/outflow valve defects. It is proposed that surgical creation of a VSD in utero will 'rescue' the LV of hearts with left-sided valvular deformities that render them susceptible to the development of HLHS later in gestation. In evaluating this hypothesis, potential techniques for surgical creation of a VSD in utero are offered. These techniques are based on already established catheter-based in utero interventions, and conventional postnatal percutaneous procedures for VSD creation. Further discussion is also offered on techniques to avoid, and manage, potential complications (i.e. conduction system damage) of the proposed technique(s). Finally, if VSD creation in utero is indeed practically feasible, and successfully establishes the hypothesised hemodynamic and myocardial growth normalisation within the abnormally developing LV, the clinical implications are profound. This procedure may hold a potential cure for almost every sub-type of HLHS.