Aortic Valve Neo-Cuspidization in Children – Ready for Prime Time Yet?

Aortic valve disease in the adult can result from age-related sclerotic degeneration, leaflet damage secondary to infection, or accelerated calcification of a congenitally bicuspid valve. Several options exist to repair or replace the diseased adult aortic valve. Ozaki and colleagues have pioneered a novel technique of “neo-cuspidization” of the aortic valve using glutaraldehyde-treated autologous pericardium trimmed on predesigned leaflet templates. ¹ A recent report from this group showed excellent durability of this procedure in 534 adults with a median age of 71 years, demonstrating 96% freedom from reintervention at 54-month follow-up. ²

The spectrum of abnormalities and, therefore, the resulting pathophysiology is quite different in pediatric aortic valve disease. Bicuspid aortic valve is the most common anatomic etiology of aortic valve disease in the pediatric population. ³ However, a significant proportion of patients have more complex pathologic lesions. Stenotic lesions can range from those that are caused by leaflet fusion with otherwise normal leaflet and annular morphology to those seen in Shone complex or hypoplastic left heart syndrome wherein all the left heart structures are underdeveloped. Aortic regurgitation may result from leaflet pathology or an inherently abnormal aortic root as may be seen in tetralogy of Fallot ⁴ or truncus arteriosus or following arterial switch for transposition. ⁵ Consequently, tailoring the surgical approach to the individual pathology at hand is imperative to achieve durable outcomes in children.

Techniques for aortic valve repair have significantly evolved over the past two decades, and it is the preferred surgical approach when pathology is restricted to a single leaflet. Open commissurotomy, valve thinning, valve resuspension, and plication are reproducible and well-established repair techniques. When the primary pathology is in the root of the aorta, root remodeling or valve-sparing root replacement techniques produce durable results. ³ Not infrequently, valve pathology extends to more than one leaflet and is not amenable to repair. Aortic valve replacement in children presents unique challenges. The availability of appropriate size prosthetic valves is a significant limitation, especially in small children. Lack of growth of the prosthetic valve subjects children to repeated valve replacements to keep up with somatic growth. Lifelong anticoagulation for mechanical valves can also be particularly challenging. Tissue valves and homografts undergo rapid degeneration and have extremely limited durability in children.

Extrapolating from the success of the Ozaki neo-cuspidization in the adult, several centers, including ours, have applied this technique to pediatric aortic valve disease. Anecdotal reports have suggested promising early results. However, longer term results demonstrating durability of the repair and, in particular, ability of the neo-cusps to keep up with somatic growth are lacking. In addition, Ozaki procedure in children requires specific modifications. The commercially available templates are not suitable for use in the very small child. The outcomes of the procedure have not been evaluated when concomitant subvalvar obstruction requires surgical correction, such as in the setting of a Konno operation, or with additional annular or aortic wall pathology, such as supravalvar aortic stenosis. Further, autologous pericardium may not be universally available in the pediatric population, most often due to prior use. The most appropriate alternative material is not known. Based on individual surgeon preference, xeno-pericardium, polytetrafluoroethylene patches, or extracellular matrix-derived patches have all been tried. Bovine pericardium is the most frequently used substitute and is available in various forms—fixed in glutaraldehyde, tissue-engineered, and detoxified using patented technology following glutaraldehyde cross-linking (CardioCel® from Admedus, Malaga, Australia), or decellularized and photo-oxidized (Photofix® from Cryolife, Kennesaw, Georgia). There is insufficient evidence to directly compare these different patches. In this issue of World Journal for Pediatric and Congenital Heart Surgery, Chivers et al ⁶ report their experience with use of CardioCel for Ozaki procedure in five children and young adults. Although initial results were excellent, two repairs failed within two years, and in both cases, accelerated degeneration of the neo-cusps was demonstrated. Such rapid deterioration of CardioCel in areas of high shear stress has been demonstrated in other studies as well. ⁷ Given the small sample size, one cannot conclusively determine whether the suboptimal results in Chivers’ study were related to the choice of procedure or patch material. However, as elegantly pointed out by the authors, reports such as these reinforce the need for cautious ponder as one evaluates the role of Ozaki procedure in the pediatric population.

At our center, we continue to favor the pulmonary autograft as our primary choice to replace the aortic valve and root (Ross procedure) in children. Our results have clearly shown that, regardless of the nature of aortic valve disease, Ross procedure is a safe, effective, and anticoagulation-free alternative. ⁸ The autograft root grows with the child and maintains a highly favorable functional and symptom profile. Autograft dilation is rare in the smaller children and can be minimized in older children by wrapping within a Dacron tube. ⁹ The procedure, however, is technically more challenging. In addition, there is a definite need for reintervention on the reconstructed right ventricular outflow, where a homograft is generally used to replace the explanted autograft. In this context, we currently view a role for procedures such as Ozaki when a suitable pulmonary autograft is not available, such as for truncal valve replacement.

Aortic valve neo-cuspidization is an attractive option to replace aortic valves not amenable to repair. It is imperative that centers with early experience with this procedure continue to refine the technique for specific application in the pediatric population. At the same time, rigorous analysis of long-term outcomes and careful evaluation of failures are required for more appropriate and successful utilization.