Summary
Correction of malformations affecting the right ventricular outflow tract often results in residual abnormalities that require valve implantation at a later stage to prevent right ventricular deterioration. In the paediatric population, the pathology of congenital valve stenosis or insufficiency is often complex, options for surgical repair are limited, and valve replacement remains the only–albeit unattractive–alternative. Prosthetic heart valve implantation can be performed either surgically or, nowadays, percutaneously. Current transcatheter devices allow less invasive percutaneous valve implantation in selected patients after surgical repair, but are suitable for only a small portion of paediatric patients. In addition, there is a large heterogeneous group of patients who undergo surgical constriction of the pulmonary trunk, either to reduce pulmonary blood flow or to retrain or support the left ventricle. In the third part of this review series, we focus on new biomaterials, devices and technologies that have the potential to extend transcatheter valve implantation to a broader spectrum of congenital cardiovascular lesions, with safe and durable results in children, and on transcatheter options for the creation of a partial obstruction within the pulmonary trunk (pulmonary artery banding).
Résumé
La correction des malformations de la voie d’éjection droite se traduit souvent par des anomalies résiduelles, qui nécessitent l’implantation de valves pour empêcher la détérioration du ventricule droit. Dans la population pédiatrique, la pathologie congénitale des valves cardiaques est souvent complexe. Les options de réparation chirurgicale sont limitées et le remplacement de la valve reste la technique la plus utilisée. Les dispositifs percutanés permettent l’implantation moins invasive de valves chez une petite partie de patients soigneusement sélectionnés. De plus, il y a un groupe hétérogène et important de patients nécessitant un cerclage de l’artère pulmonaire, soit pour réduire le débit sanguin pulmonaire et le risque d’artériolite pulmonaire ou pour ré-entrainer un ventricule gauche sous-pulmonaire. Dans la troisième partie, nous nous concentrons sur les nouveaux biomatériaux, dispositifs et technologies, qui ont le potentiel d’élargir les indications du remplacement valvulaire percutané, et sur les options percutanées de création d’un cerclage endovasculaire de l’artère pulmonaire.
Background
There is an ever-growing population of patients who survive surgical correction of congenital heart defects. Often, these patients have residual abnormalities that require reinterventions at a later stage. In particular, correction of right ventricular outflow tract (RVOT) obstruction mostly results on long-term in either regurgitant pulmonary valve or stenotic valved conduit. To prevent right ventricular deterioration, valve implantation is needed, which can be performed surgically or percutaneously. In the paediatric population, the pathology of congenital valve stenosis or insufficiency is often complex, options for surgical repair are limited, and valve replacement remains the most performed–albeit unattractive–strategy. Transcatheter pulmonary valve insertion is nowadays performed widely. The transcatheter devices currently available, however, are suitable for only a small portion of children. The majority of prosthetic valve implantations in children are performed surgically.
In addition, there is a large heterogeneous group of patients who undergo surgical constriction of the pulmonary artery (PA), either to reduce pulmonary blood flow or to “retrain” or support a left ventricle. Surgery is currently the only option to achieve pulmonary banding.
In the third part of this review series, we focus on transcatheter options to create a partial PA obstruction and revalvulate the wide regurgitant RVOT, and on advances in the development of a durable transcatheter prosthetic heart valve for growing patients.
Transcatheter creation of partial pulmonary trunk obstruction
Small patients with large left-to-right shunt and at high surgical risk, infants with univentricular heart lesions and an unprotected pulmonary vascular bed, and patients with ventricular septal defects not suitable for primary closure, currently undergo the PA banding procedure. PA banding is also used to “retrain” the subpulmonary left ventricle, before or not before anatomical repair, in patients with late-diagnosed transposition of the great arteries, with systemic right ventricular dysfunction after atrial switch procedures, and with the congenitally corrected transposition . Furthermore, clinical interest has recently emerged in PA banding as an alternative option to support the left ventricle in small children with severe dilated cardiomyopathy . During the PA banding procedure, a small tape is fixed around the pulmonary trunk, which may result on long-term in arterial wall fibrosis, which often needs surgical reconstruction after debanding. To reduce the risk of PA deformation, an alternative technique was proposed, consisting of partial obstruction of the pulmonary trunk by an intraluminal membrane ( Fig. 1 A) . Although surgical PA banding is a technically simple operation, it may be associated with considerable morbidity and mortality, largely because of the inability of the fixed banding to meet the individual physiological demands.
Optimal tightening of the band is often problematic, and some patients need surgical revision of the banding because of excessive or insufficient tightening. Additionally, left ventricular “retraining” before an arterial switch procedure is based on a staged increase of the pressure gradient across the banding, to allow the ventricle to adapt. Therefore, several proposals were made to produce surgically-implantable but percutaneously-adjustable PA banding, ranging from straightforward modification of regular materials to technically sophisticated devices . One particular device consists of an inflatable cuff placed around the PA and connected to a subcutaneous valve ; simply by adding or withdrawing the fluid from the cuff, the PA banding is tightened to a greater or lesser extent ( Fig. 1 E, F). Despite the obvious advantages, however, no surgical percutaneously-adjustable PA banding has achieved wide clinical use.
To overcome the invasiveness of surgical PA banding, several attempts have been made to develop a transcatheter device that is able to produce a partial PA obstruction percutaneously . Thus, an hourglass-shaped dilatable stent and self-expanding flow restrictors were implanted within either the pulmonary trunk or the PA branches, to effectively reduce pulmonary blood flow ( Fig. 1 B–D). Diabolo-shaped stents have been created clinically by using the properties of two different available stents used simultaneously, with one fitted on the other . A bare-metal stent with limited expansion capacity creates a restrictive region in the middle part of the stent in stent assembly. A covered stent with more expansion capabilities allows anchoring to the vessel wall and sealing of the assembly. Fenestrated occluders, with or without a stent, have been also used to create such a limitation of flow across the PA. However, similar to conventional external PA banding, the percutaneous options for adjusting the diameter of these devices are limited to balloon dilation of the artificial obstruction. To date, there is no transcatheter device with the feature of bidirectional adjustability. Another drawback is the incorporation of the devices in the PA wall, needing extraction and potentially complicating the definitive surgical correction of the underlying cardiac defect. Unfortunately, despite preliminary reports on the clinical use of PA flow restrictors, and initial enthusiasm, transcatheter PA banding devices are currently neither used nor commercially available. Nonetheless, a transcatheter percutaneously-adjustable device will create the opportunity for effective and minimally-invasive pulmonary vasculature protection for a large group of patients at high risk from primary surgical correction, such as those with late-diagnosed ventricular septal defects and transposition of the great arteries.
Biodegradable stent technology and recent developments in the field of soft actuators have provided very attractive materials for creating a transcatheter device that is capable of producing an obstruction within the pulmonary trunk without the above-mentioned limitations. In microfluidics, actuators based on stimuli-responsive hydrogels are successfully employed to specifically regulate drug delivery ( Fig. 1 G). In particular, hydrogels that are insoluble in water and are capable of repeatedly changing their volume in response to light may be used to produce transcatheter bidirectionally-adjustable PA banding. The most promising is the hygroscopic polymeric gel made from polyacrylic acid and loaded with silver-coated titanium dioxide nanoparticles . Reversible changes in volume of this hydrogel are controlled by osmotic pressure changes produced by the photo-induced reversible redox reactions of the silver ions entrapped in the gel. Thus, the hydrogel gradually swells during exposure to ultraviolet light and gradually shrinks under visible light. Strikingly, this particular hydrogel stops changing volume upon removal of light and retains its size even in the dark ( Fig. 1 H).
Light-induced swelling of the ring of such a hydrogel mounted into a biodegradable stent and implanted within the PA will function as a partial obstruction to the flow, and will allow the graded percutaneous bidirectional adjustment of the flow restriction long term, simply by irradiating the hydrogel with the light of different wavelengths. Furthermore, resorption of the biodegradable stent frame will nearly eliminate the risk of PA deformation in the long term. Several issues need to be solved, however, before the creation of bidirectionally-adjustable transcatheter PA banding based on a light-sensitive hydrogel becomes a reality. Currently, the large volume changes in the polyacrylic acid hydrogel loaded with silver-coated titanium dioxide particles take several hours, which is too slow for clinical application. The stability and biocompatibility of the hydrogel when exposed to blood for a long time also need to be evaluated. However, further evolution of light-responsive hydrogels has the potential to make percutaneously-implantable and bidirectionally-adjustable PA banding available for future clinical use.
Transcatheter management of wide regurgitant RVOT
Corrective surgery in patients with tetralogy of Fallot and related congenital obstructions of the RVOT generally includes relief of obstruction, using either a conduit or transannular patch enlargement. Transannular patch enlargement is relatively straightforward, and is an extensively used approach, producing a wide unobstructed RVOT with obligatory pulmonary regurgitation. In the long term, revalvulation of the RVOT is indicated to preserve right ventricular function and prevent complications . Percutaneous implantation of the biological valve prosthesis into the dysfunctional conduit or stenotic RVOT has become widespread practice. Several reports have confirmed that the currently available transcatheter valves–the Melody ® valve (Medtronic, Minneapolis, MN, USA) and the SAPIEN valve (Edwards Lifesciences, Irvine, CA, USA)–have relatively long durability . Patients with a conduit or stenotic RVOT, however, are only a minority after surgical repair of tetralogy of Fallot. As the currently available transcatheter valves are not suitable for implantation into the purely regurgitant RVOT, several approaches have been suggested to enable percutaneous implantation of currently available transcatheter valve prostheses in this subset of patients.
Thus, implantation of transcatheter valves in both PA branches, and modifications to current valve implantation techniques have been used to avoid surgery in some selected patients . Using the Russian dolls technique (deployment of several stents into the wide RVOT) or the PA branch jailing technique (telescopic deployment of several stents between the PA and the wide RVOT), a reduction in RVOT size and the creation of a stable landing zone for the transcatheter valve can be achieved . These modifications, however, need implantation of a considerable amount of stents within the PA and RVOT. The hybrid two-stage approach may also be applied in high-risk patients, where surgical banding of the wide regurgitant RVOT is followed by percutaneous implantation of the valved stent into the sized RVOT . Furthermore, stent deployment into the RVOT any time before the RVOT dilates to a diameter of > 22 mm will prevent it from further dilation, and will provide a secure landing zone for future transcatheter valve implantation.
Another, conceptually different approach using a hourglass-shaped device has allowed safe percutaneous valve implantation into the wide RVOT with durable results and without complications ( Fig. 2 A , B). Such an hourglass-shaped outflow tract reducer has been developed and tested in a surgical sheep model of the wide RVOT . Deployment of the outflow tract reducer restricted the diameter of the landing zone and permitted successful Melody valve implantation, abolishing severe pulmonary valve regurgitation. The hourglass-shaped outflow tract reducer has wide flaring ends, which conform to the inner surface of the wide proximal ventricular outflow tract and the PA bifurcation distally, preventing stent migration. Covering of the stent prevents leakage along the outer surface of the valved stent ( Fig. 2 C). Modifications and further improvements to this early prototype have led to the commercialization of two similar transcatheter devices, containing valve leaflets made from pericardium: the Native Outflow Tract Transcatheter Pulmonary Valve (Medtronic) and the Transcatheter Venus P-valve™ (MedTech, Indianapolis, IN, USA) ( Fig. 2 D–G). The first reports on the clinical use of these devices, although mostly without any reported experimental evaluation in animal models and without any reference to the original invention, are very encouraging. The availability of these new transcatheter valves has opened new horizons for the large group of patients with wide and regurgitant RVOT.
