Summary
Management of congenital defects of the heart and great vessels constitutes the largest part of paediatric cardiology practice. Most of these defects require interventions, either corrective or palliative, to guarantee patient survival, symptom relief and/or better quality of life. Interventions can be performed either surgically or transcatheter percutaneously. The surgical repairs are invasive, with long-term results often being suboptimal for complex lesions and after the use of grafts, especially in small patients. Nowadays, various transcatheter devices allow much less invasive percutaneous management in some carefully selected patients with congenital heart disease. However, the currently available materials and devices are only suitable for a small proportion of children, while the majority of young patients with cardiac defects still need surgery, as no transcatheter alternatives exist. There are, however, numerous new biomaterials, devices and technologies that have the potential to expand the transcatheter approach to a much broader spectrum of congenital cardiovascular lesions and conditions. In this three-part review, we describe new advances in transcatheter devices and materials, which promise to extend the application of the percutaneous approach to younger and more complex patient groups with congenital heart disease. The first part focuses on new possibilities for the transcatheter treatment of vascular stenoses in growing patients and the closure of intracardiac defects.
Résumé
Le traitement des malformations congénitales du cœur et des gros vaisseaux constituent la plus grande partie de cardiologie pédiatrique. La plupart de ces malformations nécessitent des interventions, correctives ou palliatives, pour garantir la survie des patients, soulager les symptômes, et/ou assurer une meilleure qualité de vie. Les interventions peuvent être effectuées chirurgicalement ou par cathétérisme interventionnel. Les réparations chirurgicales sont invasive avec les résultats à long-terme qui restent souvent sous-optimale, en particulier dans les petits patients, avec des lésions complexes, et lorsque des greffons exogènes sont utilisés. Aujourd’hui, divers dispositifs transcutanés permettent un traitement percutané moins invasif de certaines cardiopathies congénitales sélectionnées. Cependant, les dispositifs actuellement disponibles ne sont appropriés que pour une petite partie des patients pédiatriques. La grande majorité des jeunes patients avec les malformations cardiaques ont encore besoin de chirurgie. Il y a, cependant, de nombreux nouveaux biomatériaux, dispositifs et technologies, qui pourraient élargir le champ d’application du cathétérisme cardiaque congénital. Dans cette revue, nous décrivons de nouvelles avancées dans les matériaux et dispositifs. La première partie est consacrée au traitement percutané des sténoses vasculaires chez les patients en croissance et à la fermeture de défauts septaux.
Novel materials and devices in congenital interventional cardiology: possibilities versus obstacles
Most important discoveries pass through three stages:
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it is impossible because it never can be;
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there is something in it;
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and it is the only way it should be.
Although such a passage from one stage to another serves to filter out senseless proposals, it can also considerably delay the implementation of useful ideas. The latter case was true for several transcatheter devices during the early years of interventional cardiology; even after the first successful reports, transcatheter closure of intracardiac defects and transcatheter aortic valve implantation were considered impossible for a long period of time. Nowadays, device closure of most secundum-type atrial septal defects is the safe first-choice management approach in children and adults. Similarly, the indications for transcatheter aortic valve implantation in adult patients are being extended continuously to include younger patients with lower surgical risk.
Numerous works have been published reviewing in detail the current options for transcatheter management of patients with congenital heart disease. Current materials used in congenital interventional cardiology include various balloons, bared and covered stents, different closure devices and transcatheter biological valves. The majority of current transcatheter management options have limitations, drastically reducing the numbers of patients who are suitable for the transcatheter approach. Most commercialized materials and devices currently used in congenital interventional cardiology originate from the late 1990s and early 2000s, and only slight improvements have been made since then. The various modifications that have been made to standard transcatheter techniques and available devices, although aiming to expand the applicability of currently available materials, are pushing safety limits rather than being novel. Minimally invasive cardiac surgery and hybrid approaches to some cardiac lesions are rapidly becoming popular; however, although invasiveness is reduced, surgical incisions and–for some procedures–cardiopulmonary bypass are still required. On the other hand, as described below, there are numerous reports on the development and animal testing of truly novel biomaterials and transcatheter devices aimed at the wide spectrum of congenital cardiovascular lesions. Further improvements to these biomaterials and devices would result in new commercially available devices that allow purely percutaneous management of a much larger group of patients, with more durable results than are achieved currently. However, for no readily apparent reasons, the commercialization and clinical application of these developments in interventional congenital cardiology are extremely slow.
There are several obstacles to the further development and widespread use of the transcatheter approach in the management of children with congenital heart disease. One of the major disadvantages of transcatheter techniques is the lack of direct overview of the structures, which drastically reduces the safety of complex intracardiac interventions. Besides the experimental use of videocardioscopy, direct and clear vision of the intracardiac structures can only be achieved currently during open-heart surgery using cardiopulmonary bypass. Rapid advances in three-dimensional echocardiography and magnetic resonance imaging, however, will soon provide real-time envisioning of the cardiac structures, with an image quality that is close to direct exposure. Improved real-time intraprocedural visualization of intracardiac structures will make percutaneous delivery of devices, patches and sutures safe and effective in children, eliminating the need to open the heart. Interestingly, in contrast to the past, the leading roles in research into new devices for children with congenital heart defects are nowadays taken, in the majority of projects, by biomedical engineers and cardiac surgeons. Paediatric interventional cardiologists, who mostly lack a comprehensive knowledge of bioengineering, stay largely outside the field, becoming solely consumers. Another obstacle is the existence of two extreme mindsets–hyperconservative and hyperactive–towards the novel transcatheter management options. In the past, a hyperactive attitude often resulted in all the latest proposed devices being tried out on patients without sufficient safety and efficacy data, leading to complications and a further increase in scepticism. Additionally, there are considerable complexities and high costs associated with the process of commercialization of new devices. Such a situation makes the breakthrough of novel, purely nonsurgical, percutaneous options for congenital cardiovascular lesions into clinical practice extremely difficult.
The process leading to a new commercially available transcatheter device that is efficient and safe ideally includes comprehensive computer simulations, the manufacture of numerous prototypes, in vitro evaluation and animal and pilot human testing. All of these stages need substantial monetary investment, which nowadays only large companies can afford. Revenues from device sales must not only recoup the production costs, but also produce a profit for the manufacturing companies. Although, to some extent, the revenue is determined by the selling price of the device, the number of devices sold is of even more importance. In the case of adult structural heart disease, large numbers of patients and high potential revenues are the major motivators for monetary investment in the process of design, testing and commercialization of new transcatheter devices. Additionally, the size of the cardiac structures in adults allows device robustness, simplification of manufacturing and the possibility of safe introduction through large sheaths. In contrast, in the Western world, the caseload of patients with congenital heart defects is significantly smaller, which results in lower revenues, lack of investment and high product prices. The paucity of investment results in a scarcity of new products on the market, with low revenues, which, in turn, sustains the lack of interest of companies in investment. However, as we will describe in our review, there is no lack of new biomaterials, devices and techniques in the field of congenital interventional cardiology, which could lead to the development and commercialization of conceptually different transcatheter devices, allowing less invasive management of a much wider spectrum of congenital cardiac patients, with more durable results. As result, the extension of the transcatheter approach to new groups of patients will increase the caseload and numbers of sales significantly. Consolidation of the process of developing, testing and commercializing new transcatheter devices for congenital heart diseases within one large dedicated company would allow experience and revenues to be concentrated within one organization, making this long and complex process efficient and financially beneficial.
In our review, we describe new advances in transcatheter device materials and technology, which promise to extend the application of the percutaneous approach to younger and more complex patient groups with congenital heart disease. Such new technology will revolutionize the management of congenital heart defects once again, this time with more safe and durable results. The first part of this review focuses on new possibilities for the transcatheter treatment of vascular stenosis in growing patients and on a novel transcatheter option to close any intracardiac defect.
Transcatheter management of congenital vascular stenosis in growing patients
The percutaneous treatment of vascular stenosis, mostly of the pulmonary arteries and aortic arch, by placement of bare-metal or covered stents in adult patients has been shown to be equally effective as or even superior to surgical angioplasty . Permanent stenting after balloon dilation of congenital stenosis of the aorta and pulmonary arteries in smaller children or infants is, however, rarely performed, because of the high risk of vascular complications during placement of the large rigid stents, which require large sheaths . Smaller stents, in turn, have limited options for enlargement after the two- to three-fold increase in vessel diameter that occurs in children as they grow. Recent advances in open-cell design stent technology, such as the recently marketed Formula™ stent (Cook Medical, Bloomington, IN, USA) and VALEO ® stent (Bard Peripheral Vascular, Tempe, AZ, USA), enable the balloon expansion of some stents to nearly two times their nominal diameter , and even breaking their struts . This may provide new opportunities for permanent vascular stenting as an initial approach, even in small children. There are, however, several unanswered questions and controversies about the durability of these stents, given how easy they can be cracked. The long-term fatigue resistance of small stents expanded greatly over their limits is virtually unknown. Furthermore, patients who are stented very early in life remain exposed to eventual complications and recurrent in-stent stenosis caused by neointimal proliferation during follow-up and multiple stent redilations . Relief of congenital vascular stenosis in small children by means of temporal stenting, by applying biodegradable stents is, in contrast, an elegant and attractive alternative, as the disappearance of the stent with time will support the vessel wall without the drawbacks of permanent stenting.
The concept of the biodegradable stent, providing a temporary support for the vascular wall after balloon dilation of the stenosed vessel, was primarily developed for atherosclerotic coronary arteries in adult patients. Balloon angioplasty of atherosclerotic coronary arteries may induce acute effects, such as inflammation, intimal dissection and recoil effect of the vascular wall . These adverse effects generally last for a short time after angioplasty, and resolve with remodelling of the coronary arterial wall, which needs only a short duration of vascular stenting after balloon angioplasty, being an ideal indication for the biodegradable stents. The nature of congenital native or postoperative vascular stenosis is profoundly different, and the increase in lumen diameter during balloon angioplasty of the native pulmonary artery or aortic stenosis involves intimal and medial tears, with considerable recoil effect . The remodelling of the vascular wall after balloon dilation of congenital stenosis usually results in recurrence of the narrowing, and may demand permanent support of the vascular wall after angioplasty. The need for permanent stenting after balloon dilation of congenital vascular stenosis conflicts with the concept of the temporary support using biodegradable stents. If true, such a conflict will considerably limit the use of biodegradable stents in congenital heart disease, where it is usually not desirable that the stent-supporting vascular wall will disappear. In that case, repeated implantations of new biodegradable stents after resorption of the previous ones could be an attractive alternative . A series of biodegradable stent implantations in the growing infant or child with congenital aortic or pulmonary artery stenosis will allow unrestricted vascular growth until a diameter is reached that allows an appropriate permanent stent to be deployed safely and with a good final result, sparing small patients from surgery. Furthermore, based on recent developments in materials and devices for recanalization of congenital or acquired chronic total occlusions , the combination of biodegradable stents with an elastic, strong, but highly stretchable and biologically inert covering material with high potential for endothelialization, will create a less invasive alternative for restoration of continuity of interrupted vessels in infants by the percutaneous approach.
There are numerous biodegradable stents available; unfortunately, at present, all are for interventions on coronary arteries, and all have diameters limited to 3.5–5 mm, which is clearly insufficient for the adequate management of the whole spectrum of stenoses of the pulmonary arteries or aorta ( Fig. 1 A–D) . Various materials, from metals to polymers, have been used to construct biodegradable stents. The two most studied and reported are Biotronik’s magnesium stent (DREAMS; Berlin, Germany) and Abbott Vascular’s polylactic acid stent (ABSORB; Chicago, IL, USA) , with many more stents in development and (pre)clinical evaluation . Alloys of magnesium, an essential mineral needed for a variety of physiological functions in the human body, appear to have ideal mechanical and biological properties to be used as a material for fully bioresorbable vascular scaffolds. Furthermore, magnesium alloys have a strength-to-weight ratio that is similar to that of strong aluminium and steel alloys .
