Summary
Percutaneous pulmonary valve implantation now has a key role in the setting of dysfunctional right ventricle-to-pulmonary artery conduits or failing bioprosthetic pulmonary valves. However, despite the excellent results obtained with the two devices available currently (the Melody ® valve [Medtronic Inc., Minneapolis, MN, USA] and the Edwards SAPIEN ® valve [Edwards Lifesciences, Irvine, CA, USA]), many patients eligible for pulmonary valve replacement remain unsuitable for percutaneous pulmonary valve implantation, mainly because of large native outflow tracts. Accordingly, one of the major challenges for the future is to expand percutaneous pulmonary valve implantation to a broader population of patients. Moving forward, there is important ongoing research that is intended to improve patient outcomes, expand percutaneous pulmonary valve implantation therapy and continue to reduce the number of open-heart surgeries in this population. In this review, we underline the limitations and issues associated with the devices available currently, and we focus on the development of new strategies (such as hybrid approaches or magnetic resonance-guided procedures), new devices (such as right ventricular outflow tract reducers or the novel Native Outflow Tract valved stent from Medtronic) and new technologies (such as tissue-engineered valves), which may help to take up these challenges and represent the future of transcatheter valve implantation.
Résumé
Le remplacement valvulaire pulmonaire percutané a désormais un rôle clé dans la prise en charge des dysfonctions de conduits entre le ventricule droit et l’artère pulmonaire ou de bioprothèses pulmonaires. Cependant, malgré les excellents résultats obtenus avec les prothèses percutanées actuellement disponibles (Melody ® [Medtronic Inc., Minneapolis, MN, États-Unis] et Edwards SAPIEN ® [Edwards Lifesciences, Irvine, CA, États-Unis]), de nombreux patients nécessitant un remplacement valvulaire pulmonaire ne sont pas éligible pour cette technique percutanée, essentiellement du fait d’une large voie droite native. De ce fait, un des principaux défis pour l’avenir est d’étendre l’implantation valvulaire percutanée à une plus large proportion de patients. Il existe ainsi un important champ de recherche ayant pour but d’améliorer le devenir des patients, d’étendre les indications de cette thérapie et de continuer de réduire le nombre de chirurgies dans cette population. Dans cette revue, nous souligneront les principales limites des dispositifs actuels et nous nous focaliseront sur le développement de nouvelles stratégies (comme les procédures hybrides ou les procédures guidées par IRM), de nouveaux dispositifs (comme les réducteurs de taille de voie droite ou la nouvelle prothèse Native Outflow Tract de Medtronic) et de nouvelles technologies (stents valvés crées par bio-engineering) qui pourraient permettre de relever ces challenges et constitueront le futur du remplacement valvulaire pulmonaire percutané.
Introduction
Patients with complex congenital heart defects are subject to numerous open-heart surgeries, usually performed to relieve right ventricular outflow tract (RVOT) abnormalities, with incremental risks and significant morbidity. In September 2000, the first successful percutaneous pulmonary valve implantation (PPVI) was performed, using a bovine jugular vein sutured on a platinum stent . Since this first-in-man report, catheter-based valve implantation has evolved rapidly over the last decade. This novel treatment option has changed the culture of paediatric cardiology, adult cardiology and cardiovascular surgery. Moreover, it has modified the way in which the expectant family of a foetus likely to undergo several RVOT surgeries is counselled .
Currently, there are two devices used for PPVI: the Melody ® valve (Medtronic Inc., Minneapolis, MN, USA), a bovine jugular vein valve sutured within a platinum and iridium stent; and the Edwards SAPIEN ® valve (Edwards Lifesciences, Irvine, CA, USA), made of bovine pericardium mounted in a rigid stainless steel stent, although the SAPIEN valve is not widely available. Multiple studies have demonstrated that PPVI with the Melody valve is safe and effective, with a high rate of procedural success, and durable in short- and medium-term follow-up in properly selected patients . The SAPIEN transcatheter heart valve is an alternative device with similar safety and efficacy in limited studies . PPVI with these revolutionary devices provides a non-surgical alternative in the treatment of dysfunctional RVOT and allows a reduction in the number of open-heart surgeries in these patients.
However, despite these excellent results, the heterogeneity of this population and the wide variety of implantation site morphologies, sizes and dynamics, limits the suitability of PPVI to approximately 15% of patients who require pulmonary valve replacement (PVR), indicating surgical PVR in 85% of patients . Accordingly, one of the major challenges for the future is to expand PPVI to a broader population of patients, including those with large and/or patched RVOTs or complex lesions with a vulnerable neighbourhood, and small children.
Several authors have described advanced techniques or device modifications to make these patients suitable for the transcatheter technique . The hybrid approach, including strategies to surgically and/or percutaneously prepare the outflow tract for subsequent transcatheter valve deployment, is another key area of pulmonary valvulation development.
Furthermore, extensive research and development is being conducted to design a suitable transcatheter valve for patients with a dysfunctional native or patched RVOT, typically with significant pulmonary regurgitation rather than obstruction, which is too large for the devices available currently. The first-in-human implantation of a large RVOT transcatheter valve developed by Medtronic was reported in 2010 .
In this review we aim to: underline the limitations and issues associated with the Melody and SAPIEN valved stents; focus on the alternative techniques and approaches that allow effective PPVI with these valves; and describe the ongoing research into and design of new transcatheter pulmonary devices.
Percutaneous pulmonary valve implantation in large right ventricular outflow tract
Current transcatheter pulmonary valves have demonstrated a high rate of procedural success with acceptable safety profiles and favourable outcomes. However, of the patients with a clinical indication for PVR, only 15% can be treated with the devices available currently, indicating surgical PVR in 85% of patients, as they have a history of transannular patch reconstruction of the RVOT, leading to distortion and dilation of that region and precluding PPVI because of the absence of an appropriate landing zone (16–24 mm for the Melody valve; 21–27 mm for the SAPIEN valve) .
To extend PPVI indications, some authors started to propose valve implantation in selected native outflow tracts with stenotic and/or non-distensible physiology . Other reports described advanced techniques to make these patients suitable for the transcatheter technique (i.e. the use of two Melody valves implanted in respective pulmonary arteries in a single patient; jailing and/or Russian doll techniques) . Cheatham et al. showed that PPVI using a 24 mm balloon catheter for the deployment of the Melody valve was feasible, without impairment of valvular function (RVOT diameter of 26 mm) . The SAPIEN valve diameters are 23, 26 and 29 mm, which makes it potentially more suitable for PPVI in large-diameter conduits and native outflow tracts (up to 27 mm) than the Melody valve, but the device is not widely available.
Nevertheless, most patients with transannular patch repair have a dilated and distensible RVOT, making device embolization a concern in this population. Accordingly, there is worldwide interest in developing new strategies with the current devices and/or a new design of transcatheter heart valve to make these patients suitable for PPVI, avoiding the risk of surgical PVR.
A new transcatheter pulmonary valve
The first-in-human implantation of a new self-expandable transcatheter pulmonary valve was reported in 2010 . This was done under compassionate use in a 42-year-old man with pulmonary insufficiency. The device design was tested in animals and modified to fit the patient’s anatomy and to allow safe implantation. The authors did computed tomography of the patient’s RVOT to create prototyping models to customise and test the device, which was successfully implanted into the patient with a satisfactory result. No stent fracture and only trivial paradevice leak were observed at 6-month follow-up. This new prosthesis is called the Native Outflow Tract device (Medtronic Inc., Minneapolis, MN, USA). Besides the use of porcine pericardium to make the valve, the main modifications to this valved stent, compared with the Melody and SAPIEN valves, are an hourglass geometry (i.e. larger diameters at the proximal and distal end; smaller diameters in the central portion holding the valve) and the use of a self-expanding nitinol stent with a polymeric graft, which should help the stability of the device in various RVOT anatomies ( Fig. 1 ).
An Investigational Device Exemption trial of the Native Outflow Tract device has been enrolling subjects since April 2013 (clinicaltrials.gov identifier: NCT01762124 ; 10 patients enrolled so far). Given the limitations in the animal model regarding confirmation of device boundary conditions, this feasibility study aims to characterize that information as well as to evaluate safety, procedural feasibility and performance data, which will be used in the future development of the device. This innovative device may be the future of PPVI. However, regarding the wide anatomical variability of the RVOT and the frequently associated pulmonary artery disease encountered in this patient population, alternative techniques allowing valve replacement are still being explored by investigators . Another device (Venous P Valve; Medtech, Shenzhen, China) is presently under investigation; 18 patients have been implanted in China, India and Thailand, but no data have been published so far. A European study should start before the end of 2015.
Finally, one major innovation in PPVI may be the development of repositionable valved stents and low-profile devices. The Lotus Valve System ® (Boston Scientific Corporation, Natick, MA, USA), a bovine pericardial valve attached to a braided nitinol stent used for transcatheter aortic valve replacement, features this specific function. The braided nitinol frame has a locking system that allows controlled precise deployment, recapture and subsequent repositioning or removal, as necessary .
RVOT reducers
Patients who underwent surgical repair of tetralogy of Fallot during infancy using a transannular patch can have large pulmonary trunks that often exceed 30 mm in diameter, making PPVI technically unfeasible with the current valves. To extend the indications of PPVI, the use of percutaneously implanted RVOT size reducers has been described. Boudjemline et al. designed and developed several versions of a preshaped self-expandable stent, forming a covered double cylinder, with the internal diameter calibrated to authorize implantation of available valved stents. The device is available with various external diameters (30–40 mm ; Fig. 2 ). This device was implanted in sheep ( n = 30) that had previously had surgical RVOT enlargement. During the same procedure, a valved stent (bovine jugular vein) was subsequently deployed in the central part of the filler. The main complications were device embolization ( n = 1) and paraprosthetic leaks (6/24 animals; 25%). The leak was related to undersizing of the device. Indeed, 5/6 leaks (83%) occurred in animals where the size of the device was less than 5 mm larger than the pulmonary artery diameter ( P < 0.05), which confirms that oversizing the device is mandatory for stent anchoring and ultimately for definitive fixation to the vascular wall .
