生物全降解器械——治疗结构性和先天性心脏病的关键发展阶段？

Over the past decades, transcatheter therapy has become the primary option for the treatment of simple congenital heart diseases with the advantages of minimal invasiveness and rapid recovery. However, currently used metal occluders may cause nickel allergies, inflammation, and erosion. In the treatment of ventricular septal defects (VSD), due to the close proximity of the electrical conduction tissue, implantation of conventional occluders may cause conduction abnormalities. Complete atrioventricular block can occur in up to 2% of patients undergoing percutaneous perimembranous VSD closure with conventional devices [1]. The timing of this event varies, ranging from immediate/intraprocedural to years after the procedure. Most commonly, it is observed within the first five days [1], however, late-onset atrioventricular block is fairly common. For this reason, no perimembranous VSD closure device has been approved by the US Food and Drug Administration [2]. The complicated anatomical structure of VSDs and its anatomical relationship to the atrioventricular node complicates device design and development. In this context, bioresorbable occluders have potential advantages. It is conceivable that, due to implant degradation over time and native cardiac tissue coverage, surrounding tissue compression and persistent arrhythmias are less prevalent.

Taking the aforementioned limitations of conventional devices into consideration, Wang et al. [3] reported on the efficacy and safety of a new fully bioabsorbable device for the treatment of perimembranous ventricular septal defects. One-hundred-and-eight patients were enrolled in this non-inferiority, multicenter, randomized trial. Patients received either a fully bioabsorbable device (intervention arm) or a conventional nitinol-based device (control arm). All devices were implanted successfully. The incidence of postprocedural (sustained) arrhythmia was numerically lower in the intervention group. The degradation process was semi-quantitatively assessed by transthoracic echocardiography and judged to be completed at 24-month follow-up. No residual shunt >2 mm was observed. The authors also demonstrated that the degradation rate of the occluder was faster on the left ventricular side which has not been reported previously.

The authors should be congratulated for their pioneering work in this field. Innovative biomedical engineering was translated into clinical practice and led to the development of specific material characteristics for the framework, fabric, and design of this new device which appears to overcome a key limitation of previous, bioresorbable occluders: mismatch between device degradation and incomplete endothelialization and consequent defect recanalization. This novel device, as compared with other bioresorbable and conventional occluders, contains two distinct bioresorbable frameworks, one with a fast and one with a slow degradation rate: polydioxanone (PDO) filaments offer enough stability to allow complete endothelialization before it starts to degrade at an early stage (i.e., after 3 months), and the covering poly-L-lactic acid fabric which has a lower degradation rate thereby prevents VSD recanalization at a later stage. As compared with a metal framework, the PDO framework is less elastic and occluder shaping is supported by a shape line on the left disc of the device. However, the PDO filaments have good echocardiographic visibility and allow device implantation under complete echocardiographic guidance. A zero-fluoroscopy approach is especially appealing in young children included in this study population (mean age 4 years), to minimize lifetime X-ray exposure. Especially in the young, lifetime management is important. Fully bioresorbable devices may have the ability to change our management and improve the quality of care. With the here presented technology, serious complications including device erosion, perforation, thrombus formation, or infection might be prevented. Furthermore, with the rising number of transcatheter-based left-sided heart interventions requiring transseptal access, the development of similar fully bioabsorbable occluders for the closure of patent foramen ovale and atrial septal defects potentially allowing uncomplicated repeat transseptal access is an unmet, yet important need, starting to be addressed [4]. There are potential risks related to any fully resorbable technology. First, it will be difficult to impossible to localize and retrieve a device in the untoward event of embolization because it is not radio-opaque. Hence, the embolization of such a device may have more serious consequences than the embolization of conventional devices. Second, the resilience of new tissue formed in the process of device resorption may not be adequate in the long term, especially in the presence of large pressure differences between chambers (i.e., between the ventricles). Third, it is conceivable that ‘‘neo-tissue” will not grow and continue to seal the defect in a growing individual. Fourth, though ultimately replaced by new tissue, it may not prevent potential initial compression, trauma, or inflammation of the conduction tissue. In this context, the absence of complete atrioventricular block with the here-described device is intriguing and encouraging.

In summary, the results reported by Wang et al. [3] provide favorable evidence regarding the future use of bioresorbable devices for VSD closure. The study portrayed detailed characteristics of polymer degradation rate, providing valuable experience for subsequent device development. Furthermore, the promising results offer further valuable points in the discussion regarding the safety of biodegradable devices such as residual shunt, device displacement, or inadequate support. Further developments regarding this device may include strengthening of the PDO framework to exclude the shape-line, omission of additional steps for occluder shaping to reduce procedure time and conduction of a trial with a less invasive access route. Importantly, longer follow-up is needed to assess for long-term complications and durability of closure.