Breakthrough One-Year functionality of Transvenously Implanted, Decellularized Tissue-Engineered Pulmonary Heart Valves (dTEHV) in a Sheep Model

Objectives: Many congenital heart defects and degenerative valve diseases require replacement of heart valves in children and young adults. Transcatheter xenografts degenerate over time. Tissue engineering might overcome this limitation by providing valves with ability for self-repair. In a European consortium, a transcatheter decellularized tissue-engineered heart valve (dTEHV) was developed. A first prototype showed progressive regurgitation after 6 months in vivo due to a suboptimal design. Here we present the second generation of dTEHV, re-designed by computer simulations.

Methods: dTEHV based on vascular-derived cells on a polymeric scaffold and a nitinol stent were transvenously implanted in 10 sheep. Prior and after implantation MRI, CT and intracardiac echocardiography (ICE) were performed. Functionality was assessed monthly by MRI and ICE. Study end-point was regurgitation >30%. Histology was performed on the explanted valves.

Results: Nine Animals reached the set follow-up time of 52 weeks. One animal had to be euthanized after 24 weeks due to regurgitation fraction exceeding 30% in MRI measurements.

Initial valve function was excellent. Pressure measurements showed no elevated pressure gradients over the dTEHV (7 mm Hg before implantation vs. 6 mm Hg after implantation). No elevated gradient was detected by ICE throughout follow up. 8 animals showed no and only 2 animals mild insufficiency in ICE.

Valve function was generally good during follow-up. Median regurgitation fraction by MRI was 9% after implantation and 14.2% after 52 weeks (range: 7.7–25.7%). At explantation one animal showed no, 6 mild and only 2 animals moderate insufficiency in ICE. No severe insufficiencies were detected.

Histological analysis showed complete engraftment of the dTEHV, endothelialization of the leaflets and the graft wall; very few scaffold remnants were visible. Leaflets consistent of collagenous tissue and some elastic fibers. Adaptive leaflet remodeling was visible in all animals. No fusion between leaflet and wall was found.

Conclusion: The improved design geometry resulted in very good valve function of the implanted dTEHV over a period of 52 weeks. Computer simulation helped in overcoming the failing mechanisms of the first generation of dTEHV. However, sufficient in-vivo functionality needs to be proven over an even longer period of time.