A Novel Regenerative Autologous Heart Valve for Adults and Children: From Bench to Bedside: An Interim Report

Background: Valvular heart diseases represent a major global cause of morbidity and mortality. If left untreated, pediatric and adult patients alike, face serious risks of progressive heart failure and death. Until now, there is no ideal prosthesis available that has the capacity to self-repair, grow, adjust to functional and somatic changes, be implanted minimally invasive, is not immunogenic, does not necessitate anticoagulants, and provide a lifelong solution. Furthermore, many patients with a repaired RVOT are left with residual symptoms including pulmonary regurgitation and stenosis. The research group GrOwnValve of the German Heart Center Berlin/Charité Berlin is currently developing a novel procedure to manufacture an autologous TPVR, which should overcome these limitations and offer the first solution for pediatric and an improved solution for adult patients.

Method: A first proof-of-concept in vivo study demonstrated the feasibility and safety. Therefore, a pulmonary heart valve was shaped from autologous tissue and implanted for up to 21 months in 15 sheep. Intracardiac echocardiography and angiography were performed to assess the position, morphology, function, and dimensions, showing good results regarding, paravalvular leakage, insufficiency, and migration. Subsequently, the procedure, consisting of a preparation- and intervention phase, was optimized. For the preparation phase, a CT-based model has been developed utilizing a 4D straightened segmentation approach to identify the prosthesis' landing zone and prevent a prosthesis-patient mismatch. For the intervention phase, the treatment procedure was optimized by characterizing the cross-linking degree, mechanical behavior, and cyto-compatibility. Therefore, the treatment could be adjusted for an intra-operative procedure. Furthermore, the heart valve's geometry was iterated and tested hydrodynamically in a pulse duplicator, showing improved results regarding the valve closing behavior.

Conclusion: The newly developed method showed great functionality. The iteratively adapted procedure will now be investigated in a further preclinical in vivo study. Afterward, the first-in-human study is planned, which is designed as a prospective, nonrandomized, single-center trial in seven adult study subjects. In the future, the procedure can also be utilized for manufacturing autologous aortic heart valves.

Publication History

Article published online:
28 January 2023