Young patients with severe aortic valve disease today are facing a real dilemma. Once the indication for aortic valve replacement (AVR) has been confirmed by their physician, one of the options they can choose is a mechanical valve replacement, which directly affects their quality of life as strict life-long blood anticoagulation is needed. These “blood thinners” have an inherent risk for severe bleeding episodes, which needs to be considered in both professional and leisure activities. Biological heart valve prostheses as another option unfortunately do degenerate much quicker in young patients. The Ross autograft procedure, as another option for aortic valve replacement in young patients, is a very complex surgical procedure which has the disadvantage of creating a “two-valve disease” as the patient`s pulmonary valve, which replaces the diseased aortic valve has to substituted by another heart valve prosthesis itself.
The lack of reasonable aortic valve prostheses for young patients has driven research in tissue engineering concepts. The basis for current tissue-engineering concepts is either artificial polymeric or biological scaffolds, which may derive from human tissue donation or animals. Total artificial tissue-engineered heart valve concepts would solve many unmet clinical demands such as permanent availability of different sizes and lengths. However, long-term animal models have not delivered satisfactory results so far due to the lack of mechanical stability of the total artificial matrices, leading to early failure of valvular function. Tissue-engineered biological scaffolds of porcine origin have failed dramatically in a number of paediatric patients, resulting in cautious scepticism regarding animal-derived matrices. In contrast, decellularised matrices based on non-cryopreserved human valves, which formed the basis for ARISE, have provided initial auspicious clinical results, which warranted further prospective clinical research.
The project’s objective was therefore to determine the feasibility, safety and efficacy of decellularised regenerative heart valves for aortic valve replacement. The ARISE consortium comprised six leading European centres for cardiac surgery (Hannover Medical School, Royal Brompton and Harefield National Health Service Trust, August Pi i Sunyer Biomedical Research Institute and the Hospital Clinic of Barcelona, Leiden University Medical Centre, Padua University and the Azienda Ospedaliera di Padova Clinical Center, University Hospitals Leuven) and the innovative small enterprise corlife oHG, that processed the valves. Project management for the study and support regarding ethical issues was organized by the Leibniz University Hannover.
Within the ARISE clinical trial a total of 144 patients were treated with decellularised aortic homograftes (DAH). The initial results of the prospective multi-centre ARISE trial proved DAH as safe for AVR with excellent hemodynamics in the short follow-up available. Early DAH results compared well with the early outcome of contemporary Ross-operation cohorts despite more than twice the amount of previous cardiac procedures in the DAH patients.
