Early failure of the tissue engineered porcine heart valve SYNERGRAFT® in pediatric patients

Objectives: The first tissue engineered decellularized porcine heart valve, Synergraft® (Cryolife Inc., USA) was introduced in Europe as an alternative to conventional biological valves. This is the first report of the rapid failure of these new grafts in a small series. Materials and methods: In 2001, 2 model 500 and 2 model 700 Synergraft® valves were implanted in four male children (age 2.5–11 years) in the right ventricular outflow tract as a root. Two patients had a Ross operation and two had a homograft replacement. Results: The cryopreserved Synergraft® valves appeared macroscopically unremarkable at implantation. Recovery from surgery was uneventful and good valve function was demonstrated postoperatively. Three children died, two suddenly with severely degenerated Synergraft® valves 6 weeks and 1 year after implantation. The third child died on the 7th day due to Synergraft® rupture. Subsequently the fourth graft was explanted prophylactically 2 days after implantation. Macroscopically all four grafts showed severe inflammation starting on the outside (day 2 explant) leading to structural failure (day 7 explant) and severe degeneration of the leaflets and wall (6 weeks and 1 year explant). Histology demonstrated severe foreign body type reaction dominated by neutrophil granulocytes and macrophages in the early explants and a lymphocytic reaction at 1 year. In addition significant calcific deposits were demonstrated at all stages. Surprisingly pre-implant samples of the Synergraft® revealed incomplete decellularization and calcific deposits. No cell repopulation of the porcine matrix occurred. Conclusion: The xenogenic collagen matrix of the Synergraft® valve elicits a strong inflammatory response in humans which is non-specific early on and is followed by a lymphocyte response. Structural failure or rapid degeneration of the graft occurred within 1 year. Calcific deposits before implantation and incomplete decellularization may indicate manufacturing problems. The porcine Synergraft® treated heart valves should not be implanted at this stage and has been stopped.