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

Objectives: The first tissue engineered decellularized porcine heart valve, Synergraft(TM) (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(TM) 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(TM) 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(TM) valves 6 weeks and 1 year after implantation. The third child died on the 7th day due to Synergraft(TM) 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(TM) revealed incomplete decellularization and calcitic deposits. No cell repopulation of the porcine matrix occurred. Conclusion: The xenogenic collagen matrix of the Synergraft(TM) 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. Calcitic deposits before implantation and incomplete decellularization may indicate manufacturing problems. The porcine Synergraft(TM) treated heart valves should not be implanted at this stage and has been stopped. (C) 2003 Elsevier Science B.V. All rights reserved.