Evaluation of a Hybrid Surgical Approach for Transcatheter Mitral Valve Replacement in the Domestic Sheep Model

Background Novel cardiac valve prostheses require long-term studies assessing safety in animal models prior to clinical use. Although sheep are well-established preclinical models, the anatomy and morphology of the sheep heart impart unique challenges in the positioning and securement of transcatheter mitral valve replacement (TMVR) devices, resulting in early postoperative mortality. We developed a refined hybrid surgical approach to study the chronic in vivo performance of a novel TMVR device intended for regulatory approval. Methods Eleven adult sheep were enrolled in this study. Eight Abbott Next-Generation Cephea (Cephea) TMVR devices were implanted using a hybrid surgical approach, with the valve deployed and secured under direct visualization on cardiopulmonary bypass. For a control, three Medtronic Mosaic bioprostheses (Mosaic) were implanted with standard techniques. Sheep were survived for 20 weeks per regulatory guidance, followed by humane euthanasia and comprehensive necropsy. Results All sheep were successfully implanted and recovered from surgery, with 7/8 Cephea and 3/3 Mosaic animals surviving to the 20-week study endpoint. A surgical complication unrelated to TMVR performance resulted in one early death at 58 days post-operatively. At term, all Cephea valves performed comparably to controls, appearing well-healed within the annulus with competent, unobstructed leaflets. Conclusions Our novel hybrid surgical approach allowed for a comprehensive evaluation of the long-term performance of the Cephea, with 100% survival at 30 days and 88% at the 20-week endpoint. These results suggest that this approach may improve chronic survival in animal studies evaluating the safety of novel TMVR devices prior to clinical investigation.