The overall goal of this Phase I STTR project is to develop a biomimetic size-adjustable prosthetic heart valve (Autus Size-Adaptable Valve) that can be expanded post-implantation to accommodate changes in blood flow due to somatic growth or cardiac remodelling, to prevent the complications of valve prosthesis-patient mismatch (PPM). By design, all existing surgical prosthetic valves have a fixed functional diameter, leaving tens of thousands of patients at risk of developing valve PPM due to changes in body size, or heart remodeling. Growing children who undergo valve replacement develop PPM and currently need repeated invasive open-heart operations to replace outgrown valves. In adults, over 50% of patients who undergo surgical aortic valve replacement develop PPM, leading to higher risk of mortality. The Autus Size- Adaptable Valve is intended for surgical pulmonary or aortic valve replacement and can be expanded post- implantation, via minimally invasive transcatheter balloon dilation. Autus Valve Technologies, Inc. developed the Autus Size-Adaptable Valve as a biomimetic bileaflet prosthetic heart valve that is size-adjustable to prevent PPM. The design mimics the dynamic structure- function relationship of the human venous valve to provide a size-adaptable valve replacement that maintains optimal function across a wide range of dimensions. Benchtop durability testing, computational modeling, acute in vivo studies, and 20-week survival studies in growing lambs validated functional performance and structural integrity of the biomimetic design. The next technical challenge is to optimize the frame geometry and select materials that will minimize the risk of stent failure in preparation for clinical testing in children. The objective of Phase I is to confirm feasibility by completing two design objectives: 1) Optimize the frame geometry to minimize risk of failure at each stage of device expansion and in response to external compression, and 2) Identify the optimal frame material to proceed with design verification testing and a first-in- human clinical study. Therefore, Aim 1 is to optimize the design of the expandable bileaflet valve frame using finite element computational modelling. The frame geometry will be optimized to minimize von Mises stress and plastic strain in the frame at all stages of device expansion. Aim 2 is to perform a failure and fatigue analysis of the optimized expandable bileaflet valve frame and evaluate the mechanical response to expansion and compression to develop a finalized prototype for in vitro validation studies. Safety factors for frame failure and fatigue will be established and the optimal frame material will be identified. The final deliverables will be an advanced prototype that has: 1) an optimized frame design to minimize the risk of failure with expansion and under external compression; 2) established safety factors for frame failure and fatigue at all stages of device expansion; and 3) a frame material suitable for first-in-human clinical use.
Public Health Relevance Statement: NARRATIVE This project will develop the Autus Size-Adaptable Valve, a biomimetic size-adjustable prosthetic heart valve that can be expanded after implantation to increase blood flow as recipients grow or undergo other changes in heart function. The Autus Valve will eliminate the need for additional invasive surgeries to replace valves that are outgrown or no longer match to current heart function. This technological breakthrough will avoid multiple invasive surgeries, reduce healthcare costs and lifetime risk of morbidity and mortality, and improve patient quality of life. Terms: Adult; 21+ years old; Adult Human; adulthood; Affect; Anatomy; Anatomic; Anatomic Sites; Anatomic structures; Anatomical Sciences; aortic valve replacement; Balloon Dilatation; Balloon Catheterization; Balloon Dilation; Balloon Tamponade; Bioprosthesis device; Bioprosthesis; Bioprosthetic; Body Size; Boston; Child; 0-11 years old; Child Youth; Children (0-21); youngster; Clinical Research; Clinical Study; Clinical Trials; Elements; Environment; Fatigue; Lack of Energy; Feasibility Studies; Future; Goals; Growth; Generalized Growth; Tissue Growth; ontogeny; Heart; Congenital Heart Defects; Congenital Cardiac Defects; congenital cardiac anomalies; Cardiac Surgery procedures; Cardiac Surgery; Cardiac Surgical Procedures; Heart Surgical Procedures; heart surgery; Heart Valve Prosthesis; Cardiac Valve Prothesis; artificial heart valves; artificial valves; prosthetic heart valve; Heart Valves; Cardiac Valves; Pediatric Hospitals; Children's Hospital; Human; Modern Man; implantable device; biomedical implant; implant device; indwelling device; In Vitro; Morbidity - disease rate; Morbidity; mortality; Patients; Pulmonary artery structure; Pulmonary Artery; Pulmonary valve structure; Pulmonary Valve; Pulmonic Valve; Quality of life; QOL; Risk; Safety; Sheep; Ovine; Ovis; Stents; Sternum; Stress; Structure-Activity Relationship; chemical structure function; structure function relationship; Technology; Testing; Generations; Health Care Costs; Health Costs; Healthcare Costs; congenital heart disorder; congenital cardiac abnormality; congenital cardiac disease; congenital cardiac disorder; congenital cardiac malformation; congenital heart abnormality; congenital heart anomaly; congenital heart disease; congenital heart malformation; Prosthesis; Prosthetic device; Prosthetics; improved; Acute; Clinical; Phase; Physiological; Physiologic; Right ventricular structure; Right Ventricles; Failure; heart function; cardiac function; function of the heart; Blood flow; young adult; adult youth; young adulthood; Venous; mechanical; Mechanics; Investigation; Dimensions; System; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; Performance; kinematic model; kinematics; Structure; novel; validation studies; semilunar valve; Devices; Position; Positioning Attribute; response; Biological Mimetics; Biomimetics; preventing; prevent; Diameter; Caliber; valve replacement; Address; Animal Testing; in vivo; research clinical testing; Clinical Evaluation; Clinical Testing; clinical test; lifetime risk; life-time risk; Small Business Technology Transfer Research; STTR; Preparation; Ventricular; Cardiac; pre-clinical; preclinical; design; designing; implantation; prototype; commercialization; high risk; minimally invasive; product development; risk minimization; operation; Geometry; mechanical properties; experimental study; experiment; experimental research; in vivo evaluation; in vivo testing; first-in-human; first in man; mortality risk; death risk; Computer Models; Computerized Models; computational modeling; computational models; computer based models; computerized modeling
