Design and preclinical feasibility of a pediatric heart valve stent that spontaneously adapts to growth via a spring mechanism

Figures

• 

  Fig. 1.. Growth-adaptive LEAP Valve concept. (A) LEAP Valve prototype device used in animal studies, fully expanded configuration (14 mm in diameter, 15 mm in length), on a fingertip. (B) The device is designed to be implanted during open-heart surgery for PV replacement, positioned within the main PA. (C) Cross-sectional schematic demonstrates how the stent adapts its diameter (Ø) while the expandable valve maintains function with growth. The LEAP Valve is implanted in a compressed configuration in neonates or infants (top) and then expands up to twofold as the child grows (bottom). Renders and insets of stent elements illustrate the function of the spring mechanism. (D) Comparison of LEAP Valve to current PV replacement technologies for children with valve defects, emphasizing the age range of critical unmet need (birth to 4 years old; orange vertical dotted line). Commercial valves are designed for older patients, with discrete diameter sizes available at 18 mm and larger (9). Young patients typically receive a RV-PA conduit soon after birth, which fail within about 2 years (47, 48), leading to repeat surgeries before adulthood (49). Emerging technologies include balloon-expandable…

• 

  Fig. 2.. Growth-adaptive LEAP stent design and simulation. (A) Example stress-strain curves of two common stent materials: stainless steel and nitinol. Stainless steel balloon-expandable stents permanently and plastically deform when expanded. The nitinol LEAP stent passively expands over a large range of diameters by exploiting nitinol’s superelastic regime. (B) Render of the device showing key features of the stent. (1) Longitudinal struts provide stability and maintain a constant device length of 15 mm with changes in diameter (black arrow). (2) Small clocking features allow for detailed dimensional characterization for quality control (blue circle and inset; strut width: 400 μm). (3) Suture features along the struts provide anchoring points for valve attachment to the stent during device assembly (yellow circle and inset). (4) Springs provide the growth-adaptive function of the stent (red box), further detailed in (C) and (D). (C) Finite element simulation showing the concentration of strains in the spring bends when the stent diameter is compressed to 7 mm in diameter (red box). (D and E) Example strain plots for a single spring element and single spring bend show the maximum…

• 

  Fig. 3.. Manufacturing and radial force testing of growth-adaptive stents. (A) Growth-adaptive stent in the expanded state next to a dime for size comparison. (B) Close-up of spring features on manufactured stent, pretesting. (C) Stent radial force as a function of stent diameter was measured by a RX550/650 radial compressor as a stent was unloaded from the 7-mm-diameter compressed state to the ~14-mm-diameter expanded state. (D) Force-diameter unloading curves of the stents selected for use in animal studies (N = 10). Individual stents are shown in gray, and the mean unloading behavior is shown in black. (E) Same spring elements shown in (B), post–radial force testing. (F) Representative top view image of the stent used for diameter measurements. Scale bar, 2 mm. (G) Measurements of stent diameter pre– and post–radial force testing.

• 

  Fig. 4.. Device assembly and implantation strategy. (A) The valve is identified within the vein graft and demarcated by two sutures (black arrowheads). (B) The fully expanded stent is placed over the graft, and the valve is inflated with saline until flush against the inner surfaces of the stent. The valve is attached to the stent via suturing at the suture features along the stent struts. (C) Example of an integrated LEAP Valve device after all sutures have been placed. The excess graft tissue outside of the stented region is then trimmed (dotted lines). (D) Valve function is checked by applying forward and back pressure on the valve to open and close the leaflets, respectively. (E) Immediately before implantation, valve competency is checked again. (F) Anchoring sutures are attached to the proximal end of the stent (red arrows). (G) The device is then crimped down to 7 mm in diameter with the radial compressor tool, and a restraining suture is placed around the middle of the stent. (H) Crimped device at 7 mm in diameter, ready for implantation. The restraining suture “tail” is indicated by yellow arrows in (G) and (H). (I) Surgical procedure for implantation: The chest is opened, and…

• 

  Fig. 5.. Acute LEAP Valve function and short-term growth studies. (A) Echocardiogram showing the LEAP Valve (yellow dotted outline) immediately after implantation. (B) Doppler flow image showing flow through the LEAP Valve immediately after implantation. (C) Explanted piglet heart with LEAP Valve after acute implantation, showing conformational device fit to the PA, constraint of the device to ~9 mm in diameter, and no acute thrombosis. (A to C) Data for piglet #3 in the acute cohort. (D) Graph of the PA diameter pre- and postimplant in the acute cohort measured by epicardial echo, indicating an average 9.8% increase in PA diameter upon implantation of the LEAP Valve, and the overall constraint of the device. Note that the device buckled upon implantation in piglet #2. (E) Echocardiogram image showing LEAP Valve leaflets (red arrow) at 2 weeks postimplantation. (F) Doppler flow image showing flow through the valve at 2 weeks. (G) The maximum pressure gradient was calculated using continuous wave Doppler through the implanted valve, according to the Bernoulli principle. Velocity, 1.22 m/s; pressure gradient, 6.0 mmHg in piglet #2 (2-week follow-up). (E to G) Piglet with 2-week follow-up.…

• 

  Fig. 6.. Explant of LEAP Valve at 2 weeks. (A) Cross section of the explanted heart viewed from the ventricular side. Inset shows section cuts. (B) View of the LEAP Valve from the RV side (top images) and PA side (bottom images), in open and closed states. (C) Partial removal of the PA around the LEAP Valve indicates good fitting of the device to the implantation site with no signs of tissue damage. (D) Partially extracted LEAP Valve. (E) Photo of the implantation site after removal of the LEAP Valve. Slight indentation from stent springs was observed (blue arrow). (F) Side and (G) top views of the explanted LEAP Valve. (H) View of valve leaflets and (I) adventitial side after removal of the stent. There were no obvious blood clots and no tearing/degradation of the leaflets. (A to C) Fresh. (D to I) After formalin fixation and hemosiderin staining.

• 

  Fig. 7.. Macroscopic views of LEAP Valve inflow and outflow at endpoint. (Top) Inflow of the LEAP Valve in the explanted heart for 2- to 6-week follow-up. (Bottom) Corresponding images of the outflow of the device for each time point.

• 

  Fig. 8.. Noninvasive, spontaneous growth-adaptation of the stent. (A) X-ray images of the explanted heart with LEAP Valve at 4 weeks postimplantation. A fully expanded stent is shown in the x-rays for comparison (red arrows). (B) X-ray of LEAP Valve in the explanted heart after 6 weeks implantation. X-ray images show the uniform expansion of the stent. (C) Growth of piglets pre- and postimplantation. All piglets in the growth cohort gained weight. (D) Measurements of the LEAP Valve stent diameter at implantation (by echo) and termination (at explant: macroscopic photos for 2 and 3 weeks; x-ray images for 4, 5, and 6 weeks) for piglets #2 to #6 ranging 2- to 6-week follow-up. Piglet #1 is not shown because it was euthanized same day. PA diameter measurements by echo in piglets, which did not receive implants, are shown for comparison (gray), derived from a previous study (36).