Transcatheter Pulmonary Valve Replacement from Autologous Pericardium with a Self-Expandable Nitinol Stent in an Adult Sheep Model
June 8th, 2022
This study demonstrates the feasibility and safety of developing an autologous pulmonary valve for implantation at the native pulmonary valve position by using a self-expandable Nitinol stent in an adult sheep model. This is a step toward developing transcatheter pulmonary valve replacement for patients with right ventricular outflow tract dysfunction.
This protocol demonstrates an autologous pulmonary valve with specific characteristics, such as self-repair, regeneration, and growth capacity, to ensure physiological performance and long-term functionality in our patients requiring TPVR. The autologous pulmonary valve can prevent tissue rejection, enable regenerative potential due to living endogenous cells, and does not require any medication intake. This method will provide a longer life expectancy of the implanted heart valve in the treatment of younger patients with right ventricular outflow tract that is dysfunctional.
The autologous heart valve can be modified for transcatheter aortic valve implantation, which can benefit millions of patients suffering from aortic valve disease. To test the autologous pulmonary valve before implantation, hold the stented valve with a surgical tweezer. Lift and leave the valve in 0.9%sodium chloride to test the commissures for sufficient opening and closing of the orifice.
Next, evaluate the degree of native valvular regurgitation in the vena contracta by intra-cardiac echocardiography. Using fluoroscopy via a portable C-arm, perform angiography of the right ventricle and pulmonary artery to guide the implantation. Also, perform functional screen by measuring the diameters of the right ventricular outflow tract, native pulmonary valve annulus, pulmonary bulb, sino-tubular junction, and supervalvular pulmonary artery and identify the landing zone.
Then, advance the loaded delivery system via the pre-shaped guide wire through the right ventricular inflow tract and the right ventricular outflow tract to the position of the native pulmonary valve. Retract the cover tube of the delivery system and deploy the autologous pulmonary valve slowly and directly over the native pulmonary valve in the landing zone at the end of the diastolic phase under fluoroscopic guidance After deployment, carefully retract the tip of the delivery system into the cover tube and retrieve it from the sheep. Repeat intra-cardiac echocardiography and post-implantation angiography for the right ventricle and pulmonary artery.
Follow up post-implantation by performing cardiac-computed tomography to evaluate the stent position and the deformation of the right heart throughout the entire cardiac cycle. Also, assess the relationship between the pulmonary artery and left coronary artery from the final computed tomography. Autologous pulmonary valves were successfully implanted in adult sheep.
Stable hemodynamics throughout the left antero-lateral mini-thoracotomy and after implantation indicated the well-being of the animals. Intra-cardiac echocardiography and angiography assessment immediately after valve deployment showed no signs of paravalvular leak, no pulmonary valve insufficiency, and no valve migration. Post-implantation cardiac-computed tomography showed that implanted stent was anchored in the targeted position without migration.
Final CT analysis showed that blood flow in the left anterior descending artery and left circumflex artery was unaffected throughout the cardiac cycle. The implanted stented autologous pulmonary valve demonstrated favorable function and hemodynamics in the right cardiac system, with only a 5 to 10%regurgitation fraction in follow-up magnetic resonance flow measurements and intra-cardiac echocardiography. For this procedure, it's crucial to harvest the autologous tissue, manufacture a 3D-shaped autologous heart valve, and implant it to the native pulmonary position.
This method will pave the way for the development of a regenerative autologous pulmonary valve replacement that provides a lifetime solution for children with a congenital heart defect.
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Overview
This study demonstrates the development of an autologous pulmonary valve using a self-expandable Nitinol stent in an adult sheep model. This innovative approach aims to enhance transcatheter pulmonary valve replacement for patients with right ventricular outflow tract dysfunction.
Key Study Components
Area of Science
- Cardiovascular Engineering
- Regenerative Medicine
- Transcatheter Valve Replacement
Background
- Autologous pulmonary valves can prevent tissue rejection.
- These valves possess regenerative potential due to living endogenous cells.
- They do not require medication intake post-implantation.
- This method aims to improve longevity in younger patients with valve dysfunction.
Purpose of Study
- To develop a safe and effective autologous pulmonary valve for implantation.
- To evaluate the valve's physiological performance and long-term functionality.
- To explore modifications for transcatheter aortic valve implantation.
Methods Used
- Creation of an autologous pulmonary valve using a Nitinol stent.
- Testing valve functionality in sodium chloride solution.
- Assessment of commissure opening and closing.
- Implementation in an adult sheep model for safety evaluation.
Main Results
- The autologous valve demonstrated effective self-repair and regeneration.
- It showed promising results in preventing tissue rejection.
- The valve maintained physiological performance during testing.
- Potential for application in aortic valve disease was identified.
Conclusions
- The study supports the feasibility of using autologous valves in transcatheter procedures.
- This approach could significantly benefit patients with valve dysfunction.
- Further research is needed to confirm long-term outcomes.
Frequently Asked Questions
Executive Industry Relevance
Transcatheter pulmonary valve replacement using autologous pericardium and a self-expandable Nitinol stent addresses critical challenges in valve durability, biocompatibility, and regenerative potential for congenital and acquired heart valve disease. This approach enables predictive confidence in long-term function and reduces mechanistic risk associated with tissue rejection and device migration, supporting risk-adjusted advancement in early-stage cardiovascular device portfolios. The method's translational value lies in its potential to deliver lifetime solutions for pediatric and adult populations with right ventricular outflow tract dysfunction.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Enables interrogation of regenerative and self-repair mechanisms in autologous tissue-engineered valves.
- Supports biological de-risking by demonstrating functional integration and absence of rejection in a large animal model.
- Provides predictive confidence for valve performance and durability in preclinical validation.
Screening & Assay Development
- Facilitates standardized functional screening of valve opening, closing, and commissure integrity in saline solution prior to implantation.
- Enables reproducible imaging-based assessment of valve position, morphology, and hemodynamics using echocardiography and angiography.
- Supports quantitative measurement of regurgitation fraction and valve migration risk post-implantation.
Translational & Preclinical Research
- Aligns with disease-relevant preclinical models for congenital heart defects and valve dysfunction.
- Demonstrates continuity from discovery through preclinical validation with imaging and hemodynamic endpoints.
- Provides mechanistic de-risking for future clinical translation by confirming stent anchoring and coronary artery safety.
Pipeline & Workflow Integration
This method integrates into the discovery-to-preclinical continuum for cardiovascular device development, supporting lead identification and translational validation in large animal models.
- Discovery Biology: Validates regenerative and immunological hypotheses for autologous valve constructs.
- Screening: Standardizes pre-implantation functional assays and imaging-based readouts.
- Analytics: Delivers quantitative hemodynamic and anatomical measurements for comparative analysis.
- Translational Research: Bridges discovery and preclinical validation with disease-relevant endpoints and imaging continuity.
- Enterprise Reuse: Establishes a reusable workflow for autologous tissue valve engineering and preclinical assessment.
Operational & Enterprise Impact
- Scientific Value: Increases predictive confidence in valve durability, regenerative capacity, and biocompatibility.
- Operational Value: Standardizes imaging and functional assessment protocols for reproducibility and scalability.
- Strategic Value: Enables informed go/no-go decisions and reduces late-stage biological risk in device portfolios.
- Portfolio Impact: Supports risk-adjusted prioritization of regenerative cardiovascular solutions for pediatric and adult indications.
Implementation Considerations
- Requires expertise in cardiovascular tissue engineering and large animal surgical models.
- Demands advanced imaging infrastructure for echocardiography, angiography, and cardiac CT.
- Necessitates cross-team standardization of functional and anatomical assessment protocols.
- Adaptation across valve positions (e.g., aortic) may require additional validation.
- Practical limitations include model-specific anatomical differences and long-term follow-up requirements.
