Tissue engineered heart valves for transcatheter aortic valve implantation: current state, challenges, and future developments

ABSTRACT

Introduction

The establishment of transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic stenosis. However, with TAVI being approved for low-risk patients, valve durability is becoming of central importance. Here, we summarize how tissue engineered heart valves (TEHVs) may provide a clinically-relevant durable valve replacement compatible with TAVI.

Areas covered

Since its introduction, TAVI prostheses have advanced in design and development. However, TAVI bioprostheses are based on fixed xenogeneic materials prone to progressive degeneration. Transcatheter TEHVs may have the potential to overcome the drawbacks of current TAVI bioprostheses, with their remodeling, self-repair, and growth capacities. So far, performance and remodeling of transcatheter TEHV with in-situ regenerative potential were demonstrated in the low-pressure system, with acute performance proved in the systemic circulation. However, several challenges remain to be solved to ensure a safe clinical translation of TEHVs for TAVI approaches.

Expert opinion

With TAVI rapidly evolving, the establishment of long-term valve durability represents the top priority to reduce the rate of patient re-interventions, remove the associated risks and adverse events, and improve patients’ life quality worldwide. With long-term performance and remodeling proved, TEHVs may represent the next-generation technology for a life-long TAVI prosthesis.

KEYWORDS:

• Aortic stenosis
• bioprostheses
• heart valve replacement
• remodeling
• tissue engineered heart valves

Article highlights

• TAVI technology has revolutionized the field of heart valve replacement and is currently being extended to low-risk patients.

• The presently available bioprostheses for TAVI are prone to progressive degeneration, with a particularly increased risk for re-operation or re–intervention in younger patients.

• TEHV may represent a promising alternative to overcome the problems of current bioprostheses by providing next-generation implants with self-repair, remodeling, and growth capacities.

• TEHVs have been successfully validated as surgical and transcatheter pulmonary replacements, and clinical pilot studies are ongoing.

• To date, the availability of TEHVs for TAVI is limited due to the particular challenges in the aortic high pressure circulation from a mechanical, design and anatomical viewpoint.

• Computational modeling may support the safe clinical translation of TEHV for TAVI by providing analytical valve designs, guiding valve remodeling, and by offering patient-tailored solutions.

• Developing countries have limited resources to implement current TAVI devices. Therefore, design of cost-effective TEHVs and delivery devices for TAVI could represent a potential option for low-income countries.

Supplementary material

Supplemental data for this article can be accessed here.

Acknowledgments

N.P. and E.S.F. were funded through the Swiss National Science Foundation (PZ00P3_180138) which is gratefully acknowledged. M.Y.E. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program, grant agreement no. 852814 (TAVI4Life).

Author contributions

N.P., P.Z., E.G., S.E.M., E.S.F, and M.Y.E. drafted and/or revised the manuscript for critical content. Administrative, technical, or supervisory tasks were handled by S.E.M., E.S.F., M.Y.E, and S.P.H. All authors provided critical input to the manuscript.

Declaration of interest

V.F. has disclosed relevant financial activities outside the submitted work with following commercial entities: Medtronic GmbH, Boston Scientific, and Edwards Lifesciences in relation to educational grants (including travel support) fees for lectures and speeches, fees for professional consultation and research and study funds. S.P.H. is a shareholder at Xeltis BV and LifeMatrix AG. M.Y.E. is a shareholder at LifeMatrix AG. The other authors do not have any other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.