Polymeric Heart Valves

Cardiovascular diseases represent the leading cause of morbidity and mortality worldwide, whereas over 80% of cardiovascular deaths occur in low- and middle-income countries (LMICs).¹ In LMICs, over 30 million people live with rheumatic heart disease (RHD), a condition of poverty with considerable surgical needs as valves deteriorate.² However, 6 billion people, including over 90% of people in LMICs, lack access to safe, timely, and affordable cardiac surgical care when needed.³ Numerous challenges underlie the global gaps in care but notably include scarce surgical workforce and supply challenges, the latter of which are predominantly driven by expensive consumables such as prosthetic heart valves.⁴ Meaningfully addressing the disparities in cardiac surgical care facing the world’s poorest populations will require innovations in the available therapies.

Rheumatic heart disease and valvular surgery

In high-income countries, RHD has been nearly eradicated due to improvements in primary care and antibiotic management in the late 20th century. In LMICs, streptococcal pharyngitis often remains undetected or untreated, frequently resulting in progression to RHD in children and adolescents. This is particularly worrisome in poorer populations that are at higher risk for primary infection when living in crowded environments and are less likely to be able to access primary care, afford antibiotics, or get a diagnosis of pharyngitis, acute rheumatic fever, or RHD. Ultimately, RHD results in the gradual deterioration of heart valves, most commonly affecting the mitral and aortic valves, which may eventually result in heart failure. Valve repair is preferred over replacement due to its superior long-term survival and freedom from reoperation while avoiding the economic cost of the valve prosthesis. However, in LMICs, patients often present at a stage where repair is no longer feasible or recommended.⁵ Valve replacement with bioprosthetic or mechanical valves is effective but carries the disadvantages of structural valve deterioration and lifelong anticoagulation, respectively, further placing financial burdens on lower-income populations who often lack health insurance.

Polymeric heart valves: history and recent developments

Existing valve prostheses have a long and successful history in managing severe and symptomatic valvular disease; however, they remain imperfect due to the limited durability of bioprosthetic valves and the need for anticoagulation in mechanical valves.⁶ In the context of limited health budgets in single-payer health systems and LMICs, as well as growing medical debt in the United States, affordability and scalability are further important. As such, durability, biocompatibility, and accessibility must be safeguarded in developing novel heart valves. The essence of polymeric heart valves is to address the limitations of existing valves. The first polymeric valve, made from polyurethane, was introduced in the 1950s and studied in the 1960s. However, it failed to provide durability, abandoning its exploration in favor of bioprosthetic and mechanical valves.⁷ In recent years, however, other polymers, in isolation or as copolymers, have improved prospects. Polymeric valves use resistant polymer materials; for example, polytetrafluoroethylene demonstrates a durability of more than 25 years and favorable biocompatibility.⁷ Compared to conventional valves, polymeric valves undergo less immune-mediated deterioration, do not require long-term anticoagulation, and combine the durability of mechanical valves with the hemodynamic profile of biological valves. Moreover, the robotic manufacturing of polymeric valves enables greater control of the leaflet thickness and valvular geometry and manufacturing can be more readily upscaled through developments in electrospinning and 3D printing. Only recently entering first-in-human trials, the clinical performance of polymeric valves remains to be seen. Initial concerns included the risk of polymer degradation and embolism from mechanical stress and material oxidation, as well as accommodating valve delivery through a transcatheter approach. Table 1 summarizes existing polymeric heart valves.

Table 1.

Overview of Polymeric Heart Valves

Valve	Company	Type	Leaflet Material	Country	Stage/Adoption
Foldax TRIA	Foldax Inc	TAVR-SE SAVR SMVR	Siloxane polyurethane-urea (LifePolymer)	United States India	Clinical trial
Hastalex	NanoRegMed Inc	SAVR	Functionalized graphene oxide and poly(carbonate-urea) urethane	United Kingdom	In vivo testing
Inflow	I4HV Inc	TAVR-BE	Copolymers of polyurethane-co-carbonate and polycarbonate-co-silicone	Poland	In vivo testing
Innovia	Innovia LLC	SAVR	xSIBS	United States	In vitro testing
MASA	PECA Labs	SPVR	Expanded polytetrafluoroethylene	United States	Clinical trial
PoliaValve	HeartHill Medical	SAVR	-	China	Clinical trial
PoliValve	Universities of Cambridge and Bristol	SAVR	Styrene triblock copolymers copolymers	United Kingdom	In vivo testing
Polynova	PolyNova Cardiovascular Inc	SAVR	xSIBS	United States	In vitro testing
SAT	Strait Access Technologies Inc	TAVR-BE	Triblock polyurethane combining siloxane and carbonate segments	South African	In vitro testing
SIKELIA	MitrAssist Lifesciences Ltd	TAVR-SE	BioDurapolymer composites	China	Clinical trial
TaurusApex	Peijia Medical	TAVR	-	China	In vivo testing
Triskele	University College London Cardiovascular Engineering Laboratory	TAVR-SE	Urethane-polyhedral oligomeric silsesquioxanes polymer	United Kingdom	Clinical trial pending

BE = balloon-expandable; SAVR = surgical aortic valve replacement; SE = self-expandable; SMVR = surgical mitral valve replacement; SPVR = surgical pulmonary valve replacement; TAVR = transcatheter aortic valve replacement; xSIBS = cross-linked styrene-block-isobutylene-block-styrene polymer.

Although clinical trials represent the gold standard of evidence in medicine, there are only a few ongoing trials for polymeric heart valves. The TRIA valve by Foldax, made of siloxane polyurethane-urea, is being evaluated as part of 2 early first-in-human feasibility studies for aortic and mitral diseases (NCT03851068 and NCT04717570), enrolling up to 40 and 15 patients, respectively, with follow-up of up to 5 years after surgery. Recently, Foldax entered an agreement with India-based Dolphin Life Science to manufacture the polymer valve outside the United States and facilitate the trials in India.⁸ In China, Suzhou HeartHill Medical will evaluate the safety and efficacy of their styrene triblock copolymer-based PoliaValve to manage severe aortic valvulopathy in 10 patients followed up for up to 5 years (NCT06518681). After the first-in-human polymeric valve for right ventricular outflow tract reconstruction at the Children’s Hospital of Philadelphia, the MASA Valve Early Feasibility Clinical Study will enroll 10 to 15 patients for up to 5 years of follow-up postimplant. While the Triskele self-expandable transcatheter aortic valve replacement was initially projected to start enrollment for a first-in-human trial in 2023, the recent 1-year results of the SIKELIA self-expandable transcatheter aortic valve replacement in 12 patients, presented at TCT2024, showed promising functional and safety performance.

Expanding access to heart valves to meet global RHD needs

The ideal valve ensures optimal hydrodynamics, biocompatibility, low thrombogenicity, affordability, and global accessibility.⁹ These targets can each be addressed through the iterative development of polymeric valves and will require a multipronged and collaborative approach.

Surgical supply chains and the cost of procurement of valves limit the availability and distribution of heart valves for the world’s population.¹⁰ Whereas industry is prominent across high-income countries with streamlined distribution centers and channels, they have few sites in LMICs, where procurement processes are less standardized, irregular, and often require purchasing from high-income country-based companies. Expanding local industry in LMICs, such as the production of the TRIA valve in India, may facilitate local procurement.

The cost of polymeric heart valves is still unknown in their early stages of development. Future costing will depend on the manufacturing processes, regulatory approvals, and health system pricing. Nevertheless, with the application of robotic manufacturing and exponential developments in 3D printing, costs may be considerably reduced compared to the production of conventional valve prostheses. Increasing manufacturing and associated economies of scale can further reduce costs if polymeric valves prove noninferior (and even more durable).

Beyond accessibility, evidence generation and contextual evaluation are critical to ensure patients receive the optimal intervention for their condition and context. This requires polymeric heart valves to be studied in larger and more specialized trials, particularly in LMIC contexts and, where appropriate, RHD. In addition, observational studies can further inform real-world practice across multiple countries and contexts, optimizing clinical knowledge translation and future guideline development.

Lastly, the production and optimization of polymeric heart valves will require multidisciplinary and multisectoral collaboration, including bioengineers, patients, and families. The complexities of polymer valves differ considerably from those of conventional valves and must be feasible to scale across regions. Moreover, patient-centered care requires a recognition of the needs and wishes of patients and families, with special attention to the realities of patients with RHD, who may stand to benefit disproportionately from developments in this space.

Conclusions

The growing burden of valvular disease, including the pressing and unmet need of RHD in LMICs, along with the notable drawbacks of existing prostheses, requires innovative approaches to providing more durable and accessible heart valves. Polymeric valves present an opportunity to complement the current arsenal of prostheses in the management of valvular disease and may help bridge gaps in meeting the needs of the tens of millions of people with RHD. Increased research and development in this domain will be essential to improving the availability of valves in underserved regions of the world and ensuring the optimal valve option for each patient in need.

Funding support and author disclosures

Drs Vervoort and Deng are supported by the Canadian Institutes of Health Research (CIHR) Vanier Canada Graduate Scholarship for work outside this manuscript. Dr Vervoort serves as an editorial consultant for JACC: Advances and serves on the Medical Advisory Council for the Global Alliance for Rheumatic and Congenital Hearts. Dr Kpodonu has reported that he has no relationships relevant to the contents of this paper to disclose.