TAVR’s “Third Wave” has arrived. Here’s what it means for medical device innovators and patients.
By Nicolas Borenstein, DVM, PhD | Co-President, Preclinical Contract Research Services, Veranex
Heart valve replacement has always been a story of tradeoffs.
Mechanical valves last a lifetime. But the metal demands lifelong anticoagulation, and with it a roughly one-in-ten chance of a serious bleeding or clotting event over a decade. Bioprosthetic valves, made from bovine pericardium or porcine leaflets, require no anticoagulants, only antiplatelets. But they degenerate; in as few as five years if the treatment of the tissue is poor and the patient is young. Fifteen to twenty if it's excellent. Not a comfortable proposition for a patient in their forties.
The ambition of cardiovascular device developers for decades has been a valve that is non-metallic, non-degenerative, and non-thrombogenic. Polymeric heart valves represent one of the most compelling attempts to get there.
Foldax’s latest preclinical results suggest a meaningful step toward that long-imagined goal.
"There is no single magic sauce. We have worked with many groups over many years, tested many approaches in accelerated animal models, and seen the full range, from leaflets that failed early to results like these. The difference is always in the specificity and rigor of the science. We know how to test it. We know how to tell the difference."
In npj Cardiovascular Health, one of the most respected journals in the cardiovascular field, Stanfield, Johnson, Belais et al. present the preclinical development and results of a transcatheter aortic valve implant using Foldax's next-generation LifePolymer™ (SiPUU) leaflets, specifically designed to enhance mechanical performance, hemocompatibility, and long-term durability. In vitro testing demonstrated effective orifice areas of 1.3–1.5 cm² and 1.7–2.1 cm² (for 21 and 24 mm annulus sizes, respectively, under simulated expansion conditions), a regurgitant fraction below 6%, and preserved coaptation. Critically, the leaflets showed no meaningful calcification. This result stands in sharp contrast to historical outcomes with early-generation polymer valves and to what we regularly observe with bioprosthetic materials in our own accelerated calcification models.
This is a preclinical result. The TRIATM TAVR has not yet been implanted in humans. But these are precisely the results that make a first-in-human trial a credible next step. That is no small thing in a space where so many polymeric valve programs have stalled before getting there.
Foldax has already crossed the clinical threshold with the mitral version of this technology. The TRIA surgical mitral valve has been implanted in a significant number of patients, including an active clinical study in India, with one-year data demonstrating durable hemodynamic performance.
TAVR itself has its own history worth a moment's pause. From the first implant in 2001, it grew slowly, reserved initially for patients too frail for open surgery, and has since become one of the fastest-growing procedures in cardiac surgery. Annual TAVR procedures in the United States now exceed all forms of surgical aortic valve replacement.¹ A second wave of refinement followed: smaller profiles, reduced rates of AV block and pacemaker dependence, expanding indications. What this publication gestures toward is something that could constitute a third wave entirely, addressing the durability problem that neither mechanical surgical valves (SAVR) nor bioprosthetic transcatheter valves (TAVR) valves have fully solved. Not just a valve you can deliver through a catheter, but one that may not need to be replaced.
¹ Bowdish ME, Badhwar V. The future direction of post-transcatheter aortic valve replacement re-interventions: insights from the Society of Thoracic Surgeons National Database. Ann Cardiothorac Surg. 2025;14(2):151–153. doi:10.21037/acs-2024-etavr-0136
TAVR presents a fundamental preclinical problem: the procedure depends on calcification. In humans, a stenotic aortic valve (hardened, calcified, narrowed) provides the anchoring structure that holds a TAVR device in place. Non-human animals’ anatomies, animals with sufficient anatomical equivalence required for many preclinical cardiology studies, don't calcify the same way as humans. Implant a TAVR in a healthy ovine model without preparation, and more often than not, it will not stay. It can embolize. Upstream, downstream, gone. Some TAVRs behave well in animals, but they are not common. [Image credit: Foldax]
Solving that problem requires building the anchor yourself.
Our team at Veranex Paris developed the landing zone by surgically implanting an annular ring at the aortic annulus under cardiopulmonary bypass, mimicking the calcified anatomy a TAVR device requires to seat correctly, without compromising the integrity of the native leaflet apparatus surrounding the annular ring. It is demanding open-heart surgery, performed on a surviving animal, followed by recovery, imaging, transcatheter valve deployment into the ring, long-term follow-up, and ultimately histopathological evaluation. Every phase of that process, from preoperative CT planning through final pathology, was executed here.
There are, at most, three to five preclinical labs in the world with the surgical capability, interventional expertise, and integrated pathology to do this end to end. For the complete model as described, probably fewer.
We are proud of our contribution to this work and grateful to Foldax and the publishers for the acknowledgment. We are prouder still of what the results represent: the first credible preclinical evidence that a transcatheter aortic valve with non-degenerative, non-calcifying polymeric leaflets can perform opening the door for the patient in their forties who today faces an impossible choice between a mechanical valve that demands lifelong anticoagulation and a bioprosthetic that may not outlast them.
Image of the first TAVR procedure at Veranex (then IMMR) with Alain Cribier (right), Nicolas Borenstein (left) and colleagues. This pioneering work paved the way for a revolution in endovascular structural heart disease treatment.
Congratulations. What you have built and proven, first in the mitral position in human patients, now in the aortic position in this preclinical publication, is genuinely exciting. The leaflets showed almost nothing growing on them. No meaningful calcification at the commissures. No structural degeneration of the kind that limits today's bioprosthetics. We are very hopeful. We cannot wait to see this technology come to fruition in a larger human cohort.
You have earned this publication. We were glad to be part of the work that made it possible.
If you are working on polymeric valve leaflet technology; on the chemistry and physical properties of the material itself, on hemocompatibility and resistance to calcification, on the coaptation geometry that determines whether flow through the valve is laminar or turbulent, on the structural engineering that keeps leaflets supple under millions of cycles of dynamic cardiac loading, there is room here. The unmet clinical need is real and it is large. Every approach that makes these leaflets more durable, more physiological, more laminar in their flow characteristics, is worth pursuing.
There is no single magic sauce. We have worked with many groups over many years, tested many approaches in accelerated animal models, and seen the full range, from leaflets that failed early to results like these. The difference is always in the specificity and rigor of the science. We know how to test it. We know how to tell the difference.
One of the most exciting frontiers in this work (and something our Paris team is actively developing) is 4D flow MRI validation of valve hemodynamics in large animal models. The ability to visualize and quantify blood flow through a valve in three dimensions, across the full cardiac cycle, without waiting months for histopathology, means we can tell you not just whether the device survived, but how it performs in a living, beating system. Whether the flow is laminar or turbulent. Whether the design is working the way the engineering predicted.
That capability is coming. And for the developers working on the next generation of synthetic or bioprosthetic valves, the ones asking whether their leaflet design, their material choice, their coaptation geometry is truly optimized, it will matter enormously.
The story of the polymeric heart valve is not finished. If anything, it is accelerating.
About the author: Nicolas Borenstein, DVM, PhD, is Co-President of Preclinical Contract Research Services at Veranex. He has led cardiovascular preclinical research at the Paris facility for more than 25 years and is a widely published author and peer-reviewed journal contributor in surgical and transcatheter preclinical science.
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