Home Is Where the Heart (Valve) Is

I pay close attention to heart valve replacement technology because my father underwent surgical aortic valve replacement in 2017. Researching this was different from my usual forays into medtech sectors for more information—I felt it my duty as a son to fully understand the technology, the risks it posed, and the life adjustments my father would need to make. The road to recovery was tough, but the Edwards Lifesciences surgical aortic valve has kept my father’s heart beating as strongly as ever for the past four years.

The artificial heart valve pioneer reached a number of milestones despite the pandemic’s global squeeze. Edwards did pause enrollments for its pivotal transcatheter mitral and tricuspid trials in March 2020 in response to the urgent COVID-19 response around the globe. However, favorable two-year results for the PARTNER 3 study were also released in March comparing Sapien 3 transcatheter valve treatment in low-risk patients to surgical treatment.

Edwards’ Pascal transcatheter valve won CE mark approval for tricuspid repair in May. A month later, the Sapien 3 valve earned Chinese approval. The Konect Resilia Aortic Valved Conduit grabbed FDA approval for complex aortic valve surgeries in July, and the firm began a trial for the investigational Harpoon Beating Heart Mitral Valve Repair System to treat severe degenerative mitral valve regurgitation in December. The Harpoon system requires only a small incision to repair the mitral valve.

The company’s most recent news arrived at the end of January’s 57th annual meeting of the Society of Thoracic Surgeons. There, Edwards presented new five-year data from the COMMENCE clinical trial evaluating its bioprosthetic surgical aortic valve with the company’s proprietary Resilia tissue platform. The Resilia platform showed favorable safety and hemodynamic performance through a median of five years follow-up.

“There continues to be a significant focus placed on tissue valve durability given the increase in life expectancy and lifestyle implications for more active patients who historically would receive mechanical valves,” Joseph E. Bavaria, M.D., lead enroller and site principal investigator for the COMMENCE study and the Brooke Roberts-William M. Measey professor of surgery and vice chief of the division of cardiovascular surgery, University of Pennsylvania, told the press.

Currently, however, researchers haven’t been able to develop a heart valve that can grow and maintain function for pediatric patients. The only options for children with heart defects are valves composed of chemically treated animal tissues, which often become dysfunctional thanks to calcification, and need replacement because they don’t grow with the child. These children might need to endure up to five (or more) open heart surgeries until a mechanical valve is placed in adulthood, requiring them to take blood thinners for the rest of their lives.

A new study led by University of Minnesota Twin Cities researchers aims to provide a solution. Researchers for the College of Science and Engineering and Medical School implanted lab-created hearts valves in young lambs for a year, and found the valves were capable of growth within the recipient. The valves also demonstrated reduced calcification and improved blood flow function compared to animal-derived valves used in the same growing lamb model.

If confirmed in humans, the new heart valves could prevent repeated valve replacement surgeries for children with congenital heart defects. The valves can also be stored for at least six months as potential “off the shelf” options for treatment. The valve-making procedure has already been patented and licensed by University of Minnesota startup Vascudyne Inc.

“This is a huge step forward in pediatric heart research,” said Robert Tranquillo, the senior researcher on the study and a University of Minnesota professor in the Departments of Biomedical Engineering and the Department of Chemical Engineering and Materials Science. “This is the first demonstration that a valve implanted into a large animal model, in our case a lamb, can grow with the animal into adulthood. We have a way to go yet, but this puts us much farther down the path to future clinical trials in children. We are excited and optimistic about the possibility of this actually becoming a reality in years to come.”

The study combined tissue engineering and regenerative medicine to create the novel heart valves. The specialized tissue engineering technique generated vessel-like tubes from a post-natal donor’s skin cells.
To develop the tubes, donor sheep skin cells were combined with fibrin in tubular form. The tubes were then provided nutrients for cell growth using a bioreactor. Special detergents were used to wash away the sheep cells from the tissue-like tubes, leaving behind a cell-free collagenous matrix that doesn’t stimulate immune reaction when implanted. Three tubes were precisely sewn together into a closed ring and trimmed to replicate a structure similar to about a 19-mm diameter valve.

At a year, the valve regenerated as its matrix became populated by the recipient lamb’s cells and the diameter increased from 19 mm to a physiologically normal valve about 25 mm. The next steps are to surgically implant the tri-tube valve into the heart’s right ventricle, then begin the process of requesting FDA approval for human clinical trials over the next few years.

“If we can get these valves approved someday for children, it would have such a big impact on the children who suffer from heart defects and their families who have to deal with the immense stress of multiple surgeries,” Tranquillo said. “We could potentially reduce the number of surgeries these children would have to endure from five to one. That’s the dream.”