A growth-accommodating valve for patients with Tetralogy of Fallot

Last summer, the Heart Center quietly launched a device-development project that has the potential to significantly advance the treatment of children with Tetralogy of Fallot (ToF).

sophie-hofferberthSophie-Charlotte Hofferberth, MBBS, a surgical resident at Brigham and Women’s Hospital and new member of the cardiac surgery research lab, is leading efforts to create an expandable valve for pediatric patients with ToF.

“We actually refer to the valve as ‘growth-accommodating,' because the device itself won’t grow, but instead will be size-adjustable to adapt to the child’s growth,” says Hofferberth.

When Hofferberth discusses all the obstacles facing the team — and there are many — she lists them off excitedly, as if describing foes soon to be vanquished rather than roadblocks.

Challenges include:

  • Size: “It’s important to consider the size of the heart structures in young infants,” says Hofferberth. “We need to design a valve that can function immediately, but also has the right size to avoid obstructing blood flow.”
  • Durability: Young children have a particularly strong immune response, which can lead to early breakdown of artificial heart valves. Thickening and calcification of leaflet material can also adversely impact valve function. 
  • Rapid growth: Young children are growing at an extremely rapid rate. “Creating a valve that can be implanted in infancy and remain functional throughout childhood is a unique and complex challenge,” says Hofferberth.

Driven by data

Recently, in primary repair of ToF, there has been a movement towards preserving the native pulmonary valve where possible, using a variety of surgical techniques. But new data show this strategy may not have the longevity doctors have hoped for. A significant number of patients need re-interventions while they are still in infancy, or they develop progressive pulmonary regurgitation over time. More research is needed to determine the exact implications. 

“We know these patients require surgery at three or four months of age,” says Hofferberth. “But a persistent problem is how to preserve the function of the pulmonary valve from the time of their first surgery. A leaky valve can have long-term implications for these patients; it can lead to a dilated right ventricle, arrhythmias, exercise intolerance, and many require a second open heart operation to replace the valve later in life.” 

Outlining the strategy

To understand the required expansion parameters, the team measured the pulmonary valve in ToF patients from the time of their initial surgery through adolescence. Says Hofferberth, “Based on these data, we estimate that the valve would need to at least double in diameter to successfully accommodate growth of the patient through to adolescence.”

Materials under consideration for the valve leaflet include emerging bio-absorbable polymers that can remodel over time to resemble the architecture of normal heart valve tissue. “We plan to test these materials under different conditions to evaluate their mechanical properties and behavior,” says Hofferberth.

After establishing the optimum design features of the valve, the team will proceed with large animal studies to prove they can expand the valve in vivo and maintain function.

Hofferberth says the concept of an expandable valve was inspired by recent work done by Peter Hammer, PhD, a mechanical bioengineer in the Department of Cardiac Surgery at Boston Children’s Hospital, who demonstrated that a two-leaflet valve, which mimics the geometry of a venous valve, has considerable growth-accommodating capacity. The group is also collaborating with labs in the greater Boston community.

“ToF is such a common problem — there is an urgent need to further advance the care of these patients,” says Hofferberth. “It’s one of the major unsolved problems in pediatric cardiac surgery. And, if we can prove this concept works for ToF patients, our hope is that it could also be applied in other children who need a valve replacement early in life.”

“It is very motivating to have the opportunity to work together with such an incredible group of clinicians and scientists ,” says Hofferberth. “My goal of pursuing a career in congenital heart surgery was inspired by the two months I spent as a medical student on the cardiac surgery service here at Children’s. To now have the opportunity to join Dr. del Nido’s lab is  a dream come true”.