Innovations in pediatric heart transplantation

The virtual crossmatch is a tool that makes it easier and safer to perform transplants for children with "antibody sensitization." Virtual crossmatching has become the standard of care across the world and we continue to make improvements to our process. Here's how it works.

When children or adults are exposed to blood or tissue from another person (either through a blood transfusion, during heart surgery, with a tissue graft or even during pregnancy), their immune system can make antibodies that fight cells from that other person. Called "antibody sensitization," this process can make it harder to find a match for them later in life if they need an organ transplant. In the past, most centers would solve this problem by wait listing patients who have these types of antibodies with the requirement for a "prospective crossmatch" test. This means they would only be able to accept a heart from a center located nearby where a sample of the heart donor's blood could be tested with that of the recipient to see if the match was compatible. Unfortunately, this led to much longer wait times for sensitized patients and, tragically, a higher risk of death while waiting.

In 2003, researchers at the Children's Wisconsin decided to overcome this problem. We hypothesized that we could use a laser-based technology for cell identification to determine exactly which antibodies a person has. We could then use this data to make decisions about whether a heart donor would be a good match without requiring direct blood-to-blood testing. Working with the Blood Center of Wisconsin, we ran a series of tests on blood samples from a donor against a sample from a boy who had been waiting on the list at our center for more than two years. The test was highly successful. We called this a "virtual crossmatch" and reported our results in the journal Pediatric Transplantation.

Following the successful test, we applied the approach to our patients, including the little boy who was our original test case. Two years later, we reported our impressive outcomes in another research paper entitled "The Practical Application of the Virtual Crossmatch". The paper outlined our results as we compared our virtual crossmatch outcomes with those of previous patients who required a prospective crossmatch test. The previous group (who required a prospective crossmatch) included eight patients, only one of whom (12 percent) lived to receive a transplant. The virtual crossmatch was used in a group of 10 patients, nine of whom (90 percent) were transplanted with 100 percent survival by the time the article appeared.

The Herma Heart Center's heart transplant team developed a care approach, or protocol, to improve outcomes for heart transplant patients with a positive crossmatch and high risk for rejection, helping make transplant possible for more patients too critical to wait.

As mentioned, we at Children's pioneered the use of the virtual crossmatch to help with donor heart selection for patients who have antibodies that may increase the chance of rejection. However, we recognized that not all patients could wait for the "right heart" (a negative crossmatch) because they just have too many antibodies. For these patients, we developed a risk-minimizing protocol of care techniques for before, during and after surgery that allows us to perform a transplant despite a positive crossmatch. In these cases, we still use our virtual crossmatch to select an organ with the least chance of rejection. In other words, the selected heart may not be a perfect match, but it will be better than a random match. Then, we use this care protocol to minimize the rejection risk as much as possible.

The heart transplant team developed a blood test for heart transplant patients as an alternative to frequent, painful and expensive post-transplant biopsies to check for donor organ rejection.

Finding the right size heart for pediatric transplant patients can be challenging. The heart size of children listed for transplant can vary greatly; some children with cardiomyopathy may have very large, dilated hearts while others with congenital heart disease may have abnormally small hearts with fewer than the heart's normal four chambers.

The Children's Wisconsin heart transplant team created a more concrete way to compare the size of the hearts of our waiting list patients with the actual size of donor hearts. Our heart-size matching technique uses a combination of magnetic resonance imaging (MRI), to measure the heart's capacity to pump (total cardiac volume), and echocardiography, to size-match heart transplant donors and recipients.

Currently, most pediatric heart transplant centers use the weight of the donor and recipient to make these decisions, along with judging the heart sizes by viewing them through chest X-rays. Our new approach lets us more precisely measure the donor heart so that we can immediately tell if the size of the donor and the recipient hearts are a match. A good size match is critical to successful transplant. Accepting an undersized heart increases the risk of early graft failure. Accepting an oversized heart can cause problems with the lungs and make it difficult to close the chest incision immediately after the surgery.

Screening is important for patients who receive heart transplants because they are at risk for developing problems with their coronary arteries (graft vasculopathy). To monitor the arteries, cardiologists use cardiac catheterization so that they can inject contrast directly into the coronary arteries and take pictures. The contrast substance makes the structures of the coronary arteries easier to see.

The heart transplant team at Children's uses new cardiac cath technology, called rotational angiography, to improve coronary artery screening for heart transplant recipients. Using the new technology allows us to get more information from each contrast injection. The method uses a camera that swings around the patient in real time, essentially taking a movie during each injection, which allows cardiologists to see the coronary artery from a wide arc of different angles. Many views are generated during each swing, which means fewer injections may be required to provide the information needed to keep an eye on the arteries. The technique can boost accuracy, shorten procedure times and, in some cases, require less contrast and radiation exposure.