New tests show promise in tracking rejection after heart transplant

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During the first year after heart transplantation, patients endure about 20 biopsies -- procedures in which a catheter is threaded through a groin or neck vein into the heart so that tiny pieces can be snipped out and scrutinized for signs of rejection.

But soon, new tests that are far less intrusive and possibly more informative could reduce or perhaps eliminate the need for invasive biopsies.

Carnegie Mellon University's Chien Ho and his colleagues at the Pittsburgh NMR Center for Biomedical Research, which he directs, are reporting this week on a method for using MRI scans to track rejection.

The report will be published in the online edition of Proceedings of the National Academy of Sciences.

Also, a blood test called AlloMap has shown promise in studies of heart transplant patients at the University of Pittsburgh Medical Center and elsewhere.

"Both these strategies hopefully will give us a lot more insight into our patients and how best to treat them," said Dr. Jeffrey Teuteberg, a cardiologist at the UPMC Cardiovascular Institute.

In Dr. Ho's project, paramagnetic iron oxide particles were injected into the veins of rodents, where they were quickly swallowed up by macrophages, the scavenger cells of the immune system.

A second heart was transplanted into the animal abdomens. With magnetic resonance imaging, the researchers could see if the iron-oxide-tagged macrophages flocked to the donor organ, indicating that the immune system was rejecting the transplant.

"The iron particles show up as sort of a black spot in the heart," Dr. Teuteberg explained.

The number of macrophages can be quantified by MRI, as well.

Dr. Teuteberg did not participate in those experiments, but he is working with Dr. Ho on a followup project to see if the technique will work in larger animals such as pigs.

Success must be seen in a larger animal model before human studies can begin.

For safety and accessibility reasons, conventional biopsies tend to be taken from the same area of the heart, so it's possible to miss rejection if it's happening elsewhere in the organ, Dr. Ho pointed out. With MRI, the entire heart can be viewed.

In the animal studies, serial scans revealed the immune cell onslaught starts at the outside of the heart and moves inward.

"Nobody has seen that before," Dr. Ho said.

Physicians perform a balancing act in prescribing anti-rejection drugs -- too much suppression of the immune system puts the patient at risk for infections and cancer; too little can allow rejection to occur.

The MRI technique could gauge the immune system response to help tailor drug treatment to the individual patient, Dr. Ho said.

AlloMap, a blood test made by San Francisco-based XDx Inc. that looks for heart transplant rejection, could do the same thing.

Rather than checking for the presence of a specific gene or mutations in it, AlloMap reflects patterns of gene activity, which scientists refer to as expression, in 20 genes that are involved in the immune response.

A low score on the test indicates that rejection is not occurring and a biopsy probably isn't needed. A high one suggests that the immune system could be getting ready to attack donor tissue, so a change in drug dose or a biopsy might be the next step, Dr. Teuteberg said.

AlloMap is one of the first tests of its kind. It will soon be available at Allegheny General Hospital and is already being used at UPMC, where researchers are participating in studies that could expand its use.

"There are some centers that are already starting to use it in everyday clinical practice," Dr. Teuteberg said. "There's still a little bit of skepticism, and I think that's reasonable with a new technology like this."

Up to 40 percent of heart transplant patients will have a significant rejection episode in the first year after the surgery, he said. Most will recover with a short course of steroids.

Acute rejection is still a leading cause of death in the early post-transplant course, and it can create trouble later by setting the stage for narrowing of blood vessels in the transplanted heart.

Preventing early rejection episodes, perhaps by using the MRI technique or AlloMap to fine-tune immunosuppressive drug treatment, might improve long-term prognosis, Dr. Teuteberg said.

The MRI process could also be used to track cells in other conditions, such as autoimmune disease or heart failure.

"This might be a really useful tool in assessing inflammation and assessing therapy," Dr. Teuteberg said.

Anita Srikameswaran can be reached at or 412-263-3858.


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