A genetic test that looks for activation of genes involved in the rejection of transplanted hearts may be as good as the conventional technique of heart biopsies, but is much less invasive, Stanford researchers reported online Thursday in the New England Journal of Medicine.
The findings are "an important advance in the assessment of noninvasive methods for monitoring rejection after heart transplantation," wrote Dr. John A. Jarcho, a deputy editor of the journal, in an editorial accompanying the report. But the findings also suggest that routine monitoring for rejection may not be necessary after the crucial first year.
About 2,200 heart transplants are performed each year in the United States, a number that is limited primarily by the low availability of donor organs. About one-quarter of the recipients will have a rejection episode requiring medical treatment in the first 12 months after the surgery, and acute rejection is responsible for 12% of deaths in the first year.
Heart specialists check for rejection by biopsies, inserting a thin catheter through a vein in the neck, threading it to the heart and snipping off a small piece of tissue that can be examined under a microscope. Such tests are often performed weekly in the immediate aftermath of the transplant, then less frequently over time. The risk of a serious complication arising from the biopsy itself is about 1%, but the procedure terrifies patients, said Dr. Hannah Valentine of Stanford, the lead author of the new report. "They are anxious for weeks before. They hate it," she said in a statement.
The new test, called AlloMap and developed by XDx Inc. of Brisbane, Calif., measures the activity of 11 genes and those levels are used to calculate a score that measures the likelihood that a rejection episode is occurring. The test was approved by the Food and Drug Administration in 2008, but the new study is the first large one to assess its activity.
Valentine and her colleagues enrolled 602 patients at 13 heart transplant centers. All had survived at least six months after surgery. Half were assigned to receive regular biopsies and half received the gene test and biopsies only as needed. The endpoint of the study was a combination of rejection, graft dysfunction, death or a new transplant. After an average of 19 months of follow-up, 14.5% of the patients receiving the genetic test had suffered at least one of those events, compared to 15.3% of those receiving biopsies. Patients in the biopsy group had an average of three biopsies during the period of the study, compared to an average of 0.5 biopsies in the genetic test group.
The new test is slightly cheaper than a biopsy, $3,000 for the test compared to $4,000 to $5,000 for a biopsy.
The primary limitations of the study were that it did not include patients in the first months immediately after their surgery and that it probably did not include patients who were at high risk of rejection, the authors said.
The trial calls into question the need for such tests, however, Jarcho said. Of the 34 rejection episodes in the gene test group, only six were detected by the test. The rest were observed because of clinical manifestations of rejection or echocardiograms that identified the problem. What is needed now, Jarcho said, is a trial to compare testing to not testing.
The new study was funded by XDx and Valentine is a consultant to the company. Stanford holds an equity interest in XDx.
-- Thomas H. Maugh II