Gene-expression profiling of patients who received a prior cardiac transplant may be a good alternative to routine biopsies, as rates of adverse events and risk were similar between the two methods, according to the IMAGE trial published May 18 in the New England Journal of Medicine.
“Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant,” the authors wrote; however, it may be uncomfortable for patients and laced with risks. “Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy.”
To help prove this, Michael X. Pham, MD, of Stanford University Medical Center in Stanford, Calif., and colleagues assessed 602 patients for rejection via use of gene-expression profiling or routine endomyocardial biopsies on top of a clinical and echocardiographic assessment of graft function.
According to the authors, rejection is linked to an increased risk of allograft vasculopathy and loss.
The researchers compared use of the two approaches by evaluating the primary endpoint of hemodynamic compromise, graft dysfunction, death or retransplantation.
According to the researchers, all IMAGE study participants previously underwent a cardiac transplantation six months to five years prior to the study and were randomized to undergo either gene-expression profiling or endomyocardial biopsies to evaluate rejection between January 2005 and October 2009.
During the study, 297 patients were randomized to undergo gene-expression profiling using the AlloMap test (XDx) to test 11 informative genes and 305 underwent routine biopsies.
After a mean follow-up of 19 months, the researchers found that rates of primary outcomes were similar in the gene-profiling group and the biopsy group, 14.5 and 15.3 percent, respectively.
Rates of survival between the two groups were also statistically similar, 6.3 and 5.5 percent, respectively.
According to the authors, 409 biopsies were performed in the gene-profiling group, while 1,249 were performed in the biopsy group.
For the gene-profiling arm, most biopsies were a result of elevated gene-profiling scores (67 percent), due to signs, symptoms or echocardiographic manifestations of graft dysfunction (17 percent), as part of follow-up (13 percent) and 3 percent were outside the study protocol.
There were 34 reported incidences of rejection within the gene-profiling arm compared to the 47 episodes that occurred in the biopsy arm.
“Only six of the 34 treated episodes of rejection in the gene-profiling group were detected with the use of the gene-expression test,” the authors wrote.
“These observations raise the possibility that clinical observation may detect the majority of serious rejection episodes.”
During the trial, the researchers also evaluated the physical-health and mental-health of patients in both study arms. While the physical-health scores were higher in the biopsy group, the results were not statistically different between the two, 47.3 versus 44.7, respectively.
“There has not been sufficient equipoise to justify a comparison of monitoring by means of clinical observation with monitoring by means of routine biopsies, but our findings may provide the basis for such comparisons in future studies,” the authors wrote.
While the researchers said that the study results show that gene-profiling may be a good alternative to biopsy, a larger trial with a longer follow-up period would reach better conclusive results.
In an accompanying NEJM editorial, John A. Jarcho, MD, asked: “Should the AlloMap test replace routine endomyocardial biopsies for monitoring rejection in heart-transplant recipients?”
He said that it is “certainly very encouraging to learn that serious adverse clinical events were no more frequent when this diagnostic strategy was used than when endomyocardial biopsies were routinely performed, and many patients would enthusiastically embrace an approach that requires fewer biopsies.”
He also offered that the trial had a number of limitations including using a patient population with lower risk of rejection and it “calls into question the importance of any form of routine screening for the early detection of rejection in the longer term after transplantation.”
Jarcho suggested that a clinical trial to evaluate the use and discontinued use of endomyocardial biopsies is needed and said that centers should use data to tailor biopsy schedule by patient.