A blood test may offer heart transplant patients a less invasive way to assess rejection risk, according to a study published online today in the New England Journal of Medicine. As with most organ donations, heart transplants can potentially be rejected by a recipient’s body. To minimize rejection risk, organ recipients are routinely placed on life-long regimes of immunosuppressant medication, and are also tested for signs of rejection risk. Currently, the standard method for assessing risk is an invasive procedure known as an endomyocardial biopsy (EMB)—in which a device is inserted into the heart, through a catheter placed into the neck, to take a sample of tissue for testing. Yet, while rare, EMB can introduce potential complications for patients, in addition to causing physical discomfort and anxiety. As a result, researchers have long been investigating different methods for assessing rejection risk by less invasive means. And, for the first time, one of those alternatives has been tested in a clinical trial. In the Invasive Monitoring Attenuation through Gene Expression (IMAGE) trial, a large team of cardiologists from universities across the U.S. studied 602 patients ages 18 and older who had undergone heart transplant between 6 months and 5 years earlier. Patients were randomly assigned to standard treatment, which includes routine EMB tests, or to treatment regimes that instead involved blood tests that use gene-expression profiling to assess rejection risk. At the end of two years, patients in both treatment groups had similar risks for organ rejection and death, though those in the blood test group underwent 73% fewer biopsies.
The blood tests used in the trial, an AlloMap blood test, was approved by the U.S. Food and Drug Administration in September 2008 and assesses rejection risk by examining gene expression in patients’ white blood cells. Researchers say that the comparable outcome for both groups—death rates from any cause were 6.3% in the blood test group compared to 5.5% among those who underwent routine EMB—indicate that, for certain patients the AlloMap blood test may provide a promising and effective alternative to invasive biopsies.
Authors of the new research, led by Dr. Michael X. Pham at Stanford University Medical Center, conclude that:
“[O]ur study suggests that gene-expression profiling of peripheral-blood specimens may offer reasonable alternative to routine biopsies for monitoring cardiac-transplant recipients for rejection if the interval since transplantation is at least 6 months and the patient is considered to be at low risk for rejection.”
Understanding those caveats—that the blood test has only shown comparable results for a very select, low-risk population—is critical, argues Dr. John A. Jarcho, a deputy editor of the New England Journal of Medicine and a cardiologist at Brigham and Women’s Hospital in Boston. Additionally, study authors note that the necessary unblinding (patients knew whether or not they were getting biopsies) may have impacted immunosupression in the blood test group. (That said, the researchers indicate that they saw no difference in immunosuppressant use or other immunosuppresion indicators between the two groups.) The blood test costs roughly $3,000 while heart biopsies cost about $4,000.
The major significance of this research, argues Jarcho, is that it “calls into question the importance of any form of routine screening for the early detection of rejection in the longer term after transplantation.” As he points out, of 34 rejection incidents among study participants in the blood test group, only 6 were detected using gene-expression profiling. The other incidents were detected through clinical signs of heart failure or using echocardiograms (EKG). “This observation suggests that, even if rejection is not identified until [transplant] dysfunction is present, the clinical outcomes may not be substantially worse than when rejection is tested early.” As Jarcho points out, some cardiology centers have already stopped using biopsies in patients between 1 to 5 years of transplantation.
Jarcho suggests that a logical next step in the research may be conducting a large scale study examining the long-term benefits of rejection risk assessment, and that, in the meantime, perhaps cardiologists should tailor risk screening by patients’ specific histories—incorporating the risk factors associated with gender, age and the individual patient’s own medical history. He sums up: “The IMAGE trial suggests there may be room for such innovations in the often tradition-bound practice of transplantation cardiology.”