For years, endomyocardial biopsies have been the gold standard for monitoring potential cardiac rejection. But because rejection can be sporadic or patchy in its presentation, the biopsy can sometimes miss it, or pathologists can overdiagnose it or underdiagnose it.
“Biopsies have been the gold standard, but it’s a flawed gold standard,” says Shelley Hall, MD, Chief of Transplant Cardiology, Mechanical Circulatory Support and Heart Failure at Baylor University Medical Center. “There is about 70 percent agreement among pathologists, who tend to overcall rejection because they don’t want to miss anything. But overtreatment is not benign. Further suppression of the immune system can lead to a whole host of other complications.”
Baylor University Medical Center is currently enrolling patients in the Surveillance HeartCare® Outcomes Registry (SHORE), a study to assess the clinical utility of surveillance using a combination of HeartCare® testing technologies to monitor post-transplant recipients for signs of rejection. The study which is being conducted through Baylor Scott & White Research Institute aims to enroll 1,600 participants who will be followed for five years. Baylor Dallas is one of eight sites in Texas and one of more than 60 sites nationwide to participate in the study. To date, Baylor Dallas has enrolled more than 130 participants, the most in the nation.
The first testing technology is AlloMap®, a measure of host immune activity that assesses risk of acute rejection. AlloMap is the first FDA-cleared test and is the only non-invasive, blood test method recommended in the International Society for Heart and Lung Transplantation (ISHLT) guidelines for surveillance of heart transplant recipients for rejection.
The AlloMap test is derived from a panel of 20 genes, 11 informative genes and nine genes used for normalization and quality control, which produces data used in the calculation of an AlloMap score. This score is associated with activity of the recipient immune system, and a lower score is associated with a quiescent allograft.
“There are a multitude of genes related to rejection,” Dr. Hall says. “If a patient’s score is under the threshold, there is a greater than 99 percent chance he or she is not experiencing rejection.
We’ve used AlloMap since it was approved in 2008. By 2010, we had eliminated more than half of surveillance biopsies performed. We use AlloMap to screen patients with no adverse outcomes.
The second component of the testing strategy is AlloSure®, which was approved just last year to monitor graft injury. AlloSure measures the amount of donor-derived cell-free DNA (dd-cfDNA) in the bloodstream to help identify graft injury, which could be due to cellular or antibody-mediated rejection, infections or vasculopathy. AlloSure is the first commercially viable test that allows transplant centers to obtain these results rapidly. The combination of AlloSure and AlloMap provides a more accurate picture of the graft’s health than either test alone.
“We’ve incorporated these tests as part of our standard process of surveillance,” Dr. Hall says. “We do minimal surveillance biopsies in the first year and none after the first year, but rely on the information provided by these two blood tests. This combination of information should increase the efficacy of monitoring even more. If the registry data confirms what we think, we will only have to do biopsies ‘for cause,’ when high test scores indicate something is going on with the graft.”