The prospective, multi-center trial was designed to evaluate the clinical usefulness of a multi-gene molecular expression assay test developed to identify the "quiescent" state after heart transplantation and to determine the assay's ability to predict clinical outcomes. A major challenge physicians face in managing transplant patients is finding the right balance of drug therapy – one that suppresses the patient's immune response enough to prevent rejection of the transplanted organ, but not so much that the immune system no longer competently fights infection and cancer. With this balance reached, the immune system is "quiescent."
Analysis from the eight-center trial revealed molecular testing using peripheral leukocyte gene expression can identify the quiescent state and predict future occurrence of rejection during the first year after cardiac transplantation.
"The development of alternative, non-invasive procedures, such as gene expression-based monitoring of the immune response, may provide us with the ability to predict organ rejection and provide better post-operative care," said Mandeep Mehra, M.D. and lead investigator for the study.
"This technology has many benefits. It can be used to identify patients with acute rejection early when it is most treatable, help us better manage patients' immunosuppression regimens and provide a means to resolve uncertainties of a biopsy."
For patients, the test could mean less discomfort during the constant monitoring for rejection and prolonged transplant success. Worldwide, approximately 4,500 cardiac transplants are performed annually. The most common cause of death in the first year after transplantation is acute cardiac rejection; the patient's immune system attacks the heart as if it were a foreign object until it no longer functions properly. As a result, physicians continuously monitor transplant patients for rejection.
The current gold standard for diagnosing acute rejection is the heart biopsy. Patients undergo at least 12 heart biopsies in their first year following transplant, and periodic biopsies may continue for years. This is an invasive, uncomfortable and time-consuming procedure where biopsy shears are inserted into a vein near the patient's neck and threaded through blood vessels to the heart. Part of the heart muscle is clipped off and sent to pathologists to evaluate the specimen for signs of rejection. This costly procedure also has limitations – by the time rejection is apparent, damage to the transplanted organ may already be done.
Based on the Cardiac Allograft Rejection Gene Expression Observation (CARGO) study, the research presented today at the ISHLT meeting points toward the viable use of molecular testing of a blood sample to identify quiescent patients and distinguish the quiescent state from acute rejection. Clinical use of this test would give physicians a noninvasive, quantitative tool with which to manage their transplant patients' immunosuppression regimen and biopsy schedule.
Studies are ongoing to provide further validation of the results and determine how molecular testing can be used to guide the use of specific immunosuppressive agents, in particular weaning off from corticosteroid therapy.
About ISHLT
The International Society for Heart and Lung Transplantation (ISHLT) is a not-for-profit organization dedicated to the advancement of the science and treatment of end-stage heart and lung diseases. Created in 1981 at a gathering of about 15 cardiologists and cardiac surgeons, the Society now includes more than 2,200 members from 45-plus countries, representing a variety of disciplines involved in the management and treatment of end-stage heart and lung disease.
ISHLT maintains two databases. The International Heart and Lung Transplant Registry is a one-of-a-kind registry that has been collecting data since 1983 from 223 hospitals from 18 countries. The ISHLT Mechanical Circulatory Device (MCSD) database has been collecting data since 2002 with the aim of identifying patient populations who may benefit from MCSD implantation; generating predictive models for outcomes; and assessing the mechanical and biological reliability of current and future devices.