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A simple blood test may detect whether a chronic heart transplant patient is rejecting their heart, and may reduce the need for invasive heart-muscle biopsies, according to the results of a multi-center study called CARGO (Cardiac Allograft Rejection Gene Expression Observational Study), led by NewYork-Presbyterian Hospital and Columbia University Medical Center and to be published in the December 19 The American Journal of Transplantation. (The study is available online now.) The findings describe a new methodology that may impact the way heart transplant patients are treated.

The four-year, eight-site CARGO study included data from centers accounting for approximately 22 percent of the yearly U.S. heart transplant population.

The gene-expression test, called AlloMap™ molecular expression testing, developed in partnership with XDx, a molecular diagnostics company in South San Francisco, CA, and using data from more than 600 patients, presents a snapshot of the immune status of the transplanted heart recipient. This snapshot represents a profile of 20 genes representing molecular pathways in white blood cells that were found to be associated with heart transplant (allograft) rejection, and control genes. Following its development, the study conducted a blinded clinical validation of the AlloMap test. The AlloMap test in this study appeared to distinguish patients who were rejecting their heart from those who were not. Patients with a low AlloMap score had a less than one percent chance of rejection.

"The genomics revolution ushered in by the completion of the Human Genome Project has made possible what was only dreamed about before namely the ability to detect rejection of the transplanted heart without taking a tissue sample," says Dr. Mario Deng, the study's co-principal investigator and co-lead author of the publication. He is director of cardiac transplantation research at Columbia University Medical Center, assistant professor of medicine at Columbia University College of Physicians and Surgeons, and attending cardiologist at NewYork-Presbyterian/Columbia.

AlloMap molecular expression testing is a service provided by XDx through its clinical laboratory, which is CLIA- (Clinical Laboratory Improvement Amendments) certified to perform AlloMap testing for heart transplant patients nationwide. NewYork-Presbyterian/Columbia will begin offering patients AlloMap testing on January 1, 2006.

After the first year of transplant, heart transplant patients have an average risk of three to five percent for moderate/severe rejection. Consequently, for the rest of their lives, patients must be monitored for rejection to guide their immunosuppressant drug therapy. Rejection of a transplanted heart can lead to heart damage and eventual failure and loss of life.

The heart-muscle biopsy has for decades been the most reliable method for detecting rejection of the transplanted heart. While no official guidelines for administration of heart biopsies exist, generally, biopsies are performed initially once a week and then slowly tapered over time to once every three to six months. The AlloMap test is a non-invasive, objective measurement of molecular signals in the blood that could detect the rejection process before damage occurs. However, the Allomap has not been tested in patients immediately post transplant when the risk of rejection is the highest. Moreover, the number of rejection episodes reported in the CARGO study were few and more data will be needed prior to discontinuing the routine use of endomyocardial biopsies.

A Model for Other Studies

Importantly, the CARGO study presents a general methodology for clinical implementation of genomics. Its three-phase design of discovering genes by a combination of array-screening techniques and literature search; developing a gene-expression test; and independently validating this test will likely be employed in numerous follow-up studies currently underway or in development. More than 10 follow-up projects of the CARGO consortium will seek to expand the results of CARGO, better understand the biochemical relationships it has uncovered, and apply its methodology to the development of gene expression tests for other populations, organs, and disease entities.

NewYork-Presbyterian/Columbia has the largest heart transplant program in the country, with more than 110 transplants completed in 2005 and more than 1,500 since the inception of the program in 1977.

Dr. Howard Eisen of Drexel University in Philadelphia is co-principal investigator. Additional principal investigators include Dr. Mandeep Mehra at the University of Maryland; Dr. Jon Kobashigawa at UCLA; Dr. Randall Starling at Cleveland Clinic; Dr. Srinivas Murali at University of Pittsburg; Dr. Dan Pauly at University of Florida; and Dr. Sharon Hunt at Stanford University.

XDx funded the study and XDx will be the sole proprietor of this technique. Though the collection of the sample is a simple blood draw, the analysis has the potential to, but may not necessarily, reduce the overall cost of transplant.

The American Journal of Transplantation is published by Blackwell Publishing on behalf of the American Society of Transplant Surgeons and the American Society of Transplantation.

New York-Presbyterian Hospital is the largest not-for-profit, non-sectarian hospital in the country. It provides state-of-the art inpatient, ambulatory and preventive care in all areas of medicine at five major centers: New York-Presbyterian hospital/Columbia University Medical Center, New York-Presbyterian Hospital/Weill Cornell Medical Center, Morgan Stanley Children's Hospital of New York-Presbyterian, the Allen Pavilion, and the Westchester Division. It consistently ranks as one of the top hospitals in the country in U.S.News & World Report's guide to "America's Best Hospitals." The New York-Presbyterian Healthcare System an affiliation of acute-care and community hospitals, long-term care facilities, ambulatory sites, and specialty institutes serves one in four patients in the New York metropolitan area.

Columbia University Medical Center provides international leadership in pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders in health care and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the School of Dental & Oral Surgery, the School of Nursing, the Mailman School of Public Health, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center researchers are leading the discovery of novel therapies and advances to address a wide range of health conditions.