cfDNA Test Developed to Detect Acute Rejection After Heart Transplant

cfDNA Test Developed to Detect Acute Rejection After Heart Transplant
Cardiac surgeon or interns holding heart during open heart surgery. Heart transplant or artificial heart transplant operation. Surgical tools, gloves.

Researchers have developed a blood test to detect acute heart transplant rejection, a potentially deadly condition that occurs in the early months after a patient has received a donor heart.

Typically, these patients must undergo endomyocardial biopsy (EMBx) to monitor for acute rejection. But EMBx is an invasive procedure and provides limited information. The new test uses a blood biomarker of donor-derived cell-free DNA (ddcfDNA) measured by shotgun sequencing.  The researchers estimate that the test could eliminate up to 80% of invasive heart tissue biopsies currently used to detect rejection.

In studies of a group of 171 heart transplant recipients, the new blood test performed better than tissue biopsies, signaling problems even when no outward signs of rejection were evident.

“We showed in our initial assessment that this ‘liquid biopsy’ is highly sensitive for detecting acute rejection, finding it weeks to months before current clinical tools. This could potentially save lives in the wake of a critical shortage of donor organs,” said Hannah Valantine, MD, senior study author and the former lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at the NHLBI. Valantine is currently a professor of cardiovascular medicine at Stanford University in Palo Alto, California.

The study was primarily sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. Its findings were posted online yesterday in Circulation.

In their press release, Valantine added that the test is also important for addressing serious health disparities. Because African Americans tend to have higher rates of heart transplant rejection and experience poorer transplant outcomes than other groups nationwide, the test could help reduce existing transplant-related health disparities that have persisted for decades.

The ddcfDNA test tracks DNA markers from the organ donor that appear in the blood of the transplant recipient. Because injured or dying cells from the donor organ release lots of donor DNA fragments into the bloodstream compared to normal cells, higher amounts of donor DNA indicate a higher risk for transplant rejection in the recipient.

In the current study, the research team collected blood samples from 171 people who had recently undergone heart transplantation at one of five regional transplant centers within or near the Washington, DC metropolitan area. The sampling included nearly 2,000 cell-free DNA measurements. The population included a high percentage (about 44%) of African Americans. The researchers monitored the patients for signs of acute rejection for nearly 18 months using both traditional endomyocardial (heart tissue) biopsy and the new blood test.

The researchers found that the blood test performed better in their study than tissue biopsy, detecting higher amounts of rejection markers and earlier signs of rejection. It also detected more instances of other types of transplant injury that were missed by biopsy, including antibody mediated rejection, one of the deadliest forms of rejection and the hardest to treat and diagnose. The new ddcfDNA test may be able to detect rejection as early as 28 days after heart transplantation and at least three months before rejection is detectable using heart tissue biopsy.

The new test still has limitations. “This test will not completely eliminate the need for invasive procedures, but it can eliminate about 80% of the biopsies currently performed after heart transplant,” said study co-author Palak Shah, MD, a heart disease specialist at Inova Heart and Vascular Institute, Falls Church, Virginia.

Researchers need to conduct additional clinical studies, including a randomized controlled trial, to confirm these findings, but they are using the blood test to further study the mechanisms underlying acute rejection and explore why African Americans tend to have higher rates of transplant rejection.