Baylor Team Discovers Reason For Heart Transplant Failure

"This finding should lead to a change in diagnostic testing and treatment," said Dr. Jeffrey A. Towbin, a professor of pediatric cardiology at Baylor. "It could also improve long-term survival."

The discovery, reported in the May 17 issue of the New England Journal of Medicine, shows why many children suffer heart transplant failure months and even years after surgery, including cardiac rejection and the development of transplant coronary artery disease. The study indicates that frequent biopsies are the best method to identify the virus.

The research team, led by Towbin and Dr. Neil E. Bowles, an assistant professor of pediatric cardiology at Baylor, has been studying for the past decade the reasons for heart transplant failure in children. "It's been the bane of all transplant doctors -- the development of coronary artery disease in transplant patients leads to either sudden death or the need for retransplantation," said Towbin, also associate chief of pediatric cardiology at Texas Children's Hospital and director of the Heart Failure and Transplant Service and Cardiac Research. "Nobody has understood why this happens, but now we know there's a viral connection."

The team studied 553 biopsies from 149 transplant recipients, ages newborn to 18 years old, over a five-year period. The biopsies were evaluated for common viral infections by using a polymerase chain reaction, or PCR, test. All of the biopsies were sent from Loma Linda University Children's Hospital in California.

Results showed that 85 percent of the patients who at some point after transplant tested PCR-positive suffered an adverse event within three months of that result.

"The infection isn't there at transplant, it wasn't there along the way and suddenly it's there," Towbin said. "It's likely to be due to an upper respiratory illness."

In the majority of cases, the infection was late onset, appearing more than two years after transplant, Bowles said. The infections or evidence of rejection did not show up on non-invasive tests.

The findings indicate that the current therapy for transplant rejection should be changed, Towbin said. Now, when the heart shows signs of rejection, indicated by inflammation within the heart, the therapy is anti-inflammatory medications, such as steroids and increased immunosuppresent drugs. After the therapy reduces the inflammation, the patient is sent home with a clean bill of health, he said.

"But, nothing has been done about the virus. It's still sitting there as a low-level illness that over time creates the problem," Towbin said.

Towbin and Bowles said the discovery suggests that all heart transplant patients should be biopsied routinely with PCR evaluation performed each time. They believe these results could lead to new therapies and preventative measures, such as an anti-viral vaccine for use prior to transplant.

Collaborators included Dr. Girish S. Shirali, Medical University of South Carolina, Charleston; Dr. Jiyuan Ni, Baylor College of Medicine; Dr. Richard E. Chinnock and Joyce K. Johnston, Loma Linda University Children's Hospital; and Dr. Geoffrey L. Rosenthal, University of Washington.