For children requiring heart transplants, the journey doesn’t end after they receive their new heart. Following transplantation, patients must undergo frequent invasive biopsies to check for heart rejection. To help prevent these invasive procedures, MCRI researchers are developing a non-invasive method for monitoring heart rejection from patient blood samples.

Childhood heart disease (CHD) is a chronic disease that significantly burdens patients and their families, as well as the Australian healthcare system. In Australia, it is estimated that CHD affects 65,000 children and young people, with more than 2,400 Australian babies born every year with a form of CHD.

It is also one of the leading causes of death and hospitalisations in infants, with seven per cent of all infant deaths due to an underlying CHD.

Some CHD patients will go onto develop heart failure later in life, which has around 50 per cent survival rate within five years of diagnosis. The only option for CHD patients in end-stage heart failure is a transplant, which despite being a lifesaving procedure is associated with high mortality rate and requires life-long immunosuppression to prevent organ rejection.

In addition to lifelong immunosuppression, patients require frequent endomyocardial biopsies (EMBs) to monitor for heart rejection. EMBs are highly invasive and expensive procedures where small pieces of the heart are removed under general anaesethetic, using a pincer-type tool inserted via a blood vessel catheter.

The heart biopsy samples are then analysed by pathologists to look for cellular changes or abnormalities, which could be a sign of heart rejection.

EMBs take up to 10 hours to perform in children and are typically taken seven times in the first year the following intervals post-transplant. The frequent hospital admissions, general anaesthesia and illness associated with the EMB procedure increase the risk of cardiac complications for transplant patients. In addition, EMBs pose a significant cost to the healthcare system with each procedure costing around $7,000.

To help prevent these invasive procedures and provide a better solution for heart transplant recipients, Murdoch Children’s Research Institute’s (MCRI) Professor Igor Konstantinov and Associate Professor Daniel Pellicci are developing a test that could monitor heart rejection without the risks involved with EMBs.

Professor Konstantinov said, “The majority of heart transplantations in children in Australia are performed at the Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (CardioRegen), hosted at MCRI within The Royal Children’s Hospital (RCH), so our team are uniquely positioned to investigate alternative approaches to EMBs.

Image: Professor Igor Konstantinov

“This has allowed us to establish a biobank of over 500 blood samples collected from 81 transplant patients at the time of their EMBs. Using those blood samples, we are now validating the use of flow cytometry (using lasers to sort and analyse different cell types) as an accurate and minimally-invasive blood test to detect specific T-cell populations in paediatric heart transplant patients,” he said.

T-cells are an important type of white blood cell in the immune system and play a central role in the adaptive immune response. By identifying certain types of T-cells in blood that are associated with transplant rejection, it could be possible to predict which patients will reject their heart transplants.

Associate Professor Pellicci said, “Professor Konstantinov has previously developed a blood test to predict low-grade transplantation rejection based on next generation sequencing (a method of analysing genetic material that allows for rapid sequencing of large amounts of DNA or RNA).

“Based on this work, we are currently profiling different types of T-cells using flow cytometric analysis of patient blood samples. This technology offers a faster, cheaper, and less stressful approach to check for heart rejection than the current method of EMBs.”

Professor Pellicci said, if successful, the blood test would result in an immediate 10-fold reduction in the cost of rejection surveillance and reduce the risk of surgical complications associated with EMBs.

Image: Professor Dan Pellicci

Tyler Airey needed a heart transplant in 2010 at age 15 due to an undiagnosed inherited heart disease called dilated cardiomyopathy. Tyler’s heart muscle thinned and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated).

Two years after the transplant Tyler was infected with the common Epstein-Barr Virus and developed Post-Transplant Lymphoproliferative Disease (a rare complication of organ transplants that causes cancer to grow in the lymph system). He then underwent chemotherapy/monoclonal antibody treatment for around eight weeks.

“In the first few months to years after receiving a heart transplant, patients need to be close to the hospital and organise their life around appointments such as EMBs,” Tyler said. “This might involve extensive travel arrangements including accommodation.

Image: Tyler Airey had a heart transplant at age 15

“An EBM requires a lot of preparation both before and after for patients and their families, and the procedure is typically a whole day event, requiring fasting, inserting the IV cannula, anesthesia, resting and recovering.

“Patients would have a lot more freedom and would be less burdened with the disruptions and challenges associated with EBMs if they could be prevented with a simple blood test,” he said.

If successfully translated into clinical practice, Professor Konstantinov and Associate Professor Pellicci said they hoped the blood test would help patients like Tyler prevent heart transplant rejection and improve their quality of life after transplantation.

This article is republished from INSPIRE. Read the original article on page 32-33.