Non-Invasive Phenotypic Detection of Cardiac Allograft Rejection

Doctor Yiling Situ, University of New South Wales

Postgraduate Scholarship

Years funded: 2025 - 2027

Over 144,000 Australians are living with heart failure and those with end-stage cardiomyopathy may require heart transplantation. While this remains the most effective treatment, heart transplantation carries significant risks and involves lifetime surveillance of acute cardiac allograft rejection (ACAR) and graft function. ACAR remains the major complication following heart transplantation. The current gold standard for detecting ACAR is by endomyocardial biopsy (EMB) and histological assessment. This procedure is invasive and carries significant procedural-related risks such as bleeding, perforation, and cardiac tamponade. Prior studies have demonstrated the feasibility of CMR for rejection surveillance, however, there are cross-vendor and cross-field strength variations which hinders the adoption of this technique worldwide. Other non-invasive methods such as genomic assessment have been validated and adopted in some centres as routine surveillance strategy. To date, there is insufficient knowledge on the utility of combined non-invasive strategies for rejection surveillance, with a particular focus on clinical outcomes.

This project “Non-Invasive Phenotypic Detection of Cardiac Allograft Rejection: A randomised safety outcomes study (NIDACT-3)” will be a prospective longitudinal randomized non-inferiority study. The study will incorporate both 1.5T and 3T CMR multiparametric imaging, and genomic assessment of donor derived cell-free DNA (dd-cfDNA) for detecting cardiac allograft rejection and for guiding immunosuppression management in the first year after heart transplantation. The aim of the study is to: Assess the safety of CMR imaging for guiding immunosuppression management in the first two years after cardiac transplantation;

1. Assess the utility of high-field strength (3T) CMR imaging for the detection of ACAR and compare this to low-field strength (1.5T) CMR; and
2. Assess the utility of a combined non-invasive CMR imaging and genomic approach for routine surveillance of ACAR. This study will hopefully prove reliability of non-invasive surveillance of ACAR and revolutionize the guidelines and management of heart transplant patients.