Grant: Project Grant

Heart transplantation (HTx) is a life-saving surgery for patients with end-stage heart failure. A major complication is cardiac allograft vasculopathy (CAV), a condition in which the arteries of the donated heart gradually narrow, increasing the risk of heart failure, graft loss, and death in the recipient. CAV often develops silently and is usually detected only after irreversible damage has already occurred. Currently, diagnosis relies on invasive procedures such as coronary angiography or intravascular ultrasound. These tests are expensive, uncomfortable, and not practical for regular monitoring. A simple blood test to detect CAV earlier would allow for timely intervention and may help prevent disease progression. This project aims to develop such a blood test using metabolomics and proteomics, which measure molecules and proteins in blood to reveal early biological changes before symptoms appear. We will analyze stored blood samples from HTx patients who later developed CAV and compare them to matched patients who remained healthy. Specifically, we will: 1) analyze early post-HTx samples (60-180 days) to identify metabolic markers that may predict future CAV; 2) validate 18 protein markers previously discovered by our team; 3) examine how all of these markers change over time using serial samples collected during the first year after HTx, to see whether patterns predict risk; 4) assess how well these markers detect disease at the time of standard diagnosis; 5) combine metabolite and protein data to build a predictive model for early detection. This study will use samples from the HEARTBiT cohort, a multicentre study of HTx patients led by Dr. Tebbutt. All samples are already collected and stored in a secure hospital biobank. If successful, this work will support the development of a simple, accurate blood test to detect disease early, improve patient care, reduce the need for invasive procedures, and ultimately improve survival and quality of life after HTx.