Grant: Project Grant

Heart transplantation is a life-saving procedure for patients with severe heart failure. A major challenge post-transplantation is acute cellular rejection (ACR), where the immune system attacks the new heart. ACR affects 20-30% of heart transplant recipients within the first three months and can lead to serious health problems or even death if not detected and treated early. The standard diagnosis for ACR is an endomyocardial biopsy (EMB), which involves examining a small piece of heart tissue. While effective, it is invasive, costly, and may lead to bleeding and infection. It can also sometimes miss the signs of rejection due to sampling errors. There is a pressing need for a simpler, non-invasive method to detect ACR early and accurately. This research project aims to develop a blood test to identify ACR in heart transplant patients. Our approach is to study the small molecules in the blood (metabolites), which can reveal important information about the body's metabolic processes and immune responses. By identifying specific metabolic changes associated with ACR, we aim to create a reliable blood test that diagnoses rejection without the need for EMB. We will: 1) analyze blood samples to find metabolic biomarkers linked to ACR; 2) examine how immunosuppressive drugs, which are used to prevent rejection, affect these biomarkers; 3) validate these findings using additional patient samples to ensure accuracy; and combine these metabolic biomarkers with existing RNA-based tests to improve diagnostic performance. Our multidisciplinary team will work with major transplant centres across Canada to access a comprehensive collection of patient samples and clinical data. The development of a non-invasive, accurate blood test will help doctors quickly identify and treat rejection, improving the health and longevity of heart transplant recipients. Understanding the metabolic changes associated with ACR could lead to new treatments and personalized care strategies.