Trifecta-Heart Study

Calibrating circulating donor-derived cell-free DNA against molecular biopsy assessments.

Investigators

Philip F Halloran, and the Trifecta-Heart Study Group ()

Current methods for detecting rejection in heart transplant patients, particularly through histological assessment of endomyocardial biopsies, have notable limitations. To overcome these challenges, the ¾ÅÐãÖ±²¥ Transplant Applied Genomics Centre has developed the Molecular Microscope® Diagnostic System (MMDx)—a definitive molecular assessment tool for evaluating rejection and injury in heart biopsies based on gene expression.

We are proud to introduce a new screening test that monitors donor-derived cell-free DNA (dd-cfDNA) in blood, specifically the Natera, Inc. dd-cfDNA Prospera™ test. This study aims to calibrate dd-cfDNA levels detected at the time of indication or protocol biopsies against MMDx measurements for various stages of rejection, including T-cell mediated rejection (TCMR), antibody-mediated rejection (ABMR) and its stages, as well as acute (early) and chronic (late) injury. We also want to determine whether resolution of dd-cfDNA levels after treatment can monitor response to therapy and avoid follow-up biopsies.

Our research will compare blood dd-cfDNA measurements taken at the time of biopsies with MMDx results, while also assessing HLA antibodies in blood samples. This study is an extension of the INTERHEART project (ClinicalTrials.gov ID: ) and is currently being conducted at nine  centers across the US, Canada, and Europe.

Trifecta-Heart Study Publications

  1. Halloran PF, Reeve J, Mackova M, Madill-Thomsen KS, Demko Z, Olymbios M, et al. Comparing Plasma Donor-derived Cell-free DNA to Gene Expression in Endomyocardial Biopsies in the Trifecta-Heart Study. Transplantation. 2024;108(9):1931-42.