Diagnosis of Rejection Following Heart Transplantation: Diving into the Future

Shaline Rao^1,2*Zain Ali²Arushi Singh²Mittal Rana²Mohamed Moussa²Kinza Ahmed²Stephanie Golob²Lauren Cusumano²Alana Harrington²Andrew Wang²Sanjay Chandrasekhar²Amit Alam²

• ¹Langone Medical Center, New York University, New York City, United States
• ²NYU Langone Health, New York, United States

Since the standardization of the grading system for pathologic diagnosis of antibody-mediated and acute cellular rejection, endomyocardial biopsy has remained the gold-standard. However, biopsies are invasive, costly, and limited by sampling error. As such, adjuvant non-invasive methods including cardiac biomarkers, imaging including cardiac magnetic resonance and echocardiography, and donor-specific antibodies and non-HLA antibodies have been traditionally used. However, all these techniques are limited by either sensitivity or specificity. More recently, there has been a shift to other contemporary non-biopsy surrogate markers for rejection surveillance including donor-derived cell free DNA, gene expression profiling, and messenger RNA and micro-RNA in tissue. Herein we review the methods currently utilized to diagnose rejection and their limitations. We find that while there have been significant advancements in technology and non-invasive techniques, no current method alone adequately diagnoses rejection (Central Image). Thus, future studies are warranted to investigate new strategies involving a multi-modal approach that incorporates non-invasive diagnostic methods and personalized medicine to monitor postoperative progression in heart transplant patients.