UPMC Children’s Heart Institute Team Publishes Latest Findings on Minimally Invasive Heart Transplant Rejection Monitoring Using Donor-Derived Cell-Free DNA Blood Testing

Faculty at the Heart Institute at UPMC Children’s published updated findings on their use of a minimally invasive donor-derived cell-free DNA (dd-cfDNA) approach to monitoring pediatric heart transplant recipients for organ rejection. Results of the new investigation were published in May 2023 in Clinical Transplantation.¹

Leading the study was Brian Feingold, MD, MS, FAHA, professor of Pediatrics and Medical Director of the Heart Failure and Transplant Program at the Heart Institute at UPMC Children’s. Collaborating with Dr. Feingold were co-authors Kirsten Rose-Felker, MD; Shawn C. West, MD; MSc, Susan A. Miller, MD, MBA; and Matthew D. Zinn, DO, all from the Heart Institute. 

The new study builds upon previously published work by the group² in which they reported the first real-world clinical use data on the feasibility, reliability, and success of dd-cfDNA testing as part of routine care of infants, children, teens, and young adults following heart transplantation. The promise of these early findings led the team to revise the rejection surveillance protocol at UPMC Children’s to utilize dd-cfDNA screening in combination with clinical assessment instead of repeated heart biopsies for routine rejection surveillance assessments after 3 months from transplantation.

Clinical Picture

Following heart transplantation, patients have traditionally undergone routine, life-long surveillance with heart biopsies to look for acute rejection. Heart biopsies are invasive (it requires general anesthesia for infants, children, and most adolescents), costly, and of low yield for detecting acute rejection when clinical examination and immunosuppressant drug levels are normal. Less invasive approaches to surveillance for acute rejection benefit patients by avoiding repeated invasive biopsies, simplifying and speeding up the diagnostic routine while at the same time improving patient quality of life. Which is where the use of dd-cfDNA enters the scene.

New Study Supports Continued Clinical Expansion and Research of dd-cfDNA for Transplant Rejection Surveillance

In their new study, Dr. Feingold and colleagues compared the results of two surveillance protocols following pediatric heart transplantation: the traditional protocol using repeated biopsies and the new protocol relying upon dd-cfDNA surveillance. Dr. Feingold and the team examined clinical outcomes prior to and following a switch from EMB to dd-cfDNA in pediatric and young adult heart transplant recipients at UPMC Children’s Hospital. They also explored the cost outcomes for both surveillance protocols, extrapolating the results to make reasoned predictions of long-term cost comparisons of the two approaches.

Results showed that over the course of nearly three years of clinical follow-up among 120 pediatric heart transplant recipients, the use of dd-cfDNA-led surveillance decreased the need for invasive EMBs by almost 82%. After the protocol dd-cfDNA was implemented, there was no increase in rejection events, the need for re-transplantation, or death. Additionally, dd-cfDNA-led surveillance is projected to cost between $8,500 and $24,500 less, per-patient over 20 years after heart transplantation, than traditional biopsy-led surveillance.

This work is helping to shift the standard of care after pediatric heart transplantation, enabling more cost-effective and less invasive care for patients.

In addition, dd-cfDNA has shown promise to detect rejection not apparent or not well seen on biopsy. This is a particularly exciting possibility because it may help unlock treatments for chronic rejection, a slow process of injury after transplant which leads to heart failure, usually over decades.

Additional research will be required to validate further the clinical utility and generalizability of the study's findings across institutions with varying rejection surveillance protocols.

References

1. Feingold B, Rose-Felker K, West SC, Miller SA, Zinn, MD. Short Term Clinical Outcomes and Predicted Cost-Savings of dd-cfDNA-led Surveillance After Pediatric Heart Transplant. Clin Transplant. 2023 May; 37(5): e14933. Open Access.
2. Feingold B, Rose-Felker K, West SC, Zinn MD, Berman P, Moninger A, Huston A, Stinner B, Xu Q, Zeevi A, Miller SA. Early Findings After Integration of Donor-Derived Cell-Free DNA Into Clinical Care Following Pediatric Heart Transplantation. Pediatr Transplant. 2021; 00: e14124. Epub ahead of print.