UPMC Children's Hospital of Pittsburgh is at the forefront of pediatric heart and lung transplant research. Its research programs allow researchers and clinicians to work side-by-side to study relevant cardiovascular- and transplant-related problems in children. The goals are not only to increase the overall body of knowledge about heart disease and transplantation in children, but also to discover methods to enhance success of heart failure treatments and transplant procedures.
Pioneering Less Invasive Rejection Surveillance
An example of how UPMC Children’s Hospital physician scientists are leading in the field of heart transplant research can be seen in its successful pursuit of less invasive methods of monitoring for signs of rejection in heart transplant recipients. Heart transplant recipients require life-long monitoring to watch for signs of acute rejection. The current standard of care, endomyocardial biopsy, is costly and invasive, requiring general anesthesia for children and adolescents. When clinical examination and immunosuppressant drug levels are normal, biopsies can also be of low yield for detecting acute rejection.
The multidisciplinary team of investigators at the Heart Institute at UPMC Children’s Hospital of Pittsburgh is focused on developing better, less invasive approaches to surveillance for acute rejection that will ultimately benefit patients by helping them to avoid routine invasive biopsies while simplifying and expediting the diagnostic routine, thus improving quality of life for patients.
A 21st Century Approach
In a cohort of 58 pediatric heart transplant recipients, researchers used a blood-based biomarker in lieu of endomyocardial biopsy to look for signs of heart rejection following transplantation. Led by Brian Feingold MD, MS, FAHA, medical director of the Heart Institute’s Heart Failure and Transplantation Programs, researchers looked at donor-derived cell-free DNA (dd-cfDNA), acquired non-invasively through blood draws. Significantly, this initiative was the first real-world clinical use data to report on the feasibility, reliability, and success of dd-cfDNA testing as part of routine care of pediatric patients following heart transplantation. Findings of the study were published in the journal Pediatric Transplantation.
“In the 2020s, we should not be using a 1980s approach to screen for rejection in our patients,” Dr. Feingold said. “While we can obtain useful clinical data from endomyocardial biopsy, its routine use for screening for rejection is an old paradigm. We can and must devise more robust and patient-friendly clinical diagnostic approaches for our heart transplant recipients.”
The care protocol that Dr. Feingold’s team implemented using dd-cfDNA for surveillance included a gradual introduction of dd-cfDNA assessments in place of every other planned surveillance biopsy and only among patients more than seven months post-transplant whose health status and clinical presentation were deemed to be well. These patients underwent dd-cfDNA analysis and were only referred for biopsy if an elevated dd-cfDNA was detected. Importantly, most patients (81%) had normal dd-cfDNA results and were able to forego their invasive heart biopsy with no adverse effects.
Foundation for Future Advances
Based on this experience, Dr. Feingold’s team revised its rejection surveillance protocol to utilize dd-cfDNA screening in combination with clinical assessment instead of surveillance biopsy for all routine rejection assessments after three months from transplantation. In a recently published follow-up study in Clinical Transplantation, Dr. Feingold and team expanded these findings to well over 100 patients. They continued to observe that four out of five patients who would have undergone invasive biopsy were able to safely avoid this invasive procedure. They also found that rejection surveillance using dd-cfDNA is likely to be cost saving as compared to biopsy-based surveillance. Additional research at UPMC Children’s and other institutions will help to further refine the protocols.
Dr. Feingold noted that dd-cfDNA has also shown promise to detect rejection not seen or not well seen on biopsy.
“Reducing the number of biopsies needed while maintaining or improving surveillance approaches and transplant outcomes, or perhaps being able to identify signs of acute rejection before they become clinically recognizable by biopsy, will undoubtedly benefit our patient population,” said Dr. Feingold.
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