The American Transplant Congress (ATC) is the annual international meeting for the American Society of Transplantation (AST) and the American Society of Transplant Surgeons (ASTS). Heart transplant physician researchers from the Center for Advanced Heart and Lung Disease at Baylor University Medical Center at Dallas (Baylor Dallas) played a prominent role in ATC 2024, which was held in early June in Philadelphia, PA.
The Baylor Dallas physicians contributed to key themes at ATC 2024, as highlighted below.
Modifiers of Cell-free DNA Levels in Heart Transplant Patients
Donor-derived cell-free DNA (DD-cf-DNA) is rapidly becoming an essential part of the toolkit for assessing the allograft status of solid organ transplants. When the allograft is injured, cf-DNA is released into the peripheral circulation, where it can be monitored with routine blood collection. When dd-cf-DNA levels are low, acute rejection can be ruled out. However, elevated dd-cf-DNA levels are more complicated to interpret, and multiple factors may influence dd-cf-DNA release.
In one Baylor Dallas poster presentation, the researchers described an investigation of sex differences as a potential modifier of cf-DNA levels in transplant patients. In a multi-site retrospective analysis, they found a higher median dd-cf-DNA level in women than men, even when accounting for patient age. They also found that dd-cf-DNA levels increase over time, with the highest levels seen three or more years after transplant. This trend differed between women and men, with the increase occurring earlier in women.
Shelley Hall, MD, chief of Transplant Cardiology and Mechanical Circulatory Support at Baylor Dallas and senior author on the ATC 2024 abstract, says, “Given that women are more likely to have both moderate and acute rejection, we could be seeing a sex difference in allograft injury. However, there could be non-injury-related biological mechanisms at play. It will be important to understand the drivers of this sex difference so we can provide personalized care to our transplant patients.”
Another Baylor Dallas poster presentation at ATC 2024 reported on the relationship between maximal cardiopulmonary exercise testing (CPET) and dd-cf-DNA levels in a cohort of seven immunologically quiescent heart transplant recipients, four of whom had ischemic times > 180 minutes. In six of seven patients, there was no observed release of dd-cf-DNA after maximal CPET. In one patient, there was some dd-cf-DNA observed, which rose to 0.20% at 24 hours and returned to baseline levels by day seven. These results add further clarity on the drivers of dd-cf-DNA levels, and the authors note that they provide “reassurance that dd-cf-DNA levels are not impacted by the acute metabolic stress of exercise.” This study further highlights the need for individualized consideration of dd-cf-DNA levels in light of clinical parameters and environmental stressors.
New look at Ventricular Assistive Devices
Multiple symposia at ATC 2024 explored trends in using left ventricular assistive devices (LVADs) as a potential alternative to transplant. One interactive symposium, entitled “Godzilla vs Kong: The Epic Battle Between Heart Transplant and LVAD!” focused on the lack of randomized controlled trial data comparing heart transplant and LVAD, though there are ethical challenges in conducting such a trial. According to Dr. Hall, symposium moderator, “It was important to highlight that the technology has improved to the point where intermediate survival is equivalent between heart transplant and LVAD, which is a great place to be. The real difference comes in the comorbidity burden and risk of complications.”
Another interactive symposium focused on considerations for transplant among patients who received LVAD as a destination therapy. Although a patient may be transplant-ineligible at the time of LVAD placement, with support and treatment for other health issues, some of these patients become transplant-eligible over time. Topics in this symposium included pathways to using higher-risk donors, managing the complications of LVAD, and the potential for xenotransplantation. Dr. Hall, who also moderated this symposium, says, “The discussion highlighted the need to find innovative ways to expand our transplant options to meet the needs of an increasing pool of transplant-eligible patients while maintaining high standards for success.”
Improving Effective Use of Donor Organs
A key topic at ATC 2024 was the need to improve the effective use of donor organs. Many patients have transplantation as their only medical option, and they rely on a complex national system to identify eligible donor organs and transport each organ to a matched patient.
Baylor Dallas contributed to a plenary session presentation on a national registry for extracorporeal donor organ perfusion in heart transplantation. The use of extracorporeal perfusion expands the donor heart pool by extending the donor eligibility criteria. This is one of multiple technologies being developed to minimize the number of discarded donor organs. The researchers reported increasing utilization of the extracorporeal perfusion technology since 2022 and observed similar post-transplant survival among transplants that used the expanded donor criteria with extracorporeal perfusion and those that used standard donor criteria.
Part of improving the use of donor organs is modernizing the national infrastructure for organ identification and transport, and there was active discussion of strategies for improvement. According to Dr. Hall, who is also on the AST Board of Directors, “The US is a global leader in transplant infrastructure with the highest transplant volumes worldwide. However, there is room for improvement and there are many complexities in the system. The transplant community looks forward to a modernization plan that is developed thoughtfully, scientifically, equitably, and rationally for each component of the national transplant infrastructure.”
