The Transplant Forum at Columbia University Medical Center is dedicated to raising awareness and funding for transplantation research across all organ disciplines. To learn more about ongoing research in heart transplantation, please see several projects highlighted here:
Adult Heart Transplant Research
Maryjane Farr, MD
Dr. Farr is studying the potential of organ donation after cardiac death (DCD) to increase the number of viable hearts available for transplantation. In recent years, an increasing number of transplants have resulted from a designation of “cardiac death,” rather than “brain death.” Cardiac death is an ethically and legally appropriate end of life designation applied to patients whose circulatory and respiratory functions have permanently ceased. DCD only occurs after family and caregivers have independently provided consent to the protocol. In New York, DCD donors are not utilized for heart transplantation, although it is used for other types of organ transplant. Dr. Farr and her colleagues are examining the medical records of past DCD patients in the region to evaluate the possibility of extending this practice to heart donations. Preliminary research suggests use of DCD has the potential to significantly expand the number of successful heart transplants in the New York region. This research entails the development of new clinical protocols for how to manage a DCD heart transplant at CUMC and several other major New York transplant centers.
Dr. Farr is exploring a new survivorship initiative dedicated to supporting the long-term health of transplantation patients after their transplants. Transplantation is a life-changing event that shapes every aspect of a patient’s subsequent care. Most primary care physicians have limited training on the many health issues that may come into play after a transplant, which means care for these patients is dominated by referrals to specialists. Dr. Farr’s goal is to establish a new model of comprehensive care delivered at Columbia/NYP that is overseen by providers with expertise in transplantation. This effort will include additional training for nurse practitioners as well as research into the most effective therapies and interventions—both routine and specialized—for patients who have received a transplant. Dr. Farr is currently investigating a model for cardiac patients that could be expanded readily to other organ areas.
Marlena V. Habal, MD FRCP(C)
While the last decade has seen improvements in survival following heart transplant (HT), long-term outcomes remains suboptimal with graft failure being a leading cause of both early and late death. Current immunosuppression is limited by untoward side effects with over 40% of patients developing severe chronic kidney disease by 10-years, a factor that is associated with worse overall outcomes. At the same time, from an immunological perspective, patients continue to experience cellular, humoral (antibody mediated), and chronic rejection with approximately 30% of recipients developing donor specific antibodies (DSA). These antibodies, especially if they are new in onset after transplant, portend a worse outcome with increased risk of cardiac allograft vasculopathy/ graft dysfunction and reduced survival. As such, better immunosuppressive strategies are required that can improve long-term outcomes for the heart, while reducing the morbidity associated with current therapies, in particular calcineurin inhibitors (CNI).
Belatacept (CTLA-4-Ig) is an immunomodulatory drug that blocks T-cell costimulation and therefore prevents them from being activated. It is currently FDA approved for use in renal transplant based on large trials where it was associated with better renal function, less donor specific antibody (DSA) production, and improved long-term outcomes. To date, Belatacept has not been used in heart transplant recipients. However, given that DSA are associated with worse outcomes after heart transplant, and that there is a high burden of kidney disease amongst these patients, we hypothesize that Belatacept could also be of benefit after heart transplant. In this pilot trial we will determine the effects of Belatacept, used in conjunction with standard immunotherapies, on post-transplant outcomes. Specifically, we will address its role in reducing donor specific antibodies and halting the progressive decline in renal function associated with calcineurin inhibitors.
Yoshifumi Naka, MD, PhD
The heart transplant program is participating in a prospective, multi-center study of the HeartMate III Left Ventricular Assist System (LVAS). Under the leadership of Yoshifumi Naka, MD, PhD, Director of CUMC’s Cardiac Transplantation Program, Columbia will join researchers from across the country in a clinical assessment of outcomes among advanced-stage heart failure patients receiving the HeartMate III LVAS. Researchers will evaluate the device’s ability to provide long-term support, or “destination therapy,” for patients who are not candidates for cardiac transplant. The device will also be evaluated as a short-term, “bridge-to-transplantation” option for patients who are awaiting a viable donor organ.
Emmanuel Zorn, PhD; Paolo Colombo, MD; Maryjane Farr, MD and Susan Restaino, MD
Drs. Zorn, Colombo, Farr and Restaino are studying the way the immune system responds to heart pumps implanted as a bridge to transplant. Installation of a heart pump can cause an immune reaction known as sensitization, which can make it difficult for the patient to match with a heart donor and increases the risk of rejection after transplant. In recent experiments, Drs. Zorn, Colombo, Farr and Restaino identified a subset of white blood cells known as “innate B cells” that appear to be activated in patients receiving heart pumps and may contribute to sensitization. This is an important step toward understanding how the immune system is controlled in heart transplant candidates and will allow physicians to develop and test new approaches for preventing rejection after a transplant.
Mathew Maurer, MD
Mathew Maurer, M.D., is working to improve diagnosis of cardiac amyloidosis. The amyloidoses are a group of diseases caused by misfolded proteins that deposit in various organs, including the heart, and lead to organ failure. Primary (or AL) amyloidosis is caused by proteins produced in white blood cells, and can cause rapid, multiple organ failure. TTR amyloidosis progresses more slowly, resulting in heart failure and irreversible nerve damage. Both forms, if left untreated, are fatal, and it is vital to quickly distinguish between the two, as prognosis, treatment, and the risk of inheritance differ dramatically by type. TTR amyloidosis, for instance, can be caused by a genetic mutation, in which family members have a fifty percent chance of inheriting the abnormal gene. Dr. Maurer and colleagues lead the nation in offering drug trials for managing TTR amyloidosis, and are developing diagnostic tools that help discriminate between AL and TTR, as well as genetic screening programs to find people with TTR amyloidosis.
Pediatric Heart Transplant Research
Linda Addonizio, MD
Dr. Linda Addonizio is leading several studies in pediatric heart transplant, including:
- An NIH-funded multicenter study that addresses how HLA incompatibility, mediators of inflammation, and immunosuppressive drug efficacy influence cardiac transplantation outcome in pediatric patients.
- An NIH-funded multicenter study (CTOTC) with the primary objective to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity cross-match and to compare them with outcomes in non-sensitized participants.
- A retrospective chart review of pediatric patients with hypertrophic obstructive cardiomyopathy who underwent left ventricular septal myomectomy and/or mitral valve replacement.
- A retrospective chart review of pediatric patients who underwent heart transplantation to examine the impact of type of immunosuppression therapy and donor and recipient EBV status in relation to risk of subsequent PTLD.
Teresa M. Lee, MD
Dr. Teresa Lee is studying advanced human stem cell techniques, which offer a promising avenue to define the genetic and biological origins of Congenital Heart Disease (CHD). Dr. Lee can convert a CHD patient’s skin cells into actively beating heart cells that can be examined in a petri dish, which allows research as to why a patient’s cardiac muscle is not working. This approach has the potential to individualize patient treatment and is sometimes referred to as “precision medicine.”
More broadly, this line of research will examine the genetic mutations that lead to congenital heart defects and how they manifest in the heart at the cellular level.
Warren A. Zuckerman, MD
Dr. Zuckerman’s research interests include pediatric cardiomyopathies, donor- and recipient-related issues surrounding pediatric heart transplantation, and drug therapies for prevention and treatment of graft rejection following heart transplantation. He currently serves as the local site principal investigator in the Panorama trial evaluating the safety and efficacy of entresto compared with enalapril in pediatric heart failure. He has also been heavily involved in the Clinical Trial in Organ Transplantation in Children (CTOTC) studies examining outcomes and adherence in pediatric heart transplantation, and served as primary author of the consortium’s recently published initial paper.