Heart Transplant Research Program
Physician-scientists in the Heart Transplant Research Program within the Mayo Clinic Transplant Research Center focus their research efforts on improving morbidity and mortality associated with challenges in heart transplantation.
These challenges include developing novel immunosuppression strategies, managing immunosuppressive medications after transplantation to minimize adverse effects and enhance efficacy, and identifying biomarkers that help predict clinical outcomes for patients.
Specifically, novel areas of research include exploring ways to personalize treatments for patients by using biomarkers and genetics to individualize therapy.
The Heart Transplant Research Program also continues to build on well-established research to investigate the major causes of graft failure and develop therapeutic approaches to prolong graft survival.
Research focus areas
The Heart Transplant Research Program focuses on several areas of research:
- Assessing the significance of anti-human leukocyte antigen (anti-HLA) antibodies for selecting and treating heart transplant recipients
- Identifying and developing surrogate endpoints and biomarkers to help predict rejection and long-term survival
- Developing the best immunosuppression strategies to improve survival
- Individualizing immunosuppression management
Here's a closer look at the heart transplant research focus areas:
Anti-human leukocyte antigen (anti-HLA) antibodies
Mayo Clinic heart researchers are exploring how to improve outcomes and reduce the risk of rejection in transplant recipients by assessing the significance of anti-HLA antibodies.
The development of anti-HLA antibodies in patients makes it more difficult to find a donor heart that will be a compatible match, which in turn increases the risk of rejection and graft vasculopathy — transplant coronary disease, which results in thickening of the blood vessels and is a major cause of failure of transplanted hearts. Mayo Clinic investigators were leaders in showing that the presence of anti-HLA antibodies can lead to graft vasculopathy.
Surrogate endpoints and biomarkers
Investigators in the Heart Transplant Research Program are identifying surrogate endpoints and biomarkers to evaluate the effectiveness of treatment and to predict outcomes for patients undergoing heart transplant.
Mayo Clinic researchers have shown that increased thickness of the heart muscle (left ventricular hypertrophy, or LVH) after heart transplant is associated with increased mortality, exercise intolerance and the progression of graft vasculopathy.
Program researchers have developed strategies that have resulted in regression of LVH that could have an impact on improving survival of heart transplant recipients. Researchers are also exploring why heart transplant patients develop this condition in an effort to understand how it can be prevented.
Researchers in the Heart Transplant Research Program are studying ways to modulate immunosuppressive medications for patients undergoing heart transplant.
The goal of this research is to minimize the risk of rejection of the transplanted heart while reducing side effects from the medications, such as infection, renal failure and the development of malignancies.
Identifying the correct type and dose of immunosuppressive medication is critical to prevent organ rejection. In the short term, rejection can damage the transplanted heart's function, and in the long term it can result in failure of the transplanted heart.
Mayo Clinic researchers are investigating the effectiveness of different immunosuppressive medications and comparing patient outcomes with traditional calcineurin inhibitors (such as tacrolimus) with mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus).
The Heart Transplant Research Program pioneered the use of mTOR inhibitors as primary immunosuppression after heart transplantation and demonstrated that this approach prevented the development of renal failure and slowed down or prevented the development of allograft vasculopathy.
In addition, Mayo Clinic researchers showed that use of mTOR inhibitors results in regression of LVH. Preliminary investigations also show that use of mTOR inhibitors can prevent the development of malignancies, which remains one of the major complications of immunosuppression.
Research in the Heart Transplant Research Program at Mayo Clinic is also tackling immunotherapy challenges related to complications and comorbidities in patients, including:
- Allograft vasculopathy. New areas of investigation include examining the potential role of anti-thrombotic therapy to prevent progression of allograft vasculopathy and refining imaging techniques.
- Renal failure. As many as 10% of patients eventually require renal replacement therapy — either dialysis or renal transplant — because of the use of calcineurin inhibitors. Mayo Clinic now routinely uses mTOR inhibitors to help prevent and potentially reverse renal decline. Newer approaches include examination of potential biomarkers to predict and thereby prevent the development of renal failure.
- Combined organ transplantation. Mayo Clinic has performed the largest number of combined heart-liver transplants in the world. The Heart Transplant Program pioneered a new approach in which the liver is transplanted first to help remove circulating anti-HLA antibodies and decrease the risk of rejection.
Individualized immunosuppression management
Mayo Clinic investigators are exploring how genes influence treatment outcomes for patients undergoing heart transplant.
These efforts include:
- Understanding how genetic factors influence a patient's response to different immunosuppression medications. Through retrospective and prospective studies, researchers are working to identify genetic variants that can be used to direct the best dose of immunosuppressive medication for each patient. For example, researchers are examining patients for a variation in the CYP3A5 gene that requires higher doses of immunosuppressive medication. By identifying these patients prior to transplant, physicians can administer the appropriate dose of immunosuppression and reduce the chance of rejection.
- Using genetic testing, such as RNA sequencing, to understand how the messages that are sent or transcribed by genes (known as the transcriptome) impact a heart transplant patient's response to immunosuppression medications and chances of developing rejection, infection or other complications.
- Measuring metabolites in patient blood samples to identify what metabolic characteristics can predict organ rejection, infection and long-term outcomes. Metabolite levels can provide important information about molecular activity occurring in the body. By identifying which metabolite characteristics are associated with specific outcomes, researchers hope to treat heart transplant patients before they experience rejection, infection or other side effects from immunosuppressive medications.
Here's a list of faculty in the Heart Transplant Research Program by campus location.
- DeValeria, Patrick A., M.D.
- Hardaway, Brian W., M.D.
- Lanza, Louis A., M.D.
- Naqvi, Tasneem Z., M.D.
- Pajaro, Octavio E., M.D., Ph.D.
- Scott, Robert L., M.D.
- Srivathsan, Komandoor, M.D.
- Steidley, D. Eric, M.D.
- Agnew, Richard C., M.D.
- Landolfo, Kevin, M.D.
- Thomas, Mathew, M.D.
- Yip, Daniel S., M.D.
- Behfar, Atta, M.D., Ph.D.
- Boilson, Barry A., M.D.
- Clavell, Alfredo L., M.D.
- Daly, Richard C., M.D.
- Dearani, Joseph A. M.D.
- Dunlay, Shannon M., M.D., M.S.
- Frantz, Robert P., M.D.
- Kushwaha, Sudhir S., M.D.
- Pochettino, Alberto, M.D.
- Stulak, John M., M.D.
- Pereira, Naveen L., M.D.
- Rodeheffer, Richard J., M.D.
- Schirger, John A., M.D.