Q&A: New heart transplant protocol could expand donor pool
A team at Duke University in December became the first in the United States to perform a donation after circulatory death heart transplant.
Transplants with donation after circulatory death (DCD) had been performed in the U.S. with other organs, and DCD heart transplants had been performed in Europe and Australia, but a DCD heart transplant had not been attempted in the U.S. until the launch of the Donors After Circulatory Death Heart Trial, which is evaluating the performance of a perfusion system (TransMedics Organ Care System, TransMedics) to resuscitate and preserve hearts from donors after circulatory death as opposed to brain death. If the technology, which is designed to maintain organs in a living, functional state, is successful in preserving hearts from DCD donors, it could increase the size of the donor pool for heart transplants.
The randomized controlled, pivotal noninferiority trial planned for 212 patients is comparing outcomes between recipients who received a DCD heart transplant and recipients who received a standard-of-care heart transplant. The primary outcome is survival at 6 months. Secondary outcomes include patient and graft survival at 30 days, patient and graft survival at 30 days or at hospital discharge if later than 30 days, severe heart primary graft dysfunction at 24 hours and use of posttransplant mechanical circulatory support.
Healio spoke to Jacob N. Schroder, MD, surgical director of the Heart Transplantation Program, and co-director of the Cardiothoracic Surgical Intensive Care Unit in the division of cardiovascular and thoracic surgery at Duke University Medical Center, who performed the first U.S. DCD heart transplant, about the differences between the transplant types, how the technology works and what the implications could be for patients who need a heart transplant.
Question: How are DCD heart transplants different from conventional ones?
Answer: Traditionally, donors have been declared brain dead, also known as donation after brain death (DBD). After this declaration, the organs that the donor has designated for donation are procured, ie, the beating heart is “put to sleep” and removed. The heart is then transported, traditionally on ice, back to be implanted in the recipient.
In DCD, donors often have a devastating neurologic injury, but do not meet the very strict criteria for brain death. They have no chance of recovery and are kept alive with significant life support such as mechanical ventilation and infusions to maintain BP. The family has made the decision to withdraw care but want to respect the patient's desire to donate their organs. In this case, life support is withdrawn. When the patient's heart stops, there is a 5-minute “hands off” period and then they are pronounced. We then procure the organs, now including the heart. There is a period, called warm ischemic time (WIT), which we define as the time from the point when either the systolic BP is less than 70 mm Hg or the oxygenation saturation is less than 70% to when the heart is infused with a preservation solution. This represents the true time when the heart is not meaningfully perfused. All organs are susceptible to damage during this period where they are not being perfused with oxygenated blood. The heart cannot tolerate a WIT of more than 30 minutes.
Q: Why are DCD heart transplants necessary in today’s transplant environment?
A: A conservative estimate of patients with NYHA class IV HF in the U.S. is 250,000 people. Even if we assume only 10% of these people would actually qualify for a transplant, that is still 25,000 people. In 2018, we did the most heart transplants ever, 3,400. The major barrier to doing more transplants is a lack of suitable DBD heart donors. Additionally, of all of the hearts offered for donation, only 25% to 30% are actually used for transplantation. Recent research out of our institution estimated that the routine use of DCD hearts could increase the donor pool by 30%.
Q: What is the device that facilitates DCD heart transplants and how does it work?
A: The TransMedics Organ Care System (OCS) is a portable warm perfusion machine. This allows the heart to be perfused with oxygenated blood, beating and warm, during transportation. This allows for both evaluation of the organ but also possibly some rehabilitation to allow the heart to recover from the acute insult from WIT.
Q: How did your team get involved with this trial?
A: We have been involved in the other active trial involving the OCS (EXPAND Heart) and have worked with TransMedics to develop the trial.
Q: What are you hoping to learn from this trial?
A: That DCD heart transplant is equivalent to standard of care transplants in terms of survival, posttransplant rates of heart dysfunction, etc, and that we are indeed able to expand the donor pool and transplant more patients.
Q: How are the donors selected?
A: The donor's family has to consent for DCD donation. They must be categorized as Maastricht category III DCD, defined as expected death after withdrawal of life-supportive therapy; they must be between 18 and 49 years old; and the heart’s WIT must be less than or equal to 30 minutes. They cannot have had prior heart surgery, known CAD, prior MI, a reduced ejection fraction (less than 50%) or significant valvular disease.
Q: How are the recipients selected?
A: Recipients must be not have had a prior heart transplant, be on hemodialysis or need multiorgan transplant.
Q: How is the first patient responding?
A: Our first two DCD recipients are recovering well. Their postoperative courses have been pretty standard.
Q: Is there anything else you would like to mention?
A: All of this is only made possible by the courage and generosity of patients and their families who choose to give the gift of life in the face of grief and tragedy. – by Erik Swain
ClinicalTrials.gov. Donors After Circulatory Death Heart Trial. Available at: www.clinicaltrials.gov/ct2/show/NCT03831048. Accessed Dec. 31, 2019.
For more information:
Jacob N. Schroder, MD, can be reached at email@example.com.
Disclosures: The trial is being sponsored by TransMedics. Schroder reports no relevant financial disclosures.