In This Article
- Massachusetts General Hospital is one of 13 heart transplant centers in the U.S. participating in a prospective, randomized clinical trial of donation after circulatory death (DCD) heart transplants, and one of six centers who have performed the transplant
- Mass General heart surgeons have successfully transplanted 16 DCD donor hearts since completing the first DCD heart transplantation in New England
- DCD heart transplants increase the number of suitable organs available for transplant
- The DCD heart transplant trial utilizes warm machine perfusion to safely reanimate and assess the health of the donor heart before transplantation
- The warm machine perfusion system significantly extends safe out-of-body time as compared to cold storage
There is a critical need for new sources of healthy organs for transplantation, with long wait times. Massachusetts General Hospital surgeons have successfully transplanted 16 adult donation after circulatory death (DCD) donor hearts—the most in the U.S.—as part of a nationwide clinical trial. Of the 13 DCD heart transplant centers participating in the prospective, randomized clinical trial for DCD heart transplants, Mass General is one of six to have performed the transplants so far.
"All of our patients have normal function of the transplanted hearts within a few days, and I am convinced that this is safe," says David D'Alessandro, MD, surgical director for Heart Transplantation and Ventricular Assist Devices at Mass General. "When you combine the increased access to organs and outcomes we've seen, I am confident that this is the right thing to do. And while it's going to take more patients to confirm this and ensure that our results are reproducible at other centers, based on our trajectory I expect this technology will be approved within a few years."
Establishment of Brain Death Advances Heart Transplantation
Most organs for transplant come from donation after brain death (DBD) donors. State legislatures first passed the statute outlining the legal definition of brain death in the mid-1970s. Prior to brain death's uniform establishment, clinicians declared death when the heart stopped.
"In the early days of transplant, donors were required to die by allowing their hearts to stop. If they died quickly and were geographically close enough, surgeons could remove the hearts and transplant them," says Dr. D'Alessandro. "But poor heart preservation led to bad transplant outcomes."
Once death became defined by brain function, surgeons gained the ability to chemically stop and protect the heart. This process allowed them to safely keep the heart out of the body using cold storage for four to six hours before reestablishing warm perfusion.
DCD Heart Transplants Redefine Donor Pool
Organ availability remains a significant hurdle for transplantation.
"There just aren't enough organs for the number of patients who need them, so using organs from DCD donors that are not brain dead will have a big impact," says Dr. D'Alessandro. "A DCD donor, for example, would be a patient with a devastating neurologic injury and no hope for meaningful recovery. The family will often elect to remove their loved one from life support. Rather than letting that patient and their organs expire, we can quickly take those organs out and reassess them with consent from the family."
DCD heart transplantation has unique challenges and higher risks compared to DCD kidney, liver and lung transplants. If a transplanted kidney doesn't work right away, the patient can go back on dialysis. If lungs don't work right away, physicians can use ECMO for support.
"But the heart must work immediately, or you're in trouble," says Dr. D'Alessandro. "We do have ECMO as a salvage pump for a few days of support. But if the heart doesn't wake up in that period, our patient can be in real danger. Retransplantation is often not a good option. Hearts just aren't that available. So we have to have a real expectation that we're putting in a good organ. We now have a machine that enables us to both resuscitate but also evaluate the donor heart before we put our patient at risk."
DCD Heart Transplant Clinical Trials
Because of these considerations, the first DCD heart transplant was performed in Australia in 2014—more than a decade after the widespread use of other DCD organs.
"We started doing these in the U.S. within the confines of our clinical trial in October 2019," says Dr. D'Alessandro. "Mass General did the first adult DCD heart transplant in New England in November 2019, and we recently transplanted our 16th patient."
The DCD heart transplant trial features an unequal randomization ratio of 3:1 to allow investigators to obtain enough DCD hearts to compare with cold storage hearts. Study participants cannot need more than one organ transplant. The trial was initially expected to complete enrollment in August 2021 but unexpectedly brisk enrollment will likely see the trial completed almost a year early.
"Based on our experience, this seems to be safe and reproducible," says Dr. D'Alessandro. "My strong suspicion is that this trial will show that we can safely utilize DCD organs using our methods to ensure that hearts work well before we put them."
Availability Decreases Wait Times
Having access to DCD hearts is already drastically decreasing wait times. Dr. D'Alessandro's team recently listed a patient who was also listed at two programs in other states. That same day, the Mass General team found a DCD heart for him and transplanted it within 24 hours.
"If this gets approved and the whole country starts considering these organs, the wait time will not be as big an advantage," says Dr. D'Alessandro. "But right now, it's tremendous."
DCD donations also seem to give donor families additional comfort and meaning. "The families sometimes prefer to do it this way because it allows them to say goodbye," says Dr. D'Alessandro. "It's a way that some good can come out of what otherwise is just a tragic event."
Utilizing Technology to Reanimate DCD Hearts
To safely reanimate the heart until transplantation, the DCD heart transplant trial uses warm machine perfusion. The system allows the heart to pump the amount of warm, oxygenated blood required by the coronary arteries.
To assess a heart's health, surgeons measure its utilization of lactate as an energy source for approximately 90 minutes. A heart that is not functioning properly will make lactate. But if it is in good condition for transplantation, lactate will decrease in the system because the heart is using it. Once Dr. D'Alessandro's team establishes heart function, they can start the recipient operation.
"Warm machine perfusion extends the out-of-body time. With cold storage, it's four to six hours. With warm machine profusion, there have been descriptions of more than 12 hours on the machine," says Dr. D'Alessandro.
"So far, every heart that we've put on the machine we've been able to use. And I'm confident based on our experience that this is one way of utilizing these hearts that are going to be FDA-approved in the future."
A competing technique for utilizing DCD hearts called warm regional perfusion makes use of ECMO instead.
"Rather than taking out the donor's organs as quickly as possible using your own flush system, taking it back to your own center and putting them into your recipient," he says, "you open the donor and quickly put them on ECMO. This process takes the blood out, oxygenates it, and puts it back in."
One advantage to this technique is that surgeons can assess the heart's ability to pump blood in the loaded and functional state, which may be an even better indicator of function than lactate production.
However, warm regional perfusion also raises ethical concerns about reanimating the whole donor patient due to the possibility of blood inadvertently making its way to the brain.
"You have to clamp off the aortic arch vessels so you don't reanimate the brain. You're trying to resuscitate all the organs except the brain to reprofuse and resuscitate them at the same time," says Dr. D'Alessandro.
Future Transplantation Innovations
The DCD heart transplant trial is expected to run through August 2021, and Dr. D'Alessandro is equally optimistic about other heart transplantation advances.
"The future of heart transplant is really exciting right now," he says. "Along with the utilization of hepatitis donors, we now have ex vivo perfusion and other exciting perfusion and cold-storage-type apparatuses that are extending the safe out-of-body time. We're also exploring novel immune suppressants, and on the horizon is even xenotransplant and tolerance, which are going to make transplant an even more preferable option for patients in the future."
Learn more about Heart Transplantation at Mass General
Refer a patient to the Corrigan Minehan Heart Center