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Transplantation Outcomes With Donor Hearts After Circulatory Death
Quick Takes
- Six-month post-transplant survival of heart donation after circulatory death using an extracorporeal perfusion system was noninferior to standard donation after brain death using traditional cold storage.
- Organ utilization was high for donation after circulatory death.
- No differences in overall serious adverse events were noted between groups.
Study Questions:
Do post-transplant outcomes differ between recipients that receive a heart from a donor after circulatory death with subsequent cardiac reanimation and preservation with a portable extracorporeal perfusion system compared to a heart from a donor after brain death with subsequent preservation with cold storage?
Methods:
This was a multicenter, unblinded, randomized, controlled, noninferiority trial comparing heart transplantation using donor hearts after circulatory death that were reanimated and preserved with a portable extracorporeal perfusion system (Organ Care System Heart, TransMedics) (circulatory-death group) to standard care using donor hearts after brain death that were preserved using static cold storage (brain-death group). Potential recipients included adult heart transplant candidates at participating US centers. Exclusion criteria included multiorgan transplant listing, prior solid-organ or bone marrow transplantation, and chronic renal failure receiving hemodialysis.
Patients were randomized in a 3:1 ratio to the circulatory-death or brain-death group. Those assigned to the circulatory-death group were eligible to receive a heart from either a donor after circulatory or brain death to ensure no delays to transplant; those that received hearts from donors after brain death were combined with the brain-death group for an as-treated analysis. The primary efficacy endpoint was risk-adjusted post-transplant survival at 6 months.
Results:
A total of 297 heart transplant candidates at 15 US transplant centers consented for the trial and underwent randomization, with 226 in the circulatory-death and 71 in the brain-death assigned groups. At the end of the study, 180 patients eventually underwent heart transplantation, 152 from the assigned circulatory-death group and 28 from the brain-death group. Of the 152 from the assigned circulatory-death group, 62 patients received a heart from a donor after brain death and were included with the brain-death group for analysis. After exclusions for protocol violations, there were 80 patients in the as-treated circulatory-death and 86 patients in the as-treated brain-death groups.
Overall, donor characteristics were similar, except donors after circulatory death compared to brain death were younger, more likely men, and less likely Black. Recipient characteristics were similar, except those in the as-treated circulatory-death compared to the brain-death group were younger, more likely Black, and more likely to be listed as at a lower priority (43/90 [48%] at United Network for Organ Sharing [UNOS] status 4 vs. 47/90 [52%] at UNOS status 2).
For the primary endpoint, the risk-adjusted 6-month post-transplant survival for the circulatory-death group was 94% (95% confidence interval [CI], 88-99) compared to 90% (95% CI, 84-97) for the brain-death group (least-squares mean difference, −3 percentage points; 90% CI, −10 to 3; p < 0.001 for noninferiority). Similar results were seen at 1-year post-transplant. Of note, 101 hearts from circulatory-death donors were procured and 90 hearts were successfully transplanted, leading to an organ utilization rate of 89%. For the primary safety outcome of serious adverse events at 30 days, the circulatory-death compared to the brain-death group had comparable overall event rates, though had higher rates of moderate or severe primary graft dysfunction but less primary graft dysfunction requiring re-transplantation.
Conclusions:
The risk-adjusted 6-month post-transplant survival of transplantation with a heart from a donor after circulatory death with subsequent cardiac reanimation and preservation with a portable extracorporeal perfusion system is noninferior to standard care transplantation with a heart from a donor after brain death with subsequent preservation with cold storage.
Perspective:
With the growing need for heart transplantation, innovative strategies to increase the limited donor pool are critical. This study highlights two emerging areas that address this, including heart donation after circulatory death (DCD) and extracorporeal machine perfusion. DCD has emerged as a promising strategy and early studies have favorable outcomes with this approach. The prior limitation of the DCD strategy was concerns regarding limited ability to assess cardiac function after circulatory death with cold storage and preservation. Extracorporeal machine perfusion systems and thoracoabdominal normothermic regional perfusion (TA-NRP; not addressed in this study) have removed this barrier and allow for careful assessment of cardiac function prior to transplantation. This study adds significantly to the literature and provides additional evidence that DCD heart transplantation is an effective and safe approach. Higher rates of primary graft dysfunction were seen, but this is likely due to the warm ischemia time with DCD transplantation, and survival did not seem to be impacted. As this field of research grows, other questions to answer will be how this method of DCD transplant and procurement compares to one using TA-NRP, and how DCD transplant will ultimately affect transplant allocation and waitlist management.
Clinical Topics: Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Vascular Medicine, Cardiac Surgery and Heart Failure, Acute Heart Failure, Heart Transplant, Interventions and Vascular Medicine
Keywords: Brain Death, Cardiac Surgical Procedures, Extracorporeal Circulation, Heart Failure, Heart Transplantation, Perfusion, Primary Graft Dysfunction, Survival, Tissue Donors, Warm Ischemia
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