Portable Normothermic Cardiac Perfusion System in Donation After Cardiocirculatory Death: A Health Technology Assessment.

Background: Heart transplantation is the most effective treatment for people experiencing end-stage heart failure whose quality of life and life expectancy are unacceptable. However, there is a chronic shortage of donor hearts to meet the demand, so it is essential to expand the donor pool and increase supply. Heart donation mainly occurs after brain death (neurological determination of death [NDD]), but it may also be feasible after cardiocirculatory death (when the heart has stopped beating and there is no longer blood flow or a pulse), provided specialized preservation techniques are used. An investigational device, a portable normothermic cardiac perfusion system, could make it possible to procure, preserve, and transport hearts donated after cardiocirculatory death (DCD). We conducted a health technology assessment of a portable normothermic cardiac perfusion system for the preservation and transportation of DCD hearts for adult transplantation. This included an evaluation of the effectiveness, safety, value for money, and budget impact of publicly funding this system, as well as an evaluation of patient preferences and values.

Methods: We performed a systematic review of the clinical literature published since 1998 that examined the clinical safety and effectiveness of a portable normothermic cardiac perfusion system for DCD heart transplantation. We assessed the risk of bias of each included study and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also reviewed the economic evidence published during the same time period for the cost-effectiveness of a portable normothermic cardiac perfusion system for DCD hearts compared with cold storage for NDD hearts. We further estimated the 5-year net budget impact of publicly funding a normothermic cardiac perfusion system for DCD heart transplantation for adults on Ontario's waitlist. To contextualize the potential value of a portable normothermic cardiac perfusion system, we spoke with people waiting for a heart transplant, people who had received a heart transplant, and family members of organ donors.

Results: We screened 2,386 clinical citations. One study and two case reports met the inclusion criteria. The survival of recipients of DCD hearts procured with a portable normothermic cardiac perfusion system did not differ significantly from the survival of recipients of hearts donated after NDD at 30 days or 90 days, nor was there a significant difference in cumulative survival at 1 year post-transplant (GRADE: Very Low). The occurrence of rejection and graft failure also did not significantly differ between the groups (GRADE: Very Low). Cardiac function in the early post-operative period was better in DCD hearts than NDD hearts (GRADE: Very Low). There were no differences in outcomes between DCD procurement techniques.The economic literature search yielded 62 citations. One report met the inclusion criteria but was not directly applicable to the Ontario context. Given the lack of clinical and economic evidence on long-term outcomes, we did not conduct a primary economic evaluation. In the budget impact analysis, based on the number of DCD donors under 40 years of age in the last 5 years, we estimated that the increased availability of donor hearts made possible by the technology would result in an additional seven transplants in year 1, increasing to 12 in year 5. The annual net budget impact of publicly funding a normothermic cardiac perfusion system for the transplantation of DCD hearts in Ontario over the next 5 years is about $2.0 million in the first year and about $0.9 million in each of years 2 through 5, yielding a total net budget impact of about $5.6 million. This number increases to about $10.3 million if the transplant volume increases to 18 hearts in year 1 (meaning a subsequent increase of up to 21 hearts in year 5). If transplantation were limited to people who do not qualify for a ventricular assistive device or who qualify but do not wish to receive one, the total 5-year net budget impact would be about $7.9 million.People waiting for a heart transplant or who had received a heart transplant and family members of organ donors expressed no substantial concerns about the potential use of a portable normothermic cardiac perfusion system. They hope that it may increase the number of donor hearts available for transplant. For family members of organ donors, a perfusion system may provide comfort and value if it can increase the successful procurement of donor hearts.

Conclusions: Based on very low quality of evidence, the outcomes for recipients of DCD hearts preserved using a portable normothermic cardiac perfusion system appear to be similar to outcomes for recipients of NDD hearts. Owing to a lack of evidence relevant to the Ontario context, we were unable to determine whether a portable normothermic perfusion system may be cost-effective. We estimate that publicly funding a portable normothermic cardiac perfusion system for DCD heart transplantation over the next 5 years will cost about $5.6 million. The people we spoke with believe that the system may increase the number of hearts available for transplant and therefore increase the number of heart transplants that can be done.