For decades, the preservation and transport of donated hearts for transplant had changed very little. The typical approach has been decidedly low-tech ice in a cooler that might have come from the local hardware store and adorned with stickers highlighting that the contents are not headed for pregame tailgating. For such life-saving cargo, it is surprising that innovation has not reached clinical practice until recently.

The myocardium is highly sensitive to ischemia, limiting the effective ischemic time with cold storage to approximately 4 hours. This time limit creates a substantial geographic barrier to the broad sharing of organs. The penalty for delay is steep and paid by the recipients of this precious gift. Recent efforts to expand the donor pool have included the use of donors with hepatitis C,1 and ex vivo normothermic perfusion with the TransMedics (Andover, MA) Organ Care System (OCS) as shown in PROCEED-II.2 The OCS EXPAND-Heart study showed 94.7% 30-day survival and 10.7% severe primary graft dysfunction (PGD) at 24 hours3 in a series of 93 transplants with expected ischemic time ≥4 hours or ≥2 hours with additional risk factors. Applying EXPAND-Heart criteria broadly could have led to 8,637 potentially eligible donors from 1/1/15 and 6/30/19––an increase of almost 2,000 additional organs per year.4 Use for greater than 10 hours outside the body has been reported.5

OCS has also been used to provide a pathway for donation after cardiac death (DCD)6 and has recently been shown to be noninferior to standard-care transplants with a donor heart that had been preserved with the use of cold storage after brain death.7 The availability of DCD has been shown to significantly decrease wait time from a median time of 47.5–19 days and increase transplant rate from 181 per 100 patient-years to 579 per 100 patient-years without impact on mortality rate.8

Additional advantages of normothermic ex vivo perfusion include the ability to serially evaluate the donated heart, and less time pressure for surgeons to prepare the recipient, who is often undergoing a redo sternotomy. However, the OCS system is capital-intensive and requires substantial technical expertise and personnel that may not be widely available.

Another emerging option for organ transport is ex vivo hypothermic preservation (XVIVO Perfusion, Sweden) which provides continuous perfusion with cold, oxygenated cardioplegic solution.9 This approach is technically less complex than normothermic perfusion which could be advantageous, especially for smaller centers that lack the resources required for OCS.

It is in this context, Shudo et al.10 have presented results of 569 patients transplanted over a ~6-year period at 10 centers from the GUARDIAN-Heart registry using the Paragonix SherpaPak Cardiac Transport System (SCTS) (Paragonix Technologies, Cambridge, MA). The key finding in this publication is that a propensity-matched comparison of SCTS to ICS found a significantly lower rate of severe PGD, significantly lower rates of severe PGD, and lower post-transplant MCS utilization. In the subgroup analysis of patients with ischemic times exceeding 4 hours, improved 30-day survival was observed.

Although there are some differences between the cohorts, it is notable that the SCTS group had a longer organ recovery distance (by 172 miles) and ischemic time (by 24 minutes), due in part to the allocation changes in UNOS heart allocation policy from 2018. We would expect these factors to bias the groups against improved outcomes in the SCTS group.

The propensity-matched group was 300 subjects and confirmed significantly lower rates of severe PGD and lower utilization of all post-transplant MCS devices. There was a nearly 50% reduction in 1-year mortality, but this finding did not reach statistical significance. Given the robust reduction in severe PGD, it might be expected that a larger sample size would confirm improvement in 1-year mortality. With such compelling results, we are likely to be left to compare outcomes from centers that use SCTS to those that do not; it is easy to imagine that GUARDIAN-Heart sites would be skeptical that equipoise exists for a prospective, randomized trial. Multivariate analysis demonstrated that preservation modality was the most highly correlated with 1-year survival. The work of Shudo et al.10 is an important contribution to the growing literature on the use of SherpaPak for donor heart preservation. This large, propensity-matched series showing significant benefit, coupled with a publication highlighting that overall hospital plus mechanical circulatory support costs were lower by $26,700,11 should lead us to ask whether the era of ice-based storage should end. However, another, series failed to demonstrate significant differences in PGD12 and a single-center retrospective analysis found similar postoperative outcomes but fewer units of blood products,13 so not all published data is definitively supportive. These smaller, single-center examples are less compelling than large registry data such as presented by Shudo et al.,10 but remind us that more data will clarify specific benefits. We do not have data on long-term outcomes, although it is hard to imagine the lower rate of PGD and comparable 1-year survival would lead to worse outcomes over a longer time frame. This remains a relatively new technology, and refinements to improve temperature control14 and use in other settings, such as thoracoabdominal normothermic regional perfusion15 are evolving.

Going forward, it remains to be seen whether centers will use SCTS selectively, such as for anticipated longer ischemic times, or more widely with the intent to reduce the risk of PGD and cost of care? The data presently available10,11 are likely to lead many to conclude that there is insufficient equipoise to support prospective, randomized clinical trials. This novel technique may shift the duration of acceptable cold ischemic time, reducing the importance of distance16 in the careful calculus of whether to accept a donor heart for a particular recipient. If experience in practice matches the improved outcomes and lower costs described, it is not hard to imagine current equipment will be relegated to cooling Heinekens and hefeweizens before long.

1. Schlendorf KH, Zalawadiya S, Shah AS, et al.: Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies. J Heart Lung Transplant. 37: 763–769, 2018. 2. Ardehali A, Esmailian F, Deng M, et al.; PROCEED II trial investigators: Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): A prospective, open-label, multicentre, randomised non-inferiority trial. Lancet. 385: 2577–2584, 2015. 3. Schroder JN, D’Alessandro D, Esmailian F, et al.: Successful utilization of extended criteria donor (ECD) hearts for transplantation: Results of the OCS Heart EXPAND trial of evaluate the effectiveness and safety of the OCS heart system to preserve and assess ECD hearts for transplantation. J Heart Lung Transplant. 38(4S): S42, 2019. 4. Jawitz OK, Devore AD, Patel CB, Bryner BS, Schroder JN: EXPANDing the donor pool: Quantifying the potential impact of a portable organ-care system for expanded criteria heart donation. J Card Fail. 27: 1462–1465, 2021. 5. Stamp NL, Shah A, Vincent V, et al.: Successful heart transplant after ten hours out-of-body time using the TransMedics Organ Care System. Heart Lung Circ. 24: 611–613, 2015. 6. Dhital KK, Iyer A, Connellan M, et al.: Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: A case series. Lancet. 385: 2585–2591, 2015. 7. Schroder JN, Patel CB, DeVore AD, et al.: Transplantation outcomes with donor hearts after circulatory death. N Engl J Med. 388: 2121–2131, 2023. 8. Gernhofer YK, Bui QM, Powell JJ, et al.: Heart transplantation from donation after circulatory death: Impact on waitlist time and transplant rate. Am J Transplant. 23: 1241–1255, 2023. 9. Nilsson J, Jernryd V, Qin G, et al.: A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation. Nat Commun. 11: 2976, 2020. 10. Shudo Y, Leacche M, Copeland H, et al.: A paradigm shift in heart preservation: Improved post-transplant outcomes in recipients of donor hearts preserved with the SherpaPak system. ASAIO J. 69: 993–1001, 2023. 11. Voigt JD, Leacche M, Copeland H, et al.: Multicenter registry using propensity score analysis to compare a novel transport/preservation system to traditional means on postoperative hospital outcomes and costs for heart transplant patients. ASAIO J. 69: 345–349, 2023. 12. Bitargil M, Haddad O, Pham SM, et al.: Packing the donor heart: Is SherpaPak cold preservation technique safer compared to ice cold storage. Clin Transplant. 2022: e14707, 2022. 13. Zhu Y, Shudo Y, He H, et al.: Outcomes of heart transplantation using a temperature-controlled hypothermic storage system. Transplantation. 107: 1151–1157, 2023. 14. Kawabori M, Posawatz DA, Chen FY, Couper GS: A simple technique for reliable donor organ temperature management with the SherpaPak system. ASAIO J. 68: e134–e135, 2022. 15. Urban M, Castleberry AW, Siddique A, et al.: Utilization of paragonix sherpapak cardiac transport system for the preservation of donor hearts after circulatory death. Transplant Proc, 2023. In Press. 16. Rodriguez A: A heart was flown from Alaska to Boston, breaking a transplant record. Here’s how it was done. USA Today. May 23, 2023. Available at: https://www.usatoday.com/story/news/health/2023/05/23/heart-transplant-breaks-distance-record/70246473007/. Accessed October 3, 2023.