Donor heart preservation remains one of the most vulnerable and decisive steps in the transplant pathway, as it requires a careful balance between reducing cellular metabolism and preventing cold-induced injury. For decades, heart transport has relied on an apparently simple approach: storage in water ice at 0°C inside more or less specific containers. Although this practice has been universally accepted, it is far from physiologically optimal. The main problem lies in the intrinsic properties of water ice. Its phase transition, or melting point, creates an unstable and potentially harmful thermal environment, because abrupt cooling during thermal exchange may cause superficial freezing injury when temperatures are at or below 0°C. In addition, cold penetration into the deeper layers of the organ occurs unevenly, creating a false sense of safety based on the assumption that lower temperature necessarily means better protection, while being associated with impaired diastolic function and injury to the conduction system. Furthermore, as long as ice remains solid, the overall temperature stays close to 0°C, thereby perpetuating these effects on myocardial tissue.

Against this background, the development of dedicated preservation systems such as the Paragonix SherpaPak Cardiac Transport System® introduces an important conceptual shift based on precise control of the thermal environment. This device does not merely contain the organ; it creates a microenvironment designed to maintain controlled moderate hypothermia between 4°C and 6°C through the use of glycol-based cooling elements, which provide slower and more homogeneous energy transfer. This feature allows gradual cold penetration toward the myocardial core, avoiding abrupt thermal gradients and reducing the risk of cellular injury. In addition, the system incorporates advanced thermal insulation, continuous temperature monitoring, and a rigid, sealed container that protects the graft from mechanical trauma, with the heart suspended by the aorta in fluid and without contact with any air interface. Altogether, this provides a much more reproducible and safer preservation environment than traditional systems.

This change in approach is not merely technological; it is supported by a growing body of evidence questioning the suitability of storage at 0°C. Recent studies have shown that preservation within moderate hypothermic ranges may improve metabolic and functional graft parameters, suggesting that slightly higher temperatures may reduce cellular stress and optimize recovery after reperfusion. In this regard, the gradual move away from conventional ice should not be viewed as a technological trend, but rather as the logical consequence of a better understanding of graft physiology during cold ischemia.

The GUARDIAN registry should be interpreted within this context. It is the largest real-world study designed to evaluate the impact of preservation methods on heart transplant outcomes. This retrospective multicenter registry included 1261 transplants performed at 19 centers in the United States between 2015 and 2024, directly comparing conventional ice storage with the Paragonix® system. The data provided by this analysis represent a qualitative step forward in the available evidence, as this is the first study to show not only improvements in intermediate outcomes but also a significant impact on post-transplant survival.

One of the most relevant findings of the registry is the significant reduction in severe primary graft dysfunction, from 10.8% in the ice group to 6.8% in the Paragonix® group, as well as in severe right ventricular dysfunction, from 9.9% to 6.1%. These data are far from trivial, because primary graft dysfunction is the leading cause of early mortality after heart transplantation, with mortality rates that may exceed 50% in the most severe cases. The reduction in these complications suggests that more precise thermal control during transport has a direct effect on the functional integrity of the myocardium, probably by minimizing mitochondrial injury and the inflammatory cascade associated with reperfusion.

The multivariable analysis reinforces this interpretation by identifying Paragonix® use as an independent predictor of a lower risk of primary graft dysfunction, with a 40% reduction in the likelihood of this event, as well as a 25% reduction in right ventricular dysfunction. It is particularly noteworthy that these benefits were maintained and even amplified in high-risk subgroups, such as recipients older than 50 years, patients supported with ventricular assist devices, or cases with ischemic times longer than 4 hours. This suggests that the impact of the system may be greatest precisely where it is most needed.

Another key aspect of the GUARDIAN registry is that the Paragonix® transport group had more unfavorable baseline characteristics, including longer ischemic times and greater transport distances, reflecting a more complex and demanding clinical scenario. Despite this, outcomes were consistently better, strengthening the robustness of the findings and reducing the likelihood that they reflect a favorable bias. The use of propensity score matching also allowed baseline differences between groups to be balanced, confirming that the observed advantages persisted even after adjustment for multiple confounding variables.

It is precisely in this matched analysis that the most relevant finding of the study emerges: a significant improvement in 2-year survival. In the adjusted cohort, survival was 94.3% in the Paragonix® group versus 89.5% in the ice group, with an absolute risk reduction of 4.8% and a number needed to treat of 21 patients to prevent 1 death at 2 years. This finding is particularly important because this is the first study to demonstrate a survival benefit with a static preservation strategy, crossing a threshold that even normothermic perfusion systems have not consistently overcome.

Kaplan-Meier survival analysis confirmed this advantage, showing a significantly higher probability of survival throughout the 2-year follow-up period in the group in which the organ was transported with Paragonix®. Similarly, proportional hazards analysis showed a 47% reduction in the risk of death associated with the use of this system, an effect mainly attributed to fewer cardiovascular events, including primary graft dysfunction. This finding is consistent with the known pathophysiology, as more uniform myocardial preservation should translate into a lower incidence of early graft failure and, therefore, improved overall survival.

The consistency of the GUARDIAN registry results, together with the magnitude of the observed effect, places controlled hypothermic preservation systems in a prominent position among current organ transport strategies. Far from representing an incremental improvement, these devices appear to mark a paradigm shift that redefines quality standards in donor heart preservation. In a setting in which ischemic times are likely to increase because of the geographical expansion of transplant programs, the ability to maintain organ viability for longer periods becomes critically important. In Spain, where mean ischemic times are around 3.5 hours, implementation of these technologies could be particularly beneficial in prolonged transport scenarios or in extended-criteria donors, although systematic adoption is still awaiting a forthcoming position statement from the Organización Nacional de Trasplantes (ONT).

COMMENTARY:

The available evidence calls for a critical reassessment of the continued use of conventional ice as the standard method for donor heart preservation, particularly in a setting in which technologically superior alternatives supported by robust clinical data are available. Controlled moderate hypothermia not only provides a more stable thermal environment, but also appears to translate into a significant reduction in key complications and, most importantly, an improvement in mid-term survival. This is especially relevant because it represents one of the few advances in heart transplantation that has shown a direct impact on mortality, which should encourage its consideration as a standard approach in contemporary clinical practice. Transport distances in our country are not comparable with those in other settings, but this type of technology could expand the geographical radius for graft allocation, particularly in controlled donation after circulatory death. The transition toward these systems raises logistical, economic, and regulatory challenges, but the accumulating evidence suggests that maintaining strategies based on ice at 0°C is increasingly difficult to justify from a scientific standpoint. In this regard, the GUARDIAN registry does more than provide data; it points clearly toward the modernization of organ preservation, aligning clinical practice with the physiological and technological principles of the 21st century.

REFERENCE:

Silvestry S, Meyer DM, Pham SM, Jacobs JP, Shudo Y, Schroder J, et al. Improved 2-year heart transplant survival with moderate hypothermic donor heart preservation in the GUARDIAN heart registry. J Heart Lung Transplant. 2026;45:544-552.