Optimizing Temperature in Ex Situ Heart Perfusion: A Comparative Review of Traditional and Novel Methods in Heart Transplantation

Heart transplantation is still the definitive therapy for end-stage heart failure, yet the persistent shortage of suitable donor organs limits its application. Traditionally, static cold storage (SCS) has served as an effective standard preservation method, providing safe and adequate protection for preservation times under four hours. Yet, the need to extend this window and the specific metabolic requirements of donation after circulatory death (DCD) hearts have prompted interest in machine perfusion (MP) technologies. This literature review investigates the influence of temperature in ex situ heart perfusion, comparing normothermic (NMP), hypothermic (HMP), and subnormothermic (SNMP) strategies. Evidence from experimental models and emerging clinical studies suggests that MP can prolong preservation times, mitigate ischemic injury, and enable real-time metabolic and viability assessment of donor hearts prior to transplantation. These strategies represent a central trade-off: NMP enables real-time functional assessment of the beating heart, while HMP and SNMP approaches prioritize profound metabolic suppression to mitigate ischemic injury. Nonetheless, current data are limited by high costs, significant resource requirements, variability in perfusion protocols, and the scarcity of randomized controlled trials, particularly for HMP and SNMP. Standardization of methodologies, direct comparative studies, and the adoption of a risk-stratified preservation ecosystem are needed to clarify optimal temperature strategies. However, recent clinical successes with hypothermic strategies in traditionally normothermia-dependent donor types, such as DCD hearts, signal a potential paradigm shift, challenging established value propositions and prompting a critical re-evaluation of optimal preservation strategies.