Integrating emerging preservation strategies in cardiac transplantation: From nanotherapeutic frontiers to clinical translation

Hypothermic preservation remains a critical bottleneck in heart transplantation, primarily due to the exacerbation of ischemia-reperfusion injury (IRI) and tightly restricted organ viability windows. Addressing this global clinical crisis requires a departure from traditional monotherapies. This review critically appraises—rather than merely synthesizes—three multidisciplinary advancements: (1) preservation solutions supplemented with nanotherapeutics, with explicit distinction between proof-of-concept, small-animal, and clinically translatable evidence; (2) technological transitions from static cold storage (SCS) to ex vivo heart perfusion (EVHP) and nanowarming-assisted cryopreservation; and (3) bioactive compounds derived from Traditional Chinese Medicine (TCM), evaluated through a SWOT framework that acknowledges phytochemical variability and the paucity of clinical transplantation data. We further examine the emerging—but currently nascent and largely speculative---role of artificial intelligence in perfusion decision support. We emphasize that these three domains are not evidentially equivalent: perfusion technology is clinically implemented, pharmacological and nanotherapeutic adjuncts remain predominantly preclinical, and AI applications in cardiac preservation are currently confined to retrospective outcome modelling, with no published closed-loop perfusion control in clinical practice