STATE OF ART
Ex situ heart perfusion: The past, the present, and the future

https://doi.org/10.1016/j.healun.2020.10.004Get rights and content

Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected patients with advanced heart failure. However, with an increase in heart failure prevalence worldwide, the gap between donor hearts and patients on the transplant waiting list keeps widening.

Ex situ machine perfusion has played a key role in augmenting heart transplant activities in recent years by enabling the usage of donation after circulatory death hearts, allowing longer interval between procurement and implantation, and permitting the safe use of some extended-criteria donation after brainstem death hearts. This exciting field is at a hinge point, with 1 commercially available heart perfusion machine, which has been used in hundreds of heart transplantations, and a number of devices being tested in the pre-clinical and Phase 1 clinical trial stage. However, no consensus has been reached over the optimal preservation temperature, perfusate composition, and perfusion parameters. In addition, there is a lack of objective measurement for allograft quality and viability.

This review aims to comprehensively summarize the lessons about ex situ heart perfusion as a platform to preserve, assess, and repair donor hearts, which we have learned from the pre-clinical studies and clinical applications, and explore its exciting potential of revolutionizing heart transplantation.

Section snippets

EVHP for preservation

Preserving heart with ex situ perfusion was first investigated in the 1960s, with both hypothermic24,25 and normothermic26 strategies. Since then, a number of teams across the world have developed EVHP machines. Encouragingly, despite the differences in machine designs and perfusion conditions, almost all studies arrived at the conclusion that EVHP is superior to SCS for heart preservation.

EVHP for assessment

Assessment of allograft function is a key advantage offered by ex situ machine perfusion. It is vital to understand which indices accurately predict donor heart quality, especially when EVHP is used to preserve extended-criteria allografts to combat donor organ shortage. Although the OCS offers the opportunity for cardiac viability evaluation, functional assessment of hearts in the non-working mode is not reliable,67,68 and the validity of perfusate lactate as a metabolic biomarker has been

EVHP for reconditioning

During EVHP, therapies can be delivered in high concentrations directly to donor hearts without concerns of being metabolized by other organs or exerting side effects on other body systems.83

From donation to implantation, donor hearts endure different forms of injuries at each stage. In DBD donors, excessive systemic and local catecholamine release84,85 leads to myocardial hypercontracture, band necrosis, and contractile dysfunction.86,87 After procurement, metabolic acidosis and inadequate ATP

Discussion

Whereas SCS is a reliable and time-tested preservation strategy, its limitations have been reached. Its deficiencies in extended-criteria DBD and DCD heart retrieval prevent the expansion of transplant activity. With decades of research experience, both HOP and NOP have been translated into clinical application with comparable or superior outcomes to that of SCS.

Both methods have their strengths and shortcomings (Table 4). NOP integrates preservation and functional assessment, which are

Disclosure statement

S.A. and J.H.D. have received, through their host institution, research grant funding in the form of an unrestricted educational grant from XVIVO Perfusion, Sweden. The remaining authors have no conflicts of interest to disclose.

The research was funded by the National Institute for Health Research Blood and Transplant Research Unit in Organ Donation and Transplantation at the University of Cambridge (Cambridge, United Kingdom) in collaboration with Newcastle University (Newcastle Upon Tyne,

Author contributions

All authors agree to be accountable for all aspects of the work and resolve any questions related to the accuracy of the manuscript and approved the final version of the manuscript.

Concept and design: L.W., S.A., J.H.D.

Drafting of the manuscript: L.W.

Critical revision of the manuscript for important intellectual content: L.W., G.A.M., S.A., J.H.D.

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