A Randomized Controlled Trial Comparing a New State-of-the-art Non Ischemic Heart Preservation Method With the Standard Ischemic Cold Static Storage Method of Donor Hearts in Adult Heart Transplantation

SURVEY OF THE FIELD Ischemia and reperfusion (I/R) - elicited tissue injury contributes to morbidity and mortality. In organ transplantation, it is a major challenge. The imbalance in metabolic supply and demand within the ischemic organ results in tissue hypoxia and microvascular dysfunction. The following reperfusion enhances the activation of innate and adaptive immune responses resulting in a cell death program.

A damaged endothelium increases the risk of allograft rejection within 1-year after transplantation and a drug treated rejection increases the risk of chronicle rejection and five-year mortality. An improved preservation of the endothelium of the coronary arteries is therefore instrumental to achieve an improved short- and long-term outcome for the transplanted patients.

Standard heart preservation before transplantation consists of cold ischemic storage of the heart. Clinical studies have shown that the mortality risk increases sharply with extension of the allograft ischemic time over four hours. For each additional hour, the mortality risk increases with 25% the first year. Different myocardial cardioplegic preservation solutions and ex-vivo perfusion machines have been developed. Despite some promising experimental results, no consistent differences in outcome have been found. Our first-in-man pilot study, including 6 NIHP cases, show the device's feasibility and provide the first pieces of evidence that machines improves outcome of heart transplantation. However, as these results are based on a non-randomized study design with a few patients, a randomized study is needed to ensure the effect.

PURPOSE AND AIMS The purpose of this study is to compare a new state-of-the-art non ischemic heart preservation (NIHP) method, on heart allograft function, rejection episodes, and quality of life, with the standard ischemic cold static storage (SCS) method of donor hearts in adult heart transplantation.

STUDY DESIGN The study is a multicentre, prospective, randomized, open, blinded endpoint, controlled clinical trial. The study will randomly assign eligible patients to be transplanted with a donor heart preserved with either a new ex-vivo perfusion method (NIHP) or the standard cold static storage (SCS). The study will be performed at Skane University Hospital, Karolinska University Hospital, Linköping University Hospital, and Uppsala University Hospital, which cover two-thirds of the population in Sweden. Patients listed at these centres will be transplanted at Skane University Hospital and then returned to their centre for post-transplant care. The data collection, statistical analysis, and presentation of results will be done according to the CONSORT criteria. The main outcomes will be reported on intention to treat basis.