Pre-clinical heart transplantation studies have shown that ex vivo non-ischemic heart preservation (NIHP) can be safely used for 24 h. Here we perform a prospective, open-label, non-randomized phase II study comparing NIHP to static cold preservation (SCS), the current standard for adult heart transplantation. All adult recipients on waiting lists for heart transplantation were included in the study, unless they met any exclusion criteria. The same standard acceptance criteria for donor hearts were used in both study arms. NIHP was scheduled in advance based on availability of device and trained team members. The primary endpoint was a composite of survival free of severe primary graft dysfunction, free of ECMO use within 7 days, and free of acute cellular rejection ≥2R within 180 days. Secondary endpoints were I/R-tissue injury, immediate graft function, and adverse events. Of the 31 eligible patients, six were assigned to NIHP and 25 to SCS. The median preservation time was 223 min (IQR, 202-263) for NIHP and 194 min (IQR, 164-223) for SCS. Over the first six months, all of the patients assigned to NIHP achieved event-free survival, compared with 18 of those assigned to SCS (Kaplan-Meier estimate of event free survival 72.0% [95% CI 50.0-86.0%]). CK-MB assessed 6 ± 2 h after ending perfusion was 76 (IQR, 50-101) ng/mL for NIHP compared with 138 (IQR, 72-198) ng/mL for SCS. Four deaths within six months after transplantation and three cardiac-related adverse events were reported in the SCS group compared with no deaths or cardiac-related adverse events in the NIHP group. This first-inhuman study shows the feasibility and safety of NIHP for clinical use in heart transplantation. ClinicalTrial.gov, number NCT03150147

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractIschemia/reperfusion may lead to graft dysfunction in heart transplantation (HT).The purpose of this study was to evaluate the influence of ischemic and reperfusion time on acute cellular rejection (ACR) within the first-year post-HT and on long-term outcomes. Data were collected from 331 patients (mean age 49 ± 12 y, 28% females) who underwent HT 1988-2016. Endomyocardial biopsies obtained within the first year after HT were graded according to the 2004-ISHLT-WF. We classified the patients by ischemic time 4 hours, and of these, 31 (55%) patients had reperfusion with CPB ≥90 minutes. Ischemia >4 hours had an increased risk of ACR ≥ 2R during the first year (adjusted OR = 3.1, P = .016); however, an extended reperfusion ≥90 minutes reduced the risk (adjusted OR = 0.25, P = .024). The conditional probability of surviving 10 years post-transplant, given that the patients already survived first year, was inferior for recipients with ischemia ≥ 4 hours and reperfusion <90 minutes, 59%, compared with the other groups 83%, P = .016. Prolonged reperfusion appears to reduce the risk for ACR ≥ 2R and improve long-term survival. K E Y W O R D Sacute cellular rejection, heart transplantation, ischemic time, reperfusion

Currently, static cold storage (SCS) of hearts from donations after brainstem death remains the standard clinically. However, machine perfusion (MP) is considered an approach for donor organ management to extend the donor pool and/or increase the utilization rate. This review summarizes and critically assesses the available clinical data on MP in heart transplantation. We searched Medline (PubMed), Cochrane, Embase, and clinicaltrials.gov, along with reference lists of the included publications and identified 40 publications, including 18 articles, 17 conference abstracts, and five ongoing clinical trials. Two types of MP were used: hypothermic MP (HMP) and normothermic MP (NMP). Three studies evaluated HMP, and 32 evaluated NMP. Independent of the system, MP resulted in clinical outcomes comparable to traditional SCS. However, NMP seemed especially beneficial for high-risk cases and donation after circulatory death (DCD) hearts. Based on currently available data, MP is non-inferior to standard SCS. Additionally, single-centre studies suggest that NMP could preserve the hearts from donors outside standard acceptability criteria and DCD hearts with comparable results to SCS. Finally, HMP is theoretically safer and simpler to use than NMP. If a machine malfunction or user error occurs, NMP, which perfuses a beating heart, would have a narrower margin of safety. However, further well-designed studies need to be conducted to draw clear conclusions.

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The purpose of the study was to evaluate T2, T1 and extracellular volume (ECV) quantification as novel tissue markers to diagnose acute cardiac rejection. Methods: CMR was prospectively performed in heart transplant patients before or just after routine EMB and before acute rejection therapy. Images were acquired on a 1.5 Tesla scanner including T2 mapping (T2 prepared-SSFP) and T1 mapping using a modified look locker inversion recovery sequence (MOLLI) at basal, mid and apical level in short axis view. T2 and T1 values were measured before and 15 minutes (for T1 mapping) after contrast administration. The results are expressed by the median and the 5th and the 95th percentiles. Results: twenty six patients (age 52±14 years) were included providing 40 comparisons CMR/EMB. Acute rejection (cellular, humoral or clinical symptoms) was diagnosed in 13 patients. Patients with AR had significantly higher global T2 values at 3 levels (58 ms [52-61] vs 55ms [49-55], P= 0.0049 at basal; 57 ms [54-61] vs 51 ms [50-54], P= 0.0010 at median and 60 ms [54-66] vs 54 ms [50-57], P= 0.0119 at apical level). The area under the curve (AUC) for each level was: 0.78; 0.84 and 0.77 respectively. Patients with AR had significantly higher ECV at basal and median level: 35% [33-41] vs 27% [25-31] P= 0.0021 and 33% [28-38] vs 27%[24-31], P= 0.015 respectively. The AUC for each level was; 0.83 and 0.75 respectively. The sensitivity, specificity and diagnosis accuracy for basal T2 (cutoff : 58 ms) were 70%, 96 % and 79% respectively; basal ECV: (cutoff 31%) 89%, 77% and 81% respectively. The best AUC (0.88) was obtained when we combined basal T2 and basal ECV. Conclusion: In heart transplant patients, a combined CMR approach using T2 mapping and ECV quantification provides a high diagnostic accuracy for acute rejection diagnosis and could potentially decrease the number of routine EMB. Further studies are required to confirm these data.

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