A Comprehensive Review and Pooled Analysis of Clinical Results for Normothermic Ex-Vivo Machine Perfusion for Donation-after-Circulatory-Death Heart Transplantation

Abstract

Background and Objective: Donation-after-circulatory-death (DCD) hearts are now used more often thanks to normothermic ex-vivo machine perfusion (NMP), which allows for prolonged preservation and real-time functional assessment. There is still a lack of comparative outcome data, despite recent ISHLT and ACC/AHA guidelines to the contrary. Compared to traditional donation-after-brain-death (DBD), this review examined the early and intermediate results of adult DCD-NMP heart transplantation.

Methods: A PRISMA-2020 systematic review included research from MEDLINE, Embase, CENTRAL, and Scopus (January 2020–June 2025). The review compared DCD-NMP to DBD hearts, focusing on studies reporting results at least 30 days post-transplantation. The ROBINS-I tool was used to assess bias risk. Pooled risk ratios (RRs) were calculated using a random-effects model (DerSimonian–Laird) with Hartung-Knapp adjustment, and heterogeneity was measured by I2. Publication bias was examined in at least 10 studies.

Results: There were twelve multicenter observational cohorts (1,268 DCD-NMP; 9,442 DBD). Lower 1-year mortality (7.4% vs. 10.2%; RR 0.75, 95% CI 0.59–0.96; I² = 16%) and 5-year mortality (RR 0.72, 95% CI 0.54–0.97; I² = 21%) were associated with DCD-NMP. The DCD-NMP group experienced a significant reduction in ischemic time, averaging 51 minutes (95% CI –68 to –34; I² = 48%), and a lower incidence of primary graft dysfunction (9.7% vs. 14.2%; RR 0.68, 95% CI 0.51–0.91). No significant adverse events linked to the device were observed, and rates of acute rejection after one year were similar across groups (RR 1.02, 95% CI 0.81–1.28; I² = 0%). Funnel plots for 1-year mortality showed no evidence of publication bias.

Conclusions: Compared to DBD transplantation, NMP-assisted DCD heart transplantation shows similar or better survival rates, a shorter ischemic period, and less graft dysfunction, all without increasing rejection or device-related complications. To enable broader adoption, more cost-effectiveness studies and prospective trials are needed.