Extended post-ex vivo lung perfusion cold preservation predicts primary graft dysfunction and mortality: Results from a multicentric study.

Leiva-Juárez MM, Urso A, Arango Tomás E, Lederer DJ, Sanchez P, Griffith B, Davis RD, Daneshmand M, Hartwig M, Cantu E, Weyant MJ, Bermudez C, D’Cunha J, Machuca T, Wozniak T, Lynch W, Nemeh H, Mulligan M, Song T, Jessen M, Camp PC, Caldeira C, Whitson B, Kreisel D, Ramzy D, D’Ovidio F.

J Heart Lung Transplant. 2020 May 16:S1053-2498(20)31554-0. doi: 10.1016/j.healun.2020.05.002. Online ahead of print.

Background:
Ex vivo lung perfusion (EVLP) allows for a reassessment of lung grafts initially deemed unsuitable for transplantation, increasing the available donor pool; however, this requires a pre- and post-EVLP period of cold ischemic time (CIT). Paucity of data exists on how the sequence of cold normothermic-cold preservations affect outcomes.

Methods:
A total of 110 patients were retrospectively analyzed. Duration of three preservation phases was measured: cold pre-EVLP, EVLP, and cold post-EVLP. The donor and recipient clinical data were collected. Primary graft dysfunction (PGD) and survival were monitored. Risk of mortality or PGD was calculated using Cox proportional hazards and logistic regression models to adjust for baseline characteristics.

Results:
Using the highest quartile, patients were stratified into extended vs non-extended pre-EVLP (<264 vs ≥264 minutes) and post-EVLP (<287 vs ≥287 minutes) CIT. The rates of 1-year mortality (8.4% vs 29.6%, p = 0.013), PGD 2-3 (20.5% vs 52%, p = 0.002), and PGD 3 (8.4% vs 29.6%, p = 0.005) at 72 hours were increased in the extended post-EVLP CIT group. After adjusting for baseline risk factors, the extended group remained an independent predictor of PGD ≥2 (odd ratio: 6.18, 95% CI: 1.88-20.3, p = 0.003) and PGD 3 (odd ratio: 20.4, 95% CI: 2.56-161.9, p = 0.004) at 72 hours and 1-year mortality (hazard ratio: 17.9, 95% CI: 3.36-95.3, p = 0.001). Cold pre-EVLP was not a significant predictor of primary outcomes.

Conclusions:
Extended cold post-EVLP preservation is associated with a risk for PGD and 1-year mortality. Pre-EVLP CIT does not increase mortality or high-grade PGD. These findings from a multicenter trial should caution on the implementation of extended cold preservation after EVLP.

Keywords:
ex vivo lung perfusion; lung transplant; primary graft dysfunction. Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.