The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Donor hyperoxia is a novel risk factor for severe cardiac primary graft dysfunction

Published:January 05, 2023DOI:


      Primary graft dysfunction (PGD) is a major cause of early mortality following heart transplant (HT). Donor risk factors for the development of PGD are incompletely characterized. Donor management goals (DMG) are predefined critical care endpoints used to optimize donors. We evaluated the relationship between DMGs as well as non-DMG parameters, and the development of PGD after HT.


      A cohort of HT recipients from 2 transplant centers between 1/1/12 and 12/31/19 was linked to their respective donors in the United Network for Organ Sharing (UNOS) DMG Registry (n = 1,079). PGD was defined according to modified ISHLT criteria. Variables were subject to univariate and multivariable multinomial modeling with development of mild/moderate or severe PGD as the outcome variable. A second multicenter cohort of 4,010 donors from the DMG Registry was used for validation.


      Mild/moderate and severe PGD occurred in 15% and 6% of the cohort. Multivariable modeling revealed 6 variables independently associated with mild/moderate and 6 associated with severe PGD, respectively. Recipient use of amiodarone plus beta-blocker, recipient mechanical circulatory support, donor age, donor fraction of inspired oxygen (FiO2), and donor creatinine increased risk whereas predicted heart mass ratio decreased risk of severe PGD. We found that donor age and FiO2 ≥ 40% were associated with an increased risk of death within 90 days post-transplant in a multicenter cohort.


      Donor hyperoxia at heart recovery is a novel risk factor for severe primary graft dysfunction and early recipient death. These results suggest that excessive oxygen supplementation should be minimized during donor management.



      ACEI (angiotensin converting enzyme inhibitor), AMIO (amiodarone), ARB (angiotensin receptor antagonist), ARNI (angiotensin receptor - neprilysin inhibitor), AUROC (area under the receiver operating characteristic curve), BB (beta blocker), DMG (donor management goal), ECMO (extracorporeal membrane oxygenation), FiO2 (fraction of inspired oxygen), HT (heart transplant), ISHLT (International Society for Heart and Lung Transplantation), MCS (mechanical circulatory support), MRA (mineralocorticoid receptor antagonist), OPO (organ procurement organization), PGD (primary graft dysfunction), PO2 (atrial partial pressure of oxygen), ROS (reactive oxygen species), RVAD (right ventricular assist device), UNOS (United Network for Organ Sharing)
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        • Kobashigawa J
        • Zuckermann A
        • Macdonald P
        • et al.
        Report from a consensus conference on primary graft dysfunction after cardiac transplantation.
        J Heart Lung Transplant. 2014; 33: 327-340
        • Listijono DR
        • Watson A
        • Pye R
        • et al.
        Usefulness of extracorporeal membrane oxygenation for early cardiac allograft dysfunction.
        J Heart Lung Transplant. 2011; 30: 783-789
        • Benck L
        • Kransdorf EP
        • Emerson DA
        • et al.
        Recipient and surgical factors trigger severe primary graft dysfunction after heart transplant.
        J Heart Lung Transplant. 2021; 40: 970-980
        • Segovia J
        • Cosio MD
        • Barcelo JM
        • et al.
        RADIAL: a novel primary graft failure risk score in heart transplantation.
        J Heart Lung Transplant. 2011; 30: 644-651
        • Avtaar Singh SS
        • Banner NR
        • Rushton S
        • Simon AR
        • Berry C
        • Al-Attar N
        ISHLT primary graft dysfunction incidence, risk factors, and outcome: a UK national study.
        Transplantation. 2019; 103: 336-343
        • Buchan TA
        • Moayedi Y
        • Truby LK
        • et al.
        Incidence and impact of primary graft dysfunction in adult heart transplant recipients: a systematic review and meta-analysis.
        J Heart Lung Transplant. 2021; 40: 642-651
        • Franklin GA
        • Santos AP
        • Smith JW
        • Galbraith S
        • Harbrecht BG
        • Garrison RN.
        Optimization of donor management goals yields increased organ use.
        Am Surg. 2010; 76: 587-594
        • Malinoski DJ
        • Daly MC
        • Patel MS
        • Oley-Graybill C
        • Foster 3rd, CE
        • Salim A.
        Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor.
        J Trauma. 2011; 71 (discussion 6): 990-995
        • Patel MS
        • Zatarain J
        • De La Cruz S
        • et al.
        The impact of meeting donor management goals on the number of organs transplanted per expanded criteria donor: a prospective study from the UNOS Region 5 Donor Management Goals Workgroup.
        JAMA Surg. 2014; 149: 969-975
        • Patel MS
        • De La Cruz S
        • Sally MB
        • Groat T
        • Malinoski DJ.
        Active donor management during the hospital phase of care is associated with more organs transplanted per donor.
        J Am Coll Surg. 2017; 225: 525-531
        • Malinoski DJ
        • Patel MS
        • Ahmed O
        • et al.
        The impact of meeting donor management goals on the development of delayed graft function in kidney transplant recipients.
        Am J Transplant. 2013; 13: 993-1000
        • Swanson EA
        • Adams T
        • Patel MS
        • et al.
        Impact of deceased donor management on donor heart use and recipient graft survival.
        J Am Coll Surg. 2020; 231: 351-360.e5
        • Swanson EA
        • Patel MS
        • Hutchens MP
        • et al.
        Critical care and ventilatory management of deceased organ donors impact lung use and recipient graft survival.
        Am J Transplant. 2021; 21: 4003-4011
        • Schaffer JM
        • Chiu P
        • Singh SK
        • Oyer PE
        • Reitz BA
        • Mallidi HR.
        Heart and combined heart-kidney transplantation in patients with concomitant renal insufficiency and end-stage heart failure.
        Am J Transplant. 2014; 14: 384-396
        • West RM.
        Best practice in statistics: the use of log transformation.
        Ann Clin Biochem. 2022; 59: 162-165
        • Reed RM
        • Netzer G
        • Hunsicker L
        • et al.
        Cardiac size and sex-matching in heart transplantation: size matters in matters of sex and the heart.
        JACC Heart Fail. 2014; 2: 73-83
        • Kransdorf EP
        • Kittleson MM
        • Benck LR
        • et al.
        Predicted heart mass is the optimal metric for size match in heart transplantation.
        J Heart Lung Transplant. 2019; 38: 156-165
        • Moons KG
        • Donders AR
        • Steyerberg EW
        • Harrell FE.
        Penalized maximum likelihood estimation to directly adjust diagnostic and prognostic prediction models for overoptimism: a clinical example.
        J Clin Epidemiol. 2004; 57: 1262-1270
        • Orens JB
        • Boehler A
        • de Perrot M
        • et al.
        A review of lung transplant donor acceptability criteria.
        J Heart Lung Transplant. 2003; 22: 1183-1200
        • Choi AY
        • Jawitz OK
        • Raman V
        • et al.
        Predictors of older donor lung use: are we too good at saying no?.
        Ann Thorac Surg. 2020; 110: 1683-1690
        • Whitford H
        • Kure CE
        • Henriksen A
        • et al.
        A donor PaO2/FiO2 < 300 mm Hg does not determine graft function or survival after lung transplantation.
        J Heart Lung Transplant. 2020; 39: 53-61
        • Stub D
        • Smith K
        • Bernard S
        • et al.
        Air versus oxygen in ST-segment-elevation myocardial infarction.
        Circulation. 2015; 131: 2143-2150
        • Nehme Z
        • Stub D
        • Bernard S
        • et al.
        Effect of supplemental oxygen exposure on myocardial injury in ST-elevation myocardial infarction.
        Heart. 2016; 102: 444-451
        • Chew HC
        • Iyer A
        • Connellan M
        • et al.
        Outcomes of donation after circulatory death heart transplantation in Australia.
        J Am Coll Cardiol. 2019; 73: 1447-1459
      1. JA Kleinmahon, SS Patel, SR Auerbach, J Rossano and MD. Everitt, Hearts transplanted after circulatory death in children: analysis of the International Society for Heart and Lung Transplantation registry[e-pub ahead of print], Pediatr Transplant, 21, 2017.10.1111/petr.13064, accessed January 19, 2023.

        • Watson CJE
        • Kosmoliaptsis V
        • Randle LV
        • et al.
        Normothermic perfusion in the assessment and preservation of declined livers before transplantation: hyperoxia and vasoplegia-important lessons from the first 12 cases.
        Transplantation. 2017; 101: 1084-1098
        • Peng YW
        • Mohammed A
        • Deatrick KB
        • et al.
        Differential effects of normoxic and hyperoxic reperfusion on global myocardial ischemia-reperfusion injury.
        Semin Thorac Cardiovasc Surg. 2019; 31: 188-198
        • Moeslund N
        • Long Zhang Z
        • Bo Ilkjaer L
        • et al.
        High oxygenation during normothermic regional perfusion after circulatory death is beneficial on donor cardiac function in a porcine model.
        Transplantation. 2022; 106: e326-e335
        • Poptsov V
        • Khatutskiy V
        • Skokova A
        • et al.
        Heart transplantation from donors with left ventricular ejection fraction under forty percent.
        Clin Transplant. 2021; 35: e14341